Publications by authors named "Carl R Schmidt"

84 Publications

Formal robotic training diminishes the learning curve for robotic pancreatoduodenectomy: Implications for new programs in complex robotic surgery.

J Surg Oncol 2021 Feb 2;123(2):375-380. Epub 2020 Nov 2.

Department of Surgery, West Virginia University, Morgantown, West Virginia, USA.

Introduction: The learning curve associated with robotic pancreatoduodenectomy (RPD) is a hurdle for new programs to achieve optimal results. Since early analysis, robotic training has recently expanded, and the RPD approach has been refined. The purpose of this study is to examine RPD outcomes for surgeons who implemented a new program after receiving formal RPD training to determine if such training reduces the learning curve.

Methods: Outcomes for consecutive patients undergoing RPD at a single tertiary institution were compared to optimal RPD benchmarks from a previously reported learning curve analysis. Two surgical oncologists with formal RPD training performed all operations with one surgeon as bedside assistant and the other at the console.

Results: Forty consecutive RPD operations were evaluated. Mean operative time was 354 ± 54 min, and blood loss was 300 ml. Length of stay was 7 days. Three patients (7.5%) underwent conversion to open. Pancreatic fistula affected five patients (12.5%). Operative time was stable over the study and lower than the reported benchmark. These RPD operative outcomes were similar to reported surgeon outcomes after the learning curve.

Conclusion: This study suggests formal robotic training facilitates safe and efficient adoption of RPD for new programs, reducing or eliminating the learning curve.
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http://dx.doi.org/10.1002/jso.26284DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902319PMC
February 2021

Neoadjuvant Capecitabine/Temozolomide for Locally Advanced or Metastatic Pancreatic Neuroendocrine Tumors.

Pancreas 2020 03;49(3):355-360

From the Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH.

Objectives: The combination chemotherapy regimen capecitabine/temozolomide (CAPTEM) is efficacious for metastatic well-differentiated pancreatic neuroendocrine tumors (PNETs), but its role in the neoadjuvant setting has not been established.

Methods: The outcomes of all patients with locally advanced or resectable metastatic PNETs who were treated with neoadjuvant CAPTEM between 2009 and 2017 at 2 high-volume institutions were retrospectively reviewed.

Results: Thirty patients with locally advanced PNET (n = 10) or pancreatic neuroendocrine hepatic metastases (n = 20) received neoadjuvant CAPTEM. Thirteen patients (43%) exhibited partial radiographic response (PR), 16 (54%) had stable disease, and 1 (3%) developed progressive disease. Twenty-six (87%) patients underwent resection (pancreatectomy [n = 12], combined pancreatectomy and liver resection [n = 8], or major hepatectomy alone [n = 6]); 3 (18%) declined surgery despite radiographic PR, and 1 (3%) underwent aborted pancreatoduodenectomy. Median primary tumor size was 5.5 cm, and median Ki-67 index was 3.5%. Rates of PR were similar across tumor grades (P = 0.24). At median follow-up of 49 months, median progression-free survival was 28.2 months and 5-year overall survival was 63%.

Conclusions: Neoadjuvant CAPTEM is associated with favorable radiographic objective response rates for locally advanced or metastatic PNET and may facilitate selection of patients appropriate for surgical resection.
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http://dx.doi.org/10.1097/MPA.0000000000001500DOI Listing
March 2020

Evaluating the ACS-NSQIP Risk Calculator in Primary GI Neuroendocrine Tumor: Results from the United States Neuroendocrine Tumor Study Group.

Am Surg 2019 Dec;85(12):1334-1340

From the *Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio.

The ACS established an online risk calculator to help surgeons make patient-specific estimates of postoperative morbidity and mortality. Our objective was to assess the accuracy of the ACS-NSQIP calculator for estimating risk after curative intent resection for primary GI neuroendocrine tumors (GI-NETs). Adult patients with GI-NET who underwent complete resection from 2000 to 2017 were identified using a multi-institutional database, including data from eight academic medical centers. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using receiver operating characteristic curves and the area under the curve (AUC). Seven hundred three patients were identified who met inclusion criteria. The most commonly performed procedures were resection of the small intestine with anastomosis (N = 193, 26%) and partial colectomy with anastomosis (N = 136, 18%). The majority of patients were younger than 65 years (N = 482, 37%) and ASA Class III (N = 337, 48%). The most common comorbidities were diabetes (N = 128, 18%) and hypertension (N = 395, 56%). Complications among these patients based on ACS NSQIP definitions included any complication (N = 132, 19%), serious complication (N = 118, 17%), pneumonia (N = 7, 1.0%), cardiac complication (N = 1, 0.01%), SSI (N = 80, 11.4%), UTI (N = 17, 2.4%), venous thromboembolism (N = 18, 2.5%), renal failure (N = 16, 2.3%), return to the operating room (N = 27, 3.8%), discharge to nursing/rehabilitation (N = 22, 3.1%), and 30-day mortality (N = 9, 1.3%). The calculator provided reasonable estimates of risk for pneumonia (AUC = 0.721), cardiac complication (AUC = 0.773), UTI (AUC = 0.716), and discharge to nursing/rehabilitation (AUC = 0.779) and performed poorly (AUC < 0.7) for all other complications Fig. 1). The ACS-NSQIP risk calculator estimates a similar proportion of risk to actual events in patients with GI-NET but has low specificity for identifying the correct patients for many types of complications. The risk calculator may require modification for some patient populations.
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December 2019

Tumor burden score predicts tumor recurrence of non-functional pancreatic neuroendocrine tumors after curative resection.

HPB (Oxford) 2020 Aug 9;22(8):1149-1157. Epub 2019 Dec 9.

Division of Surgical Oncology, The Ohio State University Wexner Medical Center, James Comprehensive Cancer Center, Columbus, OH, USA. Electronic address:

Background: To investigate the feasibility of Tumor Burden Score (TBS) to predict tumor recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs).

Method: The TBS cut-off values were determined by a statistical tool, X-tile. The influence of TBS on recurrence-free survival (RFS) was examined.

Results: Among 842 NF-pNETs patients, there was an incremental worsening of RFS as the TBS increased (5-year RFS, low, medium, and high TBS: 92.0%, 73.3%, and 59.3%, respectively; P < 0.001). TBS (AUC 0.74) out-performed both maximum tumor size (AUC 0.65) and number of tumors (AUC 0.5) to predict RFS (TBS vs. maximum tumor size, p = 0.05; TBS vs. number of tumors, p < 0.01). The impact of margin (low TBS: R0 80.4% vs. R1 71.9%, p = 0.01 vs. medium TBS: R0 55.8% vs. R1 37.5%, p = 0.67 vs. high TBS: R0 31.9% vs. R1 12.0%, p = 0.11) and nodal (5-year RFS, low TBS: N0 94.9% vs. N1 68.4%, p < 0.01 vs. medium TBS: N0 81.8% vs. N1 55.4%, p < 0.01 vs. high TBS: N0 58.0% vs. N1 54.2%, p = 0.15) status on 5-year RFS outcomes disappeared among patients who had higher TBS.

Conclusions: TBS was strongly associated with risk of recurrence and outperformed both tumor size and number alone.
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http://dx.doi.org/10.1016/j.hpb.2019.11.009DOI Listing
August 2020

Modeling Human Cancer-induced Cachexia.

Cell Rep 2019 08;28(6):1612-1622.e4

Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University, Columbus, OH 43210, USA; Department of Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA; Hollings Cancer Center, Medical University of South Carolina, Charleston, SC 29425, USA. Electronic address:

Cachexia is a wasting syndrome characterized by pronounced skeletal muscle loss. In cancer, cachexia is associated with increased morbidity and mortality and decreased treatment tolerance. Although advances have been made in understanding the mechanisms of cachexia, translating these advances to the clinic has been challenging. One reason for this shortcoming may be the current animal models, which fail to fully recapitulate the etiology of human cancer-induced tissue wasting. Because pancreatic ductal adenocarcinoma (PDA) presents with a high incidence of cachexia, we engineered a mouse model of PDA that we named KPP. KPP mice, similar to PDA patients, progressively lose skeletal and adipose mass as a consequence of their tumors. In addition, KPP muscles exhibit a similar gene ontology as cachectic patients. We envision that the KPP model will be a useful resource for advancing our mechanistic understanding and ability to treat cancer cachexia.
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http://dx.doi.org/10.1016/j.celrep.2019.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6733019PMC
August 2019

Endoscopic Ultrasound-Guided Confocal Laser Endomicroscopy Increases Accuracy of Differentiation of Pancreatic Cystic Lesions.

Clin Gastroenterol Hepatol 2020 02 18;18(2):432-440.e6. Epub 2019 Jun 18.

Division of Gastroenterology, Hepatology, and Nutrition, The Ohio State University, Columbus, Ohio.

Background & Aims: Imaging patterns from endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) have been associated with specific pancreatic cystic lesions (PCLs). We compared the accuracy of EUS with nCLE in differentiating mucinous from nonmucinous PCLs with that of measurement of carcinoembryonic antigen (CEA) and cytology analysis.

Methods: We performed a prospective study of 144 consecutive patients with a suspected PCL (≥20 mm) who underwent EUS with fine-needle aspiration of pancreatic cysts from June 2015 through December 2018 at a single center; 65 patients underwent surgical resection. Surgical samples were analyzed by histology (reference standard). During EUS, the needle with the miniprobe was placed in the cyst, which was analyzed by nCLE. Fluid was aspirated and analyzed for level of CEA and by cytology. We compared the accuracy of nCLE in differentiating mucinous from nonmucinous lesions with that of measurement of CEA and cytology analysis.

Results: The mean size of dominant cysts was 36.4 ± 15.7 mm and the mean duration of nCLE imaging was 7.3 ± 2.8 min. Among the 65 subjects with surgically resected cysts analyzed histologically, 86.1% had at least 1 worrisome feature based on the 2012 Fukuoka criteria. Measurement of CEA and cytology analysis identified mucinous PCLs with 74% sensitivity, 61% specificity, and 71% accuracy. EUS with nCLE identified mucinous PCLs with 98% sensitivity, 94% specificity, and 97% accuracy. nCLE was more accurate in classifying mucinous vs nonmucinous cysts than the standard method (P < .001). The overall incidence of postprocedure acute pancreatitis was 3.5% (5 of 144); all episodes were mild, based on the revised Atlanta criteria.

Conclusions: In a prospective study, we found that analysis of cysts by nCLE identified mucinous cysts with greater accuracy than measurement of CEA and cytology analysis. EUS with nCLE can be used to differentiate mucinous from nonmucinous PCLs. ClincialTrials.gov no: NCT02516488.
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http://dx.doi.org/10.1016/j.cgh.2019.06.010DOI Listing
February 2020

Role of Adjuvant Multimodality Therapy After Curative-Intent Resection of Ampullary Carcinoma.

JAMA Surg 2019 08;154(8):706-714

Department of Surgery, University of Tennessee Health Science Center, Memphis.

Importance: Ampullary adenocarcinoma is a rare malignant neoplasm that arises within the duodenal ampullary complex. The role of adjuvant therapy (AT) in the treatment of ampullary adenocarcinoma has not been clearly defined.

Objective: To determine if long-term survival after curative-intent resection of ampullary adenocarcinoma may be improved by selection of patients for AT directed by histologic subtype.

Design, Setting, And Participants: This multinational, retrospective cohort study was conducted at 12 institutions from April 1, 2000, to July 31, 2017, among 357 patients with resected, nonmetastatic ampullary adenocarcinoma receiving surgery alone or AT. Cox proportional hazards regression was used to identify covariates associated with overall survival. The surgery alone and AT cohorts were matched 1:1 by propensity scores based on the likelihood of receiving AT or by survival hazard from Cox modeling. Overall survival was compared with Kaplan-Meier estimates.

Exposures: Adjuvant chemotherapy (fluorouracil- or gemcitabine-based) with or without radiotherapy.

Main Outcomes And Measures: Overall survival.

Results: A total of 357 patients (156 women and 201 men; median age, 65.8 years [interquartile range, 58-74 years]) underwent curative-intent resection of ampullary adenocarcinoma. Patients with intestinal subtype had a longer median overall survival compared with those with pancreatobiliary subtype (77 vs 54 months; P = .05). Histologic subtype was not associated with AT administration (intestinal, 52.9% [101 of 191]; and pancreatobiliary, 59.5% [78 of 131]; P = .24). Patients with pancreatobiliary histologic subtype most commonly received gemcitabine-based regimens (71.0% [22 of 31]) or combinations of gemcitabine and fluorouracil (12.9% [4 of 31]), whereas treatment of those with intestinal histologic subtype was more varied (fluorouracil, 50.0% [17 of 34]; gemcitabine, 44.1% [15 of 34]; P = .01). In the propensity score-matched cohort, AT was not associated with a survival benefit for either histologic subtype (intestinal: hazard ratio, 1.21; 95% CI, 0.67-2.16; P = .53; pancreatobiliary: hazard ratio, 1.35; 95% CI, 0.66-2.76; P = .41).

Conclusions And Relevance: Adjuvant therapy was more frequently used in patients with poor prognostic factors but was not associated with demonstrable improvements in survival, regardless of tumor histologic subtype. The value of a multimodality regimen remains poorly defined.
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http://dx.doi.org/10.1001/jamasurg.2019.1170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547142PMC
August 2019

Minimally invasive versus open distal pancreatectomy for pancreatic neuroendocrine tumors: An analysis from the U.S. neuroendocrine tumor study group.

J Surg Oncol 2019 Aug 18;120(2):231-240. Epub 2019 Apr 18.

Department of Surgery, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio.

Background: To determine short- and long-term oncologic outcomes after minimally invasive distal pancreatectomy (MIDP) with open distal pancreatectomy (ODP) for the treatment of pancreatic neuroendocrine tumor (pNET).

Methods: The data of the patients who underwent curative MIDP or ODP for pNET between 2000 and 2016 were collected from a multi-institutional database. Propensity score matching (PSM) was used to generate 1:1 matched patients with MIDP and ODP.

Results: A total of 576 patients undergoing curative DP for pNET were included. Two hundred and fourteen (37.2%) patients underwent MIDP, whereas 362 (62.8%) underwent ODP. MIDP was increasingly performed over time (2000-2004: 9.3% vs 2013-2016: 54.8%; P < 0.01). In the matched cohort (n = 141 in each group), patients who underwent MIDP had less blood loss (median, 100 vs 200 mL, P < 0.001), lower incidence of Clavien-Dindo ≥ III complications (12.1% vs 24.8%, P = 0.026), and a shorter hospital stay versus ODP (median, 4 versus 7 days, P = 0.026). Patients who underwent MIDP had a lower incidence of recurrence (5-year cumulative recurrence, 10.1% vs 31.1%, P < 0.001), yet equivalent overall survival (OS) rate (5-year OS, 92.1% vs 90.9%, P = 0.550) compared with patients who underwent OPD.

Conclusion: Patients undergoing MIDP over ODP in the treatment of pNET had comparable oncologic surgical metrics, as well as similar long-term OS.
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http://dx.doi.org/10.1002/jso.25481DOI Listing
August 2019

Evaluating the ACS NSQIP Risk Calculator in Primary Pancreatic Neuroendocrine Tumor: Results from the US Neuroendocrine Tumor Study Group.

J Gastrointest Surg 2019 11 2;23(11):2225-2231. Epub 2019 Apr 2.

Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH, USA.

Background: In a changing health care environment where patient outcomes will be more closely scrutinized, the ability to predict surgical complications is becoming increasingly important. The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) online risk calculator is a popular tool to predict surgical risk. This paper aims to assess the applicability of the ACS NSQIP calculator to patients undergoing surgery for pancreatic neuroendocrine tumors (PNETs).

Methods: Using the US Neuroendocrine Tumor Study Group (USNET-SG), 890 patients who underwent pancreatic procedures between 1/1/2000-12/31/2016 were evaluated. Predicted and actual outcomes were compared using C-statistics and Brier scores.

Results: The most commonly performed procedure was distal pancreatectomy, followed by standard and pylorus-preserving pancreaticoduodenectomy. For the entire group of patients studied, C-statistics were highest for discharge destination (0.79) and cardiac complications (0.71), and less than 0.7 for all other complications. The Brier scores for surgical site infection (0.1441) and discharge to nursing/rehabilitation facility (0.0279) were below the Brier score cut-off, while the rest were equal to or above and therefore not useful for interpretation.

Conclusion: This work indicates that the ACS NSQIP risk calculator is a valuable tool that should be used with caution and in coordination with clinical assessment for PNET clinical decision-making.
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http://dx.doi.org/10.1007/s11605-019-04120-4DOI Listing
November 2019

Compliance with preoperative care measures reduces surgical site infection after colorectal operation.

J Surg Oncol 2019 Mar 24;119(4):497-502. Epub 2018 Dec 24.

Department of Surgery, Division of Surgical Oncology, Wexner Medical Center, James Cancer Hospital, Solove Research Institute, The Ohio State University, Columbus, Ohio.

Background: Surgical site infections (SSIs) are a major cause of morbidity complicating colorectal operations. Several evidence-based preoperative strategies are associated with decreased SSI rates. We hypothesize that compliance with multiple strategies is associated with lower incidence of SSI after the elective colorectal operation.

Methods: Preoperative care measure compliance before colorectal operations were assessed. Measures included antiseptic wash the night before and day of operation, oral antibiotic, and mechanical bowel preparation, antibiotic prophylaxis, Chloraprep skin preparation, and hair clipping. Rates of SSI after colectomy and other pertinent outcomes were stratified by full and partial compliance with preoperative measures. Exclusion criteria included bowel perforation, ischemia, complete obstruction, intra-abdominal abscess, and no intraoperative skin closure.

Results: Eight hundred twenty-six subjects underwent colectomy between 2010 and 2016; 469 met inclusion criteria. Compliance with all measures occurred in 214 (46%) and was independently associated with lower postoperative infection rates (odds ratio [OR], 0.37; confidence interval [CI], 0.16-0.85; P = 0.02). SSI occurred in 51 (11%): was superficial in 35 (7%); deep in 5 (1%); and organ space in 11 (2%). SSI rates were reduced from 16% (partial or no compliance group) to 5% (full compliance group). No stand-alone intervention was independently associated with decreased SSI rate. Multivariate analysis found the following factors associated with a lower risk of SSI: full compliance with all five process measures, lower BMI, nonsmoker, and minimally invasive operation.

Discussion And Conclusion: Compliance with preoperative care strategies reduces rates of SSI after colectomy with a cumulative effect more pronounced than any single intervention reinforcing the need for protocol-driven and evidence-based care for patients undergoing colorectal operations.
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http://dx.doi.org/10.1002/jso.25346DOI Listing
March 2019

Perioperative use of blood products is associated with risk of morbidity and mortality after surgery.

Am J Surg 2019 07 27;218(1):62-70. Epub 2018 Nov 27.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, United States. Electronic address:

Background: Administration of blood products may be associated with increased morbidity and perioperative mortality in surgical patients.

Methods: Patients aged 18 + who underwent gastrointestinal surgery at the Ohio State University Wexner Medical Center 9/10/2015-5/9/2018 were identified. Multivariable logistic regression models were used to evaluate impact of blood product use on survival and complications, as well as to identify factors associated with receipt of transfusions.

Results: Among 10,756 patients, 35,517 units of blood products were transfused. Preoperative nadir hemoglobin was associated with receipt of blood product transfusion (OR 0.55, 95% CI 0.53, 0.68). After adjusting for patient and procedural characteristics, patients undergoing transfusion of blood products had an increased risk of perioperative mortality (OR 7.80, 95% CI 6.02, 10.10).

Conclusions: The use of blood products was associated with increased risk of complication and death. Patient blood management programs should be implemented to provide rational criteria and guidance for the transfusion of blood products.
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http://dx.doi.org/10.1016/j.amjsurg.2018.11.015DOI Listing
July 2019

Neutrophil Lymphocyte Ratio and Transarterial Chemoembolization in Neuroendocrine Tumor Metastases.

J Surg Res 2018 12 18;232:369-375. Epub 2018 Jul 18.

The Ohio State University Wexner Medical Center, Columbus, Ohio. Electronic address:

Background: The neutrophil-to-lymphocyte ratio (NLR) has been shown to be predictive of outcomes in various cancers, including neuroendocrine tumors (NETs), and cancer-related treatments, including transarterial chemoembolization (TACE). We hypothesized that NLR could be predictive of response to TACE in patients with metastatic NET.

Methods: We reviewed 262 patients who underwent TACE for metastatic NET at a single tertiary medical center from 2000 to 2016. NLR was calculated from blood work drawn 1 d before TACE, as well as 1 d, 1 wk, and 6 mo after treatment.

Results: The median post-TACE overall survival (OS) of the entire cohort was 30.1 mo. Median OS of patients with a pre-TACE NLR ≤ 4 was 33.3 mo versus 21.1 mo for patients with a pre-TACE NLR >4 (P = 0.005). At 6 mo, the median OS for patients with post-TACE NLR > pre-TACE NLR was 21.4 mo versus 25.8 mo for patients with post-TACE NLR ≤ pre-TACE NLR (P = 0.007). On multivariate analysis, both pre-TACE NLR and 6-mo post-TACE NLR were independent predictors of survival. NLR values from 1-d and 1-wk post-TACE did not correlate with outcome.

Conclusions: An elevated NLR pre-TACE and an NLR that has not returned to its pre-TACE value several months after TACE correlate with outcomes in patients with NET and liver metastases. This value can easily be calculated from laboratory results routinely obtained as part of preprocedural and postprocedural care, potential treatment strategies.
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http://dx.doi.org/10.1016/j.jss.2018.06.058DOI Listing
December 2018

Influence of carcinoid syndrome on the clinical characteristics and outcomes of patients with gastroenteropancreatic neuroendocrine tumors undergoing operative resection.

Surgery 2019 03 28;165(3):657-663. Epub 2018 Oct 28.

Division of Surgical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH. Electronic address:

Background: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized.

Methods: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome.

Results: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64-1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis.

Conclusion: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.
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http://dx.doi.org/10.1016/j.surg.2018.09.008DOI Listing
March 2019

Implementation and early outcomes for a surgeon-directed hepatic arterial infusion pump program for colorectal liver metastases.

J Surg Oncol 2018 Dec;118(7):1065-1073

Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, Columbus, Ohio.

Introduction: Hepatic arterial infusion pump (HAIP) therapy for colorectal liver metastases (CRLM) is beneficial in selected patients yet wide acceptance in the oncology community is lacking.

Methods: A surgeon-led team implemented a HAIP program in 2012. Pumps were placed by laparotomy for CRLM and fluorodeoxyuridine was infused via HAIP every 28 days without systemic chemotherapy supervised by the operating surgeon.

Results: Sixty patients were treated with HAIP, either in the adjuvant setting after liver resection or ablation of CRLM in 26 (43%) patients or with the unresectable disease in 34 (57%). Perioperative complications occurred in 19 (32%) and pump-specific complications in 14 (23%) that included intrahepatic biliary stricture in one (2%). Time to liver progression was a median 9.2 months (95% CI, 3.1-15.3 months) in unresectable patients and liver recurrence was a median 24.7 months (2.5-46.9 months) in the adjuvant group. Estimated 3-year overall survival from the time of HAIP placement was 64% in the adjuvant group and 37% in the unresectable group. Sarcopenia was prevalent (48%) and was associated with a worse survival (HR 2.4, 95% CI, 1.1-5.0).

Conclusion: A surgeon-led HAIP program may achieve outcomes on par with those of experienced centers and foster strong relationships between surgical and medical oncologists.
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http://dx.doi.org/10.1002/jso.25249DOI Listing
December 2018

Surgery Provides Long-Term Survival in Patients with Metastatic Neuroendocrine Tumors Undergoing Resection for Non-Hormonal Symptoms.

J Gastrointest Surg 2019 01 17;23(1):122-134. Epub 2018 Oct 17.

Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, 320 W 10th Ave, M256 Starling Loving Hall, Columbus, OH, 43210-1267, USA.

Introduction: Patients with metastatic neuroendocrine tumor (NET) often have an indolent disease course yet the outcomes for patients with metastatic NET undergoing surgery for non-hormonal (NH) symptoms of GI obstruction, bleeding, or pain is not known.

Methods: We identified patients with metastatic gastroenteropancreatic NET who underwent resection from 2000 to 2016 at 8 academic institutions who participated in the US Neuroendocrine Tumor Study Group.

Results: Of 581 patients with metastatic NET to liver (61.3%), lymph nodes (24.1%), lung (2.1%), and bone (2.5%), 332 (57.1%) presented with NH symptoms of pain (n = 223, 67.4%), GI bleeding (n = 54, 16.3%), GI obstruction (n = 49, 14.8%), and biliary obstruction (n = 22, 6.7%). Most patients were undergoing their first operation (85.4%) within 4 weeks of diagnosis. The median overall survival was 110.4 months, and operative intent predicted survival (p < 0.001) with 66.3% undergoing curative resection. Removal of all metastatic disease was associated with the longest median survival (112.5 months) compared to debulking (89.2 months), or palliative resection (50.0 months; p < 0.001). The 1-, 3-, and 12-month mortality was 3.0%, 4.5%, and 9.0%, respectively. Factors associated with 1-year mortality included palliative operations (OR 6.54, p = 0.006), foregut NET (5.62, p = 0.042), major complication (4.91, p = 0.001), and high tumor grade (11.2, p < 0.001). The conditional survival for patients who lived past 1 year was 119 months.

Conclusions: Patients with metastatic NET and NH symptoms that necessitate surgery have long-term survival, and goals of care should focus on both oncologic and quality of life impact. Surgical intervention remains a critical component of multidisciplinary care of symptomatic patients.
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http://dx.doi.org/10.1007/s11605-018-3986-4DOI Listing
January 2019

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

Surgery 2019 03 29;165(3):548-556. Epub 2018 Sep 29.

Division of Surgical Oncology, the Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, OH. Electronic address:

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.
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http://dx.doi.org/10.1016/j.surg.2018.08.015DOI Listing
March 2019

Prognostic Impact of Serum Pancreastatin Following Chemoembolization for Neuroendocrine Tumors.

Ann Surg Oncol 2018 Nov 4;25(12):3613-3620. Epub 2018 Sep 4.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Purpose: The objective of this study was to investigate the prognostic impact of the biomarker serum pancreastatin in patients with metastatic neuroendocrine tumors (NETs) treated with transarterial chemoembolization (TACE).

Methods: Patients with metastatic NET treated with TACE at a single institution from 2000 to 2013 were analyzed. Patient demographics, response to therapy, and long-term survival were compared with baseline pancreastatin level and changes in pancreastatin levels after TACE.

Results: A total of 188 patients underwent TACE during the study period. An initial pancreastatin level greater than 5000 pg/mL correlated with worse overall survival (OS) from time of first TACE (median OS, 58.5 vs. 22.1 months, p < 0.001). A decrease in pancreastatin level by 50% or more after TACE treatment correlated with improved OS (median OS 53.8 vs. 29.9 months, p = 0.032). Patients with carcinoid syndrome were more likely to have a subsequent increase in pancreastatin after initial drop post-TACE (78.1 vs. 55.2%, p = 0.002). Patients with an increase in pancreastatin levels after initial drop post-TACE were more likely to have liver progression on imaging (70.7 vs. 40.7%, p = 0.005) and more likely to need repeat TACE (21.1 vs. 6.7%, p = 0.009).

Conclusions: For patients with liver metastases from NET treated with TACE, pancreastatin measurement may be a useful prognostic indicator. Extreme high levels before TACE can predict poor outcomes, whereas significant drops in pancreastatin after TACE correlate with improved survival. An increase in levels after initial decrease may predict progressive liver disease requiring repeat TACE. As such, pancreastatin levels should be measured throughout the TACE treatment period.
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http://dx.doi.org/10.1245/s10434-018-6741-xDOI Listing
November 2018

What is the Incidence of Malignancy in Resected IPMN? An Analysis of Over 100 U.S. Institutions in a Single Year.

Ann Surg Oncol 2018 Jul 19;25(7):1797-1798. Epub 2018 Apr 19.

Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

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http://dx.doi.org/10.1245/s10434-018-6478-6DOI Listing
July 2018

Accuracy of the ACS NSQIP Online Risk Calculator Depends on How You Look at It: Results from the United States Gastric Cancer Collaborative.

Am Surg 2018 Mar;84(3):358-364

The objective of this study is to assess the accuracy of the American College of Surgeons National Surgical Quality Improvement Program online risk calculator for estimating risk after operation for gastric cancer using the United States Gastric Cancer Collaborative. Nine hundred and sixty-five patients who underwent resection of gastric adenocarcinoma between January 2000 and December 2012 at seven academic medical centers were included. Actual complication rates and outcomes for patients were compared. Most of the patients underwent total gastrectomy with Roux-en-Y reconstruction (404, 41.9%) and partial gastrectomy with gastrojejunostomy (239, 24.8%) or Roux-en-Y reconstruction (284, 29.4%). The C-statistic was highest for venous thromboembolism (0.690) and lowest for renal failure at (0.540). All C-statistics were less than 0.7. Brier scores ranged from 0.010 for venous thromboembolism to 0.238 for any complication. General estimates of risk for the cohort were variable in terms of accuracy. Improving the ability of surgeons to estimate preoperative risk for patients is critically important so that efforts at risk reduction can be personalized to each patient. The American College of Surgeons National Surgical Quality Improvement Program risk calculator is a rapid and easy-to-use tool and validation of the calculator is important as its use becomes more common.
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March 2018

Surgical Treatment of Metastatic Colorectal Cancer.

Surg Oncol Clin N Am 2018 04 15;27(2):377-399. Epub 2017 Dec 15.

Division of Surgical Oncology, Department of Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital and Solove Research Institute, 395 West 12th Avenue, Suite 670, Columbus, OH 43210-1267, USA. Electronic address:

Surgical treatment of metastatic colorectal cancer offers a chance for cure or prolonged survival, particularly for those with more favorable prognostic factors and limited tumor burden. The treatment plan requires multidisciplinary evaluation because multiple therapy options exist. Advanced surgical techniques, adjuncts to resection, and modern chemotherapy all contribute to best outcomes for patients with hepatic metastases. Although cure is less common for patients with metastasis to lung or peritoneum, surgical resection for the former and cytoreduction and intraperitoneal chemotherapy for the latter may help to achieve cancer control in selected patients.
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http://dx.doi.org/10.1016/j.soc.2017.11.010DOI Listing
April 2018

Development and prospective validation of a model estimating risk of readmission in cancer patients.

J Surg Oncol 2018 May 26;117(6):1113-1118. Epub 2018 Feb 26.

James Caner Hospital and Solove Research Institute, Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio.

Introduction: Hospital readmissions among cancer patients are common. While several models estimating readmission risk exist, models specific for cancer patients are lacking.

Methods: A logistic regression model estimating risk of unplanned 30-day readmission was developed using inpatient admission data from a 2-year period (n = 18 782) at a tertiary cancer hospital. Readmission risk estimates derived from the model were then calculated prospectively over a 10-month period (n = 8616 admissions) and compared with actual incidence of readmission.

Results: There were 2478 (13.2%) unplanned readmissions. Model factors associated with readmission included: emergency department visit within 30 days, >1 admission within 60 days, non-surgical admission, solid malignancy, gastrointestinal cancer, emergency admission, length of stay >5 days, abnormal sodium, hemoglobin, or white blood cell count. The c-statistic for the model was 0.70. During the 10-month prospective evaluation, estimates of readmission from the model were associated with higher actual readmission incidence from 20.7% for the highest risk category to 9.6% for the lowest.

Conclusions: An unplanned readmission risk model developed specifically for cancer patients performs well when validated prospectively. The specificity of the model for cancer patients, EMR incorporation, and prospective validation justify use of the model in future studies designed to reduce and prevent readmissions.
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http://dx.doi.org/10.1002/jso.24968DOI Listing
May 2018

Identification of patients at high risk for post-discharge venous thromboembolism after hepato-pancreato-biliary surgery: which patients benefit from extended thromboprophylaxis?

HPB (Oxford) 2018 07 19;20(7):621-630. Epub 2018 Feb 19.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Cancer Hospital and Solove Research Institute, Columbus, OH, USA. Electronic address:

Background: The objective of the current study was to define risk factors associated with the 30-day post-operative risk of VTE after HPB surgery and create a model to identify patients at highest risk of post-discharge VTE.

Methods: Patients who underwent hepatectomy or pancreatectomy in the ACS-NSQIP Participant Use Files 2011-2015 were identified. Logistic regression modeling was used; a model to predict post-discharge VTE was developed. Model discrimination was tested using area under the curve (AUC).

Results: Among 48,860 patients, the overall 30-day incidence of VTE after hepatectomy and pancreatectomy was 3.2% (n = 1580) with 1.1% (n = 543) of VTE events occurring after discharge. Patients who developed post-discharge VTE were more likely to be white, had a higher median BMI, have undergone pancreatic surgery, had longer median operative times, and to have had a transfusion. A weighted prediction model demonstrated good calibration and fair discrimination (AUC = 0.63). A score of ≥-4.50 had maximum sensitivity and specificity, resulting in 44% of patients being treating with prophylaxis for an overall VTE risk of 1.1%.

Conclusions: Utilizing independent factors associated with post-discharge VTE, a prediction model was able to stratify patients according to risk of VTE and may help identify patients who are most likely to benefit from pharmacoprophylaxis.
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http://dx.doi.org/10.1016/j.hpb.2018.01.004DOI Listing
July 2018

The Impact of Intraoperative Re-Resection of a Positive Bile Duct Margin on Clinical Outcomes for Hilar Cholangiocarcinoma.

Ann Surg Oncol 2018 May 22;25(5):1140-1149. Epub 2018 Feb 22.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: The impact of re-resection of a positive intraoperative bile duct margin on clinical outcomes for resectable hilar cholangiocarcinoma (HCCA) remains controversial. We sought to define the impact of re-resection of an initially positive frozen-section bile duct margin on outcomes of patients undergoing surgery for HCCA.

Methods: Patients who underwent curative-intent resection for HCCA between 2000 and 2014 were identified at 10 hepatobiliary centers. Short- and long-term outcomes were analyzed among patients stratified by margin status.

Results: Among 215 (83.7%) patients who underwent frozen-section evaluation of the bile duct, 80 (37.2%) patients had a positive (R1) ductal margin, 58 (72.5%) underwent re-resection, and 29 ultimately had a secondary negative margin (secondary R0). There was no difference in morbidity, 30-day mortality, and length of stay among patients who had primary R0, secondary R0, and R1 resection (all p > 0.10). Median and 5-year survival were 22.3 months and 23.3%, respectively, among patients who had a primary R0 resection compared with 18.5 months and 7.9%, respectively, for patients with an R1 resection (p = 0.08). In contrast, among patients who had a secondary R0 margin with re-resection of the bile duct margin, median and 5-year survival were 30.6 months and 44.3%, respectively, which was comparable to patients with a primary R0 margin (p = 0.804). On multivariable analysis, R1 margin resection was associated with decreased survival (R1: hazard ratio [HR] 1.3, 95% confidence interval [CI] 1.0-1.7; p = 0.027), but secondary R0 resection was associated with comparable long-term outcomes as primary R0 resection (HR 0.9, 95% CI 0.4-2.3; p = 0.829).

Conclusions: Additional resection of a positive frozen-section ductal margin to achieve R0 resection was associated with improved long-term outcomes following curative-intent resection of HCCA.
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http://dx.doi.org/10.1245/s10434-018-6382-0DOI Listing
May 2018

Nomogram predicting the risk of recurrence after curative-intent resection of primary non-metastatic gastrointestinal neuroendocrine tumors: An analysis of the U.S. Neuroendocrine Tumor Study Group.

J Surg Oncol 2018 Apr 15;117(5):868-878. Epub 2018 Feb 15.

Division of Surgical Oncology, The Ohio State University Wexner Medical Center and James Comprehensive Cancer Center, Columbus, Ohio.

Background: The risk of recurrence after resection of non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is poorly defined. We developed/validated a nomogram to predict risk of recurrence after curative-intent resection.

Methods: A training set to develop the nomogram and test set for validation were identified. The predictive ability of the nomogram was assessed using c-indices.

Results: Among 1477 patients, 673 (46%) were included in the training set and 804 (54%) in y the test set. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05-1.10; P < 0.001). GEP-NET invading adjacent organs had a HR of 1.65 (95% CI, 1.03-2.65; P = 0.038), similar to tumors ≥3 cm (HR 1.67, 95% CI, 1.11-2.51; P = 0.014). Patients with 1-3 positive nodes and patients with >3 positive nodes had a HR of 1.81 (95% CI, 1.12-2.87; P = 0.014) and 2.51 (95% CI, 1.50-4.24; P < 0.001), respectively. The nomogram demonstrated good ability to predict risk of recurrence (c-index: training set, 0.739; test set, 0.718).

Conclusion: The nomogram was able to predict the risk of recurrence and can be easily applied in the clinical setting.
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http://dx.doi.org/10.1002/jso.24985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5992105PMC
April 2018

Exosomes in Pancreatic Cancer: from Early Detection to Treatment.

J Gastrointest Surg 2018 04 8;22(4):737-750. Epub 2018 Feb 8.

Department of Surgery, Division of Surgical Oncology, The Ohio State University Wexner Medical Center, 320 W 10th Ave. M256 Starling Loving Hall, Columbus, OH, 43210, USA.

Background: Pancreatic cancer (PC) remains one of the most fatal forms of cancer worldwide with incidence nearly equal to mortality. This is often attributed to the fact that diagnosis is often not made until later disease stages when treatment proves difficult. Efforts have been made to reduce the mortality of PC through improvements in early screening techniques and treatments of late-stage disease. Exosomes, small extracellular vesicles involved in cellular communication, have shown promise in helping understand PC disease biology.

Methods: In this review, we discuss current studies of the role of exosomes in PC physiology, and their potential use as diagnostic and treatment tools.

Results: Exosomes have a role in diagnosing pancreatic cancer and in understanding tumor biology including migration, proliferation, chemoresistance, immunosuppression, cachexia and diabetes, and have a potential role in therapy for pancreatic cancer.

Conclusions: Exosomal analysis is beneficial in demonstrating mechanisms behind PC growth and metastasis, immunosuppression, drug resistance, and paraneoplastic conditions. Furthermore, the use of exosomes can be beneficial in detecting early-stage PC and exosomes have potential applications as therapeutic targets.
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http://dx.doi.org/10.1007/s11605-018-3693-1DOI Listing
April 2018

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

World J Surg 2018 09;42(9):2919-2929

Department of Surgery, The Urban Meyer III and Shelley Meyer Chair for Cancer Research, The Ohio State University Wexner Medical Center, Columbus, OH, USA.

Background: Time 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.

Methods: A 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.

Results: With a median follow-up of 18.0 months, 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 y = -0.465x + 16.99 and y = -0.12x + 7.16. The intercept value of the two lines was 28.5 months, and therefore, 30 months (2.5 years) was defined as the cutoff to differentiate early from late recurrence. Among 99 patients who experienced recurrence, the majority (n = 80, 80.8%) occurred within the first 2.5 years (early recurrence), while 19.2% of recurrences occurred beyond 2.5 years (late recurrence). Early recurrence was more likely present as distant disease (75.1% vs. 31.6%, p = 0.001) and was associated with a worse OS (Median OS, early 21.5 vs. late 50.4 months, p < 0.001). On multivariable analysis, poor tumor differentiation (HR 10.3, p = 0.021), microvascular invasion (HR 3.3, p = 0.037), perineural invasion (HR 3.9, p = 0.029), lymph node metastases (HR 5.0, p = 0.004), and microscopic positive margin (HR 3.5, p = 0.046) were independent risk factors associated with early recurrence.

Conclusions: Early 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.
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http://dx.doi.org/10.1007/s00268-018-4530-0DOI Listing
September 2018

Circulating monocyte chemoattractant protein-1 (MCP-1) is associated with cachexia in treatment-naïve pancreatic cancer patients.

J Cachexia Sarcopenia Muscle 2018 04 7;9(2):358-368. Epub 2018 Jan 7.

Arthur G. James Comprehensive Cancer Center Cancer Cachexia Program, The Ohio State University, Columbus, OH, 43210, USA.

Background: Cancer-associated wasting, termed cancer cachexia, has a profound effect on the morbidity and mortality of cancer patients but remains difficult to recognize and diagnose. While increases in circulating levels of a number of inflammatory cytokines have been associated with cancer cachexia, these associations were generally made in patients with advanced disease and thus may be associated with disease progression rather than directly with the cachexia syndrome. Thus, we sought to assess potential biomarkers of cancer-induced cachexia in patients with earlier stages of disease.

Methods: A custom multiplex array was used to measure circulating levels of 25 soluble factors from 70 pancreatic cancer patients undergoing attempted tumour resections. A high-sensitivity multiplex was used for increased sensitivity for nine cytokines.

Results: Resectable pancreatic cancer patients with cachexia had low levels of canonical pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), interferon-γ (IFN-γ), and tumour necrosis factor (TNF). Even in our more sensitive analysis, these cytokines were not associated with cancer cachexia. Of the 25 circulating factors tested, only monocyte chemoattractant protein-1 (MCP-1) was increased in treatment-naïve cachectic patients compared with weight stable patients and identified as a potential biomarker for cancer cachexia. Although circulating levels of leptin and granulocyte-macrophage colony-stimulating factor (GM-CSF) were found to be decreased in the same cohort of treatment-naïve cachectic patients, these factors were closely associated with body mass index, limiting their utility as cancer cachexia biomarkers.

Conclusions: Unlike in advanced disease, it is possible that cachexia in patients with resectable pancreatic cancer is not associated with high levels of classical markers of systemic inflammation. However, cachectic, treatment-naïve patients have higher levels of MCP-1, suggesting that MCP-1 may be useful as a biomarker of cancer cachexia.
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http://dx.doi.org/10.1002/jcsm.12251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5879958PMC
April 2018

The impact of caudate lobe resection on margin status and outcomes in patients with hilar cholangiocarcinoma: a multi-institutional analysis from the US Extrahepatic Biliary Malignancy Consortium.

Surgery 2018 04 3;163(4):726-731. Epub 2018 Jan 3.

Department of Surgery, University of Louisville, Louisville, KY. Electronic address:

Background: The objective of this study was to determine the impact of caudate resection on margin status and outcomes during resection of extrahepatic hilar cholangiocarcinoma.

Methods: A database of 1,092 patients treated for biliary malignancies at institutions of the Extrahepatic Biliary Malignancy Consortium was queried for individuals undergoing curative-intent resection for extrahepatic hilar cholangiocarcinoma. Patients who did versus did not undergo concomitant caudate resection were compared with regard to demographic, baseline, and tumor characteristics as well as perioperative outcomes.

Results: A total of 241 patients underwent resection for a hilar cholangiocarcinoma, of whom 85 underwent caudate resection. Patients undergoing caudate resection were less likely to have a final positive margin (P = .01). Kaplan-Meier curve of overall survival for patients undergoing caudate resection indicated no improvement over patients not undergoing caudate resection (P = .16). On multivariable analysis, caudate resection was not associated with improved overall survival or recurrence-free survival, although lymph node positivity was associated with worse overall survival and recurrence-free survival, and adjuvant chemoradiotherapy was associated with improved overall survival and recurrence-free survival.

Conclusion: Caudate resection is associated with a greater likelihood of margin-negative resection in patients with extrahepatic hilar cholangiocarcinoma. Precise preoperative imaging is critical to assess the extent of biliary involvement, so that all degrees of hepatic resections are possible at the time of the initial operation.
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http://dx.doi.org/10.1016/j.surg.2017.10.028DOI Listing
April 2018

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

World J Surg 2018 07;42(7):2242-2251

Division of Surgical Oncology, Department of Surgery, Wexner Medical Center, James Cancer Hospital, Solove Research Institute, Health Services Management and Policy, The Ohio State University, 395 W. 12th Ave., Suite 670, Columbus, OH, USA.

Background: Given 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.

Methods: Patients 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's J index (sensitivity + specificity - 1). 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.

Results: Among 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 P = 0.7137) and good discrimination (area under the curve (AUC) = 0.68; validation set, AUC = 0.70). 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%.

Conclusion: Approximately 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.
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http://dx.doi.org/10.1007/s00268-017-4447-zDOI Listing
July 2018

Adjuvant therapy is associated with improved survival after curative resection for hilar cholangiocarcinoma: A multi-institution analysis from the U.S. extrahepatic biliary malignancy consortium.

J Surg Oncol 2018 Mar 28;117(3):363-371. Epub 2017 Dec 28.

Department of Surgery, Washington University School of Medicine, St Louis, Missouri.

Background: Curative-intent treatment for localized hilar cholangiocarcinoma (HC) requires surgical resection. However, the effect of adjuvant therapy (AT) on survival is unclear. We analyzed the impact of AT on overall (OS) and recurrence free survival (RFS) in patients undergoing curative resection.

Methods: We reviewed patients with resected HC between 2000 and 2015 from the ten institutions participating in the U.S. Extrahepatic Biliary Malignancy Consortium. We analyzed the impact of AT on RFS and OS. The probability of RFS and OS were calculated in the method of Kaplan and Meier and analyzed using multivariate Cox regression analysis.

Results: A total of 249 patients underwent curative resection for HC. Patients who received AT and those who did not had similar demographic and preoperative features. In a multivariate Cox regression analysis, AT conferred a significant protective effect on OS (HR 0.58, P = 0.013), and this was maintained in a propensity matched analysis (HR 0.66, P = 0.033). The protective effect of AT remained significant when node negative patients were excluded (HR 0.28, P = 0.001), while it disappeared (HR 0.76, P = 0.260) when node positive patients were excluded.

Conclusions: AT should be strongly considered after curative-intent resection for HC, particularly in patients with node positive disease.
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http://dx.doi.org/10.1002/jso.24836DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5924689PMC
March 2018