Background: Carbohydrate antigen (CA) 19-9 is a biomarker to monitor treatment effect. A threshold to predict prognostic significance remains undefined. We evaluated the impact of CA19-9 on overall survival (OS) in patients with early-stage pancreatic cancer (PC) utilizing the National Cancer Database (NCDB). Methods: The NCDB was queried from 2010 to 2014 to identify patients with clinical stage I–II PC. Patients who had undocumented pretreatment CA19-9 were excluded. Patients were stratified into two cohorts: CA19-9 < 98 U/mL and CA19-9 ≥ 98 U/mL, and further categorized into surgery versus no surgery. Twelve- and 24-month OS rates are reported. Results: Overall, 32,382 patients (stage I: 12,173; stage II: 20,209) were included. The majority of stage I (52.1%) and II (60%) patients had CA19-9 ≥ 98 U/mL. Stage I–II patients with CA19-9 < 98 U/mL had improved OS rates (stage I: 67.5%, 42.6%; stage II: 59.8%, 32.8%) compared with stage I and II patients with CA19-9 ≥ 98 U/mL (stage I: 50.7%, 26.9%; stage II: 48.1%, 22%). Among resected stage I patients, CA19-9 <98 U/mL was associated with improved OS (< 98: 80.5%, 56%; ≥ 98: 70.2%, 42.8%), and a similar trend was seen in resected stage II patients (< 98: 77.6%, 49.9%; ≥ 98: 71%, 39.2%). Unresected stage I patients with lower CA19-9 had improved OS (< 98: 42.1%, 17.5; ≥ 98: 29.9%, 10%), with similar findings in unresected stage II patients (< 98: 41.1%, 15.3%; ≥ 98: 33.4%, 10.6%). Conclusions: Our study demonstrated the prognostic value of CA19-9 in patients with clinical stage I–II PC, with a value < 98 U/mL demonstrating improved survival. Surgery significantly improved survival at 12 and 24 months irrespective of CA19-9.

Background: Hepatic epithelioid hemangioendothelioma (HEH) is a rare vascular tumor of unknown etiology and unpredictable natural history. To date, no large-scale studies have been published evaluating this disease due to its rare occurrence. Methods: The National Cancer Database was reviewed between 2004 and 2016 to identify patients with HEH. Univariate analysis with overall survival (OS) was performed by Cox proportional hazards model. Kaplan–Meier method was used to create OS curves and compared using the log-rank test. Results: We identified 229 patients with HEH. The majority of patients were female (61.1%), white (84.3%), and had a Charlson–Deyo score of 0 (75%). Chemotherapeutic intervention was seen in 26% of the patients while 33% received surgical intervention in the form of wedge/segmental liver resection (n = 27), hepatectomy lobectomy/extended lobectomy (n = 18), and liver transplant (n = 22). Five-year survival in surgical patients was 90.5%, 66.5% and 81%, respectively (p = 0.485). Age greater than 55 years (hazard ratio [HR], 2.78; p < 0.001), Asian ethnicity compared to white (HR, 2.84; p = 0.012), and a higher Charlson–Deyo score (score 1: HR, 2.28; p < 0.001 and score ≥2: HR, 2.76; p = 0.011) were associated with worse OS. Conclusion: Treatment for HEH remains variable with only a third of the patients undergoing surgery. International collaboration is necessary to determine the optimal treatment for this rare disease.

Objective:To compare the survival outcomes associated with clinical and pathological response in pancreatic ductal adenocarcinoma (PDAC) patients receiving neoadjuvant chemotherapy (NAC) with FOLFIRINOX (FLX) or gemcitabine/nab-paclitaxel (GNP) followed by curative-intent pancreatectomy.Background:Newer multiagent NAC regimens have resulted in improved clinical and pathological responses in PDAC; however, the effects of these responses on survival outcomes remain unknown.Methods:Clinicopathological and survival data of PDAC patients treated at 7 academic medical centers were analyzed. Primary outcomes were overall survival (OS), local recurrence-free survival (L-RFS), and metastasis-free survival (MFS) associated with biochemical (CA 19-9 decrease ≥50% vs <50%) and pathological response (complete, pCR; partial, pPR or limited, pLR) following NAC.Results:Of 274 included patients, 46.4% were borderline resectable, 25.5% locally advanced, and 83.2% had pancreatic head/neck tumors. Vein resection was performed in 34.7% and 30-day mortality was 2.2%. R0 and pCR rates were 82.5% and 6%, respectively. Median, 3-year, and 5-year OS were 32 months, 46.3%, and 30.3%, respectively. OS, L-RFS, and MFS were superior in patients with marked biochemical response (CA 19-9 decrease ≥50% vs <50%; OS: 42.3 vs 24.3 months, P < 0.001; L-RFS-27.3 vs 14.1 months, P = 0.042; MFS-29.3 vs 13 months, P = 0.047) and pathological response [pCR vs pPR vs pLR: OS-not reached (NR) vs 40.3 vs 26.1 months, P < 0.001; L-RFS-NR vs 24.5 vs 21.4 months, P = 0.044; MFS-NR vs 23.7 vs 20.2 months, P = 0.017]. There was no difference in L-RFS, MFS, or OS between patients who received FLX or GNP.Conclusion:This large, multicenter study shows that improved biochemical, pathological, and clinical responses associated with NAC FLX or GNP result in improved OS, L-RFS, and MFS in PDAC. NAC with FLX or GNP has similar survival outcomes.

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000–2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P 5 0.001), lower operative blood loss (192 vs 392 mL; P 5 0.001), and shorter hospital stay(5 vs 7 days; P 5 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n 5 46) had similar advantages as laparoscopic/robotic (n 5 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P 5 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P 5 0.001) and shorter hospital stay (5 vs 7 days; P 5 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN.

OBJECTIVE: The relevance of margin positivity on recurrence after resection of intraductal papillary mucinous neoplasms (IPMNs) is poorly defined and represents one reason controversy remains regarding optimal surveillance recommendations. METHODS: Patients undergoing surgery for noninvasive IPMN at 8 academic medical centers from the Central Pancreas Consortium were analyzed. A positive margin was defined as presence of IPMN or pancreatic intraepithelial neoplasia. RESULTS: Five hundred two patients underwent surgery for IPMN; 330 (66%) did not have invasive cancer on final pathology and form the study cohort. Of these, 20% harbored high grade dysplasia. A positive margin was found in 20% of cases and was associated with multifocal disease (P = 0.02). The majority of positive margins were associated with low grade dysplasia. At a median follow-up of 36 months, 34 (10.3%) patients recurred, with 6.7% developing recurrent cystic disease and 3.6% developing invasive cancer. On multivariate analysis, margin positivity was not associated with recurrence of either IPMN or invasive cancer (P > 0.05). No association between margin status and development of recurrence at the margin was found. Only 6% of recurrences developed at the resection margin and median time to recurrence was 22 months. Of note, 18% of recurrences occurred > 5 years following surgery. CONCLUSION: Margin positivity after resection for noninvasive IPMNs is primarily due to low grade dysplasia and is not associated with developing recurrence in the remnant pancreas or at the resection margin. Long-term surveillance is required for all patients, as a significant number of recurrences developed over 5 years after the index operation.

Background Adjuvant radiation therapy (A-RT) for resected pancreatic adenocarcinoma (PAC) is controversial. We aim to determine if there is an association between overall survival (OS) and A-RT dose. Methods National Cancer Data Base (NCDB) data were obtained for all patients who underwent A-RT for resected PAC from 1998-2002. Univariate (UV) and multivariable (MV) survival analysis were performed along with Kaplan-Meier (KM) estimates for A-RT levels < 40 Gy, 40 to < 50 Gy, 50 to < 55 Gy, and ≥ 55 Gy. Results 1,385 patients met inclusion criteria. Median age was 64 (29-87); all patients underwent surgical resection and A-RT +/- chemotherapy. 231 patients were AJCC 5th edition stage I, 273 stage II, 734 stage III, and 126 stage IVA; 21 were unknown. Median A-RT dose was 45 Gy (1.63 Gy-69 Gy). Median OS was 21 months (95% CI 19 - 23). On MV analysis A-RT dose < 40 Gy (HR, 1.30 [95% CI 1.03-1.66]; p = 0.031), A-RT dose 40 to < 50 Gy (HR, 1.17 [95% CI 1.00-1.37]; p = 0.05), and A-RT dose ≥ 55 Gy (HR, 1.44 [95% CI 1.08-1.93]; p = 0.013) predicted worse OS when compared with the reference category of 50 to < 55 Gy. Conclusions A-RT doses of less than 40 Gy, 40 to < 50 Gy, and ≥ 55 Gy were associated with inferior OS. The dose of A-RT delivered appears to influence OS and a prospective study evaluating the addition of optimally delivered A-RT for resected PAC is needed.

Objective: To reach global expert consensus on the definition of TOLS in minimally invasive and open liver resection among renowned international expert liver surgeons using a modified Delphi method. Background: Textbook outcome is a novel composite measure combining the most desirable postoperative outcomes into one single measure and representing the ideal postoperative course. Despite a recently developed international definition of Textbook Outcome in Liver Surgery (TOLS), a standardized and expert consensus-based definition is lacking. Methods: This international, consensus-based, qualitative study used a Delphi process to achieve consensus on the definition of TOLS. The survey comprised 6 surgical domains with a total of 26 questions on individual surgical outcome variables. The process included 4 rounds of online questionnaires. Consensus was achieved when a threshold of at least 80% agreement was reached. The results from the Delphi rounds were used to establish an international definition of TOLS. Results: In total, 44 expert liver surgeons from 22 countries and all 3 major international hepato-pancreato-biliary associations completed round 1. Forty-two (96%), 41 (98%), and 41 (98%) of the experts participated in round 2, 3, and 4, respectively. The TOLS definition derived from the consensus process included the absence of intraoperative grade ≥2 incidents, postoperative bile leakage grade B/C, postoperative liver failure grade B/C, 90-day major postoperative complications, 90-day readmission due to surgery-related major complications, 90-day/in-hospital mortality, and the presence of R0 resection margin. Conclusions: This is the first study providing an international expert consensus-based definition of TOLS for minimally invasive and open liver resections by the use of a formal Delphi consensus approach. TOLS may be useful in assessing patient-level hospital performance and carrying out international comparisons between centers with different clinical practices to further improve patient outcomes.

Introduction: Following resection of pancreatic acinar cell carcinoma (PACC) distant recurrence remains high. We utilized the national cancer database (NCDB) to evaluate the role of systemic therapy in early-stage resected PACC. Methods: We queried the NCDB registry from 2004 to 2015 for patients with pathologic stage I-IIB PACC. For each stage, patients who underwent surgery alone (SA) were compared to patients who received systemic and/or radiation therapy in addition to surgery (surgery + therapy [S + T]). Results: A total of 271 patients (101 pI, 81 pIIA, and 89 pIIB) were analyzed. Of all clinically node positive patients (n = 41), the majority (n = 32, 78%) had node-positive disease at resection (pIIB). SA was performed in 112 patients (41.3%), whereas 159 (58.7%) patients received S + T. There was no difference in overall survival (OS) between S + T and SA with respect to pI or pIIA disease. In pIIB disease, S + T was associated with improved OS compared to SA (34.9 vs. 16.9 months, p = 0.031). Single-agent chemotherapy was associated with improved OS for pIIB disease when compared to SA (hazard ratio: 0.38, 95% confidence interval: 0.16, 0.83). Conclusion: In resectable PACC, the survival benefit of adjuvant therapy is limited to pathologic stage IIB disease. This benefit is evident even in patients treated with single-agent chemotherapy.

Background: The path of the biliopancreatic limb for reconstruction of the pancreatic anastomosis during pancreatoduodenectomy for pancreatic ductal adenocarcinoma can be trans-mesocolon or through the ligament of Treitz. Even after curative intent pancreatoduodenectomy, incidence of recurrence in the surgical bed remains high and may lead to obstruction of the biliopancreatic limb. However, the association between path of jejunal limb and incidence of biliopancreatic limb obstruction has not been studied. Primary aim was to determine whether path of reconstruction predisposes to biliopancreatic limb obstruction in the setting of local recurrence. Methods: Patients who underwent pancreatoduodenectomy for pancreatic ductal adenocarcinoma (2008–2018) from a single institution were identified. As disease recurrence is the predominant cause of biliopancreatic limb obstruction, analysis was limited to patients with known recurrence at date of last follow-up. Given a known median time to recurrence of 8 to 10 months after resection for pancreatic ductal adenocarcinoma, analysis was further limited to patients with at least 8 months of follow-up. Primary outcome was incidence of biliopancreatic limb obstruction. Results: Among the 517 patients identified, 182 were included. Median age was 65 years; 51% were male. Median follow-up was 22 months. Path of reconstruction was trans-mesocolon in 35% (n = 64) and through ligament of Treitz in 65% (n = 118). There was no difference between the two groups in clinicopathologic factors including age, tumor differentiation, grade, T-stage, N-stage, LVI, or PNI (all p > 0.05). Importantly, there was no difference in retroperitoneal margin positivity between groups (trans-mesocolon 8% vs ligament of Treitz 10%, p = 0.79). Both groups had similar post-operative outcomes including median length-of-stay (trans-mesocolon 6 days vs ligament of Treitz 6 days, p = 0.89) and median follow-up (trans-mesocolon 21 months vs ligament of Treitz 23 months, p = 0.68). Biliopancreatic limb obstruction was detected in 8% (n = 14) of which 14% (n = 2) were in the trans-mesocolon group and 86% (n = 12) were in the ligament of the Treitz group. Therefore, incidence of biliopancreatic limb obstruction was 3.1% in the trans-mesocolon group and 10.4% in the ligament of the Treitz group resulting in an absolute risk increase of 7.3%, risk ratio of 3.4, and relative risk increase of 2.3. There was no difference in median time to biliopancreatic limb obstruction between the groups (17.6 months vs 18.5 months, p = 1.0). Biliopancreatic limb obstruction was caused by locally recurrent pancreatic ductal adenocarcinoma in 93% (n = 13) and kinking of the duodenojejunal anastomosis in 7% (n = 1). Intervention was performed in 71% (n = 10) and included surgical bypass in 29% (n = 4), percutaneous drain in 21% (n = 3), and endoscopic/surgical decompression in 21% (n = 3). Conclusion: Biliopancreatic limb obstruction is a known complication after pancreatoduodenectomy for pancreatic ductal adenocarcinoma due to local recurrence in the surgical bed. This study shows that path of jejunal limb through the ligament of Treitz may be associated with a higher incidence of biliopancreatic limb obstruction compared with trans-mesocolon as the position of the biliopancreatic limb in the surgical bed may be more predisposed to obstruction after local recurrence. Larger studies are needed; however, given this potential risk of subsequent obstruction, these data suggest that the reconstruction paths may not be equivalent when performing pancreatoduodenectomy for pancreatic ductal adenocarcinoma.

Background: Both minimally invasive surgery (MIS) and open approaches for distal pancreatectomy are acceptable. MIS options include total laparoscopic/robotic (TLR) and hand-assist laparoscopy (HAL). When considering safety profile and specimen quality, the optimal approach is unknown. Methods: Patients who underwent distal pancreatectomy from 2010-2018 at two major academic institutions were included. Converted procedures were categorized into final approach. Ninety-day perioperative/pathologic outcomes of MIS and open were compared. Subset analyses between TLR vs HAL and HAL vs open were performed. Intent-to-treat analysis was performed. Results: Among 1006 patients, resection was performed by MIS in 35% (n = 352), open in 65% (n = 654). MIS had similar patient comorbidity profile as open but had increased operative time (183 vs 162 min; p < 0.01), lower estimated-blood-loss (EBL; 131 vs 341 mL; p < 0.01), fewer intraoperative blood transfusions (1.4 vs 5%; p < 0.01), shorter LOS (5.2 vs 7.2 days; p < 0.01). Tumor size was smaller (3.2 vs 4.4 cm; p < 0.01) with lower lymph node (LN) yield (14 vs 16; p < 0.01). When comparing HAL (n = 109) to TLR (n = 243), despite increased prior abdominal operations (60 vs 43%; p = 0.008), HAL had shorter operative time (167 vs 191 min; p < 0.01), similar length-of-stay (LOS; 5.4 vs 5.1 days; p = 0.27), and readmission rate (15 vs 13%; p = 0.47). When comparing HAL to open, the advantages of TLR approach persisted including lower EBL (171 vs 342 mL; p < 0.01), and shorter LOS (5.4 vs 7.2 days; p < 0.01). Although HAL had smaller tumors, it had a similar LN yield (16 vs 16; p = 0.80), and higher R0-rate (97 vs 83%; p < 0.01). Conclusion: Hand-assist laparoscopy is safe and feasible for distal pancreatectomy as operative time, complication profile, lymph node yield, and R0-rates are similar to open procedures, while maintaining the associated the advantages of a total laparoscopic/robotic approach with reduced blood loss and shorter length-of-stay.