Almerey, Tariq

Introduction: Lymph-nodal involvement (N+) represents an adverse prognostic factor after pancreatoduodenectomy (PD) for pancreatic adenocarcinoma (PDAC). Preoperative diagnostic and staging modalities lack sensitivity for identifying N+. This study aimed to investigate preoperative carbohydrate antigen 19.9 (CA 19.9) in predicting the N+ stage in resectable-PDAC (R-PDAC). Methods: Patients included in a multi-institutional retrospective database of PDs performed for R-PDAC from January 2000 to June 2021 were analysed. A preoperative laboratory value of CA 19.9 greater than 37 U/l was used in univariate and multivariate logistic regression analysis to determine a possible association with N+. Additionally, different cut-offs of CA 19.9 related to the preoperative clinical T (cT) stage was assessed to evaluate the risk of N+. Results: A total of 2034 PDs from thirteen centres were included in the study. CA 19.9 greater than 37 U/l was significantly associated with higher N+ at univariate and multivariate analysis ( P <0.001). CA 19.9 levels greater than 37 U/l were associated with N+ in 75.9%, 81.3%, and 85.7% of patients, respectively, in cT1, cT2, and cT3 tumours and with higher cut-off values for all cT stages. Conclusion: Lymph-nodal involvement is strongly related to preoperative CA 19.9 levels. Specially in patients staged as cT3 the CA 19.9 could represent a valid and easy tool to suspect nodal involvement. Due to these findings, R-PDAC patients with elevated CA 19.9 values should be considered in a more biologically advanced stage.

Abstract Purpose To compare the outcomes between patients with cirrhosis and those without who have undergone pancreatoduodenectomy (PD) in our institution. Methods A review of patients undergoing PD from the time period of January 2010 to December 2020 was performed. Patients that have undergone open or laparoscopic PD and had liver cirrhosis diagnosed prior to surgery were included and matched on a 1:2 basis with non-cirrhotic patients based on age, gender, Eastern Cooperative Oncology Group (ECOG) and date of surgery. Data was obtained from our medical records and ten major postoperative complications variables were compared to the matched group. Results Overall, 16 patients with cirrhosis were compared to 32 matched controls. No significant differences were found in pancreatic fistula (18.8% vs. 21.8%; P = 1.000), hemorrhage (6.3% vs. 6.2%; P = 1.000), delayed gastric emptying (6.3% vs. 15.6%; P = 0.648), wound infection (0% vs. 9.3%; P = 0.541) intraabdominal abscess (31.2% vs 6.2%; 0.4998) for cirrhotic vs. non-cirrhotic respectively. There were no postop ileus, gastric fistula, mesenteric portal thrombosis, biliary fistula, abdominal ischemic event in either group. The average length of stay for both groups was similar (6.9 vs. 9.3 days; P = 0.4019). There were no mortalities and major morbidity was similar (37.5% vs 34.3%;P = 0.3549). One patient required readmission for liver-related decompensation with full recovery. Conclusion PD in patients with cirrhosis can be safe and feasible in well-selected patients. In a high-volume institution, postoperative complications are similar to those patients without cirrhosis of the liver

Abstract Surgical resection of early stage soft-tissue sarcomas (STS) is a potentially curative treatment; however, many STS tumors will recur. Predicting recurrence and survival outcomes for patients with early stage STS remains a challenge. In this study, we identify prognostic biomarkers from clinical and transcriptomic data form a large set of early stage STS. Primary tumor samples from 69 subjects with STS were sequenced using the Tempus xT targeted DNA and whole transcriptome next-generation sequencing platforms. The most common histologies included were liposarcoma (n=22), gastrointestinal stromal tumor (n=19), and leiomyosarcoma (n=12). As expected, high-grade tumors were associated with decreased DFS and OS times while tumor histology was only correlated with OS. Single sample gene set enrichment analysis (ssGSEA) values for seven Hallmark genesets were correlated with both DFS and OS; including pro-tumor survival pathways (p53, Apoptosis, TNF-α via NF-κB), tumor proliferation pathways (MTORC1, MYC Targets, Mitotic Spindle), and UV Response signaling. These pathways are associated with tumor proliferation as well as an immunosuppressive tumor microenvironment (TME). To assess the TME of these tumors we estimated immune cell infiltration using CIBERSORTx. Of the 22 cell types accounted for by CIBERSORTx, only elevated infiltration of M2 Macrophages were associated with poor DFS and OS. To further determine TME activation we assessed the expression of 74 known immune response associated genes. Only PDCD1 (PD-1) was associated with reduced DFS and OS times. Clustering on the nine variables identified here to correlate with both DFS and OS revealed two distinct clusters demonstrating similar histologies. While histologies were similar across clusters, cluster 2 exclusively included high-grade tumors while cluster 1 was made up of 57.4% high-grade tumors. Sub-classifying cluster 1 into low and high-grade subgroups demonstrated a stepped biomarker expression pattern associated with both tumor grade and cluster membership. Using established TME genesets, high-grade tumors demonstrated higher tumor proliferative scores than low-grade tumors, while cluster 2 tumors demonstrated increased tumor associated macrophage signaling. In a multivariable model, cluster membership outperformed tumor grade and histology as the only significant predictor of DFS or OS. Taken together, while tumor grade is a strong predictor of clinical outcomes following surgical resection in STS, immunosuppressive signaling patters may help to identify patients at the highest risk. Citation Format: Nathan David Seligson, Yan W. Asmann, Tariq Almerey, Steven Attia, Sanjay P. Bagaria. Immune-suppressive tumor microenvironment leads to poor survival following curative intent surgical resection in soft-tissue sarcomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 990.

AbstractBackgroundThe aim of this study is to report the feasibility and short‐term outcomes of pancreaticoduodenectomy (PD) in patients who have undergone orthotopic liver transplantation (OLT).MethodsWe performed a retrospective review of a prospectively maintained pancreatic surgical database for all patients undergoing pancreaticoduodenectomy (PD) after liver transplant from January 1995 until June 2022. Demographics, indications for pancreatic resection, liver transplant and time from liver transplant to PD were reported. Operative mortality and morbidity were recorded within 90 days of surgery. Continuous variables were recorded as mean and range, while categorical variables were summarized using frequency and percentage. Postoperative complications within 90 days from PD were graded based on Clavien–Dindo classification with major complication recorded as grade IIIa or higher. Additionally, a comprehensive literature review was performed.ResultsA total of 916 patients who underwent PD at our institution between January 1995 and June 2022 were identified, and 9 patients had previous OLT. Five patients were females and 4 males with a mean age of 65 years (range 51–78). Average body mass index (BMI) was 30.8. Two patients had major complications, and three patients had minor complications. No clinically relevant POPF, PPH or DGE were observed. One patient died within 90 days from PD due to ischemic biliary pancreatic limb causing intrabdominal sepsis.ConclusionAlthough uncommon, PD after OLT is feasible with acceptable outcomes at high volume institutions and if performed by experienced surgeons.

Objectives Optimal use of surgery first (SF) vs neoadjuvant therapy (NAT) for localized pancreatic ductal adenocarcinoma (PDAC) is still unclear. There is concern that NAT may result in worsened post-operative outcomes. Our study objectives were to show the impact of NAT on post-operative morbidity and mortality. Methods All patients undergoing resection for PDAC between 1/1/2010 and 12/31/2020 were reviewed and those who underwent pancreaticoduodenectomy (PD) were included. Demographics, perioperative details, and pathology details were gathered. Data pertaining to 90-day complications were obtained and graded according to international consensus guidelines. Those undergoing SF were compared to those who had NAT. Categorical variables were compared by Fisher’s exact test and continuous variables by Student’s t-test. Results Two hundred and forty-one subjects who underwent PD for PDAC were included in this review. There was no significant difference in the rate of major morbidity between subjects who received NAT vs SF (19.4 vs 20.3%, P = 1.0). Similarly, there were no significant differences in the rates of mortality (3.1 vs 4.2%, P = .742), post-operative pancreatic fistula (8.2 vs 10.5%, P = .658), or post-pancreatectomy hemorrhage (7.1 vs 7.7%, P = 1.0), respectively. Conclusion Post-operative outcomes are not worsened by the use of the NAT approach prior to PD for PDAC. Further investigation is needed to reveal which patient subgroups may benefit from the use of NAT, especially regarding survival.

Background Surgical resection is the curative treatment for all subtypes of cholangiocarcinoma (CCA), including intrahepatic, hilar/peri-hilar, and distal. This study evaluates patients with CCA who underwent surgery and determines factors that impact their survival. Methods A retrospective cohort study was performed for patients who underwent surgical resection for CCA at our institution from 1995 to 2016. Demographics, operative variables between CCA tumors, and postoperative complications were analyzed. Predictors of overall and recurrence-free survival were determined via statistical analysis. Results A total of 170 patients with a mean age of 61 years old underwent surgical resection of intrahepatic (n = 64, 37.6%), hilar/peri-hilar (n = 75, 44.1%), and distal (n = 31, 18.2%) CCA. Operations performed included liver resections (n = 83, 48.8%), liver transplants (n = 56, 32.9%), and pancreaticoduodenectomies (n = 31, 18.2%). The overall survival rate at 1, 5, and 10 years was 81.1%, 32.4%, and 17.2%, respectively. Low pathological stage and negative resection margins were associated with lower recurrence and higher survival rates. Tumor location and the type of operation performed were not predictive of recurrence or OS in this cohort. Discussion This study shows that definitive surgical resection with negative margins can result in long-term survival even at 10 years. Small tumor size and low pathological stage are predictive of higher survival rates post-surgery, emphasizing the importance of early diagnosis and appropriate surgical treatment in achieving positive outcomes.

Contained rupture of an aortic aneurysm is a high-mortality condition that requires immediate repair. Open repair has been the gold standard; however, endovascular and hybrid open-endovascular repair techniques have also emerged as less invasive solutions to this vascular emergency. Here. we present a patient with a giant 14.0 cm contained rupture of a Thoracic aortic aneurysm and 7.4 cm juxtarenal abdominal aortic aneurysm who was successfully treated with hybrid open-endovascular repair.