Natural History of the Remnant Pancreatic Duct after Pancreatoduodenectomy for Non-Invasive Intraductal Papillary Mucinous Neoplasm: Results from an International Consortium.

BACKGROUND: Little is known about the prognostic significance of pancreatic duct (PD) dilation following pancreatoduodenectomy for intraductal papillary mucinous neoplasms (IPMN). Although PD dilation is typically the hallmark radiographic feature of IPMN, other causes of PD dilation exist, including anastomotic stricture, pancreatitis, senescence, and postsurgical passive dilation. Therefore, PD dilation after pancreatoduodenectomy for IPMN represents a diagnostic and management dilemma. The purpose of this study was to evaluate the significance of PD dilation after pancreatoduodenectomy for noninvasive IPMN. METHODS: All patients who underwent pancreatoduodenectomy for noninvasive IPMN at nine pancreatic academic centers between 2013 and 2018 were included. Variables were entered prospectively into institutional databases and retrospectively reviewed for the purpose of this study. Dilation of the PD remnant was defined as a duct diameter of ≥5 mm, according to international guidelines. RESULTS: Four-hundred and eighty-one patients were included in this study. The mean age of the patients was 66 years (range 30-90). Patients were surveilled for a median of 4.5 (+/-2.3; max 10.6) years. During follow-up, 132 patients (27.4%) developed PD dilation in the remnant tissue after a median of 3.3 years. Multivariable analysis demonstrated that older age at the time of pancreatoduodenectomy (P=0.01) and longer surveillance duration (P=0.002) were predictors of PD dilation. Interestingly, neither the pathological IPMN subtype (branch-duct vs. main duct/mixed, P=0.96) nor the preoperative PD diameter (P=0.14) was associated with an increased risk of PD dilation in the remnant. During follow-up, IPMN recurrence was suspected in the remaining 72 patients (18.4%), solely because of ductal dilation on cross-sectional imaging in 97% (70/72). Completion pancreatectomy was performed in only 16 patients (3.3%), of whom only four (0.8%) had invasive carcinoma. Three of these four patients had high-grade dysplasia in the original pancreatoduodenectomy specimen, whereas only one had a low-grade dysplastic lesion initially. On multivariable analysis, no variable was predictive of IPMN recurrence in the remnant. CONCLUSIONS: New main duct dilation in the pancreatic remnant after pancreatoduodenectomy for IPMN is common, occurring in 27% of the patients. The duration of surveillance is the main factor associated with remnant PD dilation, suggesting that this is likely a physiologic phenomenon. Although recurrence of IPMN in the remnant is often suspected, only 0.8% of patients develop an invasive carcinoma in the pancreatic remnant requiring completion pancreatectomy.

Survival Outcomes of Cytoreductive Surgery with HIPEC in Gastric Adenocarcinoma: A National Cancer Database Study.

BACKGROUND: This study aimed to assess the impact of cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) on the survival outcomes for patients with gastric cancer and peritoneal carcinomatosis (PC). METHODS: A retrospective analysis of the National Cancer Database from 2004 to 2020 identified patients with topography and histology codes consistent with gastric adenocarcinoma who underwent CRS/HIPEC. The exclusion criteria ruled out known other distant metastasis and missing key data. The study compared the CRS/HIPEC group with patients who had stage IV disease (with the same exclusions for distant metastases) and received systemic chemotherapy but no surgery to the primary site. RESULTS: The study included 148 patients who underwent CRS/HIPEC. Their median age was 57 years (interquartile range [IQR], 47-66 years), with 57.4% of the patients identifying as male and 73.6% identifying as white. Most of the CRS/HIPEC patients had locally advanced disease, with 33.8% having pT4 disease and 23% patients having pN3 status. The Charlson-Deyo scores were 0 for 77% and 1 for 16.9% of the patients. The overall survival (OS) among the stage IV patients managed with CRS/HIPEC was significantly longer than for the patients receiving only systemic chemotherapy (median survival, 18.1 vs 9.3 months; p < 0.001), and the 1-year OS was 72.6% versus 38.8% (p < 0.05)). Among the stage IV patients, CRS/HIPEC showed better survival than systemic chemotherapy (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.44-0.73; p < .001) when control was used for the Charlson Deyo score, histology, age, and sex. CONCLUSIONS: These results suggest the association of CRS/HIPEC with improved survival for selected patients with gastric adenocarcinoma and peritoneal disease. Some of this difference may have been due to selection bias, but the differences in the survival curves are robust.

Pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection and reconstruction in a child with recurrent hepatoblastoma after liver transplantation.

Pancreaticoduodenectomy with vascular reconstruction is rarely performed in children. We present a 3-year-old male with stage IV hepatoblastoma and pre-treatment extent of disease (PRETEXT) stage III with tumor into the portal vein and superior mesenteric vein (SMV), and with brain and lung metastases status post chemotherapy and stereotactic radiosurgery to left frontal brain lesion. He then underwent deceased donor liver transplant with Roux-en-Y hepaticojejunostomy complicated by two recurrences to bilateral lungs treated with wedge resections. His course lastly involved a third hepatoblastoma recurrence to the SMV that was managed with pylorus-preserving pancreaticoduodenectomy with SMV resection and reconstruction.

Dynamic Anthropometrics in Pancreatic Cancer: Associations Between Body Composition Changes During Neoadjuvant Therapy and Survival Outcomes After Resection.

BACKGROUND: Assessment of individual tumor biology and response to systemic therapy in pancreatic ductal adenocarcinoma (PDAC) remains a clinical challenge. The significance of anthropometric (body composition) changes during chemotherapy as a surrogate for tumor biology in the setting of localized PDAC is unknown. METHODS: A retrospective, single-institution analysis of patients with PDAC who received neoadjuvant therapy (NAT) and pancreatectomy from 2017 to 2021 was performed. Radiologic anthropometric analysis used artificial intelligence-driven software to segment and compute total and sub-compartment muscle area, adipose tissue area, and attenuation values at the level of the L3 vertebra. Kaplan-Meier survival estimates, log-rank tests, and multivariable Cox regression models were used in survival analyses. RESULTS: The inclusion criteria were met by 138 patients. Although decreases in muscle and adipose tissue areas during NAT were predominant, a subset of patients experienced an increase in these compartments. Increases in muscle greater than 5% (hazard ratio [HR], 0.352; 95% confidence interval [CI] 0.135-0.918; p = 0.033) and increases in adipose tissue greater than 15% (HR, 0.375; 95% CI 0.144-0.978; p = 0.045), were significantly associated with improved survival, whereas loss of visceral fat greater than 15% was detrimental (HR 1.853; CI 1.099-3.124; p = 0.021). No significant associations with single time-point anthropometrics were observed. Gains in total muscle and adipose mass were associated with improved pathologic response to systemic therapy and less advanced pathologic tumor stage. CONCLUSIONS: Dynamic anthropometric analysis during NAT for PDAC is a stronger prognostic indicator than measurements taken at a single point in time. Repeated anthropometric analysis during preoperative chemotherapy may serve as a biomarker for individual tumor biology and response to therapy.

Pathological Features Associated with Lymph Node Disease in Patients with Appendiceal Neuroendocrine Tumors.

This study aimed to evaluate the role of pathological features beyond tumor size in the risk of lymph node metastasis in appendiceal neuroendocrine tumors. Analyzing data from the national cancer database, we found that among 5353 cases, 18.8% had lymph node metastasis. Focusing on tumors smaller than 2 cm, a subject of considerable debate in treatment strategies, we identified lymphovascular invasion as one of the strongest predictors of lymph node disease. Interestingly, extension into the subserosa and beyond, a current factor in the staging system, was not a strong predictor. These findings suggest that careful interpretation of pathological features is needed when selecting therapeutic approaches using current staging systems.

Gaining a new angle on pancreas cancer: A pre-operative thrombelastographic parameter predicts recurrence and survival among patients with resected periampullary and pancreatic adenocarcinoma.

BACKGROUND: It has previously been demonstrated that Thrombelastography(TEG) angle may be associated with recurrence and survival in pancreas cancer in a cohort of patients operated on at the University of Colorado in 2016-2017. Now approaching 10 years of follow-up, we revisit these associations and strengthen these claims with multivariate analysis. METHODS: Retrospective chart review was performed. Statistical analysis was conducted using STATA. Receiver operating characteristic(ROC) curves identified the performance of angle for predicting recurrence&survival. Unadjusted and adjusted cox regression models were used to identify significant predictors of these outcomes. RESULTS: 47 patients were included with median follow-up of 29.6 months. ROC curves for angle predicting recurrence and survival identified a cutoff of 44.5°. KM curves demonstrated that patients above the cutoff were more likely to recur(90%vs46 â€‹%,p â€‹= â€‹0.001) and less likely to survive(16%vs56 â€‹%,p â€‹= â€‹0.001). Angle remained significant on multivariate analyses (HR recurrence:3.64[1.32-10.25],HR survival:3.80[1.38-10.46]). CONCLUSIONS: TEG angle is independently associated with disease recurrence and overall survival in pancreas cancer. This may be identifying virulent tumor biology, but further studies are required. A prospective study is underway.

Cholangiocarcinoma of the Middle Bile Duct: A Narrative Review.

Resectable cholangiocarcinoma (CCA) arising from the middle of the extrahepatic biliary tree has historically been classified as perihilar or distal CCA, depending on the operation contemplated or performed, namely the associated hepatectomy or pancreaticoduodenectomy, respectively. Segmental bile duct resection is a less invasive alternative for select patients harboring true middle extrahepatic CCA (MCC). A small, yet growing body of literature has emerged detailing institutional experiences with bile duct resection versus pancreaticoduodenectomy or concomitant hepatectomy for MCC. Herein, we provide a brief overview of the epidemiology, preoperative evaluation, and emerging systemic therapies for MCC, and narratively review the existing work comparing segmental resection with pancreaticoduodenectomy or less commonly, hepatectomy, for MCC, with emphasis on the surgical management and oncologic implications of the approach used.

Exploration of Patient Retention in Seeking a Second Opinion: A Retrospective Cohort Study.

INTRODUCTION: It is common for cancer patients to seek a second opinion for a variety of reasons. Understanding what drives patients to choose to receive treatment with their second opinion provider may uncover opportunities to improve the second opinion process. Therefore, we sought to identify the patient, disease, and treatment characteristics that were associated with second opinion retention rates in patients seeking a second surgical opinion for breast, colon, and pancreatic cancer. METHODS: We conducted a retrospective cohort study to evaluate patients who sought a second opinion within a large academic health-care system for breast, colon, and pancreatic cancer. Electronic medical records were reviewed for second opinions. Patient demographics and characteristics were collected and compared between the retained group and the nonretained groups. RESULTS: A total of 237 patients obtained second opinions for breast, colorectal, and pancreatic cancer. Patients that were offered a different treatment plan at their second opinion were more likely to be retained for systemic therapy (P = 0.009) for pancreatic cancer and any treatment for colon cancer (P = 0.003). Seeing a radiation oncologist (P = 0.007) or a plastic surgeon (P = 0.02) during the multidisciplinary consultation increased retention rates for breast cancer. CONCLUSIONS: Surgeons can better identify patients that are more likely to be retained after a second opinion by the individual patient characteristics and treatment factors. Understanding the factors that lead to retention for these three cancer types may help physicians provide the best possible resources for most patients presenting for second opinion evaluations.

Adjuvant Chemotherapy With or Without Radiotherapy for Resected Pancreatic Cancer After Multiagent Neoadjuvant Chemotherapy.

BACKGROUND: Adjuvant therapy is associated with improved pancreatic cancer survival after neoadjuvant chemotherapy and surgery. However, whether adjuvant treatment should include radiotherapy is unclear in this setting. METHODS: This study queried the National Cancer Database for pancreatic adenocarcinoma patients who underwent curative resection after multiagent neoadjuvant chemotherapy between 2010 and 2019 and received adjuvant treatment. Adjuvant chemotherapy plus radiotherapy (external beam, 45-50.4 gray) was compared with adjuvant chemotherapy alone. Uni- and multivariable Cox regression was used to assess survival associations. Analyses were repeated in a propensity score-matched subgroup. RESULTS: Of 1983 patients who received adjuvant treatment after multiagent neoadjuvant chemotherapy and resection, 1502 (75.7%) received adjuvant chemotherapy alone and 481 (24.3%) received concomitant adjuvant radiotherapy (chemoradiotherapy). The patients treated with adjuvant chemoradiotherapy were younger, were treated at non-academic facilities more often, and had higher rates of lymph node metastasis (ypN1-2), positive resection margins (R1), and lymphovascular invasion (LVI+). The median survival was shorter for the chemoradiotherapy-treated patients according to the unadjusted analysis (26.8 vs 33.2 months; p = 0.0017). After adjustment for confounders, chemoradiotherapy was associated with better outcomes in the multivariable model (hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.61-0.93; p = 0.008). The association between chemoradiotherapy and improved outcomes was stronger for the patients with grade III tumors (HR, 0.53; 95% CI, 0.37-0.74) or LVI+ tumors (HR, 0.58; 95% CI, 0.44-0.75). In a subgroup of 396 propensity-matched patients, chemoradiotherapy was associated with a survival benefit only for the patients with LVI+ or grade III tumors. CONCLUSION: After multiagent neoadjuvant chemotherapy and resection for pancreatic cancer, additional adjuvant chemoradiotherapy versus adjuvant chemotherapy alone is associated with improved survival for patients with LVI+ or grade III tumors.

Radiologic Occult Metastases in Pancreatic Cancer: Analysis of Risk Factors and Survival Outcomes in the Age of Contemporary Neoadjuvant Multi-agent Chemotherapy.

BACKGROUND: Radiologic occult metastatic disease (ROMD) in patients with pancreatic ductal adenocarcinoma (PDAC) who undergo contemporary neoadjuvant chemotherapy (NAC) has not been well studied. This study sought to analyze the incidence, risk factors, and oncologic outcomes for patients who underwent the NAC approach for PDAC. METHODS: A retrospective review analyzed a prospectively maintained database of patients who had potentially resectable PDAC treated with NAC and were offered pancreatectomy at our institution from 2011 to 2022. Multivariable regression analysis was performed to assess risk factors associated with ROMD. Kaplan-Meier curves with log-rank analyses were generated to estimate time-to-event end points. RESULTS: The study enrolled 366 patients. Upfront and borderline resectable anatomic staging comprised 80% of the cohort, whereas 20% had locally advanced disease. The most common NAC regimen was FOLFIRINOX (n = 274, 75%). For 55 patients (15%) who harbored ROMD, the most common site was liver-only metastases (n = 33, 60%). The independent risk factors for ROMD were increasing CA19-9 levels during NAC (odds ratio [OR], 7.01; confidence interval [CI], 1.97-24.96; p = 0.008), indeterminate liver lesions (OR, 2.19; CI, 1.09-4.39; p = 0.028), and enlarged para-aortic lymph nodes (OR, 6.87; CI, 2.07-22.74; p = 0.002) on preoperative cross-sectional imaging. Receipt of palliative chemotherapy (p < 0.001) and eventual formal pancreatectomy (p = 0.04) were associated with survival benefit in the log-rank analysis. The median overall survival (OS) of the patients with ROMD was nearly 15 months from the initial diagnosis, with radiologic evidence of metastases occurring after a median of 2 months. CONCLUSIONS: Radiologic occult metastatic disease remains a clinical challenge associated with poor outcomes for patients who have PDAC treated with multi-agent NAC.

Learning Curve of a Laparoscopic Pancreaticoduodenectomy Program at a Second Institution.

BACKGROUND: Historically, pancreaticoduodenectomy (PD) has been performed via a laparotomy, but increasingly, laparoscopic and robotic platforms are being employed for PD. Laparoscopic PD has a steep surgeon specific learning curve and programmatic elements that must be optimized. These factors may limit a surgeon who is proficient at laparoscopic PD to develop a program at another institution. We hypothesize that the learning curve for a surgeon transferring a program to a second institution is shorter than the initial laparoscopic PD learning curve for the same surgeon. METHODS: A retrospective review of patients who underwent laparoscopic PD for any indication at the first institution (FI) from 2012 to 2017 and the second institution (SI) from 2018 to 2021 was conducted. Standard statistical analysis was performed. The learning curve was identified using one-sided CUSUM analysis of operative times. RESULT: We identified 110 participants, 90 from the FI and 20 from the SI. More patients at the FI were diagnosed with periampullary adenocarcinoma on final pathology compared to the SI (65.6% vs 40.0%, P = .0132). FI operative times stabilized after the 25th laparoscopic PD and SI operative times stabilized after the 5th operation. No statistically significant difference was identified in postoperative complications. CONCLUSIONS: The learning curve and average operative time of an SI laparoscopic PD program was shorter than the initial learning curve for a single surgeon with comparable outcomes. This suggests that complex minimally invasive surgical programs can be safely transferred to another high-volume institution without significant loss of progress.

Group XIV C-type lectins: emerging targets in tumor angiogenesis.

C-type lectins, distinguished by a C-type lectin binding domain (CTLD), are an evolutionarily conserved superfamily of glycoproteins that are implicated in a broad range of physiologic processes. The group XIV subfamily of CTLDs are comprised of CD93, CD248/endosialin, CLEC14a, and thrombomodulin/CD141, and have important roles in creating and maintaining blood vessels, organizing extracellular matrix, and balancing pro- and anti-coagulative processes. As such, dysregulation in the expression and downstream signaling pathways of these proteins often lead to clinically relevant pathology. Recently, group XIV CTLDs have been shown to play significant roles in cancer progression, namely tumor angiogenesis and metastatic dissemination. Interest in therapeutically targeting tumor vasculature is increasing and the search for novel angiogenic targets is ongoing. Group XIV CTLDs have emerged as key moderators of tumor angiogenesis and metastasis, thus offering substantial therapeutic promise for the clinic. Herein, we review our current knowledge of group XIV CTLDs, discuss each's role in malignancy and associated potential therapeutic avenues, briefly discuss group XIV CTLDs in the context of two other relevant lectin families, and offer future direction in further elucidating mechanisms by which these proteins function and facilitate tumor growth.

Social vulnerability is associated with higher risk-adjusted rates of postoperative complications in a broad surgical population.

OBJECTIVE: The purpose of this study was to determine if an association between Social Vulnerability Index (SVI) and risk-adjusted complications exists in a broad spectrum of surgical patients. SUMMARY BACKGROUND DATA: Growing evidence supports the impact of social circumstances on surgical outcomes. SVI is a neighborhood-based measure accounting for sociodemographic factors putting communities at risk. METHODS: This was a multi-hospital, retrospective cohort study including a sample of patients within one healthcare system (2012-2017). Patient addresses were geocoded to determine census tract of residence and estimate SVI. Patients were grouped into low SVI (score<75) and high SVI (score≥75) cohorts. Perioperative variables and postoperative outcomes were tracked and compared using local ACS-NSQIP data. Multivariable logistic regression was performed to generate risk-adjusted odds ratios of postoperative complications in the high SVI cohort. RESULTS: Overall, 31,224 patients from five hospitals were included. Patients with high SVI were more likely to be racial minorities, have 12/18 medical comorbidities, have high ASA class, be functionally dependent, be treated at academic hospitals, and undergo emergency operations (all p â€‹< â€‹0.05). Patients with high SVI had significantly higher rates of 30-day mortality, overall morbidity, respiratory, cardiac and infectious complications, urinary tract infections, postoperative bleeding, non-home discharge, and unplanned readmissions (all p â€‹< â€‹0.05). After risk-adjustment, only the associations between high SVI and mortality and unplanned readmission became non-significant. CONCLUSIONS: High SVI was associated with multiple adverse outcomes even after risk adjustment for preoperative clinical factors. Targeted preventative interventions to mitigate risk of these specific complications should be considered in this high-risk population.

The United States experience with diagnosing and treating esophageal cancer during the SARS-CoV-2 pandemic: A retrospective cohort study.

The downstream effects on healthcare delivery during the initial wave of the COVID-19 pandemic remain unclear. The purpose of this study was to determine how the healthcare environment surrounding the pandemic affected the oncologic care of patients diagnosed with esophageal cancer. This was a retrospective cohort study evaluating patients in the National Cancer Database (2019-2020). Patients with esophageal cancer diagnoses were divided into pre-pandemic (2019) and pandemic (2020) groups. Patient demographics, cancer-related variables, and treatment modalities were compared. Among 26,231 esophageal cancer patients, 14,024 patients (53.5%) were in the pre-pandemic cohort and 12,207 (46.5%) were in the pandemic cohort. After controlling for demographics, patients diagnosed during the pandemic were more likely to have poorly differentiated tumors (odds ratio [OR] 1.24, 95% confidence interval [CI] 1.08-1.42), pathologic T3 disease compared to T1 (OR 1.25, 95% CI 1.02-1.53), positive lymph nodes on pathology (OR 1.36, 95% CI 1.14-1.64), and to be pathologic stage IV (OR 1.51, 95% CI 1.29-1.76). After controlling for oncologic characteristics, patients diagnosed during the pandemic were more likely to require at least two courses of systemic therapy (OR 1.78, 95% CI 1.48-2.14) and to be offered palliative care (OR 1.13, 95% CI 1.04-1.22). While these patients were offered curative therapy at lower rates, this became non-significant after risk-adjustment (p = .15). The pandemic healthcare environment was associated with significantly increased risk-adjusted rates of patients presenting with advanced esophageal cancer. While this led to significant differences in treatment, most of these differences became non-significant after controlling for oncologic factors.