The Florida pancreas collaborative next-generation biobank: Infrastructure to reduce disparities and improve survival for a diverse cohort of patients with pancreatic cancer

Background: Well-annotated, high-quality biorepositories provide a valuable platform to support translational research. However, most biorepositories have poor representation of minority groups, limiting the ability to address health disparities. Methods: We describe the establishment of the Florida Pancreas Collaborative (FPC), the first state-wide prospective cohort study and biorepository designed to address the higher burden of pancreatic cancer (PaCa) in African Americans (AA) compared to Non-Hispanic Whites (NHW) and Hispanic/Latinx (H/L). We provide an overview of stakeholders; study eligibility and design; recruitment strategies; standard operating procedures to collect, process, store, and transfer biospecimens, medical images, and data; our cloud-based data management platform; and progress regarding recruitment and biobanking. Results: The FPC consists of multidisciplinary teams from fifteen Florida medical institutions. From March 2019 through August 2020, 350 patients were assessed for eligibility, 323 met inclusion/exclusion criteria, and 305 (94%) enrolled, including 228 NHW, 30 AA, and 47 H/L, with 94%, 100%, and 94% participation rates, respectively. A high percentage of participants have donated blood (87%), pancreatic tumor tissue (41%), computed tomography scans (76%), and questionnaires (62%). Conclusions: This biorepository addresses a critical gap in PaCa research and has potential to advance translational studies intended to minimize disparities and reduce PaCa-related morbidity and mortality

Clockwise Anterior-to-Posterior—Double Isolation (CAP-DI) Approach for Portal Lymphadenectomy in Biliary Tract Cancer: Technique, Yield, and Outcomes

Background: Portal lymphadenectomy (PLND) is the current standard for oncologic resection of biliary tract cancers (BTCs). However, published data show it is performed infrequently and often yields less than the recommended 6 lymph nodes. We sought to identify yield and outcomes using a Clockwise Anterior-to-Posterior technique with Double Isolation of critical structures (CAP-DI) for PLND. Methods: Consecutive patients undergoing complete PLND for BTCs using CAP-DI technique were identified (2015–2021). Lymph node (LN) yield and predictors of LN count were examined. Secondary outcomes included intraoperative and postoperative outcomes, which were compared to patients having hepatectomy without PLND. Results: In total, 534 patients were included; 71 with complete PLND (36 gallbladder cancers, 24 intrahepatic cholangiocarcinomas, 11 perihilar cholangiocarcinomas) and 463 in the control group. The median PLND yield was 5 (IQR 3–8; range 0–17) and 46% had at least 6 nodes retrieved. Older age was associated with lower likelihood of ≥6 node PLND yield (p = 0.032), which remained significant in bivariate analyses with other covariates (p < 0.05). After adjustment for operative factors, performance of complete PLND was independently associated with longer operative time (+46.4 min, p = 0.001), but no differences were observed in intraoperative or postoperative outcomes compared to the control group (p > 0.05). Conclusions: Yield following PLND frequently falls below the recommended minimum threshold of 6 nodes despite a standardized stepwise approach to complete clearance. Older age may be weakly associated with lower PLND yield. While all efforts should be made for complete node retrieval, failure to obtain 6 nodes may be an unrealistic metric of surgical quality

Surgical Approach does not Affect Return to Intended Oncologic Therapy Following Pancreaticoduodenectomy for Pancreatic Adenocarcinoma:A Propensity-Matched Study

Background: The effect of minimally invasive pancreaticoduodenectomy (MIPD), including laparoscopic and robotic pancreaticoduodenectomy (LPD and RPD, respectively), on compliance and time to return to intended oncologic therapy (RIOT) for pancreatic ductal adenocarcinoma (PDAC) remains unknown. Patients and Methods: Patients with nonmetastatic PDAC were analyzed in the National Cancer Database (NCDB). Three groups were matched per propensity score: open pancreaticoduodenectomy (OPD) and MIPD, LPD and RPD, and converted and nonconverted patients. RIOT rates and time to RIOT were examined. Results: A total of 14,135 patients were included: 11,834 (83.7%) underwent OPD and 2301 (16.3%) underwent MIPD. After score matching, RIOT rates (67.2 vs. 65.3%; p = 0.112) and RIOT within 8 weeks (57.7 vs. 56.4%; p = 0.276) were similar among MIPD and OPD groups, and approach was not a significant predictor of RIOT on multivariable regression. Neither RIOT nor time to RIOT were different among LPD and RPD groups (63.9 vs. 67.0%, and 58.4 vs. 56.9%, respectively). Compared with LPD, RPD was associated with lower conversion rates (HR 0.519; p &lt; 0.001), and conversion was associated with longer median time to RIOT (10 vs. 8 weeks; p = 0.041). Conclusion: In this national cohort, approach did not impact RIOT rates or time to RIOT for patients with PDAC. While conversion was associated with longer median time to RIOT, readiness to commence adjuvant therapy was similar for LPD and RPD.</p

Perioperative Carcinoid Crisis: A Systematic Review and Meta-Analysis

Background: Surgery is the only curative option for patients with neuroendocrine tumors (NET) and is also indicated for debulking of liver metastasis. Intraoperative carcinoid crisis (CC) is thought to be a potentially lethal complication. Though perioperative octreotide is often recommended for prevention, recent NET society guidelines raised concerns regarding limited data supporting its use. We sought to evaluate existing evidence characterizing CC and evaluating the efficacy of prophylactic octreotide. Methods: A systematic review was performed on studies including patients having surgery for well-differentiated NET and/or NET liver metastasis (2000&ndash;2021), and reporting data on the incidence, risk factors, or prognosis of CC, and/or use of prophylactic octreotide. Meta-analysis was performed using random-effects models. Results: Eight studies met inclusion criteria (n = 943 operations). The pooled incidence of CC was 19% (95% CI [0.06&ndash;0.36]). Liver metastasis (odds ratio 2.85 [1.49&ndash;5.47]) and gender (male 0.58 [0.34&ndash;0.99]) were the only significant risk factors. The occurrence of CC was associated with increased risk of major postoperative complications (2.12 [1.03&ndash;4.35]). The use of prophylactic octreotide was not associated with decreased risk of CC (0.73 [0.32&ndash;1.66]). Notably, there was no standard prophylactic octreotide strategy used. Conclusions: Intraoperative carcinoid crisis is a common complication occurring in up to 20% of patients with midgut NET and/or liver metastasis undergoing surgery. Prophylactic octreotide may not provide an efficient way to prevent this complication. Future studies should focus on prospective evaluation of well-defined prophylactic protocols using a standardized definition for CC

Surgical approach to pancreaticoduodenectomy for pancreatic adenocarcinoma: uncomplicated ends justify the means.

BACKGROUND: Pancreaticoduodenectomy (PD) remains the cornerstone of managing pancreatic ductal adenocarcinoma (PDAC) of the pancreas head/neck, but it is associated with high morbidity. We hypothesize that, in absence of pancreatectomy-specific morbidity (PSM), minimally invasive PD (MIPD) provides improved short-term outcomes compared to open PD (OPD). METHODS: NSQIP pancreatectomy-targeted database 2014-2019 was utilized. PSM was defined as the occurrence of delayed gastric emptying (DGE) and/or post-operative pancreatic fistula (POPF). The cohort was divided into No-PSM and PSM groups. Propensity score match was applied in each group to compare outcomes of MIPD vs. OPD. RESULTS: 8,121 patients were selected. Patients were divided into No-PSM (N = 6267) and PSM (N = 1854) groups. In No-PSM group, we matched 1656 OPD to 552 MIPD patients. MIPD had longer operations (423 vs. 359 min; p \u3c 0.001) but less overall morbidity (22.1% vs. 29.1%; p = 0.001) mostly attributed to less bleeding and sepsis. MIPD patients also had a one-day shorter median LOS (6 vs. 7 days; p = 0.005) and higher rates of home discharge (92.8% vs. 89.6%; p = 0.027). No difference was noted in mortality and 30-day readmission. In PSM group, 441 OPD were matched to 147 MIPD peers. MIPD had longer operations but without short-term benefits. General morbidity (61.2% vs. 61.9%), median LOS (12 vs. 12 days), mortality (2.7% vs. 1.8%), and readmission rates (32.7% vs. 26.5%) were similar. Same conclusions were drawn in the per-protocol analysis. CONCLUSION: PSM is common following PD for PDAC. In the absence of PSM, MIPD is associated with less postoperative morbidity and shorter LOS

Neoadjuvant chemotherapy and stereotactic body radiation therapy for borderline resectable pancreas adenocarcinoma: influence of vascular margin status and type of chemotherapy

The influence of chemotherapy type and vascular margin status on clinical outcomes after sequential chemotherapy and stereotactic body radiation therapy (SBRT) for borderline resectable pancreatic cancer (BRPC) is unknown. A single-institution retrospective review was performed on BRPC patients treated with chemotherapy and 5-fraction SBRT from 2009 to 2021. Surgical outcomes and SBRT-related toxicity were reported. Clinical outcomes were estimated by Kaplan–Meier with log rank comparisons. A total of 303 patients received neoadjuvant chemotherapy and SBRT to a median dose of 40 Gy prescribed to the tumor–vessel interface and median dose of 32.4 Gy–95% of the gross tumor volume. One hundred and sixty-nine patients (56%) were resected and benefited from improved median OS (41.1 vs 15.5 months, P < 0.001). Close/positive pathological margins were not associated with worse OS or FFLRF. Type of neoadjuvant chemotherapy did not influence OS for resected patients, but FOLFIRINOX was associated with improved median OS in unresected patients (18.2 vs 13.1 months, P = 0.001). For BRPC, the effect of a positive or close vascular margin may be mitigated by neoadjuvant therapy. Shorter duration neoadjuvant chemotherapy as well as the optimal biological effective dose of radiotherapy should be prospectively explored

Anatomic patterns of recurrence in biliary tract cancers: does primary tumor site matter?

BACKGROUND: Recommendations for postoperative surveillance and adjuvant therapy following curative-intent resection for biliary tract cancers-including intrahepatic and extrahepatic cholangiocarcinoma (IHCCA and EHCCA) and primary gallbladder cancer (GBC)-are uniform across primary tumor site. However, these tumors may have distinct patterns of recurrence. METHODS: A retrospective observational cohort study was performed at a specialty cancer center. Patients undergoing resection of IHCCA, EHCCA, and GBC were identified (2005-2020). Recurrence-free survival (RFS) was estimated using Kaplan-Meier and Cox proportional hazard methods. Anatomic patterns of initial site of recurrence were described and compared. RESULTS: There were 142 patients included; 50 IHCCA, 32 EHCCA, and 60 GBC. Median RFS was 30.8 months, which was not significantly different between IHCCA, EHCCA, or GBC in univariate analysis or after adjustment. Nodal positivity was significantly associated with poor RFS (HR 3.92, P≤0.001). The most common initial site of recurrence overall was intrahepatic (n=49/64, 77%), in isolation (n=32) or synchronous with other site of recurrence (n=17). Significant differences in anatomic pattern of recurrence were observed (P=0.049) with IHCCAs more commonly recurring with simultaneous hepatic-pulmonary disease (n=5/22, 23%; EHCCA n=2/19, 10%; GBC n=1/23, 4%), GBC more commonly recurring within the porta (n=7/23, 30%; IHCCA n=0; EHCCA n=1/19, 5%), and EHCCA more commonly recurring within the peritoneum (n=5/19, 26%; IHCCA n=2/22, 9%, GBC n=2/23, 9%). CONCLUSIONS: Patterns of initial recurrence appear to differ between primary tumor site, likely reflecting underlying differences in anatomy and biology. These data could help inform future studies for adjuvant therapy as well as timing and anatomic focus for surveillance imaging

Patient-caregiver dyads in pancreatic cancer: identification of patient and caregiver factors associated with caregiver well-being

We aimed to examine the psychosocial well-being in the pancreas cancer patient-caregiver dyad, and determine patient and caregiver characteristics that predict caregiver distress. This was a cross-sectional, observational study. Demographics and caregiving characteristics were gathered from patients and caregivers. Caregivers completed validated instruments investigating anxiety, depression, perceived stress and caregiver burden. Over a period of eleven months, 128 patient-caregiver dyads were enrolled. Patient and caregiver distress scores were not associated with patient clinical disease burden. Patient distress was a significant predictor of concurrent caregiver distress, anxiety, depression, and perceived burden. Younger caregivers were also associated with higher caregiver anxiety and perceived burden. Additionally, number of caregiving activities and caregiver overall health status were predictors of concurrent caregiver depression and perceived stress. Certain pancreatic cancer patient and caregiver variables may negatively impact the well-being of caregivers. Future efforts should focus on development and implementation of comprehensive caregiver support programs for those at risk for psychosocial distress