Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas

BackgroundMitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM).MethodsA retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed. Patient demographics and tumor characteristics were recorded. MR was considered elevated for each AJCC8-defined T category if it was ≥2 mitoses/mm2 for T1, ≥4 mitoses/mm2 for T2, ≥6 mitoses/mm2 for T3, or ≥7 mitoses/mm2 for T4. Statistical analysis was performed to assess the predictive accuracy of MR on selected outcomes while controlling for ulceration.ResultsData from 2,984 patients with complete records were analyzed. Along with Breslow thickness and ulceration, elevated MR was associated with higher risk of MSM (HR 1.816, P=0.0001). There was no difference among patients with ulcerated T1 or T2 tumors regardless of MR, but those with non-ulcerated T1 or T2 tumors and elevated MR were more likely to have positive SLNs (P<0.0001 and P=0.0043, respectively) and recurrence (P=0.0007 and P=0.0004, respectively) compared to counterparts with low MR. There were no notable differences for T3 or T4 tumors based on MR.ConclusionsElevated MR is associated with SLN positivity and recurrence in thin melanomas, independent of ulceration. SLN biopsy should therefore be strongly considered for patients with non-ulcerated lesions <0.8 mm thick if the MR is ≥2 mitoses/mm2

Tyrosine 23 Phosphorylation-Dependent Cell-Surface Localization of Annexin A2 Is Required for Invasion and Metastases of Pancreatic Cancer

The aggressiveness of pancreatic ductal adenocarcinoma (PDA) is characterized by its high metastatic potential and lack of effective therapies, which is the result of a lack of understanding of the mechanisms involved in promoting PDA metastases. We identified Annexin A2 (ANXA2), a member of the Annexin family of calcium-dependent phospholipid binding proteins, as a new molecule that promotes PDA invasion and metastases. We found ANXA2 to be a PDA-associated antigen recognized by post-treatment sera of patients who demonstrated prolonged survival following treatment with a PDA-specific vaccine. Cell surface ANXA2 increases with PDA development and progression. Knockdown of ANXA2 expression by RNA interference or blocking with anti-ANXA2 antibodies inhibits in vitro invasion of PDA cells. In addition, post-vaccination patient sera inhibits in vitro invasion of PDA cells, suggesting that therapeutic anti-ANXA2 antibodies are induced by the vaccine. Furthermore, cell-surface localization of ANXA2 is tyrosine 23 phosphorylation-dependent; and tyrosine 23 phosphorylation is required for PDA invasion. We demonstrated that tyrosine 23 phosphorylation resulting in surface expression of ANXA2 is required for TGFβ-induced, Rho-mediated epithelial-mesenchymal transition (EMT), linking the cellular function of ANXA2 which was previously shown to be associated with small GTPase-regulated cytoskeletal rearrangements, to the EMT process in PDA. Finally, using mouse PDA models, we showed that shRNA knock-down of ANXA2, a mutation at tyrosine 23, or anti-ANXA2 antibodies, inhibit PDA metastases and prolong mouse survival. Thus, ANXA2 is part of a novel molecular pathway underlying PDA metastases and a new target for development of PDA therapeutics

Metabolism of Innate Immune Cells in Cancer

Cancer cells possess specific metabolic requirements for their survival, proliferation, and progression. Within a shared microenvironment, immune cells depend on competing metabolic pathways for their development and effector function. As a result, local acidification, hypoxia, and nutrient depletion in the tumor microenvironment can alter the antitumor immune response and even promote resistance to immunotherapies such as immune checkpoint blockade and adoptive cell transfer. Although T cells are the primary effectors of the antitumor response, growing evidence demonstrates that innate immune cells are critical to successful tumor clearance. This review aims to summarize current research related to the innate immune system, metabolism, and cancer. We first discuss the specific metabolic requirements of innate immune cells for immune activation and suppression and conclude by highlighting ongoing clinical applications of these findings

Palliative Care for Pancreatic and Periampullary Cancer

Most patients with pancreatic cancer will present with metastatic or locally advanced disease. Unfortunately, most patients with localized disease will experience recurrence even after multimodality therapy. As such, pancreatic cancer patients arrive at a common endpoint where decisions pertaining to palliative care come to the forefront. This article summarizes surgical, endoscopic, and other palliative techniques for relief of obstructive jaundice, relief of duodenal or gastric outlet obstruction, and relief of pain due to invasion of the celiac plexus. It also introduces the utility of the palliative care triangle in clarifying a patient's and family's goals to guide decision making.UTMB Clinical and Translational Science Award [UL1TR000071]; NIH T-32 Grant [5T32DK007639]; AHRQ [1R24HS022134]; Cancer Prevention and Research Institute Grant [RP140020]12 month embargo; Available online 16 November 2016This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Incidence of hepaticojejunostomy stricture after hepaticojejunostomy.

Presented at the 11th Annual Academic Surgical Congress, February 3, 2016, Jacksonville, FL.Operations requiring biliary-enteric anastomosis are uncommon, and the true incidence of postoperative stricture is unknown. Our goal was to determine the timing, incidence, and management of stricture after biliary-enteric anastomosis.UTMB Clinical and Translational Science Award #UL1TR000071, NIH T-32 Grant # T32DK007639, AHRQ Grant # 1R24HS022134Available online 6 July 2016. 12 month embargo.This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

The role of imaging and sentinel lymph node biopsy in patients with T3b-T4b melanoma with clinically negative disease

BackgroundPrevious studies demonstrate minimal utility of pre-operative imaging for low-risk melanoma; however, imaging may be more critical for patients with high-risk disease. Our study evaluates the impact of peri-operative cross-sectional imaging in patients with T3b-T4b melanoma.MethodsPatients with T3b-T4b melanoma who underwent wide local excision were identified from a single institution (1/1/2005 – 12/31/2020). Cross-sectional imaging was defined as body CT, PET and/or MRI in the perioperative period, with the following findings: in-transit or nodal disease, metastatic disease, incidental cancer, or other. Propensity scores were created for the odds of undergoing pre-operative imaging. Recurrence free survival was analyzed using the Kaplan-Meier method and log-rank test.ResultsA total of 209 patients were identified with a median age of 65 (IQR 54-76), of which the majority were male (65.1%), with nodular melanoma (39.7%) and T4b disease (47.9%). Overall, 55.0% underwent pre-operative imaging. There were no differences in imaging findings between the pre- and post-operative cohorts. After propensity-score matching, there was no difference in recurrence free survival. Sentinel node biopsy was performed in 77.5% patients, with 47.5% resulting in a positive result.ConclusionPre-operative cross-sectional imaging does not impact the management of patients with high-risk melanoma. Careful consideration of imaging use is critical in the management of these patients and highlights the importance of sentinel node biopsy for stratification and decision making