The Role of Surgery for Stage IV Melanoma.

Historically, stage IV melanoma carried a dismal prognosis and surgical resection was the only potential treatment offering long-term survival or palliation of symptomatic disease. With modern systemic therapies that can provide durable disease control for many patients with metastatic disease, we are actively redefining the role of surgery in metastatic melanoma. Contemporary treatment strategies can employ surgical resection in the upfront setting followed by adjuvant therapy, or used in tailored approach following systemic therapy.

The Future of Targeted Therapy for Leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive subtype of soft tissue sarcoma that arises from smooth muscle cells, most commonly in the uterus and retroperitoneum. LMS is a heterogeneous disease with diverse clinical and molecular characteristics that have yet to be fully understood. Molecular profiling has uncovered possible targets amenable to treatment, though this has yet to translate into approved targeted therapies in LMS.

Reprogramming of nucleotide metabolism by interferon confers dependence on the replication stress response pathway in pancreatic cancer cells.

We determine that type I interferon (IFN) response biomarkers are enriched in a subset of pancreatic ductal adenocarcinoma (PDAC) tumors; however, actionable vulnerabilities associated with IFN signaling have not been systematically defined. Integration of a phosphoproteomic analysis and a chemical genomics synergy screen reveals that IFN activates the replication stress response kinase ataxia telangiectasia and Rad3-related protein (ATR) in PDAC cells and sensitizes them to ATR inhibitors. IFN triggers cell-cycle arrest in S-phase, which is accompanied by nucleotide pool insufficiency and nucleoside efflux.

STING-driven interferon signaling triggers metabolic alterations in pancreas cancer cells visualized by [F]FLT PET imaging.

Type I interferons (IFNs) are critical effectors of emerging cancer immunotherapies designed to activate pattern recognition receptors (PRRs). A challenge in the clinical translation of these agents is the lack of noninvasive pharmacodynamic biomarkers that indicate increased intratumoral IFN signaling following PRR activation. Positron emission tomography (PET) imaging enables the visualization of tissue metabolic activity, but whether IFN signaling-induced alterations in tumor cell metabolism can be detected using PET has not been investigated.

NAD depletion by type I interferon signaling sensitizes pancreatic cancer cells to NAMPT inhibition.

Emerging evidence suggests that intratumoral interferon (IFN) signaling can trigger targetable vulnerabilities. A hallmark of pancreatic ductal adenocarcinoma (PDAC) is its extensively reprogrammed metabolic network, in which nicotinamide adenine dinucleotide (NAD) and its reduced form, NADH, are critical cofactors. Here, we show that IFN signaling, present in a subset of PDAC tumors, substantially lowers NAD(H) levels through up-regulating the expression of NAD-consuming enzymes PARP9, PARP10, and PARP14.

Histone deacetylase inhibition is synthetically lethal with arginine deprivation in pancreatic cancers with low argininosuccinate synthetase 1 expression.

Arginine (Arg) deprivation is a promising therapeutic approach for tumors with low argininosuccinate synthetase 1 (ASS1) expression. However, its efficacy as a single agent therapy needs to be improved as resistance is frequently observed. A tissue microarray was performed to assess ASS1 expression in surgical specimens of pancreatic ductal adenocarcinoma (PDAC) and its correlation with disease prognosis.

Epidural Analgesia Improves Postoperative Pain Control but Impedes Early Discharge in Patients Undergoing Pancreatic Surgery.

Objectives: The aim of this study was to evaluate the impact of epidural analgesia (EA) on postoperative length of stay (LOS), expeditious discharge, and pain relief after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP).

Methods: Retrospective reviews of 2014-2015 American College of Surgeons National Surgical Quality Improvement Program databases and our institutional pancreatic surgery database were conducted.

Results: On univariate analysis, EA was associated with statistically significant longer lengths of stay for both PD and DP.

Targeting LIF-mediated paracrine interaction for pancreatic cancer therapy and monitoring.

Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis largely owing to inefficient diagnosis and tenacious drug resistance. Activation of pancreatic stellate cells (PSCs) and consequent development of dense stroma are prominent features accounting for this aggressive biology. The reciprocal interplay between PSCs and pancreatic cancer cells (PCCs) not only enhances tumour progression and metastasis but also sustains their own activation, facilitating a vicious cycle to exacerbate tumorigenesis and drug resistance.

Lysosome inhibition sensitizes pancreatic cancer to replication stress by aspartate depletion.

Functional lysosomes mediate autophagy and macropinocytosis for nutrient acquisition. Pancreatic ductal adenocarcinoma (PDAC) tumors exhibit high basal lysosomal activity, and inhibition of lysosome function suppresses PDAC cell proliferation and tumor growth. However, the codependencies induced by lysosomal inhibition in PDAC have not been systematically explored.

Association of Hospital Length of Stay and Complications With Readmission After Open Pancreaticoduodenectomy.

This study uses data from the American College of Surgeons National Quality Improvement Program databases to evaluate associations between hospital length of stay and postoperative complications with hospital readmission among patients who underwent open pancreaticoduodenectomy.

Pasireotide does not prevent postoperative pancreatic fistula: a prospective study.

Background: Pancreatic fistula is a major cause of morbidity after pancreas surgery. In 2014, a single-center, randomized-controlled trial found pasireotide decreased pancreatic fistula rates. However, this finding has not been validated, nor has pasireotide been widely adopted.

A Comprehensive Assessment of Accurate Lymph Node Staging and Preoperative Detection in Resected Pancreatic Cancer.

Background: The current (seventh edition) American Joint Commission on Cancer (AJCC) Staging System for pancreatic ductal adenocarcinoma (PDAC) dichotomizes pathologic lymph node (LN) involvement into absence (pN0) or presence (pN1) of disease. The recently announced eighth edition also includes stratification on the number of positive nodes. Furthermore, LNs detected on preoperative imaging (CT, MRI, or endoscopic ultrasound-EUS) are considered to be pathologically involved in other gastrointestinal cancers.

Distinction of Risk Factors for Superficial vs Organ-Space Surgical Site Infections After Pancreatic Surgery.

Importance: Surgical site infection (SSI) rates are increasingly used as a quality metric. However, risk factors for SSI in pancreatic surgery remain undefined.

Objective: To stratify superficial and organ-space SSIs after pancreatectomy and investigate their modifiable risk factors.