Looking Beyond Checkpoint Inhibitor Monotherapy: Uncovering New Frontiers for Pancreatic Cancer Immunotherapy.

Pancreatic ductal adenocarcinoma (PDAC) stands out as one of the most aggressive and challenging tumors, characterized by a bleak prognosis with a mere 11% survival rate over 5 years in the United States. Its formidable nature is primarily attributed to its highly aggressive behavior and poor response to existing therapies. PDAC, being notably resistant to immune interventions, presents a significant obstacle in treatment strategies.

Spatial transcriptomic analysis of primary and metastatic pancreatic cancers highlights tumor microenvironmental heterogeneity.

Although the spatial, cellular and molecular landscapes of resected pancreatic ductal adenocarcinoma (PDAC) are well documented, the characteristics of its metastatic ecology remain elusive. By applying spatially resolved transcriptomics to matched primary and metastatic PDAC samples, we discovered a conserved continuum of fibrotic, metabolic and immunosuppressive spatial ecotypes across anatomical regions. We observed spatial tumor microenvironment heterogeneity spanning beyond that previously appreciated in PDAC.

Cholangiocarcinoma.

Cholangiocarcinoma (CC) is a heterogeneous group of malignancies that originates at any point along the biliary tree. CC is an uncommon malignancy as it represents approximately 3% of all gastrointestinal malignancies, though its global incidence is rising. CC can often be asymptomatic in its early stages and as a result, it is frequently diagnosed in later stages, leading to challenges in clinical management.

Liver regeneration after portal and hepatic vein embolization improves overall survival compared with portal vein embolization alone: mid-term survival analysis of the multicentre DRAGON 0 cohort.

Background: The purpose of this study was to compare 3-year overall survival after simultaneous portal (PVE) and hepatic vein (HVE) embolization versus PVE alone in patients undergoing liver resection for primary and secondary cancers of the liver.

Methods: In this multicentre retrospective study, all DRAGON 0 centres provided 3-year follow-up data for all patients who had PVE/HVE or PVE, and were included in DRAGON 0 between 2016 and 2019. Kaplan-Meier analysis was undertaken to assess 3-year overall and recurrence/progression-free survival.

Sarcoidosis of the Bile Duct.

Sarcoidosis is an inflammatory disease that affects multiple organs. The lungs are the most commonly involved organs. Although a large proportion of patients with sarcoidosis have liver involvement, bile duct involvement is rare.

Effect of Operative Time on Outcomes of Minimally Invasive Versus Open Pancreatoduodenectomy.

Objective: To evaluate how operative time interacts with outcomes among different approaches to pancreaticoduodenectomy (PD). Minimally invasive PDs (MIPD), which include laparoscopic (LPD) and robotic (RPD) approaches, are increasingly performed in the USA. MIPD are generally associated with longer operative times (OT) compared to open PD (OPD).

Refining colorectal cancer classification and clinical stratification through a single-cell atlas.

Background: Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells.

Current Status of Circulating Tumor DNA Liquid Biopsy in Pancreatic Cancer.

Pancreatic cancer is a challenging disease with a low 5-year survival rate. There are areas for improvement in the tools used for screening, diagnosis, prognosis, treatment selection, and assessing treatment response. Liquid biopsy, particularly cell free DNA liquid biopsy, has shown promise as an adjunct to our standard care for pancreatic cancer patients, but has not yet been universally adopted into regular use by clinicians.

Matched Whole-Genome Sequencing (WGS) and Whole-Exome Sequencing (WES) of Tumor Tissue with Circulating Tumor DNA (ctDNA) Analysis: Complementary Modalities in Clinical Practice.

Tumor heterogeneity, especially intratumoral heterogeneity, is a primary reason for treatment failure. A single biopsy may not reflect the complete genomic architecture of the tumor needed to make therapeutic decisions. Circulating tumor DNA (ctDNA) is believed to overcome these limitations.

Evolving Clinical Utility of Liquid Biopsy in Gastrointestinal Cancers.

Room for improvement exists regarding recommendations for screening, staging, therapy selection, and frequency of surveillance of gastrointestinal cancers. Screening is costly and invasive, improved staging demands increased sensitivity and specificity to better guide therapy selection. Surveillance requires increased sensitivity for earlier detection and precise management of recurrences.

National Treatment Practice for Adrenocortical Carcinoma: Have They Changed and Have We Made Any Progress?

Background: Adrenocortical carcinoma (ACC) is a rare malignancy with a dismal prognosis. Two landmark trials published in 2007 and 2012 showed efficacy for adjuvant mitotane in resectable ACC and etoposide/doxorubicin/cisplatin plus mitotane for unresectable ACC, respectively. In this study, we used the National Cancer Database to examine whether treatment patterns and outcomes changed after these trials.

Primary Tumor Site Affects Survival in Patients with Gastroenteropancreatic and Neuroendocrine Liver Metastases.

Background: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are commonly present with metastatic disease, and the liver is the most frequent metastatic site. Herein, we studied whether primary tumor site affects survival in patients with GEP-NETs and liver metastases (NELM). As a secondary endpoint, we studied whether extrahepatic disease and surgical resection impact survival in this patient population.

Do All Abdominal Neuroendocrine Tumors Require Extended Postoperative VTE Prophylaxis? A NSQIP Analysis.

Background: Venous thromboembolism (VTE) occurs at high incidence in abdominal cancer surgery; therefore, a 4-week postoperative VTE prophylaxis is advocated. However, most patients with neuroendocrine tumors (NETs) have more favorable prognoses. This study aimed to determine the incidence of VTE in patients with abdominal NETs, compare these rates to other abdominal malignancies, and identify VTE risk factors.

Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) changes management in a majority of patients with neuroendocrine tumors.

Background: Gallium-DOTATATE positron emission tomography-computed tomography (PET CT) has shown superior accuracy in detecting grade 1 and 2 neuroendocrine tumors over previous imaging modalities and was recently included in National Comprehensive Cancer Network guidelines. It remains unclear which patients benefit most from this imaging modality. We therefore reviewed our initial experience with Gallium-DOTATATE PET CT to evaluate its usefulness in diagnosing, staging, and surveilling neuroendocrine tumors.

Expression of programmed death ligand 1 and 2 in adrenocortical cancer tissues: An exploratory study.

Background: Inhibition of the interaction of programmed death 1 with programmed death ligand 1 and 2 has been used successfully for treatment of multiple advanced cancers, but expression has not been studied in adrenocortical carcinoma. In this study, we investigated programmed death ligand 1 and 2 expression in adrenocortical carcinoma to determine the potential usefulness of checkpoint inhibitors in these malignant neoplasms.

Methods: A total of 56 tissue samples from patients with adrenocortical carcinoma (34) and benign adrenal tissues (22) were identified.

Resection of primary tumor may prolong survival in metastatic gastroenteropancreatic neuroendocrine tumors.

Background: Patients with gastroenteropancreatic neuroendocrine tumors often present with stage IV disease. Primary tumor resection in these patients remains controversial. Herein, we studied the impact of primary tumor removal, identified variables associated with prolonged survival for each neuroendocrine tumor subtype, and determined factors that influence surgeons to perform primary tumor resection.

Physiologic Response to HIPEC: Sifting Through Perturbation to Identify Markers of Complications.

Context: The postoperative physiologic response to hyperthermic intraperitoneal chemotherapy (HIPEC) has been poorly studied outside of the immediate perioperative time.

Objective: To characterize the physiologic response during the first 5 days after HIPEC and identify variables associated with major complications.

Methods: Patients undergoing HIPEC and cytoreductive surgery during a 14-month interval were retrospectively identified and their records reviewed for demographics, physiologic response, and major complications.

Mixed acinar-neuroendocrine-ductal carcinoma of the pancreas: a tale of three lineages.

Most pancreatic cancers arise from a single cell type, although mixed pancreatic carcinomas represent a rare exception. The rarity of these aggressive malignancies and the limitations of fine-needle aspiration (FNA) pose significant barriers to diagnosis and appropriate management. We report a case of a 54-year-old man presenting with abdominal pain, jaundice and a hypodense lesion within the uncinate process on CT.

Clinical Features of Metastatic Hepatic Malignancies.

The liver is a common site for gastrointestinal tumor metastases as it is the first major organ reached by blood draining the portal venous system. With the development of more effective chemotherapeutic agents which may eradicate residual microscopic disease in the liver and help reduce known tumor burden, partial hepatectomy to remove gross metastatic disease will likely become increasingly utilized in the future. This chapter discusses the presentation and clinical factors in liver directed surgical resection.

The changing spectrum of surgically treated cystic neoplasms of the pancreas.

Introduction. While the incidence of pancreatic cystic lesions has steadily increased, we sought to evaluate the changes in their surgical management. Methods.

Immunohistochemistry - microarray analysis of patients with peritoneal metastases of appendiceal or colorectal origin.

Background: The value of immunohistochemistry (IHC)-microarray analysis of pathological specimens in the management of patients is controversial, although preliminary data suggest potential benefit. We describe the characteristics of patients undergoing a commercially available IHC-microarray method in patients with peritoneal metastases (PM) and the feasibility of this technique in this population.

Methods: We retrospectively analyzed consecutive patients with pathologically confirmed PM from appendiceal or colorectal primary who underwent Caris Molecular Intelligence(™) testing.