MST1R kinase accelerates pancreatic cancer progression via effects on both epithelial cells and macrophages

The MST1R (RON) kinase is overexpressed in >80% of human pancreatic cancers, but its role in pancreatic carcinogenesis is unknown. In this study, we examined the relevance of Mst1r kinase to Kras driven pancreatic carcinogenesis using genetically engineered mouse models. In the setting of mutant Kras, Mst1r overexpression increased acinar-ductal metaplasia (ADM), accelerated the progression of pancreatic intraepithelial neoplasia (PanIN), and resulted in the accumulation of (mannose receptor C type 1) MRC1+, (arginase 1) Arg+ macrophages in the tumor microenvironment. Conversely, absence of a functional Mst1r kinase slowed PanIN initiation, resulted in smaller tumors, prolonged survival and a reduced tumor-associated macrophage content. Mst1r expression was associated with increased production of its ligand Mst1, and in orthotopic models, suppression of Mst1 expression resulted in reduced tumor size, changes in macrophage polarization and enhanced T cell infiltration. This study demonstrates the functional significance of Mst1r during pancreatic cancer initiation and progression. Further, it provides proof of concept that targeting Mst1r can modulate pancreatic cancer growth and the microenvironment. This study provides further rationale for targeting Mst1r as a therapeutic strategy

Indocyanine green fluorescence-guided redo parathyroidectomy

Re-operative neck surgery for hyperparathyroidism is a technically difficult operation that requires adjunctive studies to assist with finding the parathyroid tissues. Intraoperative tests help minimise exploration of the neck and decrease injuries to the surrounding structures. Indocyanine green is a near-infrared fluorescent dye that in pre-clinical models was found to be useful in locating the parathyroid glands of dogs. No study has yet reported its use as a tool for parathyroid localisation in humans. We investigated the use of indocyanine green to assist with localisation of a recurrent parathyroid adenoma using a near-infrared imaging system. After exposure of the neck tissues, the parathyroid gland fluoresced brightly and directed our dissection. Exploration of the neck was minimal, and allowed for fast localisation and excision of the adenoma. Overall, use of indocyanine green is a simple and safe technique of intraoperative parathyroid localisation that warrants further investigation

Indocyanine green fluorescence-guided redo parathyroidectomy

Re-operative neck surgery for hyperparathyroidism is a technically difficult operation that requires adjunctive studies to assist with finding the parathyroid tissues. Intraoperative tests help minimise exploration of the neck and decrease injuries to the surrounding structures. Indocyanine green is a near-infrared fluorescent dye that in pre-clinical models was found to be useful in locating the parathyroid glands of dogs. No study has yet reported its use as a tool for parathyroid localisation in humans. We investigated the use of indocyanine green to assist with localisation of a recurrent parathyroid adenoma using a near-infrared imaging system. After exposure of the neck tissues, the parathyroid gland fluoresced brightly and directed our dissection. Exploration of the neck was minimal, and allowed for fast localisation and excision of the adenoma. Overall, use of indocyanine green is a simple and safe technique of intraoperative parathyroid localisation that warrants further investigation

Identification of circulating plasma ceramides as a potential sexually dimorphic biomarker of pancreatic cancer‐induced cachexia

Abstract Background Cancer patients who exhibit cachexia lose weight and have low treatment tolerance and poor outcomes compared with cancer patients without weight loss. Despite the clear increased risk for patients, diagnosing cachexia still often relies on self‐reported weight loss. A reliable biomarker to identify patients with cancer cachexia would be a valuable tool to improve clinical decision making and identification of patients at risk of adverse outcomes. Methods Targeted metabolomics, which included panels of amino acids, tricarboxylic acids, fatty acids, acylcarnitines, and sphingolipids, were conducted on plasma samples from patients with confirmed pancreatic ductal adenocarcinoma (PDAC) with and without cachexia and control patients without cancer (n = 10/group, equally divided by sex). Additional patient samples were analysed (total n = 95), and receiver operating characteristic (ROC) analyses were performed to establish if any metabolite could effectively serve as a biomarker of cachexia. Results Targeted profiling revealed that cachectic patients had decreased circulating levels of three sphingolipids compared with either non‐cachectic PDAC patients or patients without cancer. The ratio of C18‐ceramide to C24‐ceramide (C18:C24) outperformed a number of other previously proposed biomarkers of cachexia (area under ROC = 0.810). It was notable that some biomarkers, including C18:C24, were only altered in cachectic males. Conclusions Our findings identify C18:C24 as a potentially new biomarker of PDAC‐induced cachexia that also highlight a previously unappreciated sexual dimorphism in cancer cachexia

The impact of a malignant diagnosis on the pattern and outcome of readmission after liver and pancreatic surgery: An analysis of the nationwide readmissions database

Background and Objectives: Reducing readmissions is an important quality improvement metric. We sought to investigate patterns of 90-day readmission after hepato-pancreatic (HP) procedures. Methods: The Nationwide Readmissions Database (NRD) was used to identify patients undergoing HP procedures between 2010 and 2014. Patients were stratified according to benign versus malignant HP diagnoses and as index (same hospital as operation) versus non-index (different hospital) readmissions. Results: Among the 41 059 patients who underwent HP procedures, 26 563 (65%) underwent a liver resection while 14 496 (35%) pancreatic resection. Among all patients, 11 902 (29%) had a benign diagnosis versus 29 157 (71%) who had a cancer diagnosis. Overall 90-day readmission was 22% (n = 8 998) with a slight increase in readmissions among patients with a malignant (n = 6 655;23%) versus benign (n = 2 343;20%) diagnosis (P < 0.001). Readmission to an index hospital was more common (n = 7 316 81%) versus a non-index hospital (n = 1 682 19%). Non-index hospital readmissions were more frequent among patients with malignant HP diagnoses (OR, 1.41;P = 0.001). Conclusions: Up to one in four patients were readmitted after HP surgery. Late readmission was more common among patients with a cancer-diagnosis. While most readmissions occurred at the index hospital, 19% of all readmissions occurred at a non-index hospital and were more frequent among patients with malignant diagnoses

Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers

Introduction: Biliary tract cancers (BTC) are aggressive malignancies that require complex surgical procedures. Patients with BTC can present with skeletal muscle depletion, yet the effects of muscle wasting (sarcopenia) on outcomes have not been well studied. The objective of the current study was to define the impact of sarcopenia on survival among patients undergoing resection of BTC. Methods: Patients who underwent exploration for BTC who had a pre-operative CT scan available for review were identified. Body composition variables including total and psoas muscle area (cm2), muscle density (Hounsfield units), visceral fat area, subcutaneous fat area, and waist-to-hip ratio were analyzed at the level of L3. Outcomes were assessed according to the presence or absence of sarcopenia defined using sex- and BMI-specific threshold values for Psoas Muscle Index (PMI, cm2/m2). Results: Among 117 patients with BTC, 78 (67%) underwent curative-intent resection and 39 (33%) were explored but did not undergo resection due to metastatic/locally advanced disease. Tumor type included distal cholangiocarcinoma (n = 18, 15.4%), hilar cholangiocarcinoma (n = 27, 23.1%), gallbladder carcinoma (n = 52, 44.4%), and intrahepatic cholangiocarcinoma (n = 20, 17.1%). Median patient age was 65.6 years and 43.6% were male. Mean patient BMI was 26.1 kg/m2 among men and 27.5 kg/m2 among women. Overall, 41 (35.0%) patients had sarcopenia. Sarcopenia was associated with an increased risk of death among patients who underwent resection (HR 3.52, 95%CI 1.60\u20137.78, p = 0.002), which was comparable to patients with unresectable metastatic disease. Other factors such as low serum albumin (HR 3.17, 95% CI 1.30\u20137.74, p = 0.011) and low psoas density (HR 2.96, 95% CI 1.21\u20137.21, p = 0.017) were also associated with increased risk of death. Survival was stratified based on sarcopenia, psoas density, and serum albumin. The presence of each variable was associated with an incremental increased risk of death (0 variables ref.; 1 variable HR 3.8, 95% CI 1.0\u201314, p = 0.043; 2 variables HR 13.1, 95% CI 3.0\u201357.7, p = 0.001; 3 variables HR 14.6, 95% CI 2.5\u201387.1, p = 0.003). Patients who had no adverse prognostic factors had a 3-year OS of 67% versus no survival among patients with all 3 factors. Conclusions: Sarcopenia was common among patients undergoing resection of BTC, occurring in 1 of every 3 patients. Sarcopenia was associated with poor survival after resection, particularly among patients who experienced a recurrence. Body composition metrics such as sarcopenia and low psoas muscle density in addition to low albumin level were able to stratify patients into different prognostic categories

Early Recurrence of Neuroendocrine Liver Metastasis After Curative Hepatectomy: Risk Factors, Prognosis, and Treatment

Early tumor recurrence after curative resection typically indicates a poor prognosis. The objective of the current study was to investigate the risk factors, treatment, and prognosis of early recurrence of neuroendocrine tumor (NET) liver metastasis (NELM) after hepatic resection