Primary Hyperparathyroidism: Part Two: Surgical Management.

Primary hyperparathyroidism (PHPT) is caused by the overproduction of parathyroid hormone by 1 or more parathyroid glands resulting in hypercalcemia and its downstream clinical consequences. The definitive management of PHPT is surgery. Approaches to successful surgery include bilateral exploration or focused parathyroidectomy with intraoperative parathyroid hormone monitoring, which in experienced hands are both associated with a low risk of complications.

Primary Hyperparathyroidism: Part One: Evaluation.

Primary hyperparathyroidism (PHPT) is a disorder characterized by the autonomous overproduction of parathyroid hormone (PTH) that leads to hypercalcemia, multiple clinical sequelae, and heterogenous presentation. Whether PHPT is caused by a single benign adenoma (85%), multiglandular disease (15%), or parathyroid carcinoma (1%), surgery is the definitive treatment.

An Immunocompetent Model of Pancreatic Cancer Resection and Recurrence.

BACKGROUND: Even after surgical resection, most patients with localized pancreatic ductal adenocarcinoma (PDAC) succumb to disease recurrence. Current animal models do not recapitulate this pattern of disease recurrence. Our goal was to develop a clinically relevant, immunocompetent model of PDAC resection to study recurrence and evaluate therapy. METHODS: Pancreatic cancer cells derived from tumors arising in KPC (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) mice were co-injected with stromal cells (pancreatic stellate cells) into the pancreas of immunocompetent mice to simulate the stroma-rich tumors seen in human PDAC. After allowing tumors to form, we resected these localized tumors and followed the mice for tumor recurrence. Circulating tumor cells (CTCs) were isolated, and systemic chemotherapy or immunotherapy was administered following tumor resection. RESULTS: Tumors formed by co-injection of KPC cells and stromal cells demonstrated a dense desmoplastic reaction similar to that seen in human disease. Resection at days 15 and 21 after implantation revealed uniform tumor volumes of 92 ± 19 mm3 on day 15 and 444 ± 54 mm3 on day 21. Histology of resected tumors showed negative margins. Resembling human PDAC, mice that underwent resection showed improved median survival (58 vs 47 days) but most animals developed intra-abdominal recurrence on follow-up. Adjuvant chemotherapy (median survival 69 vs 58 days), but not immunotherapy (median survival 69 vs 65 days) tended towards improved survival as seen in human disease. Circulating tumor cells were reliably identified from mice with and without resection, suggesting utility of this model in studying tumor metastases and recurrence. CONCLUSION: We describe an immunocompetent animal model that recapitulates human disease in morphology and recurrence patterns. We show that it can be used to evaluate therapy in clinical scenarios associated with surgical resection and may help characterize factors responsible for disease recurrence.

Esophagus and Gastrointestinal Junction Tumors.

Esophageal squamous cell carcinoma and adenocarcinoma account for 95% of all esophageal malignancies. The rates of esophageal adenocarcinoma have increased in Western countries, making it the predominant type of esophageal cancer. Treatment of both types of cancer has transformed to a more minimally invasive approach, with endoscopic methods being used for superficial cancers and more frequent use of video-assisted and laparoscopic modalities for locally advanced tumors. The current National Comprehensive Cancer Network guidelines advocate a trimodal approach to treatment, with neoadjuvant chemoradiation and surgery for locally advanced cancers.

Simplified preoperative tool predicting discharge destination after major oncologic gastrointestinal surgery.

BACKGROUND: Preoperatively identifying patients who will require discharge to extended care facilities (ECFs) after major cancer surgery is valuable. This study compares existing models and derives a simple, preoperative tool for predicting discharge destination after major oncologic gastrointestinal surgery. METHODS: The American College of Surgeon National Surgical Quality Improvement datasets were used to evaluate existing risk stratification and frailty assessment tools between the years 2011 and 2015. A novel tool for predicting discharge to ECF was developed in the 2011-2015 dataset and subsequently validated in the 2016 dataset. RESULTS: Major resections were analyzed for 61 683 malignancies: 6.9% esophagus, 5.3% stomach, 20.0% liver, 21.0% pancreas, and 46.8% colon/rectum. The overall ECF discharge rate was 9.1%. The American Society of Anesthesiologist score, 11-point modified frailty index (mFI), and 5-point abbreviated modified frailty index (amFI) demonstrated only moderate discrimination in predicting ECF discharge (c-statistic: 0.63-0.65). In contrast, our weighted cancer cancer abbreviated modified frailty index (camFI) score demonstrated improved discrimination with c-statistic of 0.73. The camFI displayed >90% negative predictive value for ECF discharge at every operative site. CONCLUSION: The camFI is a simple tool that can be used preoperatively to counsel patients on their risk of ECF discharge, and to identify patients with the least need for ECF discharge after major oncologic gastrointestinal surgery.

Gut Microbiota Promotes Tumor Growth in Mice by Modulating Immune Response.

We studied the effects of gut microbiome depletion by oral antibiotics on tumor growth in subcutaneous and liver metastases models of pancreatic cancer, colon cancer, and melanoma. Gut microbiome depletion significantly reduced tumor burden in all the models tested. However, depletion of gut microbiome did not reduce tumor growth in Rag1-knockout mice, which lack mature T and B cells. Flow cytometry analyses demonstrated that gut microbiome depletion led to significant increase in interferon gamma-producing T cells with corresponding decrease in interleukin 17A and interleukin 10-producing T cells. Our results suggest that gut microbiome modulation could emerge as a novel immunotherapeutic strategy.