Unique Case of Neurogenic Thoracic Outlet Syndrome with Arterial Compression in Patient with Bilateral Cervical Ribs and Osteochondroma of the Ribs.

Background: Neurogenic thoracic outlet syndrome typically presents with paresthesia, pain, and impaired strength in the neck, shoulder, and arm, and is typically a diagnosis of exclusion. This condition is caused by compression of the brachial plexus, typically by a bony or soft tissue anomaly present congenitally and influenced by repetitive motion or significant trauma. Treatment typically involves removal of the first rib and anterior scalene to decompress the thoracic outlet and relieve stress to the brachial plexus if the patient has failed conservative treatment with physical therapy and lifestyle modifications. Case Presentation: We present a case of neurogenic thoracic outlet syndrome with arterial compression treated surgically via a transaxillary first rib and cervical rib resection in a patient with bilateral cervical ribs and osteochondromas of the ribs.

RNA binding protein HuR regulates extracellular matrix gene expression and pH homeostasis independent of controlling HIF-1α signaling in nucleus pulposus cells.

Nucleus pulposus (NP) cells reside in the hypoxic niche of the intervertebral disc. Studies have demonstrated that RNA-binding protein HuR modulates hypoxic signaling in several cancers, however, its function in the disc is unknown. HuR did not show cytoplasmic translocation in hypoxia and its silencing did not alter levels of Hif-1α or HIF-targets in NP cells. RNA-Sequencing data revealed that important extracellular matrix-related genes including several collagens, MMPs, aggrecan, Tgf-ß3 and Sdc4 were regulated by HuR. Further analysis of HuR-silenced NP cells confirmed that HuR maintained expression of these matrix genes. We confirmed decreased levels of secreted collagen I and Sdc4 and increased pro-MMP13 in HuR-knockdown cells. In addition, messenger ribonucleoprotein immunoprecipitation demonstrated HuR binding to Tgf-ß3 and Sdc4 mRNAs. Interestingly, while HuR bound to Hif-1α and Vegf mRNAs, it was clear that compensatory mechanisms sustained their expression when HuR was silenced. Noteworthy, despite the presence of multiple HuR-binding sites and reported interaction in other cell types, HuR showed no binding to Pgk1, Eno1, Pdk1 and Pfkfb3 in NP cells. Metabolic studies showed a significant decrease in the extracellular acidification rate (ECAR) and mitochondrial oxygen consumption rate (OCR) and acidic pH in HuR-silenced NP cells, without appreciable change in total OCR. These changes were likely due to decreased Ca12 expression in HuR silenced cells. Taken together, our study demonstrates for the first time that HuR regulates extracellular matrix (ECM) and pH homeostasis of NP cells and has important implications in the maintenance of intervertebral disc health.

Genetic Drivers of Pancreatic Cancer Are Identical Between the Primary Tumor and a Secondary Lesion in a Long-Term (>5 Years) Survivor After a Whipple Procedure.

Background: A new mass in the remnant pancreas of a patient with previously resected pancreatic ductal adenocarcinoma (PDA) typically represents either a recurrence of the initial primary tumor or a second primary tumor. Recent advances in next-generation sequencing (NGS) strategies allow us to compare the genetic makeup of primary and secondary lesions. Case presentation: A 50-year-old Caucasian female presented for a surgical evaluation of a new biopsy-proven PDA at the junction of the body and tail of the pancreas. Six years prior, in 2011, the patient was found to have a T3N0M0 PDA of the pancreatic head, which was surgically resected with a classic Whipple procedure and concurrent hemicolectomy. Pathology showed pancreatic intraepithelial neoplasia grade 2 and PDA with negative surgical margins, positive perineural spread, and negative lymphovascular spread, and the patient received adjuvant chemotherapy and local radiation. In 2017, she was diagnosed with a new PDA lesion in the remaining pancreatic body far from the previous anastomosis site and was taken to surgery for a completion pancreatectomy and revision of the gastrojejunostomy. NGS was performed on both specimens. Both lesions shared identical mutations in KRAS, TP53, and CDKN2A genes. Amplifications of MYC and mutant KRAS were identified in the 2017 tumor and an ACVR1B mutation was identified in the 2011 tumor, but was not found in the 2017 tumor. Conclusions: This case demonstrates the ability to evaluate similarities between key genetic drivers from a resected primary tumor and a PDA lesion that presented in the same patient 6 years later. Histological analysis and NGS can be used to understand potential differences and similarities between lesions and may be useful in future studies as predictive markers or to provide insight into resistance mechanisms (e.g., MYC amplification).

Completion Pancreaticoduodenectomy for Hereditary Pancreatitis After Prior Puestow Procedure: A Case Report.

Background: Hereditary pancreatitis (HP) is an uncommon condition resulting from an imbalance of pancreatic proteases. Most commonly, protease serine 1 genetic mutations are causative for HP and often result in recurrent early onset episodes of acute pancreatitis typically progressing to chronic pancreatitis, with a high risk of pancreatic cancer. Case Presentation: A 46-year-old female with HP, confirmed by genetic testing, presented with a 7-month history of recurrent pancreatitis. She had previously undergone a distal pancreatectomy and Puestow procedure in 1992 at 21 years of age, after having pancreatitis as a teenager. The patient now had a completion pancreaticoduodenectomy and celiac ethanol nerve block. Conclusion: A completion pancreatectomy in patients with HP can be performed after previous pancreatic surgical intervention to treat disease manifestations and as a prophylaxis against an increased risk of pancreatic adenocarcinoma.