A case of a pseudo colonic mass causing gastrointestinal bleeding in a patient with a left ventricular assist device.

There are many complications associated with the left ventricular assist devices (LVADs), including gastrointestinal bleeding (GIB). We present a case of a pseudo colonic mass visualized on colonoscopy during workup for GIB in an LVAD patient necessitating a right colectomy with final pathology negative for malignancy. A review of the literature in regards to the pathology, diagnosis, and treatment of this interesting condition is included.

Targeting myeloid-derived suppressor cells using a novel adenosine monophosphate-activated protein kinase (AMPK) activator.

Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of early myeloid cells that accumulate in the blood and tumors of patients with cancer. MDSC play a critical role during tumor evasion and promote immune suppression through variety of mechanisms, such as the generation of reactive oxygen and nitrogen species (ROS and RNS) and cytokines. AMPactivated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase that regulates energy homeostasis and metabolic stress. However, the role of AMPK in the regulation of MDSC function remains largely unexplored. This study was designed to investigate whether treatment of MDSC with OSU-53, a PPAR-inactive derivative that stimulates AMPK kinase, can modulate MDSC function. Our results demonstrate that OSU-53 treatment increases the phosphorylation of AMPK, significantly reduces nitric oxide production, inhibits MDSC migration, and reduces the levels of IL-6 in murine MDSC cell line (MSC2 cells). OSU53 treatment mitigated the immune suppressive functions of murine MDSC, promoting T-cell proliferation. Although OSU-53 had a modest effect on tumor growth in mice inoculated with EMT-6 cells, importantly, administration of OSU53 significantly (p < 0.05) reduced the levels of MDSC in the spleens and tumors. Furthermore, mouse MDSC from EMT-6 tumor-bearing mice and human MDSC isolated from melanoma patients treated with OSU-53 showed a significant reduction in the expression of immune suppressive genes iNOS and arginase. In summary, these results demonstrate a novel role of AMPK in the regulation of MDSC functions and provide a rationale of combining OSU-53 with immune checkpoint inhibitors to augment their response in cancer patients.

A novel dual AMPK activator/mTOR inhibitor inhibits thyroid cancer cell growth.

CONTEXT: Activated AMP protein kinase (AMPK) is a key regulator of intracellular energy homeostasis and may also function as a tumor suppressor by inhibiting cell growth through suppression of mammalian target of rapamycin (mTOR)/p70S6K signaling. AMPK activating agents, such as metformin and 5-aminoimidazole-4-carboxamide-ribonucleoside, have been demonstrated to inhibit thyroid cancer cell growth in in vitro and in vivo models. OSU-53, a recently developed AMPK activator, was previously shown to exhibit both in vitro and in vivo antitumor activity against aggressive breast cancer cell lines and their xenografts in nude mice. OBJECTIVE: The objective of the study was to assess the in vitro effects of OSU-53 treatment in a panel of thyroid cancer cells. DESIGN: Experiments were performed to determine the effects of OSU-53 on cell growth, oncogenic signaling, apoptosis, autophagy, and cell rescue after selective knockdown of AMPK. RESULTS: OSU-53 inhibited in vitro cell growth of all seven thyroid cancer cells tested and induced activation of AMPK. Cell lines with activating mutations in RAS or BRAF, compared with cells with phosphatase and tensin homolog deleted from chromosome 10 null and RET/papillary thyroid carcinoma mutations, were more sensitive to drug treatment and demonstrated a more robust AMPK activation, inhibition of mTOR signaling, and autophagy stimulation. After selective knockdown of AMPK, cell rescue from OSU-53 treatment was not observed. We demonstrated an off-target effect of direct mTOR inhibition by OSU-53. Increased autophagy was observed in cells with activation RAS or BRAF mutations. CONCLUSIONS: OSU-53, a novel dual-AMPK activator/mTOR inhibitor, effectively inhibits growth in a variety of thyroid cancer cell lines and is most potent in cells with activating mutations in RAS or BRAF.

Intraoperative scintigraphy using a large field-of-view portable gamma camera for primary hyperparathyroidism: initial experience.

BACKGROUND: We investigated a novel technique, intraoperative (99 m)Tc-Sestamibi (MIBI) imaging (neck and excised specimen (ES)), using a large field-of-view portable gamma camera (LFOVGC), for expediting confirmation of MIBI-avid parathyroid adenoma removal. METHODS: Twenty patients with MIBI-avid parathyroid adenomas were preoperatively administered MIBI and intraoperatively imaged prior to incision (neck) and immediately following resection (neck and/or ES). Preoperative and intraoperative serum parathyroid hormone monitoring (IOPTH) and pathology (path) were also performed. RESULTS: MIBI neck activity was absent and specimen activity was present in 13/20 with imaging after initial ES removal. In the remaining 7/20 cases, residual neck activity and/or absent ES activity prompted excision of additional tissue, ultimately leading to complete hyperfunctioning tissue excision. Postexcision LFOVGC ES imaging confirmed parathyroid adenoma resection 100% when postresection imaging qualitatively had activity (ES) and/or no activity (neck). The mean ± SEM time saving using intraoperative LFOVGC data to confirm resection versus first IOPTH or path result would have been 22.0 ± 2 minutes (specimen imaging) and 26.0 ± 3 minutes (neck imaging). CONCLUSION: Utilization of a novel real-time intraoperative LFOVGC imaging approach can provide confirmation of MIBI-avid parathyroid adenoma removal appreciably faster than IOPTH and/or path and may provide a valuable adjunct to parathyroid surgery.