Introduction

Introduction Laparoscopic adrenalectomy (LA) may be associated with reduction in postoperative pain, morbidity, length of stay, and cost compared to open adrenalectomy, and, as a result, has become a preferred approach for benign tumors. Though recent series have reported safety and oncologic non-inferiority with a minimally invasive approach to malignant and metastatic adrenal tumors, relative contraindications to LA include malignancy, large size, and invasion or abutment of vital structures.

Methods/results

We demonstrate techniques to perform LA in an obese patient with a large ([6 cm) solitary breast metastasis to the right adrenal gland that was adherent to the liver, inferior vena cava (IVC), and right renal vein. The tumor was growing behind the infrahepatic IVC and was abutting the confluence of the renal vein/IVC. The patient was monitored on systemic treatment with no new sites of disease and after achieving a maximal response to neoadjuvant treatment. Laparoscopic techniques to safely approach adrenal tumors adherent to the liver, IVC, and renal vein are stepwise demonstrated, including appropriate patient positioning and port site selection. The tumor was excised with negative margins, and the patient was discharged on postoperative day 1 with minimal pain medication and tolerating a regular diet.

Conclusion

Though malignancy is a relative contraindication to LA, even large right-sided adrenal tumors abutting the liver and growing behind the IVC can be safely approached while adhering to oncologic principles, as is demonstrated in this video.

Colon cancer is a leading cause of cancer-related mortality for which targeted therapy is needed; however, trials using apoptosis-inducing ligand monotherapy to overcome resistance to apoptosis have not shown clinical responses. Since colon cancer cells selectively uptake and rapidly metabolize glucose, a property utilized for clinical staging, we investigated mechanisms to alter glucose metabolism in order to selectively target the cancer cells and to overcome evasion of apoptosis. We demonstrate TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) resistance in the majority of human colon cancers tested and utilize the glucose analog 2-deoxy-d-glucose to sensitize TRAIL-resistant gastrointestinal adenocarcinoma cells, and not normal gastrointestinal epithelial cells, to TRAIL-induced apoptosis through enhanced death receptor 5 expression, downstream modulation of MAPK signaling and subsequent miRNA expression modulation by increasing the expression of miR-494 via MEK activation. Further, established human colon cancer xenografts treated with this strategy experience anti-tumor responses. These findings in colon adenocarcinoma support further investigation of manipulation of cellular energetics to selectively overcome resistance to apoptosis and to impart tumor regressions in established colon cancer tumors.

Pancreatic β-cell dysfunction is a common feature of type 2 diabetes. Earlier, we had cloned IG20 cDNA from a human insulinoma and had shown that IG20/MADD can encode six different splice isoforms that are differentially expressed and have unique functions, but its role in β-cell function was unexplored. To investigate the role of IG20/MADD in β-cell function, we generated conditional knockout (KMA1ko) mice. Deletion of IG20/MADD in β-cells resulted in hyperglycemia and glucose intolerance associated with reduced and delayed glucose-induced insulin production. KMA1ko β-cells were able to process insulin normally but had increased insulin accumulation and showed a severe defect in glucose-induced insulin release. These findings indicated that IG20/MADD plays a critical role in glucose-induced insulin release from β-cells and that its functional disruption can cause type 2 diabetes. The clinical relevance of these findings is highlighted by recent reports of very strong association of the rs7944584 single nucleotide polymorphism (SNP) of IG20/MADD with fasting hyperglycemia/diabetes. Thus, IG20/MADD could be a therapeutic target for type 2 diabetes, particularly in those with the rs7944584 SNP.