Robotic-assisted approach for complex cholecystectomies.

Robotic approaches have facilitated the minimally invasive completion of increasingly complex surgical procedures. In the management of the difficult gallbladder, we have found that the wristed instruments, three-dimensional camera, the ability to use indocyanine green (ICG) with integrated fluorescent imaging, and ease of intracorporeal suturing to be useful in tackling the challenges associated with complex benign gallbladder disease. We describe the rationale and technical lessons learned during four cases of complex cholecystectomies that highlight the management principles and technical advantages afforded by the use of the robotic-assisted laparoscopic (RAL) approach. The cases include a subtotal fundus-first reconstituting cholecystectomy, subtotal fenestrating cholecystectomy, a cholecystocolonic fistula managed by a RAL subtotal fenestrating cholecystectomy, and an iatrogenic cholecystoduodenal fistula managed by RAL cholecystectomy. In each case, the operation was performed safely without intraoperative injury or conversion to open, and three of the four patients were discharged from the recovery room. In our view, these favorable outcomes were greatly facilitated by the robotic platform. It is our intent to share adaptations and innovations that we found helpful to encourage other surgeons with sufficient robotic experience to tackle complex gallbladder cases minimally invasively.

Translation of a Protease Turnover Assay for Clinical Discrimination of Mucinous Pancreatic Cysts.

The classification of pancreatic cyst fluids can provide a basis for the early detection of pancreatic cancer while eliminating unnecessary procedures. A candidate biomarker, gastricsin (pepsin C), was found to be present in potentially malignant mucinous pancreatic cyst fluids. A gastricsin activity assay using a magnetic bead-based platform has been developed using immobilized peptide substrates selective for gastricsin bearing a dimeric rhodamine dye. The unique dye structure allows quantitation of enzyme-cleaved product by both fluorescence and surface enhanced Raman spectroscopy (SERS). The performance of this assay was compared with ELISA assays of pepsinogen C and the standard of care, carcinoembryonic antigen (CEA), in the same clinical sample cohort. A retrospective cohort of mucinous (n = 40) and non-mucinous (n = 29) classes of pancreatic cyst fluid samples were analyzed using the new protease activity assay. For both assay detection modes, successful differentiation of mucinous and non-mucinous cyst fluid was achieved using 1 µL clinical samples. The activity-based assays in combination with CEA exhibit optimal sensitivity and specificity of 87% and 93%, respectively. The use of this gastricsin activity assay requires a minimal volume of clinical specimen, offers a rapid assay time, and shows improvements in the differentiation of mucinous and non-mucinous cysts using an accurate standardized readout of product formation, all without interfering with the clinical standard of care.

Aging of the Immune System: Focus on Natural Killer Cells Phenotype and Functions.

Aging is the greatest risk factor for nearly all major chronic diseases, including cardiovascular diseases, cancer, Alzheimer's and other neurodegenerative diseases of aging. Age-related impairment of immune function (immunosenescence) is one important cause of age-related morbidity and mortality, which may extend beyond its role in infectious disease. One aspect of immunosenescence that has received less attention is age-related natural killer (NK) cell dysfunction, characterized by reduced cytokine secretion and decreased target cell cytotoxicity, accompanied by and despite an increase in NK cell numbers with age. Moreover, recent studies have revealed that NK cells are the central actors in the immunosurveillance of senescent cells, whose age-related accumulation is itself a probable contributor to the chronic sterile low-grade inflammation developed with aging ("inflammaging"). NK cell dysfunction is therefore implicated in the increasing burden of infection, malignancy, inflammatory disorders, and senescent cells with age. This review will focus on recent advances and open questions in understanding the interplay between systemic inflammation, senescence burden, and NK cell dysfunction in the context of aging. Understanding the factors driving and enforcing NK cell aging may potentially lead to therapies countering age-related diseases and underlying drivers of the biological aging process itself.