Hematoxylin and Eosin Architecture Uncovers Clinically Divergent Niches in Pancreatic Cancer.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the only cancers with an increasing incidence rate and is often associated with intra- and peri-tumoral scarring, referred to as desmoplasia. This scarring is highly heterogeneous in extracellular matrix (ECM) architecture and plays complex roles in both tumor biology and clinical outcomes that are not yet fully understood. Using hematoxylin and eosin (H&E), a routine histological stain utilized in existing clinical workflows, we quantified ECM architecture in 85 patient samples to assess relationships between desmoplastic architecture and clinical outcomes such as survival time and disease recurrence. By utilizing unsupervised machine learning to summarize a latent space across 147 local (e.g., fiber length, solidity) and global (e.g., fiber branching, porosity) H&E-based features, we identified a continuum of histological architectures that were associated with differences in both survival and recurrence. Furthermore, we mapped H&E architectures to a CO-Detection by indEXing (CODEX) reference atlas, revealing localized cell- and protein-based niches associated with outcome-positive versus outcome-negative scarring in the tumor microenvironment. Overall, our study utilizes standard H&E staining to uncover clinically relevant associations between desmoplastic organization and PDAC outcomes, offering a translatable pipeline to support prognostic decision-making and a blueprint of spatial-biological factors for modeling by tissue engineering methods.

Targeted Nipple Reinnervation in Gender-affirming Mastectomy Using Autologous Nerve Graft.

Our team recently described targeted nipple reinnervation (TNR) during female-to-male gender-affirming mastectomy with free nipple grafting using either direct nerve coaptation or nerve allograft. The goals of TNR are to improve sensation (including erogenous sensation) and prevent numbness, paresthesias, chronic pain, and phantom sensation. Here, we describe our modified technique, which has evolved to use autologous intercostal nerve branches as donor nerves for reinnervation if direct nerve coaptation cannot be achieved. During TNR, the T3-T5 sensory branches are preserved and coapted to the repositioned nipple-areolar complex (NAC). In patients with donor nerves that were not adequate in length to allow for direct coaptation, autologous intercostal nerve branches were not used for coaptation (branches present along the chest wall that would otherwise be lost) or one of the T3-T5 branches were harvested. An end-to-end nerve repair between the autograft and donor nerves was done, and the donor nerve/autograft complex was coapted to the NAC. Targeted muscle reinnervation was performed after autograft harvest to prevent neuroma formation. TNR with intercostal nerve autograft is technically feasible in female-to-male gender-affirming mastectomy with free nipple grafting when direct coaptation is not possible. Chest reinnervation using autologous intercostal nerve branches as donor nerves is another option for reinnervation when the nerves are too short for direct coaptation. Because the collection of long-term data is ongoing, the effectiveness of NAC reinnervation using our technique will be described in a future publication.