Dynamics of Fibril Collagen Remodeling by Tumor Cells: A Model of Tumor-Associated Collagen Signatures.

Many solid tumors are characterized by a dense extracellular matrix (ECM) composed of various ECM fibril proteins. These proteins provide structural support and a biological context for the residing cells. The reciprocal interactions between growing and migrating tumor cells and the surrounding stroma result in dynamic changes in the ECM architecture and its properties. With the use of advanced imaging techniques, several specific patterns in the collagen surrounding the breast tumor have been identified in both tumor murine models and clinical histology images. These tumor-associated collagen signatures (TACS) include loosely organized fibrils far from the tumor and fibrils aligned either parallel or perpendicular to tumor colonies. They are correlated with tumor behavior, such as benign growth or invasive migration. However, it is not fully understood how one specific fibril pattern can be dynamically remodeled to form another alignment. Here, we present a novel multi-cellular lattice-free (MultiCell-LF) agent-based model of ECM that, in contrast to static histology images, can simulate dynamic changes between TACSs. This model allowed us to identify the rules of cell-ECM physical interplay and feedback that guided the emergence and transition among various TACSs.

Laparoscopic vs. robotic colectomy for left-sided diverticulitis.

Diverticulitis is a prevalent gastrointestinal disease that often warrants surgical intervention. However, the optimal approach between traditional laparoscopy (LC) and robotic-assisted laparoscopy (RAC) for diverticulitis remains unclear. Our research compares these techniques in patients diagnosed with left-sided diverticulitis treated at a single, tertiary referral center from 2019 to 2022. Among the 134 patients, 86 underwent laparoscopic and 48 robotic-assisted surgeries. The surgeries included in this analysis are left colectomy, sigmoid colectomy, low anterior resection, and Hartmann's procedure. Primary outcomes were major morbidity and 30-day mortality. Secondary outcomes were operative time, conversion to open, length of stay, unplanned return to the operating room, 30-day readmission rate, and overall morbidity. While demographics and comorbidities were similar for both groups, the robotic-assisted group displayed a statistically significant longer operative time (198.0 ± 84.4 LC vs. 264.8 ± 78.5 min RAC, p < 0.001). When investigated further, there was a significant difference in operative time for uncomplicated diverticulitis cases favoring the LC approach (169.17 ± 58.1 LC vs. 244.82 ± 58.79 min RAC, p < 0.001). This significant difference, however, was not present in complicated diverticulitis cases. Other factors, such as overall and major morbidity, rate of conversion to open approach, ostomy creation, estimated blood loss, time to return of bowel function, length of stay, and 30-day readmission rate, did not significantly differ between the groups. There was no 30-day mortality in either group. Favorable patient outcomes, lack of significant difference in operative time compared with traditional laparoscopy, and absence of differences in morbidities or efficacy, raises an interesting question in the world of minimally invasive surgery: is the robotic-assisted approach emerging as the advantageous approach for complicated diverticulitis cases? We encourage additional, multi-center analysis of specifically complicated diverticulitis managed with both surgical approaches to investigate if these findings are replicated outside of our institution.

Morphophenotypic classification of tumor organoids as an indicator of drug exposure and penetration potential.

The dynamics of tumor progression is driven by multiple factors, which can be exogenous to the tumor (microenvironment) or intrinsic (genetic, epigenetic or due to intercellular interactions). While tumor heterogeneity has been extensively studied on the level of cell genetic profiles or cellular composition, tumor morphological diversity has not been given as much attention. The limited analysis of tumor morphophenotypes may be attributed to the lack of accurate models, both experimental and computational, capable of capturing changes in tumor morphology with fine levels of spatial detail. Using a three-dimensional, agent-based, lattice-free computational model, we generated a library of multicellular tumor organoids, the experimental analogues of in vivo tumors. By varying three biologically relevant parameters-cell radius, cell division age and cell sensitivity to contact inhibition, we showed that tumor organoids with similar growth dynamics can express distinct morphologies and possess diverse cellular compositions. Taking advantage of the high-resolution of computational modeling, we applied the quantitative measures of compactness and accessible surface area, concepts that originated from the structural biology of proteins. Based on these analyses, we demonstrated that tumor organoids with similar sizes may differ in features associated with drug effectiveness, such as potential exposure to the drug or the extent of drug penetration. Both these characteristics might lead to major differences in tumor organoid's response to therapy. This indicates that therapeutic protocols should not be based solely on tumor size, but take into account additional tumor features, such as their morphology or cellular packing density.