Modeling rectal cancer to advance neoadjuvant precision therapy.

Progress in rectal cancer therapy has been hindered by the lack of effective disease-specific preclinical models that account for the unique molecular profile and biology of rectal cancer. Thus, we developed complementary patient-derived xenograft (PDX) and subsequent in vitro tumor organoid (PDTO) platforms established from preneoadjuvant therapy rectal cancer specimens to advance personalized care for rectal cancer patients. Multiple endoscopic samples were obtained from 26 Stages 2 and 3 rectal cancer patients prior to receiving 5FU/RT and implanted subcutaneously into NSG mice to generate 15 subcutaneous PDXs. Second passaged xenografts demonstrated 100% correlation with the corresponding human cancer histology with maintained mutational profiles. Individual rectal cancer PDXs reproduced the 5FU/RT response observed in the corresponding human cancers. Similarly, rectal cancer PDTOs reproduced significant heterogeneity in cellular morphology and architecture. PDTO in vitro 5FU/RT treatment response replicated the clinical 5FU/RT neoadjuvant therapy pathologic response observed in the corresponding patient tumors (p < 0.05). The addition of cetuximab to the 5FU/RT regiment was significantly more sensitive in the rectal cancer PDX and PDTOs with wild-type KRAS compared to mutated KRAS (p < 0.05). Considering the close relationship between the patient's cancer and the corresponding PDX/PDTO, rectal cancer patient-derived research platforms represent powerful translational research resources as population-based tools for biomarker discovery and experimental therapy testing. In addition, our findings suggest that cetuximab may enhance RT effectiveness by improved patient selection based on mutational profile in addition to KRAS or by developing a protocol using PDTOs to identify sensitive patients.

Caseous calcification of the mitral annulus: case report and brief review.

BACKGROUND: Caseous calcification of the mitral annulus (CCMA) is a very rare variant of mitral annular calcification, which is typically asymptomatic but can manifest as a cardiac tumour, abscess, or in the form of mitral valve dysfunction. CASE SUMMARY: We present a patient who developed shortness of breath and was initially thought to have an intracardiac tumour, but ultimately was recognized as massive calcification of the mitral valve by computed tomography angiogram. This finding was unfortunately made only shortly before the patient's clinical deterioration, and the specific diagnosis of CCMA was made on post-mortem findings, precluding any directed treatment for this entity. DISCUSSION: Caseous calcification of the mitral annulus can lead to significant pathology, including mitral regurgitation, stenosis, or systemic embolization of caseous material. Due to its relative scarcity and tendency to be asymptomatic, a diagnosis of CCMA is often difficult to make or easily overlooked. Early recognition and appropriate treatment is crucial for avoiding these potential complications.