Smith, J Joshua

Abstract Reprogramming of aged donor tissue cells into induced pluripotent stem cells (A-iPSC) preserved the epigenetic memory of aged-donor tissue, defined as genomic instability and poor tissue differentiation in our previous study. The unbalanced expression of RNA exosome subunits affects the RNA degradation complex function and is associated with geriatric diseases including premature aging and cancer progression. We hypothesized that the age-dependent progressive subtle dysregulation of EXOSC2 (exosome component 2) causes the aging traits (abnormal cell cycle and poor tissue differentiation). We used embryonic stem cells as a tool to study EXOSC2 function as the aging trait epigenetic memory determined in A-iPSC because these aging traits could not be studied in senesced aged cells or immortalized cancer cells. We found that the regulatory subunit of PP2A phosphatase, PPP2R5E, is a key target of EXOSC2 and this regulation is preserved in stem cells and cancer.

Abstract Background The treatment of locally advanced rectal cancer now includes “watch-and-wait” (WW) management for patients who exhibit a clinical complete response (cCR) to total neoadjuvant therapy (TNT). We assessed patients’ knowledge and preferences regarding WW with the goal of incorporating patient input into clinical trial design. Methods Rectal cancer patients in advocacy groups (COLONTOWN/Rectalburgh and Fight CRC) were surveyed regarding perceptions about treatment strategies, tolerable risks of treatment failure, and preferences on clinical trial design. Surveys were initially distributed in 2019, with the shift toward WW prompting re-survey of select questions in 2023. Results All respondents preferred enrollment in trials that incorporated patient input. Most respondents (76%) preferred treatment that incorporated chemotherapy escalation over radiation escalation. Furthermore, when presented with a hypothetical patient who developed a cCR after chemoradiation (without the option for WW), 58% of patients chose surgical treatment (with 100% risk of permanent ostomy and 80% chance of cure) over omission of surgery (with <80% chance of cure). In contrast, when the hypothetical patient developed a cCR after TNT (with an option for WW), 82% of patients opted for selective WW over surgery. Conclusions This work successfully integrated patient advocacy groups as a resource for obtaining patient input. Surveys revealed patients had a strong preference for chemotherapy escalation, for selective WW when offered, and for incorporation of input into future clinical trial design. These findings describe how well-informed patients approach complex medical decision-making and serve as a starting point for future studies seeking to incorporate patient voices.

Background. Hepatic endometriosis/uterus-like mass is rare and may be overlooked during hepatic cyst workups. We report a case of uterus-like mass, misdiagnosed as hepatic abscess. Case Report: A 47-year-old woman developed abdominal pain and vomiting. Infectious colitis with hepatic abscess was diagnosed, and remained antibiotic-refractory. Fine-needle aspiration and core biopsies showed benign contents. The patient presented to our institution with symptoms and normal blood work. Laparoscopic excision demonstrated a 1.4-cm cyst composed of endometrial glands (estrogen receptor+ and progesterone receptor+) and stroma (CD10+) with smooth muscle actin (SMA+), arranged in an organoid fashion. The patient, status-post hysterectomy, had no history or symptoms of endometriosis. Conclusion. This rare case illustrates the merit of considering uterus-like mass/endometriosis in the differential diagnosis of antibiotic-refractory hepatic cysts. Cyst heterogeneity may confound needle biopsy. We report the first instance of a hepatic uterus-like mass, with a review of related entities, postulated histogenesis, and important clinical associations.