Pattern of Residual Submucosal Involvement after Neoadjuvant Therapy for Rectal Cancer: A Rationale for the Utility of Endoscopic Submucosal Resection.

Background and Objectives: Full-thickness trans anal local excision for tumors with favorable response following neoadjuvant therapy for locally advanced rectal cancer (LARC) is a common strategy for organ preservation, but it could be associated with a high rate of postoperative complications. We describe the incidence and pattern of submucosal involvement in surgical specimens following neoadjuvant therapy for LARC and whether limiting local excision of the residual tumor bed to only mucosal/submucosal layers of the rectal wall is sufficient for accurately predicting the ypT status of residual cancer, providing a pathological rationale to replace full-thickness local excision by endoscopic submucosal resection. Materials and Methods: This was a single-institution retrospective study conducted at a teaching community hospital. We reviewed clinical and pathological findings with slides of 82 patients diagnosed with LARC treated at our center between 2006 and 2020. Eligibility criteria mirrored our current organ preservation trials. Results: No tumor was found in surgical specimens in 28 cases (34%). Additionally, 4, 22, 27, and 1 cases were staged as ypT1, ypT2, ypT3, and ypT4, respectively. Residual malignant cells were found in the submucosal layer in 98% of cases with ypT+ stage, with 'skip lesions' in only 2% of cases. Conclusions: A very high incidence of submucosal involvement is noticed in residual tumors after neoadjuvant therapy, providing pathological rationale to study the role of endoscopic submucosal resection as a restaging tool for tumors with favorable response after neoadjuvant therapy when organ preservation strategy is pursued. This study was limited by its retrospective design and relatively small number of patients.

Appropriateness of patient transfer with associated orthopaedic injuries to a Level I trauma center.

OBJECTIVE: To prospectively evaluate the appropriateness, indications, risk factors, and epidemiology of patients with orthopaedic injuries transferred to a Level I trauma center. DESIGN: Prospective data were supplemented through chart review on all patients transferred to a Level I trauma center with orthopaedic injuries (n = 546) from January 1, 2007, to December 31, 2007. The accepting orthopaedic trauma surgeon evaluated the appropriateness of transfer by visual analog scale. SETTING: A Level I trauma center. PARTICIPANTS: Patients transferred to the trauma center requiring orthopaedic trauma service involvement. MAIN OUTCOME MEASUREMENTS: Demographics and visual analog scale appropriateness scores were collected on each patient. RESULTS: The authors considered 16.5% of the cohort inappropriate transfers, 49.3% appropriate, and the remaining 34.2% were designated as intermediate. The transfers came from an emergency department physician in 81% of cases, an orthopaedic surgeon in 14% of cases, and 5% by general surgeon or internist. One hundred forty-eight cases transferred primarily as a result of orthopaedic injuries had an available orthopaedic surgeon on-call at the original institution. Sixty percent were transferred as a result of orthopaedic injury complexity, but only 39% of the 148 were evaluated by an actual orthopaedic surgeon before transfer. Lack of orthopaedic coverage at the referring hospital accounted for 27% of transfers. CONCLUSIONS: A total of 16.5% of transfers were deemed completely inappropriate by the accepting orthopaedic traumatologist. Most transfers, both appropriate and inappropriate, were attributed to either complete lack of orthopaedic coverage or a lack of expertise at the referring center.

Pediatric lateral condyle humeral fractures with and without associated elbow dislocations: a retrospective study.

In the pediatric population, lateral condyle fractures are relatively common elbow injuries, but not nearly as common are traumatic elbow dislocations, and these 2 types of injuries in combination are even less common. Our literature search showed only 2 reports on these concomitant injuries. In the study reported here, we evaluated a consecutive series of pediatric patients with lateral humeral condyle fractures with and without elbow dislocation and compared the groups' results.

Resistance to mitogen-activated protein kinase kinase (MEK) inhibitors correlates with up-regulation of the MEK/extracellular signal-regulated kinase pathway in hepatocellular carcinoma cells.

The extracellular signal-regulated (ERK), mitogen-activated protein kinase (p42/p44 MAPK) pathway is up-regulated in hepatocellular carcinoma (HCC). Molecular targeting of this critical mitogenic pathway may have therapeutic potential for the treatment of HCC; however, chemoresistance to long-term therapy may develop. In the present study, we employed small-molecule MAPK kinase (MEK) inhibitors, including U0126 [1,4-diamino-2,3-dicyano-1,4-bis(2-aminophynyltio)butadiene] and PD184161 (Neoplasia 8:1-8, 2006), in HepG2 and Hep3B human HCC cell lines to identify potential mechanism(s) of resistance. U0126 dose-dependently suppressed ERK phosphorylation at both 1- and 24-h time points in HepG2 cells, previously shown to be sensitive to growth inhibition by U0126. In contrast, ERK phosphorylation was only decreased at the 1-h time point but not at 24 h in the more resistant Hep3B cells. It is interesting that the lack of prolonged phospho-ERK suppression was associated with MEK hyperphosphorylation in Hep3B cells. Several MEK/ERK pathway intermediates were up-regulated in Hep3B cells; furthermore, transfection of Raf-1 small interfering RNA to suppress MEK/ERK pathway activation sensitized Hep3B cells to U0126. MEK inhibitor resistance was independent of p53 or hepatitis Bx protein status. Finally, we showed that combining two chemically distinct MEK inhibitors enhanced growth inhibition and apoptosis compared with the single agents. Taken together, these results suggest that up-regulated expression or activity of the MEK/ERK pathway contributes to MEK inhibitor resistance in HCC cells. Our findings also provide preclinical evidence suggesting that the status of the MEK/ERK pathway in patients may predict response to MEK/ERK-targeted therapeutics.