Targeted inhibition of SCFSKP2 confers anti-tumor activities resulting in a survival benefit in osteosarcoma.

Osteosarcoma(OS) is a highly aggressive bone cancer for which treatment has remained essentially unchanged for decades. Although OS is characterized by extensive genomic heterogeneity and instability, RB1 and TP53 have been shown to be the most commonly inactivated tumor suppressors in OS. We previously generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which largely recapitulates human OS with nearly complete penetrance. SKP2 is a repression target of pRb and serves as a substrate recruiting subunit of the SCFSKP2 complex. In addition, SKP2 plays a central role in regulating the cell cycle by ubiquitinating and promoting the degradation of p27. We previously reported the DKOAA transgenic model, which harbored a knock-in mutation in p27 that impaired its binding to SKP2. Here, we generated a novel p53-Rb1-SKP2 triple-knockout model (TKO) to examine SKP2 function and its potential as a therapeutic target in OS. First, we observed that OS tumorigenesis was significantly delayed in TKO mice and their overall survival was markedly improved. In addition, the loss of SKP2 also promoted an apoptotic microenvironment and reduced the stemness of DKO tumors. Furthermore, we found that small-molecule inhibitors of SKP2 exhibited anti-tumor activities in vivo and in OS organoids as well as synergistic effects when combined with a standard chemotherapeutic agent. Taken together, our results suggest that SKP2 inhibitors may reduce the stemness plasticity of OS and should be leveraged as next-generation adjuvants in this cancer.

The Influence of Pregnancy on Weight Loss After Previous Bariatric Surgery.

Introduction: Bariatric surgery is routinely performed on obese women of reproductive age, most commonly with the laparoscopic sleeve gastrectomy (SG) and Roux-en-Y gastric bypass procedures (RYGB). This study analyzes the effects of postoperative pregnancy on excess BMI loss percentage (EBMIL%) after SG and RYGB. Methods: A retrospective study was conducted with 191 female patients of reproductive age between 20 and 40 years who underwent SG and RYGB performed at our institution between January 2017 and December 2018. A comparison of the results at 4-year follow-up was performed between patients who became pregnant after bariatric surgery with patients who did not. Results: Among 191 total cases, 32 (16.7%) patients became pregnant within a 4-year follow-up period, and 159 (83.2%) patients did not. The median postoperative body mass index (BMI) in the pregnant group was 33.3 kg/m2 (interquartile range [IQR] 30.1-38.5) and 33.5 kg/m2 (IQR 28.9-38.6) in the nonpregnant group. The mean EBMIL% within a 4-year follow-up in the pregnant group was 50.4% (standard deviation [SD] 23.5) and 55.5% (SD 30.4) in the nonpregnant group. The median weight before surgery in the pregnant group was 112 kg (IQR 107.9-132.2) and 117 kg (IQR 106-132.5) in the nonpregnant group. The median weight after surgery in the pregnant group was 89.5 kg (IQR 79.5-111) and 88.9 kg (IQR 78-103) in the nonpregnant group. There was no significant difference between outcomes. Conclusion: Weight loss maintenance after bariatric surgery is not impacted by postoperative pregnancy within a 4-year follow-up after SG and RYGB.

Transplant Ureter Inguinal Herniation Treated by Robotic Inguinal Hernia Repair.

Introduction: We report the case of a transplanted ureter obstructed by an inguinal herniation treated by a robotic-assisted approach. Case Report: This is a case of a 63-year-old male who had a kidney transplant with a graft on the left pelvis in September 2014, and presented to the clinic for evaluation of bilateral inguinal hernia. On physical examination he had bilateral palpable inguinal hernias, with the right one larger and only partially reducible. Computed tomography scan showed portion of urinary bladder and transplant ureter in the left inguinal hernia and mild hydroureteronephrosis in the transplanted kidney. Patient underwent catheterization of the transplant ureter where indocyanine green was injected for proper transplant ureter identification with the Firefly filter and robotic assisted hernia repair. Surgery was uneventful and patient was discharged home the same day with no further complications. Conclusion: The robotic approach using the Firefly filter was shown to be safe during the dissection to avoid injury to the transplant ureter.

Does the Weight Matter? Short-Term Outcomes of Lightweight Versus Heavyweight Three-Dimensional Anatomical Mesh in Minimally Invasive Inguinal Hernia Repair.

Background: The type of mesh used in inguinal hernia repairs remains controversial. There are limited data looking at specific mesh-related complications. The objective of this study is to assess postoperative 90-day outcomes in lightweight (LW) and heavyweight (HW) anatomical mesh in minimally invasive inguinal hernia repairs. Methods: A retrospective single-center database was queried for all adult minimally invasive inguinal hernia repairs with anatomical mesh from July 2016 to March 2021. Demographics and surgical outcomes were analyzed. Univariate analysis and multivariate logistic regression were performed. Results: Six hundred forty-seven minimally invasive inguinal hernia repairs were performed with 423 (65.3%) using HW and 224 (24.7%) using LW mesh. There was no difference in mean body mass index between the groups (26.9 ± 4.2 kg/m2 in the LW group and 27.1 ± 4.2 kg/m2 in the HW group; P = .69). There was no difference in type of mesh fixation used in either group, with tacker being the most common. There was no difference in postoperative emergency department (ED) visit (P = .625), readmission rates (P = .562), or postoperative complications between the two groups. Fifty patients presented with seroma within 90 days. There were five recurrences in each group and only one surgical site infection in the LW within 90 days. Multivariate logistic regression was performed, and predictors of seroma formation included age (odds ratio [OR] 1.02; confidence interval [CI] 1-1.04; P = .02) and hypertension (HTN) (OR 1.8; CI 1.03-3.4; P = .039). HW mesh was not associated with seroma formation (OR 1.04; CI 0.5-1.9; P = .895). Similarly, HW mesh was not associated with surgical site occurrences (SSO) (OR 1.04; CI 0.5-1.8; P = .872). HTN was associated with SSO (OR 1.74; CI 1-3.05; P = .048). Conclusion: Our study did not favor the use of LW or HW mesh when comparing postoperative complications or clinical outcomes. HW mesh was not associated with either seroma formation or SSO.

Incarcerated Epiploic Appendix in a Spigelian Hernia Treated by Robotic-Assisted Surgery.

Introduction: We report a case of a patient who presented with incarceration of the epiploic appendix in a spigelian hernia, subsequently treated by a robotic-assisted surgical approach. Case Description: This is a case of a 52 year-old male patient who presented with nausea and two-week history of worsening left lower quadrant pain. On examination, the patient had an irreducible left lower quadrant mass. Computed tomography scan showed an epiploic appendagitis in a left Spigelian hernia. The patient underwent a robotic transabdominal preperitoneal hernia repair successfully and was discharged home the same day. Conclusion: The robotic platform was a safe and effective approach to treating the patient with no postoperative complications.

Social media as a tool for surgical education: a qualitative systematic review.

BACKGROUND: Social media use has exploded, attaining a significant influence within medicine. Previous studies have denoted the use of social media in various surgical specialties as a means to exchange professional ideas and improve the conference experience and at the same time, some have assessed its feasibility as a method of education. This systematic review aims to characterize the use of social media as a tool for general surgery education. METHODS: A systematic review of several databases from each database inception was conducted following the PRISMA guidelines. The JBI's critical appraisal tools were used to assess quality of the studies. RESULTS: A total of 861 articles were identified of which 222 were duplicates removed. The titles and abstracts from the remaining 639 abstracts were screened and 589 were excluded. The remaining 51 full articles were analyzed for eligibility, of which 24 met inclusion criteria and were included in the systematic review. These studies covered the general surgery specialty, of which 11 (n = 46%) focused on the laparoscopic surgical approach, 1 (n = 4%) on robotic-assisted surgical procedures, 1 (n = 4%) on both surgical approaches previously mentioned and 11 (n = 46%) on the general surgery specialty regardless of the surgical approach or technique. CONCLUSIONS: Advantages that SM offers should be considered, and content creators and institutions should help collectively to make sure that the content being published is evidence and guideline-based so its use it is taken to the maximum benefit.

The interaction of SKP2 with p27 enhances the progression and stemness of osteosarcoma.

Osteosarcoma is a highly aggressive malignancy for which treatment has remained essentially unchanged for years. Our previous studies found that the F-box protein SKP2 is overexpressed in osteosarcoma, acting as a proto-oncogene; p27Kip1 (p27) is an inhibitor of cyclin-dependent kinases and a downstream substrate of SKP2-mediated ubiquitination. Overexpression of SKP2 and underexpression of p27 are common characteristics of cancer cells. The SCFSKP2 E3 ligase ubiquitinates Thr187-phosphorylated p27 for proteasome degradation, which can be abolished by a Thr187Ala knock-in (p27T187A KI) mutation. RB1 and TP53 are two major tumor suppressors commonly coinactivated in osteosarcoma. We generated a mouse model with a double knockout (DKO) of Rb1 and Trp53 within cells of the osteoblastic lineage, which developed osteosarcoma with full penetrance. When p27T187A KI mice were crossed on to the DKO background, p27T187A protein was found to accumulate in osteosarcoma tumor tissues. Furthermore, p27T187A promoted apoptosis in DKO tumors, slowed disease progression, and significantly prolonged overall survival. RNA sequencing analysis also linked the SCFSKP2 -p27T187A axis to potentially reduced cancer stemness. Given that RB1 and TP53 loss or coinactivation is common in human osteosarcoma, our study suggests that inhibiting the SKP2-p27 axis may represent a desirable therapeutic strategy for this cancer.