Squamous Cell Carcinoma in Never Smokers: An Insight into SMARCB1 Loss.

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer (NSCLC) constituting 85% of cases. Among NSCLCs, squamous cell carcinoma (SqCC) is strongly associated with smoking. However, lung cancer in never smokers (LCINS) represents approximately 25% of lung cancer cases globally and shows increasing incidence, particularly in East Asia. LCINS-SqCC is less well-characterized, especially regarding its genomic alterations and their impact on clinical outcomes. We conducted a retrospective analysis over a 20-year period (July 2003-July 2023) at two major tertiary centers in the UK. The cohort included 59 patients with LCINS-SqCC who underwent radical surgical resection. Data collected included demographic information, comorbidities, histopathological details, and outcome metrics such as disease-free and overall survival. Molecular sequencing of tumor specimens was performed to identify genomic aberrations. The cohort had a median age of 71 years (IQR 62-77) and a median BMI of 25.4 (IQR 22.8-27.8), with a slight male predominance (53%). The majority of patients (93%) had a preoperative MRC of 1-2. Recurrent disease was observed in 23 patients (39%), and 32 patients (54%) had died at a median follow-up of 3 years. Median disease-free survival was 545 days (IQR 132-1496), and overall survival was 888 days (IQR 443-2071). Preoperative creatinine levels were higher in patients who experienced recurrence (p = 0.037). Molecular analysis identified biallelic SMARCB1 loss in two younger patients, associated with rapid disease progression despite R0 resection. These patients' tumors were PDL1-negative, TTF-1-negative, and positive for cytokeratin, CD56, and p40. SMARCB1-deficient SqCC in never smokers represents a highly aggressive variant with poor disease-free survival, highlighting the importance of integrating advanced molecular diagnostics in clinical practice. This study underscores the necessity for personalized treatment strategies, including targeted therapies such as EZH2 inhibitors and immune checkpoint blockade, to address the unique molecular pathways in SMARCB1-deficient cancers. Further clinical trials are essential to optimize therapeutic approaches for this challenging subgroup of lung cancer.

Early and Long Term Outcomes Following Long Posterior Flap vs. Skew Flap for Below Knee Amputations.

OBJECTIVE: To compare outcomes between long posterior flap (LPF) and skew flap (SF) amputation over a 13 year period. METHODS: This was a retrospective observational cohort study. Consecutive patients undergoing a LPF or SF below knee amputation (BKA) over a 13 year period at one hospital were identified. Both techniques were performed regularly, depending on tissue loss and surgeon preference. The primary outcome was surgical revision of any kind. Secondary outcomes included revision to above knee amputation (AKA), length of hospital stay (LOS), and mortality. A smaller cohort of patients who were alive and unilateral below knee amputees were contacted to ascertain prosthetic use and functional status. RESULTS: In total, 242 BKAs were performed in 212 patients (125 LPF and 117 SF; median follow up 25.8 months). Outcomes for the two groups were equivalent for surgical revision of any kind (27 LPF vs. 31 SF; p = .37), revision to an AKA (18 LPF vs. 14 SF; p = .58), LOS (29 days for LPF vs. 28 days for SF; p = .83), and median survival (23.9 months for LPF vs. 28.8 months for SF; p = .89). Multivariable analysis found amputation type had no effect on any outcome. Functional scores from a smaller cohort of 40 unilateral amputees who were contactable demonstrated improved outcomes with the LPF vs. the SF (p = .038). CONCLUSION: Both techniques appear equivalent for rates of surgical residual limb failure. Functional outcomes may be better with the LPF.