Ming-Ching Lee

Right middle lobe (RML) torsion is the most common form of lobar torsion. It usually happens after right upper lobe (RUL) lobectomy, especially when pneumopexy is not performed. Although various surgical techniques have been introduced to prevent RML torsion, the efficacy of these techniques is not yet fully understood. We herein report a case of RML torsion that happened after RUL lobectomy despite pneumopexy together with a literature review. A 62-year-old female patient underwent RUL lobectomy due to adenocarcinoma of the lung. Prophylactic pneumopexy with a single stitch was performed to fix RML to the right lower lobe. RML was well inflated and did not rotate before wound closure was performed. However, the patient complained of foreign body sensation inside her chest on postoperative day 5, and a chest X-ray revealed atelectasis of RML. Bronchoscopy showed a collapsed middle lobe bronchus. Exploratory thoracotomy showed congested RML with a twisting bronchovascular pedicle, and therefore, RML lobectomy was performed. RML torsion is a rare but potentially fatal condition requiring high clinical alertness. Through our literature review and the presented case, we demonstrate that RML torsion may occur despite pneumopexy. A combination of surgical methods, such as the use of continuous sutures or fibrin glue, may be more effective in preventing torsion.

Esophageal cancer shares strong associations with oropharyngeal and hypopharyngeal cancers, primarily due to shared risk factors like excessive tobacco and alcohol use. This retrospective study at Taichung Veterans General Hospital involved 54,692 participants, including 385 with squamous cell carcinoma (SCC) of the esophagus, oropharynx, or hypopharynx. Using a polygenic risk score (PRS) derived from 8353 single-nucleotide polymorphisms, researchers aimed to assess its correlation with cancer incidence and prognosis. The study found a 1.83-fold higher risk of esophageal, oropharyngeal, and hypopharyngeal SCCs in participants with a high PRS (Q4) compared to the low-PRS group (Q1). Esophageal cancer risk demonstrated a significant positive association with the PRS, as did hypopharyngeal cancer. Clinical parameters and staging showed limited associations with PRS quartiles, and the PRS did not significantly impact recurrence or mortality rates. The research highlighted that a higher PRS is linked to increased susceptibility to esophageal and hypopharyngeal cancer. Notably, a specific polygenic risk score, PGS001087, exhibited a discernible association with SCC risk, particularly in specific subtypes and advanced disease stages. However, it was not significantly linked to clinical cancer staging, emphasizing the multifactorial nature of cancer development. This hospital study reveals that a higher PRS correlates with increased susceptibility to esophageal and hypopharyngeal cancers. Notably, PGS001087 shows a discernible association with SCC risk in specific subtypes and advanced stages, although not significantly linked to clinical cancer staging. These findings enhance our understanding of genetic factors in upper aerodigestive tract cancers, particularly esophageal SCC, guiding future research and risk assessment strategies.

Video.avi GLK co-localizes with IQGAP1 at filopodia and lamellipodia of a cell (Cell #3).

Video.avi GLK co-localizes with IQGAP1 at filopodia and lamellipodia of a cell (Cell #3).

Cell tracking in time-lapse microscopy images of primary lung epithelial cells from wild-type (WT), GLK-deficient (KO), and GLK transgenic (Polâ…¡-GLK)) mice. The tracked path of the mGFP-positive cell is shown as the line.

Video4.avi GLK co-localizes with IQGAP1 at the leading edge of a migrating cell (Cell #4)

Cell tracking in time-lapse microscopy images from of lung epithelial cells from littermate wild-type (WT), GLK transgenic (Polâ…¡-GLK), GLK transgenic/IQGAP1-heterozygous (Polâ…¡-GLK;IQGAP1+/- ), and GLK transgenic/IQGAP1 knockout (Polâ…¡-GLK;IQGAP1-/- ) mice. The tracked path of the migration cell is shown as the line.

Overexpression of the serine/threonine kinase GLK/MAP4K3 in human lung cancer is associated with poor prognosis and recurrence, however, the role of GLK in cancer recurrence remains unclear. Here, we report that transgenic GLK promotes tumor metastasis and cell migration through the scaffold protein IQ motif–containing GTPase-activating protein 1(IQGAP1). GLK transgenic mice displayed enhanced distant metastasis. IQGAP1 was identified as a GLK-interacting protein; two proline-rich regions of GLK and the WW domain of IQGAP1 mediated this interaction. GLK and IQGAP1 colocalized at the leading edge including filopodia and lamellipodia of migrating cells. GLK directly phosphorylated IQGAP1 at Ser-480 enhancing Cdc42 activation and subsequent cell migration. GLK-induced cell migration and lung cancer metastasis were abolished by IQGAP1 depletion. Consistently, human NSCLC patient tissues displayed increased phospho-IQGAP1, which correlated with poor survival. Collectively, GLK promotes lung cancer metastasis by binding to, phosphorylating, and activating IQGAP1.Significance:These findings show the critical role of the GLK–IQGAP cascade in cell migration and tumor metastasis, suggesting it as a potential biomarker and therapeutic target for lung cancer recurrence.