Electromagnetic bronchoscopy guided microwave ablation for early stage lung cancer presenting as ground glass nodule.

BACKGROUND: Patients with early-stage lung cancer are sometimes medically inoperable, and for patients with multiple primary lung cancers, surgical resection alone sometimes proves to be impractical. Local treatments like microwave ablation (MWA) are investigational alternatives for these patients. Most reported MWA procedures for lung cancers are performed percutaneously under CT guidance. MWA navigated by electromagnetic bronchoscopy (ENB) has been limitedly studied. In this study, we aimed to evaluate the safety and feasibility of MWA under ENB guidance in patients with inoperable early-stage lung cancers or multiple primary lung cancers which cannot be completely resected. METHODS: From June 2019 to December 2020, preliminary attempts of ENB-guided MWA were made in five medically inoperable patients with a single early-stage lung cancer and ten patients with multiple primary lung cancers which were difficult to resect at the same time. For patients with concomitant pulmonary nodules which needed surgical resection, thoracoscopic resections were performed following ENB-guided MWA. The safety, feasibility, and technique effectiveness of treatments were evaluated. RESULTS: ENB-guided MWA for 15 ground glass nodules (GGNs) in 15 patients was completed in accordance with the planned protocol. Biopsy of 13 GGNs showed malignancy. Five patients received simple ENB-guided MWA without simultaneous surgical resection and ten patients received simultaneous surgical resection for 13 concomitant pulmonary nodules. CT scan by the first postoperative week showed technique effectiveness of ablation for 11 nodules indicated for MWA. Four patients had mild complications after the procedure and recovered shortly after treatment. CONCLUSIONS: For medically inoperable patients with a single GGN manifesting early-stage lung cancer and patients with multiple primary early-stage lung cancers which cannot be resected at the same time, ENB-guided MWA might be a safe and feasible alternative local treatment, whether combined with surgical resection or not. However, large, prospective, randomized, multicenter studies are needed to confirm its role in the treatment of early-stage lung cancer.

Should resection extent be decided by total lesion size or solid component size in ground glass opacity-containing lung adenocarcinomas?

BACKGROUND: Indication for sublobar resections in early-stage lung adenocarcinomas has been controversial. The purpose of this study was to find appropriate selection criteria for sublobar resections in ground glass opacity (GGO)-containing early-stage lung adenocarcinomas. METHODS: We retrospectively studied 985 consecutive patients with clinical stage IA, peripheral GGO-containing lung adenocarcinomas ≤3 cm in size. According to their radiological appearance, they were divided into a pure GGO group and a part-solid nodule (PSN) group. The PSN group was further divided into a GGO-predominant subgroup and a solid-predominant subgroup. Propensity-score matching (PSM) was conducted first in PSNs with similar total lesion size and then in those with similar solid component size to eliminate potential confounders. Histological characteristics and prognosis were compared between matched patients to investigate the prognostic value of total lesion size and solid component size. Then solid component size was chosen as the selection criterion to compare the prognosis of patients receiving lobectomy or sublobar resections. RESULTS: Comparing to PSNs, pure GGO lesions had significantly more favorable histological characteristics and prognosis, with 100% 5-year overall survival (OS), even though 33.3% of patients with pure GGO lesions >20 mm in total lesion size received sublobar resections. For 157 pairs of PSNs with similar total lesion size but different solid component size after the first PSM, the solid-predominant subgroup had significantly worse histological characteristics and prognosis than the GGO-predominant subgroup. After the second PSM, histological characteristics and prognosis were comparable between 73 pairs of PSNs with similar solid component size but different total lesion size. Multivariable analysis showed that solid component size, rather than total lesion size or consolidation-to-tumor ratio (CTR), was an independent prognostic factor. For PSNs containing solid component size ≤2 cm, relapse-free survival (RFS) was similar after sublobar resections or lobectomy (95.0% vs. 93.6%, P=0.592). The results remained similar for PSNs of total lesion size >2 cm but solid component size ≤2 cm (88.9% vs. 90.0%, P=0.893). CONCLUSIONS: Solid component size better predicts histological characteristics and prognosis than total lesion size in early-stage GGO-containing lung adenocarcinomas. Instead of total lesion size, solid component size ≤2 cm may be a more appropriate selection criterion for sublobar resections in such patients.

TAT-Conjugated NDUFS8 Can Be Transduced into Mitochondria in a Membrane-Potential-Independent Manner and Rescue Complex I Deficiency.

NADH dehydrogenase (ubiquinone) Fe-S protein 8 (NDUFS8) is a nuclear-encoded core subunit of human mitochondrial complex I. Defects in NDUFS8 are associated with Leigh syndrome and encephalomyopathy. Cell-penetrating peptide derived from the HIV-1 transactivator of transcription protein (TAT) has been successfully applied as a carrier to bring fusion proteins into cells without compromising the biological function of the cargoes. In this study, we developed a TAT-mediated protein transduction system to rescue complex I deficiency caused by NDUFS8 defects. Two fusion proteins (TAT-NDUFS8 and NDUFS8-TAT) were exogenously expressed and purified from Escherichia coli for transduction of human cells. In addition, similar constructs were generated and used in transfection studies for comparison. The results showed that both exogenous TAT-NDUFS8 and NDUFS8-TAT were delivered into mitochondria and correctly processed. Interestingly, the mitochondrial import of TAT-containing NDUFS8 was independent of mitochondrial membrane potential. Treatment with TAT-NDUFS8 not only significantly improved the assembly of complex I in an NDUFS8-deficient cell line, but also partially rescued complex I functions both in the in-gel activity assay and the oxygen consumption assay. Our current findings suggest the considerable potential of applying the TAT-mediated protein transduction system for treatment of complex I deficiency.

The Feasibility and Safety of Routine Thoracic Surgeries in the Low-Risk Areas During the Coronavirus Disease 2019 Pandemic.

Coronavirus disease 2019 (COVID-19) has been under good control, and work resumption has been gradually carried out in most parts of the People's Republic of China including Shanghai after March 2020. However, intense focus and resources have been diverted to patients with COVID-19, leaving patients with diseases other than COVID-19 somehow neglected owing to limited access to routine health care. Furthermore, whether routine thoracic surgery service is safe in low-risk areas of COVID-19 infection is still unknown. We hereby retrospectively analyzed the quantity and quality of thoracic surgeries performed by a single team from the Shanghai Chest Hospital between January and May 2020, compared with the corresponding period in the past year. Results suggested that comparable qualities of diagnosis, surgical treatment, and perioperative outcomes were safely and successfully achieved. The total number of surgical procedures gradually increased and surpassed with that of the corresponding period in the past year when the situation of COVID-19 has been in good control in Shanghai by April. Importantly, neither medical staffs nor patients were diagnosed of having COVID-19 infection. In conclusion, although COVID-19 has made considerable impact on elective surgery for thoracic diseases, it is safe and feasible to carry out routine thoracic surgery services in low-risk areas, provided that careful screening of COVID-19 and thorough protection of medical staffs and patients are taken. It is hoped that these findings would serve as a useful reference for thoracic departments all over the world during the COVID-19 pandemic, especially after work resumption.

Pulmonary function changes after thoracoscopic lobectomy versus intentional thoracoscopic segmentectomy for early-stage non-small cell lung cancer.

BACKGROUND: Thoracoscopic segmentectomy is increasingly used in the surgical treatment of early-stage non-small cell lung cancer. However, it remains unclear whether pulmonary function loss after thoracoscopic lung resection is in direct proportion to the number of resected segments, and thus intentional thoracoscopic segmentectomy has the function-preserving advantage over thoracoscopic lobectomy. METHODS: In this prospective observational study, spirometry tests were performed preoperatively and 6 months postoperatively. The observed functional loss was compared with the expected loss estimated by the segment counting method. Resection extent index was introduced as the number of resected segments to total number of segments in the corresponding lobe. Spirometry changes after thoracoscopic lobectomy and intentional thoracoscopic segmentectomy were compared using propensity score matching. RESULTS: There were 338 thoracoscopic lobectomies and 321 thoracoscopic segmentectomies. Overall, the observed pulmonary function loss after segmentectomy was significantly less than after lobectomy. But the observed functional loss was significantly greater than the expected loss after segmentectomy. And pulmonary function loss per segment resected was almost doubled after segmentectomy comparing to lobectomy. For segmentectomies with a resection extent index less than 0.5, especially single segmentectomies, pulmonary function loss was significantly less than after corresponding lobectomies. Otherwise, no significant differences in spirometry changes between lobectomies and segmentectomies were detected. CONCLUSIONS: Pulmonary function loss after thoracoscopic lung resection cannot be accurately evaluated by the number of resected segments. According to the resection extent index, intentional thoracoscopic segmentectomy may help preserve more pulmonary function than thoracoscopic lobectomy only when less than half of the corresponding lobe are resected.

Therapeutic applications of the TAT-mediated protein transduction system for complex I deficiency and other mitochondrial diseases.

Among the five enzyme complexes in the oxidative phosphorylation system, NADH-coenzyme Q oxidoreductase (also called complex I) is the largest, most intricate, and least understood. This enzyme complex spans the inner mitochondrial membrane and catalyzes the first step of electron transfer by the oxidation of NADH, and thereby provides two electrons for the reduction of quinone to quinol. Complex I deficiency is associated with many severe mitochondrial diseases, including Leber hereditary optic neuropathy and Leigh syndrome. However, to date, conventional treatments for the majority of genetic mitochondrial diseases are only palliative. Developing a reliable and convenient therapeutic approach is therefore considered to be an urgent need. Targeted proteins fused with the protein transduction domain of human immunodeficiency virus 1 transactivator of transcription (TAT) have been shown to enter cells by crossing plasma membranes while retaining their biological activities. Recent developments show that, in fusion with mitochondrial targeting sequences (MTSs), TAT-MTS-bound cargo can be correctly transported into mitochondria and restore the missing function of the cargo protein in patients' cells. The available evidence suggests that the TAT-mediated protein transduction system holds great promise as a potential therapeutic approach to treat complex I deficiency, as well as other mitochondrial diseases.

Chemoselective synthesis of tetrasubstituted furans via intramolecular Wittig reactions: mechanism and theoretical analysis.

An efficient synthesis of tetrasubstituted furans was achieved from the corresponding α,ß-unsaturated ketone derivatives, acid chlorides, and Bu3P in the presence of Et3N via a chemoselective intramolecular Wittig reaction as the key step. The presence of an additional electron-withdrawing group in the α-position of Michael acceptors controlled the chemoselectivities of presumable phosphorus ylides in the intramolecular Wittig reactions, and their mechanisms were also investigated by DFT calculations.

Role of connectivity-induced weighted words in language games.

We present a modified naming game by introducing weights of words in the evolution process. We assign the weight of a word spoken by an agent according to its connectivity, which is a natural reflection of the agent's influence in population. A tunable parameter is introduced, governing the word weight based on the connectivity of agents. We consider the scale-free topology and concentrate on the efficiency of reaching the final consensus, which is of high importance in the self-organized system. Interestingly, it is found that there exists an optimal parameter value, leading to the fastest convergence. This indicates appropriate hub's effects favor the achievement of consensus. The evolution of distinct words helps to give a qualitative explanation of this phenomena. Similar nontrivial phenomena are observed in the total memory of agents with a peak in the middle range of parameter values. Other relevant characters are provided as well, including the time evolution of total memory and success rate for different parameter values as well as the average degree of the network, which are helpful for understanding the dynamics of the modified naming game in detail.