Generalizable transcriptome-based tumor malignant level evaluation and molecular subtyping towards precision oncology.

In cancer treatment, therapeutic strategies that integrate tumor-specific characteristics (i.e., precision oncology) are widely implemented to provide clinical benefits for cancer patients. Here, through in-depth integration of tumor transcriptome and patients' prognoses across cancers, we investigated dysregulated and prognosis-associated genes and catalogued such important genes in a cancer type-dependent manner. Utilizing the expression matrices of these genes, we built models to quantitatively evaluate the malignant levels of tumors across cancers, which could add value to the clinical staging system for improved prediction of patients' survival. Furthermore, we performed a transcriptome-based molecular subtyping on hepatocellular carcinoma, which revealed three subtypes with significantly diversified clinical outcomes, mutation landscapes, immune microenvironment, and dysregulated pathways. As tumor transcriptome was commonly profiled in clinical practice with low experimental complexity and cost, this work proposed easy-to-perform approaches for practical clinical promotion towards better healthcare and precision oncology of cancer patients.

Uniportal versus triportal video-assisted thoracic surgery in the treatment of tuberculous empyema.

OBJECTIVE: To examine the effectiveness of decortication to treat chronic tuberculous empyema (TE) using uniport video-assisted thoracoscopic surgery (VATS) versus conventional triport VATS. METHODS: Data from consecutive patients with stage II or III TE who underwent decortication with either uniport VATS (uniportal group) between July and December 2017, or triport VATS between January and July 2018 (triportal group), were retrospectively analysed. VATS procedures were performed under general anaesthesia with double lumen endotracheal intubation and clinical outcomes were compared between the two groups. RESULTS: Clinical data were comparable between the groups (20 patients in each) regarding demographic and baseline characteristics, operative and postoperative characteristics, surgical procedure-related complications, and postoperative adverse events. No surgical procedure-related complications occurred during the perioperative period in either group. Threshold values for mechanical pain at 8 h postoperatively were significantly higher in the triportal group versus the uniportal group. Furthermore, the incidence of nausea and vomiting was significantly lower in the uniportal versus triportal group. In the triportal group, one patient required readmission and further intervention due to recurrence. CONCLUSIONS: Uniport VATS decortication for stages II and III TE may be a feasible and safe procedure in selected patients. Moreover, uniport VATS may be less painful than triport VATS.

DNA methylation analysis explores the molecular basis of plasma cell-free DNA fragmentation.

Plasma cell-free DNA (cfDNA) are small molecules generated through a non-random fragmentation procedure. Despite commendable translational values in cancer liquid biopsy, however, the biology of cfDNA, especially the principles of cfDNA fragmentation, remains largely elusive. Through orientation-aware analyses of cfDNA fragmentation patterns against the nucleosome structure and integration with multidimensional functional genomics data, here we report a DNA methylation - nuclease preference - cutting end - size distribution axis, demonstrating the role of DNA methylation as a functional molecular regulator of cfDNA fragmentation. Hence, low-level DNA methylation could increase nucleosome accessibility and alter the cutting activities of nucleases during DNA fragmentation, which further leads to variation in cutting sites and size distribution of cfDNA. We further develop a cfDNA ending preference-based metric for cancer diagnosis, whose performance has been validated by multiple pan-cancer datasets. Our work sheds light on the molecular basis of cfDNA fragmentation towards broader applications in cancer liquid biopsy.

[Observation of Short-term and Long-term Efficacy of Bronchoscopic Interventional Therapy in the Treatment of Typical Carcinoid].

BACKGROUND: The curative potential of various bronchoscopic treatments such as electric snare, carbon dioxide freezing, argon plasma coagulation (APC), Neudymium-dopted Yttrium Aluminium Garnet (Nd:YAG) laser and photodynamic therapy (PDT) for the treatment of intraluminal tumor has been administered previously, but this regimen is not common in the treatment of typical carcinoid. The aim of this study is to investigate the curative effects both in short-term and long-term of interventional bronchoscopy in the treatment of typical carcinoid. METHODS: We retrospectively reviewed the clinical data of typical carcinoid patients who were treated with interventional bronchoscopy for tumor suppression and they were hospitalized in the Emergency General Hospital from December 2010 to December 2020, and Wilcoxon rank sum test and chi-square test were used for analysis. RESULTS: A total of 32 patients were included, including 18 cases of preoperative bronchial artery embolization (embolization rate 56%, 95%CI: 31%-79%). The grade score of dyspnea decreased from before treatment to after treatment, and the difference was statistically significant [(1.44±1.03) score vs (0.25±0.58) score, P=0.003]; The degree of bronchial stenosis decreased from pre-treatment to post-treatment, and the difference was statistically significant [(87.50%±13.90%) vs (17.50%±6.83%), P<0.001]; There was significant difference in bronchial diameter before and after treatment [(0.14±0.18) cm vs (0.84±0.29) cm, P<0.001]. CONCLUSIONS: Bronchoscopic interventional therapy has significant short-term and long-term effects in the treatment of typical carcinoid.

Reversing cold tumors to hot: An immunoadjuvant-functionalized metal-organic framework for multimodal imaging-guided synergistic photo-immunotherapy.

Immunotherapy assays using immunoadjuvants and tumor antigens could greatly increase the survival rates of patients with malignant tumors. As effective carriers, metal-organic frameworks (MOFs) have been widely utilized in cancer therapy due to their remarkable histocompatibility and low toxicity. Herein, we constructed a multimodal imaging-guided synergistic cancer photoimmunotherapy by employing a specific MOF (MIL101-NH2) as the core carrier; the MOF was dual-dressed with photoacoustic and fluorescent signal donors (indocyanine green, ICG) and immune adjuvants (cytosine-phosphate-guanine sequence, CpG) and named ICG-CpG@MOF. This nanocarrier could passively target the tumor site through the EPR effect and achieve multimodal imaging (fluorescence, photoacoustic, photothermal and magnetic resonance imaging) of the tumor. Synergistic cancer photoimmunotherapy was achieved via simultaneous photodynamic and photothermal methods with 808 nm laser irradiation. ICG-CpG@MOF achieved the GSH-controlled release of immunoadjuvant into the tumor microenvironment. Furthermore, the released tumor-associated antigen along with CpG could induce the transformation of tumor cells from cold to hot by activating the immune system, which significantly enhanced tumor cytotoxicity and achieved high cure rates with minimal side-effects. This strategy utilizing multimodal imaging and synergistic cancer photoimmunotherapy provides a promising approach for the diagnosis and treatment of cancer.

Uniportal Thoracoscopic Wedge Resection of Lung Nodules: Paravertebral Blocks Are Better Than Intercostal Blocks.

Background. Regional analgesia for tubeless, uniport, thoracoscopic wedge resection of benign peripheral nodules is generally performed by intercostal nerve block (INB). We examined the effectiveness of thoracic paravertebral block (PVB), in comparison to the traditional intercostal blocks, for the procedure. Methods. Between July 2016 and December 2016, 20 consecutive patients with solitary benign peripheral lung nodules underwent tubeless uniport thoracoscopic wedge resection using thoracic PVB (PVB group). The clinical outcomes were compared with those of 20 other consecutive patients who underwent the same procedure under the conventional INB, between January 2016 and July 2016 (INB group). In both groups, the procedures were performed without endotracheal intubation, urinary catheterization, or chest tube drainage. Results. The clinical data of patients in both groups were comparable in terms of demographic and baseline characteristics, operative and anesthetic characteristics, puncture-related complications, and postoperative anesthetic adverse events. No puncture-related complications occurred during the perioperative period in either group. The threshold values for mechanical pain at postoperative hours 4 and 8 were significantly higher in the PVB group than in the INB group. Furthermore, the incidence of nausea or vomiting in the PVB group was significantly less than that in the INB group. None of the patients required reintervention or readmission to our hospital. Conclusions. Tubeless uniportal thoracoscopic wedge resection for solitary benign peripheral lung nodules using thoracic PVB for regional analgesia is a feasible and safe procedure. Moreover, we found that thoracic PVB is less painful than INB.

Early enteral feeding on esophageal cancer patients after esophageal resection and reconstruction.

BACKGROUND: In patients under esophagectomy, early postoperative oral feeding has traditionally been contraindicated to minimize the risk of anastomotic leaks. Because early oral feeding preserves the integrity and function of gut mucosa, the aim of this study was to investigate the impact of postoperative early oral feeding on esophagectomy. METHODS: Between Oct 2013 and Jan 2016, 41 consecutive patients with esophageal carcinoma (stages I- III), who had undergone minimally invasive Ivor-Lewis surgery, were enrolled in this study. The patients were randomly arranged into the early oral feeding (EOF) group (21 cases) and the simple tube feeding (STF) group (20 cases). The nutritional goal for both groups was 25 kcal/(kg·day). The patients in the EOF group were tube-fed with enteral nutrition and orally fed with 5% glucose in normal saline during the first 4 postoperative days, after that the patients were placed on a liquid diet. The patients in the STF group were postoperatively tube-fed with enteral nutrition for 7 days before being switched to liquid diet. The length of the postoperative hospital stay, rate of perioperative complications, and overall mortality were recorded. Preoperative and postoperative levels of serum albumin (ALB), prealbumin (PA), transferrin (TP), and C reactive protein (CRP) were also monitored. RESULTS: There were no significant differences of the incidence of postoperative complications and overall mortality between the EOF group and the STF group, but the duration of hospital stay, interval until the first liquid food, and time of ambulation in the EOF group were lower than those of the STF group (P<0.05). EOF patients also showed significantly lower CRP levels compared with the STF group (P<0.05). CONCLUSIONS: EOF might reduce the duration of hospital stays and CRP levels in esophageal cancer patients who underwent esophagectomy while the mortality and complications were not affected.

Recent advances in the management of pulmonary tuberculoma with focus on the use of tubeless video-assisted thoracoscopic surgery.

Pulmonary tuberculoma are benign solitary pulmonary nodules representing up to 25% of all resected solitary pulmonary nodules. However, the differentiation between pulmonary tuberculoma and lung cancer, as well as between active tuberculoma and inactive tuberculoma remains a clinical challenge. The present review summarizes the recent advances in the management of pulmonary tuberculoma, including radiological findings, the response to anti-tuberculosis treatment and surgical treatments. Application of the novel tubeless video-assisted thoracoscopic surgery (VATS) technique in both the diagnosis and treatment of pulmonary tuberculoma has been found to be safe and feasible and leads to less surgical trauma, which results in reduced length of hospitalization and better post-operative quality of life.

Outcomes after implementing the enhanced recovery after surgery protocol for patients undergoing tuberculous empyema operations.

BACKGROUND: Enhanced recovery after surgery (ERAS) protocols provide recommendations for care in various surgical fields. However, there is scarce information on the application of these protocols in tuberculous empyema surgery. The purpose of this research is to evaluate the outcomes of ERAS recommendations for patients who received tuberculous empyema surgery. METHODS: A retrospective analysis was performed on patients who underwent tuberculous empyema surgery in our hospital from March 2011 to March 2016. The patients were divided into an ERAS group and a conventional control group. The main outcome measure was the postoperative median length of stay (including readmissions). Principles related to ERAS were documented, and the postoperative median hospital stay was analyzed statistically between the two groups. RESULTS: A total of 92 patients underwent 93 consecutive tuberculous empyema surgical treatments. The postoperative fasting time, chest tube duration, and length of stay were shorter in the ERAS group compared with the control group. The volume of chest tube drainage in the ERAS group was significantly smaller than that of the control group. No statistical differences were observed in the postoperative complications and reasons for readmission between the two groups. CONCLUSIONS: Application of ERAS recommendations in patients receiving tuberculous empyema operations decreased the length of stay and chest tube drainage compared to the control group.