Circulating tumor DNA integrating tissue clonality detects minimal residual disease in resectable non-small-cell lung cancer.

BACKGROUND: Circulating tumor DNA (ctDNA) has been proven as a marker for detecting minimal residual diseases following systemic therapies in mid-to-late-stage non-small-cell lung cancers (NSCLCs) by multiple studies. However, fewer studies cast light on ctDNA-based MRD monitoring in early-to-mid-stage NSCLCs that received surgical resection as the standard of care. METHODS: We prospectively recruited 128 patients with stage I-III NSCLCs who received curative surgical resections in our Lung Cancer Tempo-spatial Heterogeneity prospective cohort. Plasma samples were collected before the surgery, 7 days after the surgery, and every 3 months thereafter. Targeted sequencing was performed on a total of 628 plasma samples and 645 matched tumor samples using a panel covering 425 cancer-associated genes. Tissue clonal phylogeny of each patient was reconstructed and used to guide ctDNA detection. RESULTS: The results demonstrated that ctDNA was more frequently detected in patients with higher stage diseases pre- and postsurgery. Positive ctDNA detection at as early as 7 days postsurgery identified high-risk patients with recurrence (HR = 3.90, P < 0.001). Our results also show that longitudinal ctDNA monitoring of at least two postsurgical time points indicated a significantly higher risk (HR = 7.59, P < 0.001), preceding radiographic relapse in 73.5% of patients by a median of 145 days. Further, clonal ctDNA mutations indicated a high-level specificity, and subclonal mutations informed the origin of tumor recurrence. CONCLUSIONS: Longitudinal ctDNA surveillance integrating clonality information may stratify high-risk patients with disease recurrence and infer the evolutionary origin of ctDNA mutations.

Factors predictive of prognosis after esophagectomy for squamous cell cancer.

OBJECTIVE: To evaluate the prognosis after esophagectomy for squamous cell carcinoma of the thoracic esophagus and its prognostic factors. METHODS: Six hundred five patients with primary squamous cell carcinoma of the thoracic esophagus who underwent curative esophagectomy between June 1997 and June 1998 were collected from 3 medical centers. Among them, 26 patients died from the operation and 26 patients did not complete adjuvant treatment owing to toxicity. Univariate and multivariate analysis was performed to identify prognostic factors for survival. The effect of adjuvant treatment on survival was also evaluated. RESULTS: The 1-, 3-, 5-, and 10-year overall survivals of 605 patients were 90%, 65%, 36%, and 8%, respectively. Multivariate analysis identified the following as independent prognostic factors: number of lymph node metastases (P < .001), histologic differentiation (P < .001), tumor location (P = .002), depth of invasion (P = .020), and vascular invasion (P = .023). CONCLUSIONS: Several pathologic characteristics of the primary tumor are correlated with the outcome of esophagectomy for squamous carcinoma of the thoracic esophagus. Patients with fewer than 2 metastatic nodes after curative esophagectomy have a better prognosis than those with multiple involved nodes (>2). To stratify patients appropriately for prognosis, it is necessary to refine the current 6th edition TNM staging system.

[Diagnosis and treatment for postoperative lobar torsion].

OBJECTIVE: To analyze retrospectively 8 cases of postoperative lobar torsion after thoracotomy. METHODS: 8 cases of postoperative lobar torsion were collected (5 men and 3 women; median age, 55.0 +/- 7.7 years), including lobectomy 4 (left upper lobe of lung 2, right upper lobe of lung 2), esophageal carcinosectomy 2, resection of schwannoma in the right upper mediastinum 1, and descending aorta replacement 1. RESULTS: The postoperative lobar torsions were right middle lobe 2, right upper lobe 1, left upper lobe 3, left lower lobe 1, left lung 1. The median peak temperature was 38.4 degrees C (range, 37.8 - 40.2 degrees C) and the median white blood cell count was 10.6 x 10(9) cells/L (range, 9.3 - 14.9 x 10(9) cell/L) during the first 48 hours postoperatively. Postoperative radiographs demonstrated pulmonary infiltrates and volume loss in 6 patients and complete opacification in 2 patients. The diagnosis of lobar torsion was made a median of 4 days (range, 2 - 14 days) after the initial operation; 6 patients underwent resection of lung and recovered; 2 had the injured lobe or lung rotated and died. Complications after reoperation included respiratory failure in 2 patients, atrial arrhythmia in 2 patients. Median hospitalization was 24 days and range from 10 to 56 days. CONCLUSIONS: The mobilization of hilus of lung or residual pulmonary atelectasis is the main mechanism of the lobar torsion after thoracotomy. Lobar torsion represents a difficult diagnostic dilemma in the early postoperative period after thoracotomy. Exploratory thoracotomy must be performed without delay. The injured parenchyma should be sacrificed unless the diagnosis is obtained very early. When the injured lobe or lung is rotated back into normal position, simultaneous endotracheal suction is very important to prevent aspiration of fluid from the obstructed part of the bronchial tree to the uninvolved segments and dangerous postoperative hypoxia.

[A pig model of myocardial infarction by intracoronary embolization with gelatin sponge].

OBJECTIVE: We produced a large-animal model of myocardial infarction induced by transcatheter embolization of the left coronary artery using a gelatin sponge. METHODS: Seven pigs underwent transcatheter embolization of the left anterior descending artery (LAD) using gelatin sponge to produce anteroapical myocardial infarction (MI). 4 weeks later, Echocardiography, Coronary angiography and Pathology was performed, and the data were compared with those of the control group (n = 6). RESULTS: The procedure mortality was 1 of 7. In the MI group, the LV end-diastolic dimension increased (control versus MI: 37.0 mm +/- 3.4 mm and 50.8 mm +/- 6.1 mm, P < 0.01), the ejection fraction (EF) decreased (control versus MI: 62.3% +/- 2.9% and 36.6% +/- 2.1%, P < 0.001). Coronary angiography revealed the LAD remained occluded. The postmortem specimen showed a transmural MI scar in the anteroseptal and apical regions in the MI group and the LV volumes at 30 mm Hg were 81.4 ml +/- 4.3 ml, the scar areas were 18.4% +/- 1.6% of total left ventricular free wall and the scar thickness was 3.5 mm +/- 0.8 mm. Histologic samples in the MI group stained with Masson's trichrome showed massive fibrosis in the border zone and patchy fibrosis in the remote region in the LV free wall, whereas the control group showed no fibrosis. CONCLUSION: This pig model of myocardial infarction is reliable, reproducible, and similar to the human condition, amenable to investigate other investigation.