Genomic and immune heterogeneity of multiple synchronous lung adenocarcinoma at different developmental stages.

Multiple synchronous lung cancers (MSLCs) constitute a unique subtype of lung cancer. To explore the genomic and immune heterogeneity across different pathological stages of MSLCs, we analyse 16 MSLCs from 8 patients using single-cell RNA-seq, single-cell TCR sequencing, and bulk whole-exome sequencing. Our investigation indicates clonally independent tumours with convergent evolution driven by shared driver mutations. However, tumours from the same individual exhibit few shared mutations, indicating independent origins. During the transition from pre-invasive to invasive adenocarcinoma, we observe a shift in T cell phenotypes characterized by increased Treg cells and exhausted CD8+ T cells, accompanied by diminished cytotoxicity. Additionally, invasive adenocarcinomas exhibit greater neoantigen abundance and a more diverse TCR repertoire, indicating heightened heterogeneity. In summary, despite having a common genetic background and environmental exposure, our study emphasizes the individuality of MSLCs at different stages, highlighting their unique genomic and immune characteristics.

Ten-Year Survivals of Right Thoracic vs Left Thoracic Approach for Esophageal Cancer.

BACKGROUND: Esophagectomy can be performed using various surgical techniques. The aim of this study was to understand the impact of surgery on long-term survival for esophageal cancer. METHODS: Between May 2010 and July 2012, 300 patients with esophageal cancer were randomly assigned to undergo esophagectomy with either a left or right thoracic approach. Disease-free survival (DFS) and overall survival (OS) were compared based on the per-protocol principle among 286 patients with esophageal squamous cell carcinoma determined by postoperative pathologic results (146 in the right and 140 in the left thoracic arms). RESULTS: The median DFS was 92 months in the right thoracic arm and 41 months in the left thoracic arm (hazard ratio, 0.73; 95% CI, 0.54-0.99; P = .045), with a cumulative 10-year DFS of 47.6% and 37.5%, respectively. The median OS was 136 months in the right thoracic arm and 99 months in the left thoracic arm (hazard ratio, 0.75; 95% CI, 0.54-1.04; P = .081), with cumulative 10-year OS of 52.4% and 43.7%, respectively. DFS and OS were comparable between the 2 arms for patients without lymph node metastasis. Conversely, for patients with lymph node metastasis, 10-year DFS was 32.7% and 21.4%, respectively (P = .018), and 10-year OS of the right and left thoracic arms was 37.9% and 25.9%, respectively (P = .012). CONCLUSIONS: Compared with the left thoracic approach, patients who underwent esophagectomy through the right thoracic approach had better 10-year survival rates, and the survival benefit was significant for those with lymph node metastasis.

Application of random survival forest to establish a nomogram combining clinlabomics-score and clinical data for predicting brain metastasis in primary lung cancer.

PURPOSE: To establish a nomogram for predicting brain metastasis (BM) in primary lung cancer at 12, 18, and 24 months after initial diagnosis. METHODS: In this study, we included 428 patients who were diagnosed with primary lung cancer at Harbin Medical University Cancer Hospital between January 2020 and January 2022. The endpoint event was BM. The patients were randomly categorized into two groups in a 7:3 ratio: training (n = 299) and validation (n = 129) sets. Least absolute shrinkage and selection operator was utilized to analyze the laboratory test results in the training set. Furthermore, clinlabomics-score was determined using regression coefficients. Then, clinlabomics-score was combined with clinical data to construct a nomogram using random survival forest (RSF) and Cox multivariate regression. Then, various methods were used to evaluate the performance of the nomogram. RESULTS: Five independent predictive factors (pathological type, diameter, lymph node metastasis, non-lymph node metastasis and clinlabomics-score) were used to construct the nomogram. In the validation set, the bootstrap C-index was 0.7672 (95% CI 0.7092-0.8037), 12-month AUC was 0.787 (95% CI 0.708-0.865), 18-month AUC was 0.809 (95% CI 0.735-0.884), and 24-month AUC was 0.858 (95% CI 0.792-0.924). In addition, the calibration curve, decision curve analysis and Kaplan-Meier curves revealed a good performance of the nomogram. CONCLUSIONS: Finally, we constructed and validated a nomogram to predict BM risk in primary lung cancer. Our nomogram can identify patients at high risk of BM and provide a reference for clinical decision-making at different disease time points.

Genotype profile of HPV in ASC-H cytology and histologic follow-up-prevalence, distribution, and risk: A retrospective study of 1414 cases.

BACKGROUND: A cytologic diagnosis of atypical squamous cells, cannot exclude high-grade squamous lesion (ASC-H) poses a disproportionately high risk of cervical cancer development. The objective of this study was to analyze type-specific risks by mapping human papillomavirus (HPV) genotypes in ASC-H cytology. METHODS: In total, 1,048,581 Papanicolaou tests that had ASC-H cytology were retrieved. Concurrent HPV genotyping using proprietary multiplex real-time (MRT) and polymerase chain reaction (PCR) HPV tests and histologic follow-up findings were analyzed. RESULTS: Among 1678 patients who had ASC-H findings (0.16%), 1414 (84.3%) underwent concurrent HPV genotyping (MRT, 857; HPV PCR test, 557). The overall high-risk HPV (hrHPV)-positive rate was 84.4%. Of the 857 MRT cases, 63.9% were infected with a single hrHPV, and 24.4% had multiple genotypes. The most prevalent HPV types were HPV16/52/58/33/31. Lesions that were identified as cervical intraepithelial neoplasia 2 or worse (CIN2+) were detected in 498 of 906 cases (55.0%), including 81 cervical carcinomas (8.9%). The risk of CIN2+ for the composite group of HPV16/52/58/33/31-positive cases was 62.7%, representing 90.7% (264 of 291) of total CIN2+ lesions in ASC-H/hrHPV-positive cases by MRT. CIN2+ lesions were detected in 108 of 142 (76.1%) HPV16-positive and/or HPV18-positive women by the PCR the HPV test. Among 128 hrHPV-negative ASC-H cases by both methods, CIN2+ lesions were identified in 21 of 128 (16.4%), including five cervical carcinomas (3.9%). The sensitivity, specificity, positive predictive value, and negative predictive value for patients in the composite group with HPV16/52/58/33/31 were 88.0%, 40.8%, 62.7%, and 75.0%, respectively. CONCLUSIONS: Papanicolaou tests classified as ASC-H are associated with a high CIN2+ rate and warrant colposcopy, regardless of HPV status. The extent to which the risk-stratification provided by comprehensive HPV genotyping can inform the management of ASC-H cytology remains to be explored.

Calcium-sensing Receptor, a Potential Biomarker Revealed by Large-scale Public Databases and Experimental Verification in Metastatic Breast Cancer.

INTRODUCTION: Breast cancer (BC) is a common cancer characterized by a high molecular heterogeneity. Therefore, understanding its biological properties and developing effective treatments for patients with different molecular features is imperative. Calcium-sensing receptor (CaSR) has been implicated in several regulatory functions in various types of human cancers. However, its underlying pathological mechanism in BC progression remains elusive. METHODS: We utilized The Cancer Genome Atlas and Gene Expression Omnibus databases to explore the function of CaSR in the metastasis of BC. Gene ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis, and Gene Set Enrichment Analysis of biological processes and cell signaling pathways revealed that CaSR could be activated or inhibited. Importantly, quantitative reverse transcriptase-polymerase chain reaction and western blotting were used to verify the gene expression of the CaSR. Wound healing and transwell assays were conducted to assess the effect of CaSR on the migration of BC cells. RESULTS: We demonstrated that CaSR expression in metastatic BC was higher than that in non-metastatic BC. It is the first time that database information has been used to reveal the biological process and molecular mechanism of CaSR in BC. Moreover, the CaSR expression in normal breast epithelial cells was notably less compared to that in BC cells. The activation of CaSR by Cinacalcet (a CaSR agonist) significantly enhanced the migration of BC cells, whereas NPS-2143 (a CaSR antagonist) treatment dramatically inhibited these effects. CONCLUSION AND FUTURE PERSPECTIVE: Bioinformatics techniques and experiments demonstrated the involvement of CaSR in BC metastasis. Our findings shed new light on the receptor therapy and molecular pathogenesis of BC, and emphasize the crucial function of CaSR, facilitating the metastasis of BC.

The single cell immunogenomic landscape after neoadjuvant immunotherapy combined chemotherapy in esophageal squamous cell carcinoma.

Neoadjuvant immunotherapy represents promising strategy in the treatment of esophageal squamous cell carcinoma (ESCC). However, the mechanisms underlying its impact on treatment sensitivity or resistance remain a subject of controversy. In this study, we conducted single-cell RNA and T/B cell receptor (scTCR/scBCR) sequencing of CD45+ immune cells on samples from 10 patients who received neoadjuvant immunotherapy and chemotherapy. We also validated our findings using multiplexed immunofluorescence and analyzed bulk RNA-seq from other cohorts in public database. By integrating analysis of 87357 CD45+ cells, we found GZMK + effector memory T cells (Tem) were relatively enriched and CXCL13+ exhausted T cells (Tex) and regulator T cells (Treg) decreased among responders, indicating a persistent anti-tumor memory process. Additionally, the enhanced presence of BCR expansion and somatic hypermutation process within TNFRSF13B + memory B cells (Bmem) suggested their roles in antigen presentation. This was further corroborated by the evidence of the T-B co-stimulation pattern and CXCL13-CXCR5 axis. The complexity of myeloid cell heterogeneity was also particularly pronounced. The elevated expression of S100A7 in ESCC, as detected by bulk RNA-seq, was associated with an exhausted and immunosuppressive tumor microenvironment. In summary, this study has unveiled a potential regulatory network among immune cells and the clonal dynamics of their functions, and the mechanisms of exhaustion and memory conversion between GZMK + Tem and TNFRSF13B + Bmem from antigen presentation and co-stimulation perspectives during neoadjuvant PD-1 blockade treatment in ESCC.

Better Rough Than Scarce: Proximal Femur Fracture Segmentation With Rough Annotations.

Proximal femoral fracture segmentation in computed tomography (CT) is essential in the preoperative planning of orthopedic surgeons. Recently, numerous deep learning-based approaches have been proposed for segmenting various structures within CT scans. Nevertheless, distinguishing various attributes between fracture fragments and soft tissue regions in CT scans frequently poses challenges, which have received comparatively limited research attention. Besides, the cornerstone of contemporary deep learning methodologies is the availability of annotated data, while detailed CT annotations remain scarce. To address the challenge, we propose a novel weakly-supervised framework, namely Rough Turbo Net (RT-Net), for the segmentation of proximal femoral fractures. We emphasize the utilization of human resources to produce rough annotations on a substantial scale, as opposed to relying on limited fine-grained annotations that demand a substantial time to create. In RT-Net, rough annotations pose fractured-region constraints, which have demonstrated significant efficacy in enhancing the accuracy of the network. Conversely, the fine annotations can provide more details for recognizing edges and soft tissues. Besides, we design a spatial adaptive attention module (SAAM) that adapts to the spatial distribution of the fracture regions and align feature in each decoder. Moreover, we propose a fine-edge loss which is applied through an edge discrimination network to penalize the absence or imprecision edge features. Extensive quantitative and qualitative experiments demonstrate the superiority of RT-Net to state-of-the-art approaches. Furthermore, additional experiments show that RT-Net has the capability to produce pseudo labels for raw CT images that can further improve fracture segmentation performance and has the potential to improve segmentation performance on public datasets. The code is available at: https://github.com/zyairelu/RT-Net.

Prokaryotic community assembly patterns and nitrogen metabolic potential in oxygen minimum zone of Yangtze Estuary water column.

It is predicted that oxygen minimum zones (OMZs) in the ocean will expand as a consequence of global warming and environmental pollution. This will affect the overall microbial ecology and microbial nitrogen cycle. As one of the world's largest alluvial estuaries, the Yangtze Estuary has exhibited a seasonal OMZ since the 1980s. In this study, we have uncovered the microbial composition, the patterns of community assembly and the potential for microbial nitrogen cycling within the water column of the Yangtze Estuary, with a particular focus on OMZ. Based on the 16 S rRNA gene sequencing, a specific spatial variation in the composition of prokaryotic communities was observed for each water layer, with the Proteobacteria (46.1%), Bacteroidetes (20.3%), and Cyanobacteria (10.3%) dominant. Stochastic and deterministic processes together shaped the community assembly in the water column. Further, pH was the most important environmental factor influencing prokaryotic composition in the surface water, followed by silicate, PO43-, and distance offshore (p < 0.05). Water depth, NH4+, and PO43- were the main factors in the bottom water (p < 0.05). At last, species analysis and marker gene annotation revealed candidate nitrogen cycling performers, and a rich array of nitrogen cycling potential in the bottom water of the Yangtze Estuary. The determined physiochemical parameters and potential for nitrogen respiration suggested that organic nitrogen and NO3- (or NO2-) are the preferred nitrogen sources for microorganisms in the Yangtze Estuary OMZ. These findings are expected to advance research on the ecological responses of estuarine oxygen minimum zones (OMZs) to future global climate perturbations.

Unraveling the molecular mechanisms of lymph node metastasis in ovarian cancer: focus on MEOX1.

BACKGROUND: Lymph node metastasis (LNM) is a major factor contributing to the high mortality rate of ovarian cancer, making the treatment of this disease challenging. However, the molecular mechanism underlying LNM in ovarian cancer is still not well understood, posing a significant obstacle to overcome. RESULTS: Through data mining from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, we have identified MEOX1 as a specific gene associated with LNM in ovarian cancer. The expression of MEOX1 was found to be relatively high in serous ovarian adenocarcinoma, and its higher expression were associated with increased tumor grade and poorer clinical prognosis for ovarian cancer patients. Bioinformatics analysis revealed that MEOX1 exhibited the highest mRNA levels among all cancer types in ovarian cancer tissues and cell lines. Furthermore, gene set enrichment analysis (GSEA) and pathway analysis demonstrated that MEOX1 was involved in various LNM-related biological activities, such as lymphangiogenesis, lymphatic vessel formation during metastasis, epithelial-mesenchymal transition (EMT), G2/M checkpoint, degradation of extracellular matrix, and collagen formation. Additionally, the expression of MEOX1 was positively correlated with the expression of numerous prolymphangiogenic factors in ovarian cancer. To validate our findings, we conducted experiments using clinical tissue specimens and cell lines, which confirmed that MEOX1 was highly expressed in high-grade serous ovarian cancer (HGSOC) tissues and various ovarian cancer cell lines (A2780, SKOV3, HO8910, and OVCAR5) compared to normal ovarian tissues and normal ovarian epithelial cell line IOSE-80, respectively. Notably, we observed a higher protein level of MEOX1 in tumor tissues of LNM-positive HGSOC compared to LNM-negative HGSOC. Moreover, our fundamental experiments demonstrated that suppression of MEOX1 led to inhibitory effects on ovarian cancer cell proliferation and EMT, while overexpression of MEOX1 enhanced the proliferation and EMT capacities of ovarian cancer cells. CONCLUSIONS: The results of our study indicate that MEOX1 plays a role in the lymph node metastasis of ovarian cancer by regulating multiple biological activities, including the proliferation and EMT of ovarian cancer, lymphangiogenesis, and ECM remodeling. Our findings suggest that MEOX1 could serve as a potential biomarker for the diagnosis and treatment of ovarian cancer with LNM.

Hemophagocytic lymphohistiocytosis during treatment of intracranial multifocal germinoma: a case report and literature review.

Hemophagocytic lymphohistiocytosis (HLH), also known as hemophagocytic syndrome (HPS), is a benign histiocytosis with hyperreactive proliferation of the mononuclear phagocyte system caused by immune function abnormalities, which often occurs under the background of genetic mutations, inflammation, infection or tumors. Because the research on malignancy-associated HLH (M-HLH) is focused on hematological malignancies, reports on HLH secondary to solid tumors are rare. In this case, we report a 14-year-old girl who developed HLH during treatment for intracranial multifocal germinoma, and the disease was controlled after hormone combined with etoposide(VP-16) and other related treatments. To our knowledge, there have been no documented cases of HLH caused by intracranial multifocal germinoma.

Evolutionary proteogenomic landscape from pre-invasive to invasive lung adenocarcinoma.

Lung adenocarcinoma follows a stepwise progression from pre-invasive to invasive. However, there remains a knowledge gap regarding molecular events from pre-invasive to invasive. Here, we conduct a comprehensive proteogenomic analysis comprising whole-exon sequencing, RNA sequencing, and proteomic and phosphoproteomic profiling on 98 pre-invasive and 99 invasive lung adenocarcinomas. The deletion of chr4q12 contributes to the progression from pre-invasive to invasive adenocarcinoma by downregulating SPATA18, thus suppressing mitophagy and promoting cell invasion. Proteomics reveals diverse enriched pathways in normal lung tissues and pre-invasive and invasive adenocarcinoma. Proteomic analyses identify three proteomic subtypes, which represent different stages of tumor progression. We also illustrate the molecular characterization of four immune clusters, including endothelial cells, B cells, DCs, and immune depression subtype. In conclusion, this comprehensive proteogenomic study characterizes the molecular architecture and hallmarks from pre-invasive to invasive lung adenocarcinoma, guiding the way to a deeper understanding of the tumorigenesis and progression of this disease.

C-to-G editing generates double-strand breaks causing deletion, transversion and translocation.

Base editors (BEs) introduce base substitutions without double-strand DNA cleavage. Besides precise substitutions, BEs generate low-frequency 'stochastic' byproducts through unclear mechanisms. Here, we performed in-depth outcome profiling and genetic dissection, revealing that C-to-G BEs (CGBEs) generate substantial amounts of intermediate double-strand breaks (DSBs), which are at the centre of several byproducts. Imperfect DSB end-joining leads to small deletions via end-resection, templated insertions or aberrant transversions during end fill-in. Chromosomal translocations were detected between the editing target and off-targets of Cas9/deaminase origin. Genetic screenings of DNA repair factors disclosed a central role of abasic site processing in DSB formation. Shielding of abasic sites by the suicide enzyme HMCES reduced CGBE-initiated DSBs, providing an effective way to minimize DSB-triggered events without affecting substitutions. This work demonstrates that CGBEs can initiate deleterious intermediate DSBs and therefore require careful consideration for therapeutic applications, and that HMCES-aided CGBEs hold promise as safer tools.

Calcium-sensing receptor and NF-κB pathways in TN breast cancer contribute to cancer-induced cardiomyocyte damage via activating neutrophil extracellular traps formation.

Cardiovascular disorders are commonly prevalent in cancer patients, yet the mechanistic link between them remains poorly understood. Because neutrophil extracellular traps (NETs) have implications not just in cardiovascular diseases (CVD), but also in breast cancer (BC), it was hypothesized to contribute to CVD in the context of oncogenesis. We established a mouse model using nude mice to simulate liver metastasis of triple-negative BC (TNBC) through the injection of MDA-MB-231 cells. Multiple imaging and analysis techniques were employed to assess the cardiac function and structure, including echocardiography, HE staining, Masson staining, and transmission electron microscopy (TEM). MDA-MB-231 cells underwent treatment with a CaSR inhibitor, CaSR agonist, and NF-κB channel blocker. The phosphorylation of NF-κB channel protein p65 and the expression and secretion of IL-8 were assessed using qRT-PCR, Western Blot, and ELISA, respectively. In addition, MDA-MB-231 cells were co-cultured with polymorphonuclear neutrophils (PMN) under varying conditions. The co-localization of PMN extracellular myeloperoxidase (MPO) and DNA were observed by cellular immunofluorescence staining to identify the formation of NETs. Then, the cardiomyocytes were co-cultured with the above medium that contains NETs or not, respectively; the effects of NETs on cardiomyocytes apoptosis were perceived by flow cytometry. The ultrastructural changes of myocardial cells were perceived by TEM, and ELISA detected the levels of myocardial enzyme (LDH, MDA and SOD). Overall, according to our research, CaSR has been found to have a regulatory role in IL-8 secretion in MDA-MB-231 cells, as well as in the formation of NETs by PMN cells. These findings suggest CaSR-mediated stimulation in PMN can lead to increased NETs formation and subsequently to cytotoxicity in cardiomyocytes, which potentially via activation of the NF-κB signaling cascade of BC cell.

Genomic Characterization and Molecular Evolution of Sapovirus in Children under 5 Years of Age.

Sapovirus (SaV) is a type of gastroenteric virus that can cause acute gastroenteritis. It is highly contagious, particularly among children under the age of 5. In this study, a total of 712 stool samples from children under the age of 5 with acute gastroenteritis were collected. Out of these samples, 28 tested positive for SaV, resulting in a detection rate of 3.93% (28/712). Samples with Ct < 30 were collected for library construction and high-throughput sequencing, resulting in the acquisition of nine complete genomes. According to Blast, eight of them were identified as GI.1, while the remaining one was GI.6. The GI.6 strain sequence reported in our study represents the first submission of the GI.6 strain complete genome sequence from mainland China to the Genbank database, thus filling the data gap in our country. Sequence identity analysis revealed significant nucleotide variations between the two genotypes of SaV and their corresponding prototype strains. Phylogenetic and genetic evolution analyses showed no evidence of recombination events in the obtained sequences. Population dynamics analysis demonstrated potential competitive inhibition between two lineages of GI.1. Our study provides insights into the molecular epidemiological and genetic evolution characteristics of SaV prevalent in the Nantong region of China, laying the foundation for disease prevention and control, as well as pathogen tracing related to SaV in this area.

Extent of surgical resection for radiologically subsolid T1N0 invasive lung adenocarcinoma: When is a wedge resection acceptable?

OBJECTIVE: To evaluate whether wedge resection (WR) was appropriate for the patients with peripheral T1 N0 solitary subsolid invasive lung adenocarcinoma. METHODS: Patients with peripheral T1N0 solitary subsolid invasive lung adenocarcinoma who received sublobar resection were retrospectively reviewed. Clinicopathologic characteristics, 5-year recurrence-free survival, and 5-year lung cancer-specific overall survival were analyzed. Cox regression model was used to elucidate risk factors for recurrence. RESULTS: Two hundred fifty-eight patients receiving WR and 1245 patients receiving segmentectomy were included. The mean follow-up time was 36.87 ± 16.21 months. Five-year recurrence-free survival following WR was 96.89% for patients with ground-glass nodule (GGN) ≤2 cm and 0.25< consolidation-to-tumor ratio (CTR) ≤0.5, not statistically different from 100% for those with GGN≤2 cm and CTR ≤0.25 (P = .231). The 5-year recurrence-free survival was 90.12% for patients with GGN between 2 and 3 cm and CTR ≤0.5, significantly lower than that of patients with GGN ≤2 cm and CTR ≤0.25 (P = .046). For patients with GGN≤2 cm and 0.25

Value of adjuvant chemotherapy for patients with pT2N0M0 non-small cell lung cancer receiving radical resection.

BACKGROUND: Associations between adjuvant chemotherapy (ACT) and the improvement in survival for patients with pT2N0M0 non-small cell lung cancer (NSCLC) who received R0 resection remain controversial. This study aimed to evaluate the value of ACT for patients with pT2N0M0 NSCLCs, and to identify the subgroups who could benefit from ACT. METHODS: Multivariable Cox proportional hazards regression models were used to estimate independent prognostic factors. High-risk factor (HRF) included visceral pleural invasion (VPI), lymphovascular invasion (LVI) and poor differentiation/undifferentiated tumors. RESULTS: Of the 899 patients, 277 (30.8%) patients received ACT. More younger patients (p < 0.001) and male patients (p = 0.007) received ACT. With the increase of pathological tumor size (p < 0.001) and the number of HRFs (p < 0.001), there was a significant rise in the proportion of patients receiving ACT. For all patients, ACT could not improve recurrence-free survival (RFS) (p = 0.672) and overall survival (OS) (p = 0.306). For patients with pathological stage IIA or radiological pure-solid tumors, ACT could significantly improve the OS (p = 0.011 and p = 0.037, respectively), and multivariate analysis revealed that ACT was an independent prognostic factor for patients with pathological stage IIA (p = 0.005). ACT could improve the OS significantly in patients with pathological stage IB pure-solid lung adenocarcinoma (LUAD) (p = 0.043). CONCLUSION: ACT was valuable for patients with pathological stage IIA (pT2bN0M0) and patients with radiological pure-solid LUAD of pathological stage IB. A combination of radiological features and pathological subtypes could be helpful when selecting patients with pT2N0M0 NSCLCs for ACT.

Safety of omitting nasogastric decompression after esophagectomy: a propensity score-matched study.

Background: Nasogastric (NG) decompression is routinely performed after esophagectomy. However, whether it aids postoperative recovery is still controversial. This study aimed to assess the effects of NG decompression on postoperative complications after esophagectomy. Methods: Data of 1,489 consecutive patients who underwent esophagectomy between January 2019 and December 2020 were retrospectively analyzed. All patients were assigned to two groups based on whether they had undergone NG decompression or not. We conducted a propensity score matching (PSM) analysis to minimize the effect of potential confounders. Results: In total, 1,466 patients (including 1,235 patients with NG tubes and 231 without NG tubes) were included in the study, and 219 pairs were successfully matched. After PSM analysis, there was no difference in morbidity and mortality between the two groups. Postoperative hospital stay in the non-NG tube group was shorter than that in the NG tube group (8 vs. 10 days, P<0.001). The incidence of pneumonia and anastomotic leakage showed no significant differences (13.2% vs. 17.8%, P=0.235 for pneumonia; 13.7% vs. 11.0%, P=0.460 for anastomotic leakage). For patients who developed anastomotic leakage after surgery, the leakage developed earlier in the non-NG group (6 vs. 8 days, P=0.033) than in the NG group. However, no significant between-group differences were observed in the postoperative hospital stay and severity of leakage. Conclusions: Routine NG decompression may not confer any discernible benefits for patients who have undergone esophagectomy. As such, the omission of this procedure could be considered in postoperative care.

Residual tumor descriptors proposed by the International Association for the Study of Lung Cancer may not be applicable to stage I and ground-glass opacity-featured non-small cell lung cancer.

Background: The International Association for the Study of Lung Cancer (IASLC) has proposed a residual tumor descriptor, essential for subsequent treatments. This study aimed to validate the prognostic effect of the proposed R descriptor and restrict its scope of clinical application in a large-scale cohort with non-small cell lung cancer (NSCLC). Methods: Patients, who underwent lobectomy from January 2010 to May 2019, were retrospectively reviewed. Patients were categorized according to the different R classification standards proposed by Union for International Cancer Control (UICC) and IASLC. Results: Among 5,200 enrolled patients with NSCLC, 1,727 and 9 cases of UICC-R0 were re-evaluated as uncertain resection [R(un)] and R1, respectively. After reclassification, there were 3,228 (62.1%) cases of R0, 1,727 (33.2%) cases of R(un), 151 (2.9%) cases of R1, and 94 (1.8%) cases of R2. Not performing rigorous systematic nodal dissection (SND) or lobe-specific SND (68.3%) was the main reason for the alteration from R0 to R(un). Patients with R(un) showed intermediate survival between those with R0 and R1. Further multivariable Cox analysis indicated that the proposed R descriptor was an independent prognostic factor for overall survival (OS) and recurrence-free survival (RFS). However, subgroup analysis of OS and RFS revealed that there was no significant difference between R0 and R(un) in patients with ground-glass opacity (GGO) or patients with tumor-node-metastasis stage I. Conclusions: R(un) represented an intermediate type between R0 and R1. Our study provided an external validation for new residual tumor descriptors for NSCLC proposed by IASLC. Proposed residual tumor descriptors were applicable in radiologic solid NSCLC and stage II-III NSCLC, but were ineffective for GGO-featured or stage I NSCLC.

Pattern of tumor regression after neoadjuvant chemoimmunotherapy for esophageal squamous cell carcinoma.

Background: Immune checkpoint inhibitors have been increasingly applied for esophageal cancer. The aims of this study were to evaluate the pattern of tumor regression after neoadjuvant chemoimmunotherapy. Methods: From January 2020 to December 2021, 138 patients with esophageal squamous cell carcinoma who had esophagectomy after neoadjuvant chemoimmunotherapy were reviewed. Surgical and pathological results were analyzed, and tumor regression pattern was evaluated. Results: Of the 138 patients, 65 (47.1%) patients had chemotherapy combined with camrelizumab, 48 (34.8%) with pembrolizumab, 13 (9.4%) with tislelizumab, and 12 (8.7%) with sintilimab. Sixty-four patients (46.4%) underwent McKewon procedure, and 74 (53.6%) Ivor-Lewis procedure, respectively. There were 131/138 patients (94.9%) who had R0 resections, and the median number of resected lymph nodes was 28. Pneumonia was the most common complication after surgery (14.5%). Pathological complete regression occurred in 28 patients (20.3%). Regarding to residual tumor, there were 50 patients (36.2%) with residual tumor in the mucosa, 81 (58.7%) in the submucosa, 85 (61.6%) in the muscularis propria, 47 (34.1%) in the adventitia and 71 (51.4%) in the lymph nodes. There were 88 patients with no residual tumor in the mucosa, of whom 60 (68.2%) had residual tumors in other layers or in the lymph nodes. Conclusions: In this retrospective study, esophagectomy after neoadjuvant chemoimmunotherapy is safe with acceptable surgical risk. Preferential clearing of tumor cells in mucosa layer is common after immunotherapy, while the rate of complete pathological response is relatively low, indicating surgery is still necessary.