Predicting pathological response to neoadjuvant or conversion chemoimmunotherapy in stage IB-III non-small cell lung cancer patients using radiomic features.

BACKGROUND: To develop a radiomics model based on chest computed tomography (CT) for the prediction of a pathological complete response (pCR) after neoadjuvant or conversion chemoimmunotherapy (CIT) in patients with non-small cell lung cancer (NSCLC). METHODS: Patients with stage IB-III NSCLC who received neoadjuvant or conversion CIT between September 2019 and July 2021 at Hunan Cancer Hospital, Xiangya Hospital, and Union Hospital were retrospectively collected. The least absolute shrinkage and selection operator (LASSO) were used to screen features. Then, model 1 (five radiomics features before CIT), model 2 (four radiomics features after CIT and before surgery) and model 3 were constructed for the prediction of pCR. Model 3 included all nine features of model 1 and 2 and was later named the neoadjuvant chemoimmunotherapy-related pathological response prediction model (NACIP). RESULTS: This study included 110 patients: 77 in the training set and 33 in the validation set. Thirty-nine (35.5%) patients achieved a pCR. Model 1 showed area under the curve (AUC) = 0.65, 64% accuracy, 71% specificity, and 50% sensitivity, while model 2 displayed AUC = 0.81, 73% accuracy, 62% specificity, and 92% sensitivity. In comparison, NACIP yielded a good predictive value, with an AUC of 0.85, 81% accuracy, 81% specificity, and 83% sensitivity in the validation set. CONCLUSION: NACIP may be a potential model for the early prediction of pCR in patients with NSCLC treated with neoadjuvant/conversion CIT.

Chronic pulmonary mucormycosis caused by rhizopus microsporus mimics lung carcinoma in an immunocompetent adult: A case report.

BACKGROUND: Pulmonary mucormycosis is a rare but life-threatening invasive fungal infection that mostly affects immunocompromised patients. This disease usually develops acutely and progresses rapidly, often leading to a poor clinical prognosis. Chronic pulmonary mucormycosis is highly unusual in immunocompetent patients. CASE SUMMARY: A 43-year-old man, who was a house improvement worker with a long history of occupational dust exposure, presented with an irritating cough that had lasted for two months. The patient was previously in good health, without dysglycemia or any known immunodeficiencies. Chest computed tomography revealed a mass in the left lower lobe, measuring approximately 6 cm in diameter, which was suspected to be primary lung carcinoma complicated with obstructive pneumonia. Thoracoscopic-assisted left lower lobectomy was performed, and metagenomic next-generation sequencing detection, along with special pathological staining of surgical specimens, suggested Rhizopus microsporus infection. Postoperatively, the patient's respiratory symptoms were relieved, and no signs of recurrence were found during the six-month follow-up. CONCLUSION: This article reports a rare case of chronic pulmonary mucormycosis caused by Rhizopus microsporus in a middle-aged male without dysglycemia or immunodeficiency. The patient's surgical outcome was excellent, reaffirming that surgery remains the cornerstone of pulmonary mucormycosis treatment.

Surgical resection of a giant thymolipoma causing respiratory failure: A case report.

BACKGROUND: Thymolipoma is a rare benign tumor arising from the anterior mediastinal thymus and is composed of mature fatty tissue and interspersed nonneoplastic thymic tissue. This tumor accounts for only a small percentage of mediastinal masses, and the majority of them are asymptomatic and found incidentally. To date, fewer than 200 cases have been published in the world literature, of which most excised tumors weighed less than 0.5 kg and the largest weighed 6 kg. CASE SUMMARY: A 23-year-old man presented with a complaint of progressive breathlessness for 6 mo. His forced vital capacity was only 23.6% of the predicted capacity, and his arterial partial pressure of oxygen and carbon dioxide were 51 and 60 mmHg, respectively, without oxygen inhalation. Chest computed tomography revealed a large fat-containing mass in the anterior mediastinum that measured 26 cm × 20 cm × 30 cm in size and occupied most of the thoracic cavity. Percutaneous mass biopsy revealed only thymic tissue without signs of malignancy. A right posterolateral thoracotomy was successfully performed to remove the tumor along with the capsule, and the excised tumor weighed 7.5 kg, which to our knowledge, was the largest surgically removed tumor of thymic origin. Postoperatively, the patient's shortness of breath was resolved, and the histopathological diagnosis was thymolipoma. No signs of recurrence were observed at the 6-mo follow-up. CONCLUSION: Giant thymolipoma causing respiratory failure is rare and dangerous. Despite the high risks, surgical resection is feasible and effective.

Replication-driven HBV cccDNA loss in chimeric mice with humanized livers.

Hepatitis B virus (HBV) infection is largely noncytopathic and requires the establishment of covalently closed circular DNA (cccDNA), which is considered stable in the nuclei of infected cells. Although challenging, approaches to directly target cccDNA molecules or kill infected cells are recommended to eliminate cccDNA. Herein, cccDNA levels were investigated in HBV-infected chimeric mice with humanized livers. HBV-infected cells support robust replication, progressively retain viral products, and head for cytopathic destruction and cccDNA loss. It is difficult for infected cells to retain cccDNA and remain noncytopathic. Replication-driven cccDNA loss is observed at both phases of spread of and persistent infection. The cccDNA replenishment is required to compensate for cccDNA loss. Blocking cccDNA replenishment pathways reduces cccDNA levels by >100-fold. These results prove an unconventional cccDNA elimination strategy that does not directly target cccDNA but aims to transform spontaneous cccDNA loss into progressive cccDNA elimination by blocking cccDNA replenishment.

Clinicopathological parameters predicting recurrence of pT1N0 esophageal squamous cell carcinoma.

AIM: To identify the clinicopathological characteristics of pT1N0 esophageal squamous cell carcinoma (ESCC) that are associated with tumor recurrence. METHODS: We reviewed 216 pT1N0 thoracic ESCC cases who underwent esophagectomy and thoracoabdominal two-field lymphadenectomy without preoperative chemoradiotherapy. After excluding those cases with clinical follow-up recorded fewer than 3 mo and those who died within 3 mo of surgery, we included 199 cases in the current analysis. Overall survival and recurrence-free survival were assessed by the Kaplan-Meier method, and clinicopathological characteristics associated with any recurrence or distant recurrence were evaluated using univariate and multivariate Cox proportional hazards models. Early recurrence (≤ 24 mo) and correlated parameters were assessed using univariate and multivariate logistic regression models. RESULTS: Forty-seven (24%) patients had a recurrence at 3 to 178 (median, 33) mo. The 5-year recurrence-free survival rate was 80.7%. None of 13 asymptomatic cases had a recurrence. Preoperative clinical symptoms, upper thoracic location, ulcerative or intraluminal mass macroscopic tumor type, tumor invasion depth level, basaloid histology, angiolymphatic invasion, tumor thickness, submucosal invasion thickness, diameter of the largest single tongue of invasion, and complete negative aberrant p53 expression were significantly related to tumor recurrence and/or recurrence-free survival. Upper thoracic tumor location, angiolymphatic invasion, and submucosal invasion thickness were independent predictors of tumor recurrence (Hazard ratios = 3.26, 3.42, and 2.06, P < 0.001, P < 0.001, and P = 0.002, respectively), and a nomogram for predicting recurrence-free survival with these three predictors was constructed. Upper thoracic tumor location and angiolymphatic invasion were independent predictors of distant recurrence. Upper thoracic tumor location, angiolymphatic invasion, submucosal invasion thickness, and diameter of the largest single tongue of invasion were independent predictors of early recurrence. CONCLUSION: These results should be useful for designing optimal individual follow-up and therapy for patients with T1N0 ESCC.

Development and validation of two prognostic nomograms for predicting survival in patients with non-small cell and small cell lung cancer.

PURPOSE: This study aimed to construct two prognostic nomograms to predict survival in patients with non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using a novel set of clinical parameters. PATIENTS AND METHODS: Two nomograms were developed, using a retrospective analysis of 5384 NSCLC and 647 SCLC patients seen during a 10-year period at Xiang Ya Affiliated Cancer Hospital (Changsha, China). The patients were randomly divided into training and validation cohorts. Univariate and multivariate analyses were used to identify the prognostic factors needed to establish nomograms for the training cohort. The model was internally validated via bootstrap resampling and externally certified using the validation cohort. Predictive accuracy and discriminatory capability were estimated using concordance index (C-index), calibration curves, and risk group stratification. RESULTS: The largest contributor to overall survival (OS) prognosis in the NSCLC nomogram was the therapeutic regimen and diagnostic method parameters, and in the SCLC nomogram was the therapeutic regimen and health insurance plan parameters. Calibration curves for the nomogram prediction and the actual observation were in optimal agreement for the 3-year OS and acceptable agreement for the 5-year OS in both training datasets. The C-index was higher for the NSCLC cohort nomogram than for the TNM staging system (0.67 vs. 0.64, P = 0.01) and higher for the SCLC nomogram than for the clinical staging system (limited vs. extensive) (0.60 vs. 0.53, P = 0.12). CONCLUSION: Treatment regimen parameter made the largest contribution to OS prognosis in both nomograms, and these nomograms might provide clinicians and patients a simple tool that improves their ability to accurately estimate survival based on individual patient parameters rather than using an averaged predefined treatment regimen.

Genetic landscape of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the deadliest cancers. We performed exome sequencing on 113 tumor-normal pairs, yielding a mean of 82 non-silent mutations per tumor, and 8 cell lines. The mutational profile of ESCC closely resembles those of squamous cell carcinomas of other tissues but differs from that of esophageal adenocarcinoma. Genes involved in cell cycle and apoptosis regulation were mutated in 99% of cases by somatic alterations of TP53 (93%), CCND1 (33%), CDKN2A (20%), NFE2L2 (10%) and RB1 (9%). Histone modifier genes were frequently mutated, including KMT2D (also called MLL2; 19%), KMT2C (MLL3; 6%), KDM6A (7%), EP300 (10%) and CREBBP (6%). EP300 mutations were associated with poor survival. The Hippo and Notch pathways were dysregulated by mutations in FAT1, FAT2, FAT3 or FAT4 (27%) or AJUBA (JUB; 7%) and NOTCH1, NOTCH2 or NOTCH3 (22%) or FBXW7 (5%), respectively. These results define the mutational landscape of ESCC and highlight mutations in epigenetic modulators with prognostic and potentially therapeutic implications.

Application of video-assisted thoracic surgery in the standard operation for thoracic tumors.

OBJECTIVE: To evaluate the short-term outcomes of video-assisted thoracic surgery (VATS) for thoracic tumors. METHODS: The data of 1,790 consecutive patients were retrospectively reviewed. These patients underwent VATS pulmonary resections, VATS esophagectomies, and VATS resections of mediastinal tumors or biopsies at the Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and January 2012. RESULTS: There were 33 patients converted to open thoracotomy (OT, 1.84%). The overall morbidity and mortality rate was 2.79% (50/1790) and 0.28% (5/1790), respectively. The overall hospitalization and chest tube duration were shorter in the VATS lobectomy group (n=949) than in the open thoracotomy (OT) lobectomy group (n=753). There were no significant differences in morbidity rate, mortality rate and operation time between the two groups. In the esophageal cancer patients, no significant difference was found in the number of nodal dissection, chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS esophagectomy group (n=81) and open esophagectomy group (n=81). However, the operation time was longer in the VATS esophagectomy group. In the thymoma patients, there was no significant difference in the chest tube duration, morbidity rate, mortality rate, and hospital length of stay between the VATS thymectomy group (n=41) and open thymectomy group (n=41). However, the operation time was longer in the VATS group. The median tumor size in the VATS thymectomy group was comparable with that in the OT group. CONCLUSIONS: In early-stage (I/II) non-small cell lung cancer patients who underwent lobectomies, VATS is comparable with the OT approach with similar short-term outcomes. In patients with resectable esophageal cancer, VATS esophagectomy is comparable with OT esophagectomy with similar morbidity and mortality. VATS thymectomy for Masaoka stage I and II thymoma is feasible and safe, and tumor size is not contraindicated. Longer follow-ups are needed to determine the oncologic equivalency of VATS lobectomy, esophagectomy, and thymectomy for thymoma vs. OT.

Clinical outcomes of basaloid squamous cell carcinoma of the esophagus: a retrospective analysis of 142 cases.

BACKGROUND: Basaloid squamous cell carcinoma of the esophagus (BSCCE) is a rare and distinctive tumor with no standard treatment. This study aimed to explore treatment in relation to prognosis of the disease. METHODS: A total of 142 patients with BSCCE that underwent treatment in our hospital from March 1999 to July 2010 were retrospectively analyzed. All patients received surgery, 42 postoperative radiotherapy and 28 patients chemotherapy. RESULTS: There were 26 patients included in stage I, 60 in stage II, 53 in stage III and 3 in stage IV. The clinical symptoms and macroscopic performances of BSCCE did not differ from those of typical esophageal squamous cell carcinoma. Among 118 patients receiving endoscopic biopsy, only 12 were diagnosed with BSCCE. The median survival time (MST) of the entire group was 32 months, with 1-, 3- and 5-year overall survival (OS) of 81.4%, 46.8% and 31.0%, respectively. The 5-year OS of stage I and II patients was significantly longer than that of stages III/IV, at 60.3%, 36.1% and 10.9%, respectively (p<0.001, p=0.001). The MST and 5-year OS were 59.0 months and 47.4% in patients with tumors located in the lower thoracic esophagus, and 27.0 months and 18.1% in those with lesions in the upper/middle esophagus (p=0.002). However, the survival was not significantly improved in patients undegoing adjunctive therapy. Multivariate analysis showed TNM stage and tumor location to be independent prognostic factors. Furthermore, distant metastasis was the most frequent failure pattern, with a median recurrence time of 10 months. CONCLUSION: BSCCE is an aggressive disease with rapid progression and a propensity for distant metastasis. It is difficult to make a definitive diagnosis via preoperative biopsy. Multidisciplinary therapy including radical esophagectomy with extended lymphadenectomy should be recommended, while the effectiveness of radiochemotherapy requires further validation for BSCCE.

[Surgical treatment and prognostic analysis of 109 patients with primary esophageal small cell carcinoma].

OBJECTIVE: Since the principles of treatment of primary esophageal small cell carcinoma (PESCC) remain still in controversy, the aim of this study was to investigate the clinical characteristics, treatment modalities and prognostic factors of this malignancy. METHODS: The clinical data of 109 patients treated by surgery in our hospital between October 1989 and April 2009 were retrospectively reviewed and analyzed. According to the most recently published TNM staging system for esophageal cancer (AJCC 2009), there were 17 patients in stage Ib, 31 patients in stage II, 59 patients in stage III, and 2 patients in stage IV. All the data were analyzed using SPSS 15.0 software. The median survival time (MST) and overall survival rate (OS) were calculated and compared by the Kaplan-Meier method and log-rank test. The prognostic factors were calculated by Cox hazard regression model. RESULTS: Among all the 109 patients included, 93 patients were treated by radical esophagectomy, and 11 patients by palliative resection, while 5 patients by exploration. The median survival time (MST) of the whole group was 14.4 months and the 1-, 3- and 5-year overall survival rates (OS) were 56.9%, 17.6%, and 12.0%, respectively. The median survival time (MST) and 5-year overall survival rates (OS) were 18.5 months and 21.4% for pathological N0 cases, 23.5 months and 24.0% for N1 cases, 8.5 months and 0% for N2 cases, and 10.5 months and 0% for N3 cases, respectively (P < 0.001). The MST and 1-, 3- and 5-year OS of patients treated with postoperative chemotherapy were 17.0 months, 60.7%, 19.8%, and 13.0%, respectively, statistically significantly longer than the 7.0 months, 28.5%, 8.9% and 8.9%, respectively, of the patients without chemotherapy (P = 0.005). The pathological N stage and postoperative chemotherapy were independent prognostic factors by Cox multivariate analysis. CONCLUSIONS: Primary esophageal small cell carcinoma is an aggressive systemic disease, characterized by early and wide dissemination of lymph nodes and poor prognosis while treated with surgery or chemotherapy alone. Multimodality treatment based on radical esophagectomy should be recommended for patients in pathological stage I and II.

[Comparison of the short-term outcomes of surgical treatment for non-small cell lung cancer via video assisted thoracoscopic surgery and open thoracotomy].

OBJECTIVE: To compare the short-term outcomes of surgical treatment for non-small cell lung cancer (NSCLC) by video-assisted thoracoscopic surgery (VATS) and open thoracotomy (OT). METHODS: Data of 737 consecutive NSCLC patients who underwent surgical treatment for non-small cell lung cancer by video-assisted thoracoscopic surgery and 630 patients who underwent pulmonary resection via open thoracotomy (as controls) in Cancer Institute & Hospital, Chinese Academy of Medical Sciences between January 2009 and August 2011 were retrospectively reviewed. The risk factors after lobectomy were also analyzed. RESULTS: In the 506 NSCLC patients who received VATS lobectomy, postoperative complications occurred in 13 patients (2.6%) and one patient died of acute respiratory distress syndrome (0.2%). In the 521 patients who received open thoracotomy (OT) lobectomy, postoperative complications occurred in 21 patients (4.0%) and one patient died of pulmonary infection (0.2%). There was no significant difference in the morbidity rate (P > 0.05) and mortality rate (P > 0.05) between the VATS group and OT group. In the 190 patients who received VATS wedge resections, postoperative complications occurred in 3 patients (1.6%). One hundred and nine patients received OT wedge resections. Postoperative complications occurred in 4 patients (3.7%). There were no significant differences for morbidity rate (P = 0.262) between these two groups, and there was no perioperative death in these two groups. Univariate and multivariate analyses demonstrated that age (OR = 1.047, 95%CI: 1.004 - 1.091), history of smoking (OR = 6.374, 95%CI: 2.588 - 15.695) and operation time (OR = 1.418, 95%CI: 1.075 - 1.871) were independent risk factors of postoperative complications. CONCLUSIONS: To compare with the NSCLC patients who should undergo lobectomy or wedge resection via open thoracotomy, a similar short-term outcome can be achieved via VATS approach.

[Clinical manifestation and prognosis of the surgical treatment of esophageal carcinosarcoma].

OBJECTIVE: To investigate the clinical characteristics and prognostic factors of esophageal carcinosarcoma. METHODS: The clinical data of patients treated by surgery and pathologically diagnosed as esophageal carcinosarcoma between January 1967 and December 2008 were retrospectively reviewed. There were 28 male and 4 female patients aged from 39 to 76 years with a median age of 58 years. All the data were analyzed using SPSS 15.0 software. The overall survival rates were calculated and compared with the Kaplan-Meier method and the Log-rank test. The prognostic factors were identified by Cox hazard regression model. RESULTS: Among all the 32 patients included, 29 patients were polypoid type, 2 patients were fungoid type and 1 patient were medullary type. With regard to the depth of tumor infiltration, 17 patients involved the mucosa or submucosa (pT1), 13 patients involved the muscularis propria (pT2), 2 patients involved the adventitia (pT3). The involvement of local lymph nodes was present in 10 patients, with an incidence of 31.3%, including metastatic carcinoma alone in 7 patients and both carcinomatous and sarcomatous components in 3 patients. According to the most recently published international TNM staging system for esophageal carcinoma (AJCC 2009), 15 patients were in stage I, 13 patients in stage II, 4 patients in stage III. The 1-, 3- and 5-year overall survival rates of the whole group were 90.0%, 72.1% and 57.0%, respectively. Both in single-factor prognostic analysis and in Cox multivariate analysis, pathological N stage was the only prognostic factor (RR = 2.531, 95%CI: 1.055 - 6.070). CONCLUSIONS: Esophageal carcinosarcoma is consisted of both sarcomatous component and carcinomatous component, while the latter one appears more frequently in local lymph node metastasis. In multivariate prognostic analysis, pathological N stage is the only independent prognostic factor. Curative resection of this tumor may achieve good prognosis because of its' lower incidence of lymph node metastasis and less invasive tendency.

[Clinical analysis of 47 cases of synchronous double primary carcinomas of esophagus and cardia].

OBJECTIVE: To explore the clinical features and prognosis of the patients with synchronous double primary malignancy of esophagus and cardia. METHODS: The clinical data of patients with synchronous primary esophageal and cardiac carcinomas undergoing surgery at our hospital between April 1988 and April 2009 were retrospectively reviewed. All data were analyzed by the SPSS 15.0 software. The overall survival rates (OS) were calculated and compared with the Kaplan-Meier method and the Log-rank test. The prognostic factors were identified by Cox's hazard regression model. RESULTS: Among all 47 cases, esophageal carcinoma was missed preoperatively in 1 patients and cardiac carcinoma in 12. The 1-, 3- and 5-year overall survival rates (OS) of the whole group were 81.5%, 49.1% and 34.3% respectively. And the median survival time was 33 months. The univariate analysis of prognostic factors showed that radical resection, N stage of esophageal carcinoma (2009), N stage of cardiac carcinoma (2009) and TNM stage of cardiac carcinoma (both 2002 and 2009) might influence the long-term survival. However, according to the multivariate analysis, only radical resection and N stage of cardiac carcinoma (2009) were independent prognostic factors. CONCLUSION: With preoperative combined examination of esophagography and esophagoscopy and thorough intraoperative detection, the clinicians may reduce the rate of missed diagnosis for synchronous double primary esophageal and cardiac carcinomas. Radical resection of primary lesions and thorough dissection of locoregional lymph nodes may improve the patient survival.

Novel function of CD81 in controlling hepatitis C virus replication.

The mechanisms of hepatitis C virus (HCV) replication remain poorly understood, and the cellular factors required for HCV replication are yet to be completely defined. CD81 is known to mediate HCV entry. Our study uncovered an unexpected novel function of CD81 in the HCV life cycle that is important for HCV RNA replication. HCV replication occurred efficiently in infected cells with high levels of CD81 expression. In HCV-infected or RNA-transfected cells with low levels of CD81 expression, initial viral protein synthesis occurred normally, but efficient replication failed to proceed. The aborted replication could be restored by the transient transfection of a CD81 expression plasmid. CD81-dependent replication was demonstrated with both an HCV infectious cell culture and HCV replicon cells of genotypes 1b and 2a. We also showed that CD81 expression is positively correlated with the kinetics of HCV RNA synthesis but inversely related to the kinetics of viral protein production, suggesting that CD81 may control viral replication by directing viral RNA template function to RNA replication. Thus, CD81 may be necessary for the efficient replication of the HCV genome in addition to its role in viral entry.

Single-cell analysis of covalently closed circular DNA copy numbers in a hepadnavirus-infected liver.

Hepatitis B virus (hepadnavirus) infections are maintained by the presence of a small and regulated number of episomal viral genomes [covalently closed circular DNA (cccDNA)] in the nuclei of infected cells. Although a number of studies have measured the mean copy number of cccDNA molecules in hepadnaviral-infected cells, the distribution of individual copy numbers have not been reported. Using a PCR-based assay, we examined the number of cccDNA molecules of the duck hepatitis B virus in single nuclei isolated from the liver of a chronically infected duck over the course of 131 days of infection. Nuclei were isolated from frozen serial biopsies and individually deposited into PCR microplates by flow sorting. Each nucleus was assayed by nested PCR for cccDNA and for cellular IFN-alpha genes as an internal control. We found that 90% of the nuclei assayed contained between 1 and 17 cccDNA molecules, with the remaining 10% containing more (90% confidence), and that differences in the mean number of copies and distribution of copy numbers occurred within the same animal at different times postinfection. Overall, the data suggest (i) that the number of cccDNA molecules per cell may fluctuate over time, and (ii) that, according to these fluctuations, a substantial fraction of cells may contain only one or a few copies. We infer from the results that infected hepatocytes express virus at different levels and that during cell division it is possible to segregate cells containing no cccDNA.