Comparison of indocyanine green-near-infrared fluorescence guided and traditional mediastinal lymphadenectomy during radical esophagectomy: A randomized controlled trial.

BACKGROUND: The extent of lymph node dissection during radical esophagectomy remains a controversial topic. Thus, this study mainly aimed to explore the location of sentinel lymph nodes in esophageal squamous cell carcinoma and the application value of the indocyanine green-near-infrared fluorescence system in lymphadenectomy. METHODS: This randomized controlled clinical trial (ClinicalTrials.gov, NCT04615806) included 42 participants without neoadjuvant therapy who were lymph node negative based on positron emission tomography/computed tomography findings. Traditional esophagectomy with indocyanine green-near-infrared fluorescence imaging was performed after injecting 0.5 mL indocyanine green (1.25 mg/mL) into the esophageal submucosa in the 4 peritumoral quadrants. The primary endpoint was to determine the location of the sentinel lymph node in esophageal squamous cell carcinoma based on postoperative pathologic reports. RESULTS: A total of 40 patients, with 20 in each group, were included in the final analysis. In the indocyanine green group, indocyanine green-near-infrared fluorescence imaging was successful in all subjects. Seven cases (cases 2, 3, 9, 11, 17, 18, and 20) in the indocyanine green group exhibited lymph node metastases, all of which were near-infrared positive. The detection rate, positive predictive value, negative predictive value, sensitivity, and specificity were 100% (20 of 20 cases), 8.7% (13/150), 100% (265/265), 100% (13/13), and 65.9% (265/402), respectively. All near-infrared-negative lymph nodes were nonmetastatic lymph nodes. In addition, the number of mediastinal lymph nodes resected in the indocyanine green group was significantly higher than in the non-indocyanine green group. CONCLUSION: Indocyanine green-near-infrared might be an important and promising technique in predicting sentinel lymph nodes of esophageal squamous cell carcinoma and could significantly improve the detection rate of lymph nodes of esophageal squamous cell carcinoma.

Safety and efficacy of camrelizumab combined with radiotherapy as neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma: a prospective single-arm phase II clinical trial protocol.

BACKGROUND: Neoadjuvant chemoradiotherapy followed by esophagectomy is the standard of care for locally advanced esophageal squamous cell carcinoma (ESCC). However, approximately 30% of patients still develop distant metastases and have a high incidence of treatment-related adverse events. Immunotherapy, as a new modality for anti-cancer treatment, has shown promising clinical benefits for patients with ESCC. The synergistic effects of immunotherapy and radiotherapy make their combination promising as neoadjuvant treatment for locally advanced ESCC. METHODS: All participants who meet the inclusion criteria will be enrolled after signing the informed consent form. Patients with thoracic segment esophageal cancer with clinical stage T2-3 N0 M0 or T2-3 N + M0 will be included. A total of 25 patients are to be recruited for the study. Twelve patients will be recruited in phase I, with at least two achieving major pathological response (MPR) before entering phase II. They will be treated with radical surgery within 4-8 weeks after the completion of two cycles of neoadjuvant radiotherapy in combination with camrelizumab according to the study schedule. The primary endpoint is the major pathological remission rate of all per-protocol patients. The secondary endpoints are the R0 resection rate, pathological complete remission rate, and adverse events. The interim analysis will be conducted after 12 patients have been enrolled. The trials will be terminated when more than two treatment-related deaths occur or fewer than five patients have major pathological remission. DISCUSSION: We designed this prospective single-arm phase II clinical study to evaluate the combination of camrelizumab and standard radiotherapy as preoperative neoadjuvant therapy for patients with resectable ESCC as part of the quest for better treatment options for patients with locally advanced ESCC. TRIAL REGISTRATION: This trial protocol has been registered on the NIH Clinical Trials database ( www. CLINICALTRIALS: gov/ , NCT05176002. Registered on 2022/01/04). The posted information will be updated as needed to reflect protocol amendments and study progress.

Learning curve analysis of single-port thoracoscopic combined subsegmental resections.

Background: Combined subsegmental surgery (CSS) is considered to be a safe and effective resection modality for early-stage lung cancer. However, there is a lack of a clear definition of the technical difficulty classification of this surgical case, as well as a lack of reported analyzes of the learning curve of this technically demanding surgical approach. Methods: We performed a retrospective study of single-port thoracoscopic CSS performed by the same surgeon between April 2016 and September 2019. The combined subsegmental resections were divided into simple and complex groups according to the difference in the number of arteries or bronchi which need to be dissected. The operative time, bleeding and complications were analyzed in both groups. Learning curves were obtained using the cumulative sum (CUSUM) method and divided into different phases to assess changes in the surgical characteristics of the entire case cohort at each phase. Results: The study included 149 cases, including 79 in the simple group and 70 in the complex group. The median operative time in the two groups was 179 min (IQR, 159-209) and 235 min (IQR, 219-247) p < 0.001, respectively. And the median postoperative drainage was 435 mL (IQR, 279-573) and 476 mL (IQR, 330-750), respectively, with significant differences in postoperative extubation time and postoperative length of stay. According to the CUSUM analysis, the learning curve for the simple group was divided by the inflection point into 3 phases: Phase I, learning phase (1st to 13th operation); Phase II, consolidation phase (14th to 27th operation), and Phase III, experience phase (28th to 79th operation), with differences in operative time, intraoperative bleeding, and length of hospital stay in each phase. The curve inflection points of the learning curve for the complex group were located in the 17th and 44th cases, with significant differences in operative time and postoperative drainage between the stages. Conclusion: The technical difficulties of the simple group of single-port thoracoscopic CSS could be overcome after 27 cases, while the technical ability of the complex group of CSS to ensure feasible perioperative outcomes was achieved after 44 operations.

"Separated" precise subsegmentectomy: Single-port thoracoscopic noncombined subsegmentectomy in one lung lobe.

BACKGROUND: In clinical practice, combined segmental resection (CSS) can avoid resection of multiple segments to preserve lung function. When two or more distant lung segments or subsegments of the same lobe present with a ground glass opacity (GGO) that meets the indications for sublobar resection, conventional CSS or wedge resection could not remove all the nodules, and lobectomy is performed in most of these patients. For these particular types of nodules, we perform a single lobe noncombined subsegmental resection, or "separated" precise subsegmentectomy, to preserve more lung tissue. This study was designed to initially assess the feasibility and safety of "separated" precise subsegmentectomy. METHODS: Selected cases of specific GGO were subjected to "separated" precise subsegmentectomy and the results of general clinical data, perioperative operative time, bleeding, length of stay, computed tomography (CT) review, lung function and its dynamic changes were collected and analyzed in these patients. RESULTS: "Separated" precise subsegmentectomy was performed in 12 patients and successfully completed. The median operation time, bleeding amount, and length of hospital stay were 96 min, 50 ml and 4 days, respectively. There was one case of pulmonary infection and one case of persistent air leakage, no death or pulmonary torsion, bronchopleural fistula and other pulmonary complications occurred. After 3 months, the median percentage of lung function retention was 91.7%, and the CT scan showed that the reserved lung tissue of 12 patients was well inflated and there was no obvious imaging manifestation of atelectasis. CONCLUSION: "Separated" precise subsegmentectomy is a novel and safe surgical method that provides a more optimized way for patients with specific multiple nodules to preserve lung function. Further prospective large studies are needed to verify this finding.

Comparative analysis of electromagnetic navigation bronchoscopy versus computed tomography-guided lung puncture for the sampling of indeterminate pulmonary nodules in the middle of an anatomic lung segment: A cohort study.

BACKGROUND: To compare the diagnostic positive rate and complication rate between the electromagnetic navigation bronchoscopy (ENB) technique and computed tomography (CT)-guided lung puncture for the biopsy of lung nodules located in the middle of an anatomic lung segment. METHODS: Electronic medical records of 114 patients who underwent lung nodule biopsy between June 2021 and June 2022 were retrospectively evaluated. In all patients, the nodules were located in the middle third lung segment. To compare the diagnostic positive and complication rates between the two biopsy modalities performed in this lung region, clinical data, complication rates, nodule pathology, and imaging results were reviewed based on nodule characteristics retrieved from the electronic medical records. RESULTS: Ninety-three patients underwent CT-guided lung puncture, while the remaining 21 patients underwent the ENB technique. No significant difference was observed in the diagnostic positive rate between the two groups (73.6 and 76.1%, respectively). In the CT-guided lung puncture group, pneumothorax incidence, tube placement, postoperative hemorrhage, and symptomatic hemorrhage rates were 16.1, 6.5, 6.5, and 1.1%, respectively. In contrast, no complications occurred in the ENB group. CONCLUSIONS: The ENB technique is a safe and effective method for performing biopsies of pulmonary nodules with a diagnostic positive rate comparable to that of CT-guided lung puncture and with a lower postoperative complication rate.

Immunochemotherapy includes pembrolizumab for stage IIIB lung squamous cell carcinoma: a case report.

Background: Lung cancer is a malignant tumor with high morbidity and mortality, and its incidence continues to increase. With the emergence of new drugs and treatment modalities, the prognosis of lung cancer patients has improved to some extent. However, the prognosis of initially unresectable, locally advanced lung cancer with immunotherapy combined with chemotherapy remains uncertain. Case Description: We report a case of a 57-year-old man diagnosed with stage IIIB la with negative targeted therapy-related gene mutation and a 2% programmed death 1/programmed cell death-ligand 1 (PD-1/PD-L1) expression level, who underwent transformation treatment with pembrolizumab after multidisciplinary consultation. Lung images indicated partial response after 4 cycles. However, preoperative examination found hypothyroidism considered the immune-related, and giving hormone replacement treatment after the endocrinology department consultation. Thyroid function improved after 1 month. The patient successfully underwent single-hole thoracoscopic radical lung cancer (left whole lung resection + mediastinal lymph node dissection). Postoperative pathology was consistent with major pathological remission (MPR). The patient was scheduled to receive 8 cycles of single-drug maintenance therapy with pembrolizumab after surgery. To date, no tumor recurrence and metastasis have been found at follow up, and maintenance treatment continues to improve. Conclusions: This case reminds us that the induction treatment pattern of pembrolizumab combined with chemotherapy for subsequent conversion surgery can be a potentially curative treatment option for locally advanced stage IIIB patients. The monitoring of thyroid-related indicators is important during immunotherapy, especially in the first 1-2 months. The cause of thyroid dysfunction should be detected early so that it can be treated promptly to improve the prognosis of the patient. Pembrolizumab in combination with paclitaxel and platinum drugs provides a new option for patients with locally advanced stage IIIB lung squamous cell carcinoma who eager to undergo radical surgery.

A novel form of precise segmentectomy-Triumphal arch-like anatomical segmentectomy.

The increasingly accurate sublobar anatomical resection is constantly being explored and practiced. Surgeons try to preserve as much viable lung tissue as possible. Sublobar resection of the target tissue is similar with a cone-shaped structure which penetrates deeply into the pulmonary parenchyma and runs through the lobe at both ends. This has not previously been described. The remaining lung tissue resembles the Triumphal Arch in Paris, France. Here, we describe triumphal arch-like sublobectomy in detail, aiming to provide clinicians with an idea to explore this novel sublobectomy under similar conditions.

The clinical characteristics, treatments and prognosis of post-esophagectomy airway fistula: a multicenter cohort study.

Background: Post-esophagectomy airway fistula (PEAF) is a serious complication after esophageal cancer resection. At present, the clinical characteristics, treatments and prognosis of PEAF patients remain inconclusive. We aimed to investigate these problems of patients with PEAF through a multi-center retrospective cohort study. Methods: We included consecutive patients who underwent esophagectomy for esophageal cancer in seven major Chinese esophageal cancer centers from January 2010 to December 2020. Based on the anatomic characteristics of PEAF patients, PEAFs were divided into Union type I (without digestive fistula) and Union type II [respiratory-digestive fistula (RDF)], and subtypes a and b (tracheal or bronchial fistulas), as well as L1 and L2 (same or different level of fistulas). The clinical characteristics, diagnoses, managements, and effects of the various types were retrospectively analyzed. Results: PEAF occurred in 85 of 26,608 patients (0.32%), including eight females and 77 males. There were 16 patients with type I and 69 with type II. The numbers of healings, non-healings, and deaths at discharge were 45 (52.9%), 20 (23.5%), and 20 (23.5%), respectively. Type Ib was common in type I, and type II L1 was common in type II. The healing rates of surgical, stent, and conservative treatments were 50%, 60%, and 50%, respectively. All type I patients treated with stent implantation were healed at discharge. The healing rates, mortality, and 3-year survival of type II L1 and type II L2 patients were 55.4% and 30.8%, 17.9% and 30.8%, and 34.3% and 15.4%, respectively. The 5-year survival rates of all PEAFs were 21.1%. Conclusions: PEAF is an infrequent and life-threatening complication after esophagectomy. Patients with different types of PEAF often have different inducements. In this study, we found that the healing rates of surgical and conservative treatments were similar, and stent implantation may have the potential to improve efficacy. Type II L2 patients were the most difficult to cure.

Combined Analysis of the Aberrant Epigenetic Alteration of Pancreatic Ductal Adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) remains one of the most fatal malignancies due to its high morbidity and mortality. DNA methylation exerts a vital part in the development of PDAC. However, a mechanistic role of mutual interactions between DNA methylation and mRNA as epigenetic regulators on transcriptomic alterations and its correlation with clinical outcomes such as survival have remained largely uncovered in cancer. Therefore, elucidation of aberrant epigenetic alteration in the development of PDAC is an urgent problem to be solved. In this work, we conduct an integrative epigenetic analysis of PDAC to identify aberrant DNA methylation-driven cancer genes during the occurrence of cancer. METHODS: DNA methylation matrix and mRNA profile were obtained from the TCGA database. The integration of methylation and gene expression datasets was analyzed using an R package MethylMix. The genes with hypomethylation/hypermethylation were further validated in the Kaplan-Meier analysis. The correlation analysis of gene expression and aberrant DNA methylation was also conducted. We performed a pathway analysis on aberrant DNG methylation genes identified by MethylMix criteria using ConsensusPathDB. RESULTS: 188 patients with both methylation data and mRNA data were considered eligible. A mixture model was constructed, and differential methylation genes in normal and tumor groups using the Wilcoxon rank test was performed. With the inclusion criteria, 95 differential methylation genes were detected. Among these genes, 74 hypermethylation and 21 hypomethylation genes were found. The pathway analysis revealed an increase in hypermethylation of genes involved in ATP-sensitive potassium channels, Robo4, and VEGF signaling pathways crosstalk, and generic transcription pathway. CONCLUSION: Integrated analysis of the aberrant epigenetic alteration in pancreatic ductal adenocarcinoma indicated that differentially methylated genes could play a vital role in the occurrence of PDAC by bioinformatics analysis. The present work can help clinicians to elaborate on the function of differentially methylated expressed genes and pathways in PDAC. CDO1, GJD2, ID4, NOL4, PAX6, TRIM58, and ZNF382 might act as aberrantly DNA-methylated biomarkers for early screening and therapy of PDAC in the future.

Association between cadmium exposure and diabetes mellitus risk: a prisma-compliant systematic review and meta-analysis.

Cadmium (Cd) is a pollutant with multiple adverse health effects: cancer, renal dysfunction, osteoporosis and fracture, and cardiovascular disease. Several population-based studies found an association between Cd and diabetes mellitus (DM), but this association is inconsistent with other research. We conducted meta-analysis to examine relationship between urinary/blood Cd exposure and DM risk. Pertinent studies were identified by searching PubMed and Embase databases, and combined odds ratio (OR) and corresponding 95% confidence interval (CI) were applied to evaluate said association. Meta-analysis showed that high U-Cd exposure is not correlated with DM risk (OR = 1.19; 95% CI = 0.83-1.71), and high B-Cd exposure is also not associated with increased risk of DM (OR = 1.16; 95% CI = 0.84-1.62) in the general population. Subgroup and sensitivity analysis proved similar results, with little evidence of publication bias. This meta-analysis suggests that high U-Cd/B-Cd exposure may not be risk factor for DM in general populations. However, large prospective studies are needed to confirm this finding.

Association between tooth loss and risk of oesophageal cancer: a dose-response meta-analysis.

Many epidemiological studies have found that tooth loss is associated with susceptibility to oesophageal cancer. However, a definitive answer is yet to be discovered, and the findings are inconclusive. We performed a meta-analysis to assess the relationship between tooth loss and oesophageal cancer risk. We searched PubMed and Embase databases to screen eligible studies up to June 2015. Nine observational studies (eight articles) involving 2604 patients and 113,995 participants were included in the meta-analysis. The combined odds ratio for tooth loss and oesophageal cancer was 1.53 (95 % CI 1.02-2.29) for the high versus lowest teeth loss categories. However, inconsistent results were detected in the stratified and sensitivity analysis. In dose-response analysis, the summary odds ratio for each one tooth loss increment was 1.01 (95 % CI 1.00-1.02). The current evidence, based solely on six case-control studies and three cohort studies, suggests that tooth loss is a potential marker of oesophageal cancer. However, no firm conclusion can be drawn at this time that tooth loss may play a causal role in development of oesophageal cancer. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of oesophageal cancer.

Association between Tooth Loss and Gastric Cancer: A Meta-Analysis of Observational Studies.

Observational studies showed that tooth loss is associated with gastric cancer, but the findings are inconsistent. In this study, a meta-analysis was conducted to evaluate the relationship between tooth loss and gastric cancer. Relevant studies were screened in PubMed and Embase databases, and nine observational studies were considered eligible for the analysis. The combined relative risks for the highest versus the lowest categories of tooth loss were 1.86 (95% CI: 1.08-3.21) and 1.31 (95% CI: 1.12-1.53) in case control and cohort studies, respectively. However, unstable results were observed in the stratified and sensitivity analysis. The current evidence, based solely on four case-control studies and five cohort studies, suggested that tooth loss is a potential marker of gastric cancer. However, we can not concluded at this time that tooth loss may be a risk factor for gastric cancer due to significant heterogeneity among studies and mixed results between case-control studies and cohort studies. Additional large-scale and high-quality prospective studies are required to evaluate the association between tooth loss and risk of gastric cancer.

Cadmium Exposure and Risk of Any Fracture: A PRISMA-Compliant Systematic Review and Meta-Analysis.

Several observational studies have investigated the relation between cadmium exposure and risk of any fracture. However, the results from epidemiological studies for the association are inconsistent.We conducted a meta-analysis to evaluate the relationship between cadmium exposure and risk of any fracture. The pertinent studies were identified by a search of PubMed and Embase databases from 1966 to June 2015.Seven articles involving 21,941 fracture cases and 504,346 participants were included. The meta-analysis showed that the pooled relative risk of any fracture for the highest versus lowest category of cadmium concentration was 1.30 (95% confidence interval = 1.13-1.49). In subgroup analyses, the significant association remained consistent when stratified by study type, geographical region, method of cadmium exposure assessment, and gender.Our meta-analysis showed that a high cadmium exposure may be a risk factor for any fracture. However, this result should be interpreted cautiously because of the heterogeneity among studies and existence of publication bias. Additional large, high-quality prospective studies are needed to evaluate the association between cadmium exposure and the risk of development of fracture.

Exposure to ionizing radiation during dental X-rays is not associated with risk of developing meningioma: a meta-analysis based on seven case-control studies.

BACKGROUND: Many observational studies have found that exposure to dental X-rays is associated with the risk of development of meningioma. However, these findings are inconsistent. We conducted a meta-analysis to assess the relationship between exposure to dental X-rays and the risk of development of meningioma. METHODS: The PubMed and EMBASE databases were searched to identify eligible studies. Summary odds ratio (OR) estimates and 95% confidence intervals (95% CIs) were used to compute the risk of meningioma development according to heterogeneity. Subgroup and sensitivity analyses were performed to further explore the potential heterogeneity. Finally, publication bias was assessed. RESULTS: Seven case-control studies involving 6,174 patients and 19,459 controls were included in the meta-analysis. Neither exposure to dental X-rays nor performance of full-mouth panorex X-rays was associated with an increased risk of development of meningioma (overall: OR, 0.97; 95% CI, 0.70-1.32; dental X-rays: OR, 1.05; 95% CI, 0.89-1.25; panorex X-rays: OR, 1.01; 95% CI, 0.76-1.34). However, exposure to bitewing X-rays was associated with a slightly increased risk of development of meningioma (OR, 1.73; 95% CI, 1.28-2.34). Similar results were obtained in the subgroup and sensitivity analyses. Little evidence of publication bias was observed. CONCLUSION: Based on the currently limited data, there is no association between exposure to dental X-rays and the risk of development of meningioma. However, these results should be cautiously interpreted because of the heterogeneity among studies. Additional large, high-quality clinical trials are needed to evaluate the association between exposure to dental X-rays and the risk of development of meningioma.

Association between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphisms and esophageal cancer risk: A meta-analysis.

Many observational studies have found that microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 are associated with esophageal cancer risk. However, the results were mixed and inconsistent among these studies. We conducted a meta-analysis to assess the relationship between the polymorphisms of three microRNAs and esophageal cancer susceptibility. We systematically searched the PubMed and EMBASE databases to screen relevant studies. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to compute the risk of esophageal cancer. Because of the differences in ethnicities, sources of controls, and genotyping methods, the meta-analysis was conducted using a random-effect model regardless of heterogeneity. To further explore potential heterogeneity, we performed subgroup and sensitivity analyses, and publication bias was also evaluated. A total of 6 case-control studies on microRNA-196a2 rs11614913, 4 studies on microRNA-146a rs2910164, and 4 studies on microRNA-423 rs6505162 were considered eligible in the meta-analysis. No statistical association was found between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphisms and esophageal cancer susceptibility in any genetic model. Subgroup and sensitivity analyses showed similar results. In summary, based on the currently limited proof, no association exists between microRNA-196a2 rs11614913, microRNA-146a rs2910164, and microRNA-423 rs6505162 polymorphism and esophageal cancer risk. However, the result should be cautiously interpreted because of the heterogeneity among studies. Large, high quality clinical trials are required to verify our findings.