[The ninth edition of TNM staging for lung cancer: precise staging for precise diagnosis and treatment].

The ninth edition of TNM staging for lung cancer has been announced at the 2023 World Lung Cancer Congress and implemented from January 1, 2024. Te focus of the ninth TNM staging change is dividing N2 into N2a and N2b, as well as M1c into M1c1 and M1c2. Although the T staging has not changed, it has played an important role in verifying the eighth edition of the T staging. The subdivision of stage N2 has led some patients with ⅢA of the eighth edition to experience ascending or descending stages, which will more accurately help to assess the condition and prognosis of patients with mediastinal lymph node metastasis, as well as the design of related clinical studies. Modifying the M1c staging will help define oligometastasis and explore new treatment models in the future. The ninth edition of the TNM staging system provides a more detailed division of different tumor loads, but there is no clear explanation for the staging of lung cancer after neoadjuvant therapy. Further data analysis is needed, and it is expected to be answered in the tenth edition of TNM staging.

[Introduction to the 9th edition of TNM classification for lung cancer].

Lung cancer is the second commonly diagnosed cancer and remained the leading cause of cancer-related death, with an estimated 1.8 million deaths in 2020. The identification of driver gene mutation and administration of corresponding tyrosine kinase inhibitor have improved overall survival and quality of life in advanced lung cancer patients. Check point inhibitor has revolutionized treatment strategy of driver gene negative advanced NSCLC patients. TNM staging system is the most widely used classification method, providing an international common language during academic communication and important tool for predicting prognosis and subsequent treatment decision making. Accumulating knowledge about prognostic factors in lung cancer promotes the update of TNM classification. In the World Conference on Lung Cancer (WCLC) held in Singapore, September, 2023, International Association for Study of Lung Cancer (IASLC) released the forthcoming 9th edition of TNM classification for lung cancer, which is supposed to be adopted at January, 2024. The manuscript discussed the history, data resource and limitation of the TNM staging system.

[The role of neoadjuvant therapy in multimodality treatment of locally advanced esophageal squamous cell carcinoma: perspective from the NEOCRTEC5010 trial].

The efficacy of surgery alone for locally advanced esophageal cancer is poor, which requires the active participation of multimodality treatment. Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, could significantly lead to tumor downstage, bring higher radical resection rate and improve the prognosis. The NEOCRTEC5010 trial, a multicenter prospective randomized controlled trial on neoadjuvant chemoradiotherapy for locally advanced esophageal squamous cell carcinoma has provided sufficient and valuable evidence for us, especially for some key questions after neoadjuvant chemoradiotherapy, such as perioperative complications, value of systemic lymphadenectomy, the post-operation recurrence pattern, pathological complete response, long-term prognosis and survival. In addition, the current development of tumor immunotherapy is so rapid that the role of immunotherapy in the first line treatment of advanced or relapsed/metastatic esophageal cancer has been confirmed. In the near future, neoadjuvant therapy based on immunnology-led combined with traditional chemoradiotherapy or chemotherapy is expected to become a new theraputic strategy to further improve the treatment efficacy of locally advanced esophageal squamous cell carcinoma. This paper focused on the classical research of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma and the development of immunotherapy for esophageal cancer, aiming to improve the understanding of neoadjuvant therapy for locally advanced esophageal squamous cell carcinoma. This will help to carry out optimal clinical work and to design better clinical study.

[Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database].

Objective: To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China. Methods: A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014. Results: Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusions: The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

[Minimally invasive surgery for centrally located lung cancers].

Minimally invasive surgery helps enhance postoperative recovery and improve quality of life of the patients by minimizing surgical trauma and decreasing incisional pain. Minimally invasive pulmonary resection, including both video-assisted thoracoscopic surgery and robotic surgery, is mainly used for surgical management of peripheral early stage lung cancers. Because of tumor location, lymph node involvement, and treatment modalities, surgery for central lung cancers is often technically demanding. Open thoracotomy is still the dominant approach for these tumors, especially when complex procedures such as sleeve lobectomy or pneumonectomy are needed. With the advent of surgical techniques, minimally invasive techniques have started to be tried in treatment of central lung cancers. Initial results have proven their feasibility and safety in sleeve lobectomy and pneumonectomy, showing a great potential of minimally invasive surgery in the future. Further study is necessary to prove its functionally superiority and oncological equivalence to open surgery, so that more lung cancer patients could benefit for minimally invasive surgery.

Analysis of a registry database for esophageal cancer from high-volume centers in China.

Esophageal cancer has a high incidence among malignancies in China, but a comprehensive picture of the status of its surgical management in China has hitherto not been available. A nationwide database has recently been established to address this issue. METHOD: A National Database was setup through a network platform, and data was collected from 70 high-volume centers (>100 esophagectomies/per year) across China. Data was entered between January 2009 and December 2014, and was analyzed in June 2015 after a minimal follow-up of 6 months for all patients. 8181 patients with complete data who received surgery for primary esophageal cancer on the Database were included in the analysis. RESULT: In this series, there were 6052 males and 2129 females, with a mean age of 60.5 years (range: 22-90 years). The pathology in 95.5% of patients was squamous cell carcinoma. The pathological stage distribution was 1.2% in stage 0, 2.5% in Ia, 11.5% in Ib, 14.8% in IIa, 36.1% in IIb, 19.3% in IIIa, 8.3% in IIIb, 6.2% in IIIc. 1800 patients (22.0%) with locally advanced disease received preoperative neoadjuvant therapy and 3592 patients (43.9%) underwent postoperative adjuvant chemotherapy and/or radiotherapy. The esophagectomies were performed through left thoracotomy approach in 5870 cases (72.6%), through right chest approach in 2215 cases (27.4%) including right thoracotomy (21.3%) and VATS (6.1%). The 30-day postoperative mortality rate was 0.6% (43 patients), and the overall postoperative complication rate was 11.6% (951 patients). The 1-, 3-, and 5-year overall survival rates were 82.6%, 61.6%, and 52.9%, respectively. CONCLUSION: This National Registry Database from high-volume centers provides a comprehensive picture of surgical management for esophageal cancer in China for the first time. Squamous cell carcinoma predominates, but there is heterogeneity with respect to the surgical approach and perioperative oncologic management. Overall, surgical mortality and morbidity rates are low, and good survival rates have been achieved due to improvement of surgical treatment technology in recent years.

[Opportunities and challenges for Chinese thoracic surgery in the golden age].

With the emergence of new concepts and new technologies, the mode of diagnosis and treatment of thoracic surgery in China has changed greatly. Under this background, Chinese thoracic surgery ushered in its "golden age" . This paper expounds the new challenges of thoracic surgery in China from many aspects, and points out that with the advent of precision medicine and modern science and technology, thoracic surgery will continue to develop rapidly. We should seize the opportunity, further expand our advantages, and strive to create a new era of Chinese thoracic surgery.

Impact of hepatic encephalopathy on liver transplant waiting list mortality in regions with different transplantation rates.

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates.

Concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma: treatment results from a prospective observational study.

A prospective observational study was performed to evaluate the results of treatment with concurrent chemoradiotherapy (CCRT) in patients with cervical esophageal squamous cell carcinoma (CESCC). Patients had CESCC, no distant metastasis, were 18-75 years old, and had PS 0-2. Radiotherapy (RT) was administered as either three-dimensional conformal radiation therapy (3D-CRT) or intensity-modulated radiation therapy (IMRT) with a total dose of 60 Gy/30 fractions. All patients were treated with platinum-based doublet concurrent chemotherapeutic regimens. CCRT was followed by 2-3 cycles of consolidation chemotherapy. The endpoints were overall survival (OS), progression-free survival (PFS), toxicities, and failure patterns. Ninety-two patients were enrolled from March 2007 to July 2014. The median follow-up time was 34 months. For all patients, the 3-year OS was 49.8% (median OS: 36 months, 95% CI: 24.963-47.051), and the 3-year PFS was 42.1%, (median PFS: 25 months, 95% CI: 17.097-32.903). Treatment failures occurred in 54 patients, including 30 cases (32.6%) with locoregional failure alone, 14 cases (15.2%) with distant metastasis alone, and 10 cases (10.9%) with both locoregional failure and distant metastasis. There were 51 (55.4%) and 3 cases (3.3%) of grade 3 and grade 5 radiation esophagitis, respectively. One patient (1%) had grade 5 laryngeal edema. Overall, CCRT has tolerable acute toxicities, and this regimen is an option for the treatment of patients with CESCC.

Hemodynamic response to primary prophylactic therapy with nonselective ß-blockers is related to a reduction of first variceal bleeding risk in liver cirrhosis: a meta-analysis.

The current primary prophylaxis for esophageal variceal bleeding in cirrhotic patients consists of nonselective ß-blocker (NSBB) therapy. However, only approximately half of the patients achieve a sufficient hemodynamic response to NSBB therapy. Clinical application of hemodynamic response monitoring is still under debate. The aim of this meta-analysis is to assess the potential clinical value of monitoring the hemodynamic response to NSBB therapy using hepatic venous pressure gradient (HVPG) measurements in the primary prophylaxis for variceal bleeding. A systematic literature search was performed in PubMed, Embase, Web of Science, and the COCHRANE Library. Randomized-controlled trials and case series that included cirrhotic patients receiving primary prophylaxis for variceal bleeding with NSBBs and hemodynamic response monitoring using HVPG measurements were included for analysis. The primary outcome measure was variceal bleeding. A fixed-effect analysis was carried out using the Mantel-Haenszel method for relative risks. Six of the 1172 papers found were selected on the basis of stringent selection criteria. Hemodynamic response (HVPG ≤12 mmHg and/or a reduction of ≥20%, or ≥10% in one study, from baseline) to ß-blocker therapy was associated significantly with a lower risk of variceal bleeding (relative risk=0.13, 95% confidence interval=0.06-0.29) compared with a nonresponse. Patients achieving a hemodynamic response to NSBB therapy have a lower risk of variceal bleeding than hemodynamic nonresponders. Hemodynamic monitoring in primary prophylaxis is of potential clinical value and requires further assessment in large cohort randomized-controlled trials.

Copeptin as an Indicator of Hemodynamic Derangement and Prognosis in Liver Cirrhosis.

BACKGROUND: Advanced liver cirrhosis is associated with systemic hemodynamic derangement leading to the development of severe complications associated with increased mortality. Copeptin is a stable cleavage product of the precursor of arginine vasopressin, a key-regulator in hemodynamic homeostasis. Copeptin is currently considered a reliable prognostic marker in a wide variety of diseases other than cirrhosis. The present study aimed to assess copeptin, both experimentally and clinically, as a potential biomarker of hemodynamic derangement and to evaluate its prognostic significance in cirrhosis. MATERIALS AND METHODS: Two studies were executed: 1) in 18 thioacetamide-induced cirrhotic rats and 5 control rats, plasma copeptin and hemodynamic measurements were performed, 2) in 61 cirrhotic patients, serum copeptin concentration was measured in samples collected at time of registration at the waiting list for liver transplantation. In 46 patients, also a second copeptin measurement was performed during follow-up while registered at the waiting list for liver transplantation. To determine the association of serum copeptin and clinical data with outcome, Cox proportional hazard regression analysis and Kaplan Meier analysis were performed. RESULTS: Plasma copeptin concentration was significantly higher in cirrhotic rats than in controls (1.6 ± 0.5 vs. 0.9 ± 0.1 pmol/L, p< 0.01) and was negatively correlated to the mean arterial blood pressure (r = -0.574, p = 0.013). In cirrhotic patients, serum copeptin concentration was high [11.0 (5.2-24.0) pmol/L] and increased significantly during the time of registration at the waiting list for liver transplantation. MELD and MELD-sodium score were significantly correlated to serum copeptin [MELD: (r = 0.33, p = 0.01), MELD-sodium: (r = 0.29, p = 0.02)], also at time of the second copeptin measurement [MELD and MELD-sodium: r = 0.39, p< 0.01]. In cirrhotic humans, serum copeptin concentration was significantly associated with outcome, independently of the MELD and MELD-sodium score. Patients with a low serum copeptin concentration at time of registration at the liver transplant waiting list had significantly better transplant-free survival rates at 3, 6 and 12 months of follow-up as compared to those with a high serum copeptin concentration (Log-rank: p< 0.01, p< 0.01 and p = 0.02 respectively). CONCLUSIONS: Circulating copeptin levels are elevated in rats and humans with cirrhosis. Copeptin is independently associated with outcome in cirrhotic patients awaiting liver transplantation.

Analysis of trends in water quality: constructed wetlands in metropolitan Taipei.

Meandering through the most densely populated metropolitan areas of Taipei, Taiwan, the Danshui River and its tributaries have undergone the construction of 14 wetlands since 2004, as a means to improve water quality. This study was conducted to examine the functional capabilities associated with treating non-point source pollution through these riparian wetlands. Trend analysis was used to differentiate dissolved oxygen, biochemical oxygen demand, suspended solids, ammonia, and Escherichia coli, among 13 sampling sites using both functions of a Mann-Kendall test and a seasonal Mann-Kendall test. The results show that water quality in Taipei metropolitan rivers has been improving since increasing the number of constructed wetlands and connecting households to the public sewage system. The concentration of pollutants such as those influencing biochemical oxygen demand have gradually declined in drought seasons because riparian wetlands contribute a base flow to dilute riverine pollutants. This paper indicates that the creation of treatment systems influences dissolved oxygen conditions at the municipal scale, suggesting that constructed wetlands could stabilize water quality during extreme hydrological events and improve water quality particularly in times of drought.

Selective three-field lymphadenectomy for thoracic esophageal squamous carcinoma.

The purpose of this study was to examine metastasis in different nodal stations and the extent of lymphadenectomy for esophageal carcinoma. Eighty-seven thoracic esophageal squamous carcinoma patients underwent esophagectomy with two-field or three-field lymphadenectomy based on cervical ultrasonography. Thirty-five patients (40.2%) with ultrasonography-detected cervical nodes underwent cervical dissection. Significantly more patients with primary tumors in the upper thoracic esophagus had cervical dissection than patients with tumors in the middle and lower esophagus (66.7%vs. 30.2%, P=0.002). Metastasis to cervical, superior mediastinal, mid-mediastinal, and abdominal nodes were 19.5%, 25.3%, 23%, and 24.1%, respectively. Cervical metastasis was 29.2%, 20.8%, and 10% for upper, middle, and lower thoracic esophageal tumors. Regional lymphadenopathy was found in 48 patients (55.2%) and was significantly related to cervical metastasis (31.3%vs. 5.1%, P=0.002). It was significantly less in upper (37.5%) than in middle (62.3%) and lower (60%) thoracic esophageal tumors (P=0.041). When cervical metastasis was included into regional lymphadenopathy, the difference was no longer significant (45.8%vs. 63.5%, P=0.135). Cervical dissection was associated with significantly more morbidities (60%vs. 34.6%, P=0.020), especially recurrent laryngeal nerve palsy (22.9%vs. 9.6%, P=0.089). Recurrent laryngeal nerve palsy was related significantly to anastomotic leakage (53.8%vs. 13.5%, P=0.001). There was no significant difference between the 2-year survivals for patients with or without cervical metastasis (50.0 vs. 72.0%, P=0.094). We conclude that cervical metastasis is of a similar rate as metastasis to mediastinal or abdominal nodes. Cervical nodes should be taken as regional lymph nodes for thoracic esophageal cancer. Cervical dissection is associated with increased morbidity and should be reserved for patients who may benefit from the procedure. Selective three-field dissection based on ultrasonography is helpful in reducing surgical morbidity while increasing the completeness of resection.

[Iodine deficiency induces thyroid cancer in rats and mice].

Wistar rats and Km mice were fed with a normal diet or a diet deficient in iodine (0.12 micrograms/l iodide in drinking water and 195.3 micrograms/kg iodide in the grain, collected from an iodine deficient area). The animals were sacrificed at 4, 7 and 12 months, one-third of the animals for each, respectively, after initiation of the experiment. It was found that, under iodine deficiency, the thyroid gland increased in weight with marked epithelial hyperplasia of the follicles, and nodular, diffuse goiter, epithelial atypia which eventually progressed to carcinoma in 19 (8 rats and 11 mice) of the 122 animals studied. Histologically, papillary carcinoma was observed in 14 and follicular carcinoma in 5. No malignant tumor developed in animals on normal iodine intake. Moreover, there was marked hyperplasia of basophilic cells in the anterior pituitary with an increase in serum thyroid stimulating hormone (TSH) level. The results suggest that, the development of thyroid carcinoma is the result of feedback hypersecretion of TSH in response to hypofunction of the thyroid gland due to iodine deficiency.