Drug-induced interstitial lung disease(DI-ILD)is the most common form of drug-induced pulmonary adverse events,with antican-cer drugs being the primary cause.DI-ILD first gained attention as a notable adverse event due to the use of antibody-drug conjugates(ADC).As the development of drugs,particularly ADCs,continues to expand and more ADCs are approved or nearing approved for clinical use,DI-ILD has become an area of growing concern.However,the mechanisms by which ADCs induce ILD remain unclear.This article reviews the mechanisms of DI-ILD in the most commonly used ADCs targeting human epidermal growth factor receptor 2(HER2).

Since the beginning of the 21st century, with the continuous development of anti-HER2-targeted drugs, more treatment options have been provided for patients with HER2-positive breast cancer and the survival prognosis has been significantly improved. At present, anti-HER2 targeted drugs mainly include monoclonal antibody drugs such as trastuzumab and pertuzumab, small molecule tyrosine kinase inhibitors such as lapatinib and neratinib, and antibody-drug conjugates such as TDM1 and T-DXd, which play an extremely important role in different disease processes. The treatment of HER2-positive breast cancer is based on targeted therapy with trastuzumab. Early-stage patients with high risk factors can be treated with intensive targeted therapy to further improve the prognosis, while advanced patients need a reasonable arrangement of targeted therapy to overcome drug resistance and prolong survival. This article will review the current status, the latest research progress and the future prospects of anti-HER2 targeted therapy in different stages of the disease.

Objective:To investigate the clinical efficacy of Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve.Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 404 patients with esophageal cancer who underwent Da Vinci robot-assisted esophagectomy in Tianjin Medical University Cancer Hospital and Institute from June 2017 to June 2022 were collected. There were 349 males and 55 females, aged (62±8)years. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) comparison of clinical features in patients who were admitted in different time periods. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the one way ANOVA. Measurement data with skewed distribution were represented as M(IQR), and comparison among multiple groups was conducted using the Kruskal-Wallis H test. Count data were described as absolute numbers or percentages, and com-parison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Intraoperative conditions. The operation time, volume of intraoperative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, left recurrent laryngeal nerve lymph node metastasis rate, right recurrent laryngeal nerve lymph node dissection rate, the number of right recurrent laryngeal nerve lymph node dissected, right recurrent laryngeal nerve lymph node metastasis rate were (306±56)minutes,200(100)mL, 29.9±13.1, 18.5±9.7, 78.47%(317/404), 4.0(3.0), 17.35%(55/317), 94.55%(382/404), 3.0(2.0), 21.20%(81/382). (2) Postoperative conditions. The tumor histopathological type (squamous cell carcinoma, neuroendocrine carcinoma, adenocarcinoma, carcinosarcoma, adenosquamous carcinoma, malignant melanoma), incidence rate of overall complications, cases with recurrent laryngeal nerve paralysis, cases with pulmonary complications, cases with anastomotic fistula, cases with incision infection, cases with chylothorax, cases with arrhythmia, cases with deep vein thrombosis, cases with other complications, incidence of re-admission to the intensive care unit, duration of postoperative hospital stay, 90-day mortality were 377, 11, 7, 5, 3, 1, 27.48%(111/404), 8.91%(36/404), 10.64%(43/404), 6.93%(28/404), 0.99%(4/404), 2.48%(10/404), 1.73%(7/404), 0.50%(2/404), 1.98%(8/404), 6.93%(28/404), 16(11)days, 0.50%(2/404). (3) Comparison of clinical features in patients who were admi-tted in different time periods. The number of patients who were admitted from June 2017 to May 2018, from June 2018 to May 2019, from June 2019 to May 2020, from June 2020 to May 2021, from June 2021 to June 2022 was 40, 56, 57, 116, 135, respectively. There were significant differences in age, tumor histopathological type, pT staging, neoadjuvant therapy, operation time, volume of intra-operative blood loss, the total number of lymph node dissected, the number of thoracic lymph node dissected, left recurrent laryngeal nerve lymph node dissection rate, the number of left recurrent laryngeal nerve lymph node dissected, the number of right recurrent laryngeal nerve lymph node dissected, incidence rate of overall complications among patients who were admitted in different time periods ( P<0.05). Conclusion:The Da Vinci robot-assisted superior mediastinum lymph node dissection around recurrent laryngeal nerve is safe and feasible, which can achieve good short-term efficacy.

Malignant tumor blood vessels,with phenotypes that are similar to high endothelial venules(HEVs)in secondary lymphoid or-gans(SLO),are known as tumor-associated high endothelial venules(TA-HEVs).The formation mechanism of TA-HEVs is similar to that of HEVs.Moreover,TA-HEVs play an important role in promoting the infiltration of lymphocytes into tumor tissues.With ongoing research,the positive effect of TA-HEVs in the context of radiotherapy,chemotherapy,immunotherapy,and antiangiogenic therapy is being elucidated.The clinical value is gradually becoming prominent,and the mechanisms and pathways involved with TA-HEVs are still under investigation.

Breast cancer is the malignancy with the highest number of new cases worldwide and is the leading cause of cancer-related deaths in women. More than 90% of breast cancer-related deaths are related to its metastasis. Paclitaxel, one of the most commonly used chemotherapeutic agents for the treatment of breast cancer, is an effective means of inhibiting breast cancer metastasis. To overcome the adverse effects of paclitaxel's hydrophobicity and its co-solvent, its nano-drugs have been a hot research topic. Some nanomedicines delivering paclitaxel have been used in clinical practice and have shown satisfactory efficacy and good tolerability. In this review, the research progress on the inhibition of breast cancer metastasis by co-delivered paclitaxel nanomedicines was summarized with the aim of providing a reference for their anti-breast cancer metastasis research.

Esophagectomy and lymph node dissection are the cornerstones for the treatment of esophageal cancer. Upper mediastinal lymph node dissection is of great value for accurate staging and improving the prognosis of patients. Lymph node dissection along the left recurrent laryngeal nerve is the most challenging procedures in esophageal surgery, and there has been no relevant consensus on the scope and boundary of lymph node dissection. In recent years, with the application of endoscopic technology, especially robotic surgery system in esophagectomy, and the introduction of the concept of superior mediastinal microdissection, the authors have proposed the border of lymph node dissection along the left recurrent laryngeal nerve, so as to achieve precise, radical and standardized dissection. Combined with their own experiences, the authors elaborate on the anatomic boundary, extent and technique of lymph node dissection along the left recurrent laryngeal nerve.

Breast cancer is one of the most common malignant tumors in women, and its incidence has increased year by year, which is one of the most important causes of death among women, especially young women. Studying related cell signal transduction that affects the development and progression of breast cancer can help prevent the occurrence of breast cancer, slow down the cancer progression and improve the prognosis of patients. nitric oxide (NO) is a kind of signaling molecule. Many studies have shown that the production and expression of NO are closely related to breast cancer. NO-related cell signal transduction significantly affects the occurrence and development of breast cancer. However, the understanding of the relationship between NO and breast cancer associated cell signal transduction needs to be further improved. In this paper, the related studies on NO-related cellular signal transduction in breast cancer were reviewed with a view to improving the understanding of the development and progression of breast cancer.

Objective To investigate the effect of the number of lymph nodes examined (NLNE) on the prognosis of esophageal squamous cell carcinoma (ESCC).Methods The retrospective case-control study was conducted.The clinicopathological date of 628 ESCC patients who underwent radical resection in the Tianjin Medical University Cancer Institute and Hospital from January 2005 to March 2013 was collected.Patients underwent radical resection of ESCC through right thorax.Observation indicators:(1) surgical and postoperative pathological examinations;(2) follow-up and survival situations;(3) effect of NLNE on the prognosis of ESCC;(4) factors analysis affecting prognosis of ESCC patients;(5) subgroup analysis.Follow-up using outpatient examination,telephone interview and mail was performed to detect postoperative survival up to February 2018.Measurement data with skewed distribution were described as M (range).Receiver operating characteristic (ROC) curve analysis was used to determine the appropriate cut-off of the NLNE.The survival curve and survival rate were respectively drawn and calculated by the Kaplan-Meier method,and the survival analysis was done by the log-rank test.Multivariate analysis was done by the Cox proportional hazard model.Results (1) Surgical and postoperative pathological examinations:472 and 156 patients underwent respectively Ivor-Lewis and Mckeown operations.There were 284 patients with tumor diameter ≤ 3.5 cm and 344 patients with tumor diameter ＞ 3.5 cm.The total NLNE was 11 139 for all of the 628 patients,with an average NLNE of 18 per case(range,2-78 per case) and a median NLNE of 16 per case.Of 628 patients,high-,moderate-and low-differentiated tumors were respectively detected in 48,469 and 111 patients;staging T0-1,T2,T3 and T4a of depth of tumor invasion in 30,119,260 and 219 patients;N0,N1,N2 and N3 of degree of lymph node metastasis in 349,173,69 and 37 patients;rN0,rN1,rN2 and rN3 of rate of lymph node metastasis in 349,184,54 and 41 patients.(2) Follow-up and survival situations:all the 628 patients were followed up for 3-144 months,with a median time of 36 months.The 1-,3-and 5-year survival rates were 82.4％,53.7％ and 41.3％,respectively.(3)Effect of NLNE on the prognosis of ESCC:ROC curve showed that the appropriate cut-off value of the NLNE was 16.Using NLNE =16 as a cut-off value,5-year survival rate was respectively 36.7％ in patients with NLNE ＜ 16 and 45.1％ in patients with NLNE ≥ 16,with a statistically significant difference in survival (x2 =9.527,P＜0.05).According to a median NLNE of 23,the patients with NLNE ≥ 16 were further divided into patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23.Results showed that 5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 36.7％,41.2％ and 50.3％,with a statistically significant difference in survival among them (x2 =10.588,P＜0.05),between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =4.419,P＜0.05).There was no statistically significant difference between patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23 (x2 =1.413,P＞0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞23 was respectively 38.6％ and 50.3％,with a statisctically significant difference (x2 =5.885,P＜0.05).(4)Factors analysis affecting prognosis of ESCC patients:results of univariate analysis showed that age,smoking history,BMI,tumor diameter,NLNE,depth of tumor invasion,degree and rate of lymph node metastasis were related factors affecting the prognosis of ESCC patients (x2 =5.454,4.875,7.669,10.691,10.588,30.612,59.780,76.565,P＜0.05).Results of muhivariate analysis showed that age,tumor diameter,NLNE,depth of tumor invasion and rate of lymph node metastasis were independent factors affecting the prognosis of ESCC patients [HR=1.268,1.300,0.762,1.354,1.357,95％ confidence interval (CI):1.034-1.556,1.038-1.629,0.662-0.878,1.183-1.549,1.089-1.692,P＜0.05].(5) Subgroup analysis:among 279 patients with lymph node metastasis,5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 23.7％,19.4％ and 39.5％,with a statistically significant difference among them (x2 =8.397,P＜0.05),between patients with 16≤ NLNE ≤ 23 and NLNE ＞ 23 (x2=5.425,P＜0.05).There was no statistically significant difference between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =0.389,P＞ 0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞ 23 was respectively 21.9％ and 39.5％,with a statisctically significant difference (x2=7.942,P＜ 0.05).Among 349 patients without lymph node metastasis,5-year survival rate in patients with NLNE ＜ 16,16 ≤ NLNE ≤ 23 and NLNE ＞ 23 was respectively 45.6％,60.3％ and 59.2％,with a statistically significant difference among them (x2 =9.755,P＜0.05) and between patients with NLNE ＜ 16 and 16 ≤ NLNE ≤ 23 (x2 =8.208,P＜0.05).There was no statistically significant difference between patients with 16 ≤ NLNE ≤ 23 and NLNE ＞ 23 (x2 =0.284,P＞0.05).Five-year survival rate in patients with NLNE ≤ 23 and NLNE ＞ 23 was respectively 51.1％ and 59.2％,with no statisctically significant difference (x2 =1.147,P＞ 0.05).Conclusions The NLNE is an independent factor affecting the prognosis of ESCC patients,and at least 16 to 23 lymph nodes should be dissected.For patients with lymph node metastasis,and more than 23 lymph nodes should be dissected.For patients without lymph node metastasis,more than 23 lymph nodes dissection cannot obviously improve the prognosis of patients.

OBJECTIVETo investigate the log odds of positive lymph nodes(LODDS) on the prognosis of patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy.

METHODSClinical data of 136 patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy from January 2005 to January 2009 were retrospectively analyzed. LODDS was estimated using the calculation: log(pnod+0.5)/(tnod-pnod+0.5), in which pnod indicates the number of positive lymph nodes and tnod indicates the total number of lymph nodes retrieved. The best cut-off value for LODDS was identified by using the receiver operating characteristic (ROC) curve. Drawing of survival curves was employed with the Kaplan-Meier estimator, and survival rate was analyzed using Log-rank test. The Cox proportional hazard model was used to identify independent factors associated with prognosis.

RESULTSA total of 136 patients, including 112 males and 24 females, seventy-nine patients were 65 years or older(range 27-92 years), and were included in the present study. Among them, the most cancer site was the middle third of the thoracic esophagus(115 cases), followed by the lower third(13 cases), and the upper third(8 cases). There were 70 patients with tumor diameter ≤3.5 cm and 66 patients with tumor diameter >3.5 cm. There were 32 patients with stage pT1-2, and 104 with stage pT3-4. The number of patients in TNM classification I, II and III was 14, 85 and 37, respectively. All the patients received radical esophagectomy with primary tumor resection and lymph node dissection. The median follow-up time was 44.2 months(range, 4.4-98.4 months). Five-year overall survival rate was 43.2%, and the median total survival time was 48 months. ROC analysis showed that the appropriate cut-off value of LODDS was -1.2. There were 99 patients with LODDS≤-1.2(LODDS1 stage), 37 patients with LODDS >-1.2(LODDS2 stage), the median survival time and 5-year survival rate were 56.5 months and 48.3% in patients with LODDS1 stage and 30.0 months and 29.7% in patients with LODDS 2 stage, respectively, with significant difference(χ(2)=4.980, P=0.026). Multivariate analyses showed that recurrence(HR=0.627, 95% CI:0.395 to 0.996; P=0.048) and LODDS >-1.2(HR=1.853; 95% CI:1.155 to 2.974; P=0.011) were the independent factors affecting the prognosis of patients.

CONCLUSIONSFor patients with node-negative squamous cell carcinoma of the thoracic esophagus after radical esophagectomy, LODDS stage has a unique prediction for prognosis, and patients with LODDS less than -1.2 (cut-off value) have a better prognosis.

Adult ; Aged ; Aged, 80 and over ; Carcinoma, Squamous Cell ; diagnosis ; surgery ; Esophageal Neoplasms ; diagnosis ; surgery ; Esophagectomy ; Female ; Humans ; Kaplan-Meier Estimate ; Lymph Node Excision ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Prognosis ; Proportional Hazards Models ; Retrospective Studies ; Survival Rate

OBJECTIVETo analyze the clinical features and risk factors of anastomotic leakage after radical esophagectomy of esophageal carcinoma.

METHODSThe clinical data of 547 esophageal cancer patients underwent radical esophagectomy in Tianjin Medical University Cancer Hospital from January 2012 to December 2013 was analyzed retrospectively. There were 421 male and 126 female patients, with a median age of 65 years (ranging from 29 to 82 years). There were 155 cases of upper esophageal carcinoma, 340 cases of middle esophageal carcinoma and 52 cases of lower esophageal carcinoma. The surgical procedures included 41 cases completed through Sweet, 145 cases completed through McKeown, 279 cases completed through Ivor Lewis, 82 cases completed through minimally invasive esophagectomy. Moreover, 24 of 547 cases underwent preoperative neoadjuvant radiochemotherapy. χ² test and Cox's proportional hazards regression model were used for univariate analysis and multivariate analysis of the risk factors of postoperative anastomotic leakage.

RESULTSTwenty-seven of 547 cases with esophagectomy occurred anastomotic leakage and the incidence rate was 4.94% (27/547). One of 27 cases died and the mortality rate was 3.70% (1/27). The time of anastomotic leakage found was 4 to 45 days, with a median time of 10 days. There were 0 case of early leakage, 20 cases of mid-term leakage, 7 cases of late leakage. Three of 27 cases with anastomotic leakage had tracheoesophageal fistula, while 3 cases had contralateral pleural fistula. As to the incidence rate of anastomotic leakage, there was statistically significant difference between cervical anastomotic leakage (8.14%, 18/221) and intrathoracic anastomotic leakage (2.76%, 9/326) (χ² =7.41, P=0.000), among Sweet (4.88%, 2/41), McKeown (9.66%, 14/145), Ivor Lewis (2.51%, 7/279) and MIE (4.88%, 4/82) (χ² =21.48, P=0.000), and between with (16.67%, 4/24) and without (4.40%, 23/523) neoadjuvant radiochemotherapy (χ² =9.20, P=0.000). The multivariate analysis showed that anastomotic site (HR=2.594, P=0.048), surgical approach (HR=5.689, P=0.003) and preoperative neoadjuvant radiochemotherapy (HR=3.604, P=0.027) are independent risk factors for anastomotic leakage after esophagectomy.

CONCLUSIONSThe mid-term anastomotic leakage after esophagectomy occurs higher. McKeown is a main surgical procedure and neoadjuvant radiochemotherapy is an important factor for the anastomotic leakage.

Adult ; Aged ; Aged, 80 and over ; Anastomotic Leak ; Carcinoma ; surgery ; Chemoradiotherapy ; Esophageal Neoplasms ; surgery ; therapy ; Esophagectomy ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Retrospective Studies ; Risk Factors