CALGB140503 study: Is sublobectomy the standard procedure for early peripheral lung cancer? / 中国胸心血管外科临床杂志

@#While lobectomy is the standard surgical procedure for early-stage non-small cell lung cancer (NSCLC), sublobectomy (segmentectomy/wedge resection) has been gaining progress in early-stage peripheral NSCLC in recent years because it preserves more lung parenchyma and has the advantages of good postoperative lung function, relatively less trauma, and faster recovery. However, there has been a lack of standardized randomized clinical trials to study the survival benefits of sublobectomy. The results of a high-profile study from the USA, CALGB140503, have been the subject of intense industry debate since its presentation at the 2022 World Conference on Lung Cancer (IASLC WCLC 2022). The study, which was published in The New England Journal of Medicine on February 9, 2023, was designed to investigate whether sublobectomy was not inferior to lobectomy in terms of survival in patients with early-stage peripheral NSCLC (tumor diameter≤2 cm). The results showed that sublobectomy was not worse than lobectomy for survival in patients with T1aN0M0 peripheral NSCLC with tumor diameter≤2 cm and pathologically confirmed negative hilar and mediastinal lymph nodes. Sublobectomy, including anatomical segmentectomy and wedge resection is an effective NSCLC treatment. The results of this study provide strong evidence for the improved outcomes of sublobectomy in terms of lung function protection and are expected to promote the further use of sublobectomy. However, given the limitations of this study, whether sublobectomy, especially wedge resection, can become a standard procedure still needs to be explored. This paper presents an interpretation of this study and we invite experts in the field to discuss its usefulness in guiding clinical practice and summarise its limitations.

Study on HO-1 expression in hunman esophageal carcinoma and correlates with chemotherapy sensitivity of fluorouracil / 重庆医学

Objective To explore the HO-1 expression levels with 5-FU chemosensitivity in esophageal squamous cell carcinoma.Methods Eca109 cells used in all experiments,MTT assay was used in cell growth curve and inhibit rate.RT-PCR and Western blot was used to detect HO-1 in cells treated with different concentrations of ZnppⅨ (0,20,80,100 μmol/L).Results The inhibitory rate of cells was significantly increased when the concentrition of ZnppⅨ increased.The inhibitory rate of cells in 80 μmol/L ZnppⅨ was higher than 20 μmol/L ZnppⅨ group(P＜0.05).The expression of HO-1 mRNA in each group was 0.50± 0.17,0.55±0.15,0.58 ± 0.09 and 0.55 ± 0.16,respectively,there was no significant difference between the two groups (P＞ 0.05).The expression of HO-1 was 0,85±0.07,0.63±0.11,0.43±0.12 and 0.25±0.10,respectively.The expression of HO-1 had significant difference (F=20.01,P＜0.01).Conclusion Eca109 cells inhibition rate positive correlated with ZnppⅨ concentrations,and ZnppⅨ were inhibited the expression of HO-1.not from gene level,but after the translation level.

Clinical effect of preoperative neoadjuvant chemoradiotherapy plus esophagectomy in treatment of locally advanced esophageal cancer / 中华放射肿瘤学杂志

Objective To evaluate the tolerance of preoperative neoadjuvant chemoradiotherapy (neoCRT) plus esophagectomy, as well as the short-term outcome, tumor resection rate, incidence of postoperative complications, and perioperative mortality, in patients with locally advanced esophageal cancer.Methods This study included 74 patients with thoracic esophageal cancer who were admitted to our hospital from May 2011 to June 2015.Chemotherapy and radiotherapy were performed concurrently.The chemotherapy consisted of vinorelbine (25 mg/m2 on days 1, 8, 22, and 29) and cisplatin (25 mg/m2 on days 1-4 and 22-25).The radiotherapy was conventionally fractionated with a total dose of 40 Gy (2.0 Gy/d).At 4-8 weeks after chemoradiotherapy, esophagectomy was performed (neoCRT+surgery group);definitive chemoradiotherapy (DCRT) was performed in the patients who refused surgery (DCRT group);follow-up was performed in the patients who refused any anti-cancer therapies after neoCRT (neoCRT group).Results Forty-four patients underwent neoCRT+surgery, with a radical resection (R0) rate of 100% and a pathological complete response (pCR) rate of 43%;17 patients received DCRT;13 patients received neoCRT alone.For the neoCRT+surgery group, DCRT group, and neoCRT group, the 2-year overall survival (OS) rates were 79%, 75%, and 17%, respectively, and the 2-year disease-free survival (DSF) rates were 75%, 55%, and 17%, respectively.There were significant differences in OS between the neoCRT group and the neoCRT+surgery group (P=0.000) and between the neoCRT group and the DCRT group (P=0.001), but no significant difference was observed between the neoCRT+surgery group and the DCRT group (P=0.415).There were significant differences in DFS between the neoCRT group and the neoCRT+surgery group (P=0.000) and between the neoCRT group and the DCRT group (P=0.002), but no significant difference was observed between the neoCRT+surgery group and the DCRT group (P=0.416).The rate of clinical response to preoperative neoCRT was 87% for all patients.Fifty-six patients (76%) developed grade ≥3 myelosuppression due to preoperative neoCRT.The incidence rates of postoperative pulmonary infection, anastomotic leakage, and anastomotic stenosis were 21%, 12%, and 7%, respectively, and the perioperative mortality rate was 2%.Conclusions For patients with locally advanced esophageal cancer, preoperative neoCRT plus surgery can increase the clinical response rate and pCR rate, reduce the tumor stage, and improve the survival, but chemoradiotherapy toxicities and perioperative complications cannot be ignored.

The risk of esophageal squamous cell carcinoma associated with microsatellite polymorphism in promoter of heme oxygenase-1 / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship between (GT)n polymorphism and esophageal cancer by analyzing the connection between microsatellite polymorphisms in the promoter of heme oxygenase-1 and the clinicopathological characteristics of esophageal squamous cell carcinoma (ESCC) in Han chinese population.</p><p><b>METHODS</b>The (GT)n repeats in HO-1 gene in 83 male and 43 female hospital-based patients with ESCC (aged between 40 and 79 years with a mean of (61 ± 8) years) and 134 healthy control individuals were obtained by DNA sequencing. Polymorphisms of the (GT)n repeats were generally grouped into three classes based on allele frequencies: class S alleles (<25 repeats), class M alleles (25 to 29 repeats), and class L alleles (≥30 repeats). The correlation between susceptibility and clinicopathological characteristics of ESCC were analyzed by χ2 test. For in vitro experiments, the transient-transfection assay was performed to explore the correlation between different lengths of (GT)n repeats and promoter activity by assessing the promoter activities of HO-1 gene in cultured Ecal09 cells treated with H2O2 by analysis of cariance.</p><p><b>RESULTS</b>Higher frequencies of L-allele (25. 8% vs. 14. 9%, χ2 = 9. 520, P = 0. 002), L-allele carrier (41. 3% vs. 27. 6%, χ2 = 5. 381 , P = 0. 020) were found in patients with ESCC. Furthermore, the lymphatic metastasis rate (63. 5% vs. 41. 8%, χ = 5. 685, P = 0. 017) and the detection rate of poorly differentiated ESCC cell (53. 8% vs. 28. 4%, χ2 = 8. 335, P = 0. 004) was significantly higher in L-allele carriers compared to non-L-allele carriers. In transfection experiments, promoter activities of 5'-flanking regions of the HO-1 gene in Eca109 cells transfected with the recombinant gene carrying (GT)16 repeat after treatment with H2O2 increased (F = 23. 615,P = 0. 008). In H2O treated control group, compared to (GT)26 and (GT)36, the basal promoter activities of HO-1 gene carrying (GT)16 repeat increased (F =41. 376, P = 0. 003; F = 50. 761, P = 0. 002).</p><p><b>CONCLUSION</b>The long (GT)n repeats of HO-1 gene promoter can increase the susceptibility of esophageal squamous cell carcinoma and the risk of lymphatic metastasis.</p>

Effects of recombinant human erythropoietin on angiogenesis in chronic ischemic porcine myocardium / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effect and mechanism of recombinant human erythropoietin (rhEPO) on angiogenesis in chronic ischemic porcine myocardium.</p><p><b>METHODS</b>A ameroid constrictor was placed around the proximal circumflex branch of the left coronary artery in 12 Bama miniatures' swine artery by thoracoscopy. Electrocardiogram and coronary angiography were used to confirm the establishment of myocardial ischemia. The animals were divided into rhEPO treatment group (n = 6) and negative control group (n = 6). Treatment group received subcutaneous injection of rhEPO at 1, 3, 7, 14, 21 days, control group received saline. The expression of vascular endothelial growth factor (VEGF) in serum was assessed by ELISA. Ultrasonography and coronary angiography were assessed 28 days after therapy. Western blot was used to detect the expression of VEGF, phosphorylated protein kinase B (p-Akt) and phosphorylated extracellular signal regulated kinases (p-Erk). The degree of angiogenesis was assessed by immunohistochemical analysis.</p><p><b>RESULTS</b>Serum VEGF rose significantly in both control and treatment groups, peaking at 3 days and then returning to the near-baseline level at 28 days, but the two groups showed no significant difference at each time point (P > 0.05). Echocardiographic measurements showed that the left ventricular systolic function of animals in treatment group increase significantly after rhEPO therapy. the expression levels of VEGF, p-Akt and p-Erk had markedly increased, which resulted in a 2.5-fold increased of VEGF, 1.1-fold increased of p-Akt, 1.5-fold increased of p-Erk (t = 37.721, 10.907, 12.957, all P = 0.000). there were significant increase in capillary density and arteriole density in the two groups ((944 ± 98) %/mm² vs. (569 ± 102) %/mm², (73 ± 13) %/mm² vs. (45 ± 10) %/mm², t = 4.214, 2.869, P = 0.016, 0.023).</p><p><b>CONCLUSIONS</b>rhEPO can promote angiogenesis and arteriogenesis and improve the left ventricular systolic function in porcine model of chronic myocardial ischemia. The potential mechanism is to up-regulated the expression of p-Akt and p-Erk.</p>

Clinical research of extensive regional field radiotherapy concurrent with chemotherapy for locally advanced esophageal cancer / 中华放射肿瘤学杂志

Objective To evaluate the efficacy and side effects of extensive regional field radiotherapy concurrent with chemotherapy for locally advanced esophageal cancer.Methods Of the 101 patients with locally advanced esophageal cancer patients,44 patients were treated by involved field radiotherapy alone,29 patients treated by involved field radiotherapy combined with chemotherapy,and 28 patients received extensive regional field radiotherapy combined with chemotherapy,the total dose of radiotherapy was 60 Gy.The clinical target volume (CTV) of involved field included the gross tumor volume (GTV) plus a 0.8 cm lateral margin,the tumor plus a nominal 3-5 cm cephalad and caudal margin.Extensive regional field radiotherapy was delivered in two steps:the CTV included the CTV of the involved field plus elective nodal region in the first step;in the second step,the CTV definition was same with the CTV of the involved field.Synchronous chemotherapy regimens included TP and NP.Results 90.1％patients completed planned radiotherapy,all patients in the concurrent chemotherapy groups completed at least one cycle of chemotherapy.The follow-up rate was 99％.Twenty-four and 42 patients completed followed-up more than 24 months in the radiotherapy alone and concurrent chemoradiotherapy group,respectively.The median survival time of the involved field radiotherapy group,involved field chemoradiotherapy group and extensive regional field chemoradiotherapy group was 13,21 and 19 months,respectively;the 2-year overall survival (OS) rate was 15％,48％ and 46％,respectively for the three groups.The 2-year OS rate was improved significantly in the chemoradiotherapy group (x2 =6.83,P =0.033).Compared with radiotherapy alone group,the incidence of grade three or four bone marrow suppression was higher in the concurrent chemoradiotherapy group (53％: 0 ％,x2 =32.94,P =0.000),the remaining adverse events (acute radiation pneumonitis,acute radiation esophagitis,esophageal fibrosis,late radiation lung injury) had no significant intergroup differences (x2 =5.56,6.70,2.39,0.42,P =0.235,0.349,0.881,0.981).Conclusions Compared with radiotherapy alone,concurrent chemoradiotherapy can improve the survival rate for locally advanced esophageal cancer.The side effects of the extensive regional field radiotherapy combined with chemotherapy is well tolerated.But the efficacy of the extensive regional field radiotherapy combined with chemotherapy needs further research.

Mutation screening of FLCN gene in Chinese patients with sporadic and familial primary spontaneous pneumothorax / 中华胸心血管外科杂志

Objective To study the mutation of FLCN gene in Chinese patients with sporadic and familial primary spontaneous pneumothorax. Methods A complete genetic analysis of FLCN by use of SSCP-PCR was performed in 102 unrelated Chinese patients with isolated PSP. Results Three novel mutations (c. 924_926del, c. 1611_1631del and c. 1740C.T) and a previously reported mutation (c. 1733insC) were identified in five familial and five sporadic PSP patients. Of the 21 family members of patients with PSP including 3 previous considered as sporadic, 4 ( 19% ) had history of at least one episode of PSP and 9 (43% ) were FLCN mutant carriers without PSP. Seven of the nine (78% ) mutant carriers had pulmonary cysts detected by high-resolution computed tomography ( HRCT) . Although c. 924_926del and c. 1611 _1631 del were found in eight patients from the same geographic district, haplotype analysis demonstrated that they did not share the same affected haplotype,thus excluding common ancestry. Conclusion This study first demonstrates that FLCN mutation contributes to not only familial but also apparently sporadic' patients with isolated PSP. It suggests that mutation analysis and HRCT scan may be recommended for first-degree family members of PSP patients with FLCN mutations, irrespective of their family history status of PSP.

Minimally invasive esophagectomy for the treatment of esophageal cancer:a report of 81 cases / 中华胸心血管外科杂志

ObjectiveTo assess the feasibility and clinical efficacy of minimally invasive esophagectomy for esophageal cancer.MethodsFrom July 2007 to December 2009,eighty-one patients with esophageal cancer received combined thoracoscopic and laparoscopic esophagectomy with anastomosis in the neck.All clinical data were retrospectively reviewed.ResultsThe median operative time was 270.5 min (range 196-315 min).The median time of gastric mobilization and abdominal lymph node dissection was 64.5 min,and the median time of esophageal dissection and mediastinall lymph node dissection was 81.2 min.The median blood loss was 121.5 ml for the thoracic phase and 42.4 ml for abdomen phase.The mean number of disected lymph nodes was 20.4 (range 5-41) with metastastic rate of 30.9% (25/81).The mean harvest lymph node was 12.5 in chest and 7.3 in abdomen.Perioperative complications rate was 27.2%,including respiratory failure in 1 case,pulmonary infection in 10,anastomotic leak in 3,chylothorax in 2,gastric tube dilatation in 1,gastric tube leak in 1.And recurrent laryneal nerve injury in 5 .Seventy-nine patients were followed up withmMean follow up time of 14.2 months( range 2-31 months).The overall one-year survival rate was 91.1%.Postoperative complications included anastomotic stenosis in 5 cases (6.3%),reflux esophagitis in 12 (15.2%) and recurrence or metastasis in 6 (7.6%).ConclusionMinimally invasive esophagectomy for esophageal cancer can mimimus trauma,reduce post-operative complications,improve the quality of life,which is feasible and effective from the point of the clinical efficacy and the purpose of tumor therapy.

Bcl-2 Antisense Oligodeoxynucleotides Increase Apoptosis of Lung Cancer Cells Induced by Radiation / 医学研究杂志

Objective To study the effects of Bcl-2 antisense oligodeoxynucleotides(ASODN)on the apoptosis of lung cancer cells induced by radiation in vitro.Methods NCI-H446 lung cancer cell strains were divided into 5 groups:control simple radiation,lipofectin plus radiation,nonsense sqnence radiation and ASODN plus radiation.The cells cultured in five groups were collected at 6h,12h,24h,48h and 72h,with Wright-Giemsa stain,morphology analysis for which was done;the mRNA expression for p53、bcl-2 and PTEN gene was examined by RT-PCR half quantivity and DNA-ploid of the cells in five groups was detected by flow cyfometric method.Results Cell proliferation is obviously restrained and conformation is changed too with the shape crimpled and adherence function decreased obviously after irradiated for 10 Gy dose by the linac;p53 and PTEN expression clearly increased for the combination of Bcl-2 ASODN and bcl-2 mRNA expression clearly decreased.The apoptosis rate after 72 hours among control,pure radiation,lipofectin+radiation,nonsense+radiation and ASODN +radiation grouop is 0.14?0.09,13.17?2.47,11.84?1.76,13.72?1.4,21.26?2.97 respectively,the difference between ASODN combined with radiation grouop and other 4 groups are significant(P

Video-assisted thoracoscopic resection of esophageal carcinomas / 中国微创外科杂志

Objective To investigate indications of thoracoscopic resection of esophageal carcinomas. Methods A total of 75 patients with esophageal carcinomas underwent video-assisted thoracoscopic surgery (VATS) from July 1997 to July 2003. The dissection of the esophagus and radical resection of lymph nodes were performed using a right-sided VATS approach. Then the stomach was dissociated through an upper-abdominal incision and was pulled up for esophago-gastric anastomosis in the left neck. Results A conversion to open surgery was required in 3 patients, in 2 of whom the tumors had enroded into the hilum and the posterior wall of the heart, and in 1 of whom the azygous vein was ruptured. The operation time was 160~220 min, with the intrathoracic operation time accounting for 60~90 min. The postoperative blood loss was 300~400 ml. No surgery-related deaths were noted. Postoperative complications included 1 case of volvulus of stomach, 2 cases of anastomotic leakage, 1 case of anastomotic stenosis, and 1 case of chylothorax. Follow-up checkups in 60 patients for 3 months ~ 7 years (mean, 4 years) found 2 cases of supraclavicular lymph node metastasis and 1 case of abdominal lymph node metastasis. The 1-, 3- and 5-year survival rates were 85.0% (51/60), 51.7% (31/60) and 40.0% (24/60), respectively. Conclusions Video-assisted thoracoscopic resection of esophageal carcinomas is feasibly suited to patients with localized lesions at phaseⅠ or Ⅱ.

Combination of Thoracoscopy and Laparoscopy for Treatment of Esophageal Carcinoma / 中国微创外科杂志

Objective To explore the feasibility and safety of combination of thoracoscopy and laparoscopy for the treatment of esophageal carcinoma.Methods Combining thoracoscopic and laparoscopic esophagectomy was attempted in 23 patients with esophageal cancer between August 2007 and July 2008.Being placed at a left lateral decubitus position,the patients received right thoracoscopic mobilization of the intrathoracic esophagus as well as lymph node dissection;then with lithotomy position,laparoscopic mobilization of the stomach and lymph node dissection were carried out,followed by creation of a gastric tube through a small incision under the xiphoid;finally we pulled out the gastric tube from the esophageal bed to the neck and made an intermittent gastroesophageal anastomosis.Results One of the patients was converted to open abdominal surgery,whereas no one was converted to open thoracic operation.The total operation time ranged from 240 to 330 minutes with a mean of 270 minutes,the operation time for laparoscopy was 38-90 minutes(mean,65 minutes),and for thoracoscopy was 55-100 minutes(mean,70 minutes).No massive hemorrhage occurred during the operation,the total blood loss ranged from 100 to 300 ml(mean,225 ml),of which 10 to 50 ml were intra-abdominal blood loss(mean,20.4 ml).Totally 225 lymph nods were removed(9.8 per patient in average).Of the resected lymph nodes,65 were para-left gastric arterial or pericardial lymph nodes(2.8 per case).The mean hospital stay in this series was 9.2 days(range:8-12 days).During the hospitalization,no patient died;postoperative complications included pulmonary infection(3 cases),cervical anastomotic leak(one case,occurred in 8 days after the surgery),chylothorax(1 patient,cured by ligation via open thoracic surgery),and hoarseness(3 cases).Of the patient,23 received an follow-up for 1 to 11 months(mean,7.7 months),during which,1 patient died and 1 patient showed extensive metastasis to the mediastinal lymph node.Conclusion Combination of thoracoscopy and laparoscopy with cervical anastomosis is feasible and safe for the treatment of esophageal carcinoma.