RESUMO
OBJECTIVES: To retrospectively investigate the clinical characteristics, surgical treatments of the patients with lung ground-glass opacities (GGO). METHODS: All the patients, who underwent surgical resection of GGO in our department from Jan. 2013 to Dec. 2016 were retrospectively reviewed. The clinicpathological features were analyzed. RESULTS: A total of 663 patients were included in this study. The rate of malignancy was 92.6% (614/663). The diameter of GGO in benign group [(0.8±0.2) cm] was significant smaller than that in malignant group [ (1.5±0.8) cm](P<0.001). The rate of irregular margin in malignant group was far higher than that in benign group (93.8% vs. 20.4%, P<0.001), but other CT signs such as vacuole sign, plural retraction, speculation and lobulation did not show significant difference between the two groups. A total of 652 (98.3%) cases were resected by video-assisted thoracoscopic surgery (VATS), and only 11 (1.7%) cases were resected by thoracotomy. A total of 336 (50.7%) patients underwent lobectomy, 226 (34.1%) underwent segmentectomy and 101 (15.2%) undewent wedge resection. The rate of surgery-related complications was 9.0% (60/663), and one (0.2%) patient died. CONCLUSIONS: With careful selection of GGO by experienced surgeons, the rate of malignancy is very high. Surgical resection may be recommended for highly suspected malignant cases. Sublobar resection or lobcotomy by VATS can achieve good treatment effect.
Assuntos
Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/cirurgia , Humanos , Pulmão/patologia , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida , ToracotomiaRESUMO
OBJECTIVE: To evaluate the safety and technical feasibility of single-direction video-assisted thoracoscopic lobectomy for patients with pulmonary diseases. METHODS: From May 2006 to Sep 2012, 1040 patients with pulmonary diseases were treated by single-direction video-assisted thoracoscopic lobectomy. These included 565 men (54.3%) and 475 women (45.7%), with a mean age of (56.3 +/- 13.2) years. The patients suffered from lung cancer (800), benign disease (205), pulmonary metastases (34), and lymphoma (1). Their perioperative data were collected and reviewed. RESULTS: Of the 1040 patients, 7 died (0.67%); 18 (1.73%) were converted to open surgery; 134 had postoperative complications (12.88%). The patients underwent an average of (169 +/- 64) min operations, lost an average of (93 +/- 113) mL (range, 5-935 mL) blood, had an average of (3.3 +/- 1.9) cm (range, 1.2-12 cm) diameters of mass removed and an average (15.8 +/- 7.7) (range, 5-52) lymph nodes dissected. The patients had an average of (3.8 +/- 2.6) days (range, 1-16 days) drainage during an average of (7.0 +/- 2.8) days (range, 4-19 days) postoperative hospital stay. CONCLUSION: Single-direction thoracoscopic lobectomy is a safe and feasible surgical procedure in the treatment of pulmonary diseases.
Assuntos
Pneumopatias/cirurgia , Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida , Adulto , Idoso , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação , Linfonodos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Período Pós-Operatório , Estudos RetrospectivosRESUMO
OBJECTIVE: To compare acute inflammatory responses and immunosuppression to lobectomy in lung cancer patients with video-assisted thoracoscopic surgery (VATS) and posterolateral thoracotomy (PLT). METHODS: A total of 103 patients who underwent either a VATS (n = 51) or a PLT (n = 52) lobectomy for early non-small cell lung cancers (NSCLC, stage I ) were recruited for this study. Blood samples of the participants were taken preoperatively and at 24 h and 72 h post-operatively for analyses of C-reactive protein (CRP), interleukin (IL)-6, IL-2 receptors (IL-2R), and serum amyloid A (SAA). Blood samples taken pre-operatively and at 2 d and 7 d post operations were also analyzed for total lymphocytes, NK cells, CD4+ T, and CD8+ T. RESULTS: Patients in the VATS group lost significantly less blood than those in the PLT group (P = 0.001). Patients in the PLT group had significantly higher serum SAA than those in the VATS group (P = 0. 006). Significant reduction of CD8+ T was found in the patients with PLT after operations (P < 0.01). Patients in the PLT group had significantly lower at CD8+ T 7 d post operations than those in the VATS group (P = 0.015). CONCLUSION: VATS pulmonary lobectomy is associated with reduced acute inflammatory responses and immunosuppression compared with the PLT approach.
Assuntos
Neoplasias Pulmonares/imunologia , Pneumonectomia , Cirurgia Torácica Vídeoassistida , Toracotomia , Linfócitos T CD8-Positivos/citologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Humanos , Neoplasias Pulmonares/cirurgia , Proteína Amiloide A Sérica/metabolismoRESUMO
OBJECTIVES: To observe the clinical outcome of invasive thymoma, and analyze how the surgical methods, Masaoka staging, adjuvant radiotherapy and/or chemotherapy affect the prognosis. METHODS: The clinical data of 59 surgical patients with invasive thymoma and conducted follow-up from January 2000 to December 2009 was analyzed retrospectively. There were 34 male and 25 female, aged from 18 to 72 years with a mean age of 49 years. Forty-four cases underwent radical resection while the other 15 cases underwent palliative resection or biopsy. Masaoka staging: 18 cases with stage II, 30 cases with stage III, 11 cases with stage IV. Patients with stage II didn't undergo further adjuvant radiotherapy or chemotherapy after surgery. Among the patients with stage III and stage IV, 26 patients received adjuvant radiotherapy and/or chemotherapy after surgery, while the other 15 patients did not receive any further therapy. The relationship between the prognosis and the different surgical methods, Masaoka staging, adjuvant radiotherapy and or chemotherapy was evaluated. RESULTS: Fifty-nine patients had been followed up for 1 to 111 months with an average of 54 months. Three cases were lost with the rate of 6.1%. Nineteen patients suffered local recurrence or systemic metastasis, and 14 of them died. The 3-year and 5-year survival rates were 86.8% and 70.8% respectively. Univariate analysis indicated that patients with early Masaoka staging and who received radical resection, adjuvant radiotherapy and/or chemotherapy after surgery had better survival (P < 0.05). Multivariate analysis indicated that radical resection, adjuvant radiotherapy and or chemotherapy were the most significant prognostic factors which could remarkably improve the survival of patients (P < 0.05). For patients with resectable recurrence, reoperation could also improve survival. CONCLUSIONS: The Masaoka staging is related to the prognosis of patients with invasive thymoma. Radical resection, adjuvant radiotherapy, chemotherapy can significantly improve the survival of patients with invasive thymoma. Reoperation can improve the survival of some patients with recurrence.
Assuntos
Timoma/cirurgia , Neoplasias do Timo/cirurgia , Adolescente , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Radioterapia Adjuvante , Estudos Retrospectivos , Timoma/patologia , Neoplasias do Timo/patologia , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To analyze the learning curve of single-direction complete video-assisted thoracoscopic surgery (cVATS) for lung cancer. METHODS: From May 2006 to April 2009, 125 cases of cVATS for lung cancer were performed by two dedicated surgeons. Clinical data were collected prospectively and analyzed retrospectively. The patients operated by different surgeon were divided into 2 groups (group A, n = 24; group B, n = 101), and group B was further divided sequentially into 4 subgroups (B1, B2, B3 and B4) by the number of patients. The patients in group A and B were operated by the surgeons with 2-year and 5-year experience of VATS respectively. The operating time, blood loss, number of resected lymph nodes (NLN), rate of thoracotomy conversion (RTC) and postoperative complications (POC) were compared. RESULTS: Compared with group B, the operating time of group A was significantly prolonged [(237 ± 85) min vs. (187 ± 43) min, P = 0.013], but there were no significant differences in blood loss, NLN, RTC and POC. Comparing group A with B1, the same results were got. From group B1 to B4, the operating time was gradually reduced and blood loss decreased, but the difference was not statistically significant. And in group B, there was a significant reduction of blood loss for the last 51 cases compared to the first 50 cases [(122 ± 141) ml vs. (87 ± 81) ml, P = 0.009]. CONCLUSIONS: At the early stage of cVATS resection of lung cancer, the duration of operation was longer, which it was more significant for the surgeons with short carrier of thoracoscopic experience. But the morbidity of operation related complications did not increase. The indicator of proficiency in this operation is achievement of 50 cases of complete thoracoscopic resection of lung cancer.
Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adulto , Idoso , Feminino , Humanos , Curva de Aprendizado , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the feasibility and safety of single-direction video-assisted thoracoscopic lobectomy in the treatment of benign pulmonary diseases. METHODS: From May 2006 to Dec 2009, 60 patients with benign pulmonary diseases were treated by single-direction complete video-assisted thoracoscopic lobectomy. Nine cases were bronchiectasis, 7 bronchial cyst, 7 tuberculoma, 11 inflammatory pseudotumor, 6 sclerosing hemangioma, 4 hamartoma, 2 atelectasis with bronchial stenosis, 2 pulmonary aspergillosis, 2 pulmonary sequestration, 8 multiple bullae and 2 cases of mid-lobe syndrome. In the 60 patients, there were 18 cases received right upper lobectomy, and right middle lobectomy in 11 cases, right lower lobectomy in 7 cases, left upper lobectomy in 6 cases, left lower lobectomy in 18 cases. RESULTS: There was one conversion to open surgery. One patient died of postoperative pneumonia. The average operation time was 169 min (range, 70-265 min), average blood loss was 125 mL (range, 10-70 mL), average drainage was 860 mL (range, 20-3500 mL) and average duration of drainage was 4 days (range, 2-16 days). The average postoperative hospital stay was 7.9 days (range, 4-19 days). CONCLUSION: Single-direction complete video-assisted thoracoscopic lobectomy is feasible and safe in the treatment of benign pulmonary diseases.
Assuntos
Pneumopatias/cirurgia , Pneumonectomia/métodos , Cirurgia Torácica Vídeoassistida/métodos , Adolescente , Adulto , Idoso , Bronquiectasia/cirurgia , Criança , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Granuloma de Células Plasmáticas Pulmonar/cirurgia , Adulto JovemRESUMO
OBJECTIVE: To assess the metastatic frequency in different groups of lymph nodes and its influencing factors of the thoracic esophageal squamous cell carcinoma (ESCC) in order to determine the extent of lymphadenectomy during esophagectomy. METHODS: The clinical data of 730 patients with ESCC who underwent esophagectomy and lymphadenectomy were analyzed retrospectively. RESULTS: Of 730 patients, 166 had metastasis to the para-esophageal lymph nodes (22.7%), 90 to the left gastric artery lymph nodes (12.3%), 67 to the lymph nodes around gastric cardia, and 15 to the subcrinal lymph nodes (2.1%). Univariate analysis showed that metastasis to the subcrinal lymph node was positively correlated with the length and differentiation of tumor (P < 0.05), but it was not correlated with any the above parameters when analyzed by multivariate analysis. The metastasis to the para-esophageal lymph node was positively correlated with the length, invasion depth and differentiation of tumor by univariate and multivariate analysis (P < 0.05). The metastasis to the lymph nodes around gastric cardia and metastasis to left gastric artery lymph nodes were positively correlated with the position and invasion depth of tumor by univariate and multivariate analysis (P < 0.05). CONCLUSION: Lymph nodes of the para-esophagus, gastric cardia and left gastric artery usually have high frequency to harber mestastasis, therefore, it was suggested that the lymph nodes in these groups should be dissected during esophagectormy with two-field lymphadenectomy for thoracic esophageal squamous cell carcinoma. Whereas for those patients with the lesion < 3 cm in length or with tumor invasion confined within the esophageal wall or with a lesion located at the upper or lower third of the thoracic esophagus, the subcrinal lymph nodes may not be necessarily dissected.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Cárdia , Neoplasias Esofágicas/patologia , Esôfago , Feminino , Humanos , Linfonodos/cirurgia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos RetrospectivosRESUMO
OBJECTIVE: To investigate the expression of Toll-like receptors (TLRs) in thymus of myasthenia gravis (MG) patients and the relationship with clinical features. METHODS: Thymic specimens of 36 patients received extended thymectomy for MG were divided into three groups by pathological type: 13 thymoma tissues (thymoma group) and 13 thymic tissues adjacent to thymomas (parathymoma group) from 13 cases of MG patients with thymomas, and 23 thymic tissues from MG patients without thymomas (MG nonthymoma group). Twenty-one normal thymic specimens from cardiac surgery were used as controls. The levels of TLR2-4 mRNA were examined by RT-PCR, then the levels of TLR4 mRNA were assayed by real time RT-PCR and their relationship with clinical features were analyzed. RESULTS: The levels of TLR4 mRNA among the different groups had significant differences, while there was no difference in TLR2 and TLR3 levels. The real time RT-PCR showed that the level of TLR4 mRNA in nonthymoma group was significantly higher than that in control group(0.8544+/- 0.1200 vs 0.6851+/- 0.1524, P=0.018). And so is parathymoma group compared with the thymoma group (0.8214+/- 0.1019 vs 0.7101+/- 0.0916, P=0.005). No significant difference of TLR4 mRNA level was found between the parathymoma and nonthymoma groups. Nevertheless, the expression of TLR4 in both groups was increased compared with control group. The levels of TLR4 mRNA had positive correlation with Osserman type(R=0.609; P=0.004) . CONCLUSION: TLR4 may play a key role in the pathogenesis of MG. It was the thymic tissues adjacent to thymomas but not thymomas themselves participated in the onset of MG.
Assuntos
Regulação da Expressão Gênica , Miastenia Gravis/genética , Timo/metabolismo , Receptores Toll-Like/genética , Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Receptor 2 Toll-Like/genética , Receptor 3 Toll-Like/genética , Receptor 4 Toll-Like/genética , Adulto JovemRESUMO
AIM: To evaluate the risk of esophagectomy for carcinoma of the esophagus in the elderly (70 years or more) compared with younger patients (< 70 years) and to determine whether the short-term outcomes of esophagectomy in the elderly have improved in recent years. METHODS: Preoperative risks, postoperative morbidity and mortality in 60 elderly patients (> or = 70 years) with esophagectomy for carcinoma of the esophagus were compared with the findings in 1782 younger patients (< 70 years) with esophagectomy between January 1990 and December 2004. Changes in perioperative outcome and short-time survival in elderly patients between 1990 to 1997 and 1998 to 2004 were separately analyzed. RESULTS: Preoperatively, there were significantly more patients with hypertension, pulmonary dysfunction, cardiac disease, and diabetes mellitus in the elderly patients as compared with the younger patients. No significant difference was found regarding the operation time, blood loss, organs in reconstruction and anastomotic site between the two groups, but elderly patients were more often to receive blood transfusion than younger patients. Significantly more transhiatal and fewer transthoracic esophagectomies were performed in the elderly patients as compared with the younger patients. Resection was considered curative in 71.66% (43/60) elderly and 64.92% (1157/1782) younger patients, which was not statistically significant (P>0.05). There were no significant differences in the prevalence of surgical complications between the two groups. Postoperative cardiopulmonary medical complications were encountered more frequently in elderly patients. The hospital mortality rate was 3.3% (2/60) for elderly patients and 1.1% (19/1 782) for younger patients without a significant difference. When the study period was divided into a former (1990 to 1997) and a recent (1997 to 2004) period, operation time, blood loss, and percentage of patients receiving blood transfusion of the elderly patients significantly improved from the former period to the recent period. The hospital mortality rate of the elderly patients dropped from the former period (5.9%) to the recent period (2.3%), but it was not statistically significant. CONCLUSION: Preoperative medical risk factors and postoperative cardiopulmonary complications after esophagectomy are more common in the elderly, but operative mortality is comparable to that of younger patients. These encouraging results and improvements in postoperative mortality and morbidity of the elderly patients in recent period are attributed to better surgical techniques and more intensive perioperative care in the elderly.
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Envelhecimento , Neoplasias Esofágicas/cirurgia , Esofagectomia , Complicações Pós-Operatórias/epidemiologia , Idoso , Diabetes Mellitus , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/mortalidade , Esofagectomia/métodos , Esofagectomia/mortalidade , Feminino , Cardiopatias/complicações , Mortalidade Hospitalar , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Prevalência , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
AIM: To retrospectively evaluate the clinical relevance, perioperative risk factors, outcome of different pharmacological prophylaxis, and short-term prognostic value of atrial fibrillation (AF) after surgery for esophageal carcinoma. METHODS: We retrospectively studied 63 patients with AF after surgery for esophageal carcinoma in comparison with 126 patients without AF after esophagectomy during the same time. Postoperative AF incidence was related to different clinical factors possibly involved in its occurrence and short-term survival. RESULTS: A strong relationship was observed between AF and postoperative hypoxia, history of chronic obstructive pulmonary disease (COPD), postoperative thoracic-gastric dilatation, age older than 65 years, male sex and history of cardiac disease. No difference was observed between the two groups with regard to short-term mortality and length of hospital stay. CONCLUSIONS: AF occurs more frequently after esophagectomy in aged and male patients. Other factors contributing to postoperative AF are history of COPD and cardiac disease, postoperative hypoxia and thoracic-gastric dilatation.
Assuntos
Fibrilação Atrial/etiologia , Carcinoma/cirurgia , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Neoplasias Esofágicas/cirurgia , Complicações Pós-Operatórias , Idoso , Idoso de 80 Anos ou mais , Antiarrítmicos/uso terapêutico , Fibrilação Atrial/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
OBJECTIVE: To explore the feasibility of detecting p53 gene mutation in exfoliative esophageal cells, and compare gene mutation between precancerous lesions and normal esophageal exfoliative cells and correlate p53 gene mutation with esophageal carcinogenesis. METHODS: Forty-eight samples (24 normal squamous epithelia and 24 severe squamous dysplasia) were obtained by balloon cytologic technique from a high incidence area, Yanting county, Sichuan Province, China in 1982. p53 gene mutations in exons 5 and 7 were analyzed by PCR-SSCP. RESULTS: p53 genes were detected in all samples. Five samples with p53 mutation were detected in exon 7 and no mutation was detected in exon 5 in 24 severe dysplasia samples. Three of the 5 samples with mutation in exon 7 developed esophageal cancer in 1992, 1994 and 1996 respectively. No p53 gene mutation was detected in exon 5 and 7 in normal exfoliative samples. CONCLUSION: p53 mutation may have occurred in the precancerous lesions which contributes in the initiation of human esophageal carcinogenesis.
Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Genes p53/genética , Mutação Puntual , Lesões Pré-Cancerosas/genética , Adulto , Idoso , Carcinoma de Células Escamosas/patologia , Células Epiteliais/patologia , Neoplasias Esofágicas/patologia , Esôfago/citologia , Esôfago/patologia , Éxons/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo Conformacional de Fita Simples , Lesões Pré-Cancerosas/patologiaRESUMO
BACKGROUND: Thymectomy is an established treatment for myasthenia gravis (MG), and video-assisted thoracoscopic surgery (VATS) thymectomy has become an acceptable surgical procedure. This study aimed to compare the results of VATS thymectomy and open thymectomy and to identify the prognostic factors after thymectomy. METHODS: The clinical data of 187 consecutive thymectomies performed between July 2000 and December 2009 were retrospectively reviewed; 75 open thymectomies and 112 VATS thymectomies. Clinical efficacy and variables influencing outcome were assessed by Kaplan-Meier survival curves and Cox proportional hazards regression analysis. RESULTS: The operative blood loss in the VATS group was significantly less than that in the open group ((62.14 ± 55.43) ml vs. (137.87 ± 165.25) ml, P < 0.05). The postoperative crisis rate increased with the severity of preoperative MG and the prescription dose of anticholinesterase. Complete follow-up information of patients more than 12 months after the thymectomy was obtained on 151 cases, 89 cases from the VATS group and 62 cases from the open group, with a mean follow-up period of 59.3 months, range from 12 to 117 months. Complete stable remission (CSR) was the end point for evaluation of the treatment results. The overall five-year CSR rate was 57.5%. Two good prognostic factors were identified; preoperative prescription of anticholinesterase alone (P = 0.035) and non-thymomatous MG (P = 0.003). The five-year CSR rate of the ocular type of MG reached a high level of 67.4%. CONCLUSIONS: Thymectomy can achieve good long-term CSR in MG, and VATS is an ideal alternative method. High-dose prescription of anticholinesterase and the advanced stage by Myasthenia Gravis Foundation of America (MGFA) classification have higher risks of postoperative crisis. Preoperative prescription of anticholinesterase alone and non-thymomatous MG are good prognostic factors. Thymectomy should also be considered for the ocular type of MG.
Assuntos
Miastenia Gravis/cirurgia , Cirurgia Torácica Vídeoassistida/métodos , Timectomia/métodos , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Timectomia/efeitos adversos , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to compare the operative results in regard to reducing anastomotic leakage and stricture formation using a newly designed layered manual esophagogastric anastomosis versus a stapler esophagogastrostomy versus the conventional hand-sewn whole-layer anastomosis after resection for esophageal or gastric cardiac carcinoma. From January 2004 to September 2006, a total of 1024 patients with esophageal or gastric cardia carcinoma underwent a layered esophagogastric anastomosis with the assistance of a three-leaf clipper in a single university medical center. The mucosal layers of the esophagus and stomach were sutured continuously with 4/0 Vicryl plus antibacterial suture (polyglyconate). From May 2002 to December 2003, there were also 170 patients and 69 patients who underwent stapler and conventional whole-layer anastomosis, respectively; they served as control groups. The results were analyzed retrospectively. The operative mortality rate was 0.7% in the layered group compared to 5.9% and 7.2% for the stapler group and the whole-layer group (p < 0.01), The anastomotic leakage rates were 0%, 3.5%, and 5.8% for the layered group, stapler group, and whole-layer group, respectively (p < 0.01). All patients were followed postoperatively. Six patients in the layered group (0.6%) developed mild stricture formation compared to 16 patients in stapled group (9.9%) and 5 patients in the conventional whole-layer group (7.8%) (p < 0.01). The application of layered esophagogastric anastomosis could reduce the incidence of anastomotic leakage and stricture after esophagectomy compared with the stapler and whole-layer manual anastomoses. It is easy to apply and could be used as an alternative for esophagogastric anastomosis after resection for esophageal or cardiac carcinoma.