Is FDG-PET indicated for superficial esophageal cancer?

OBJECTIVE: To ascertain whether fluorodeoxyglucose positron emission tomography is indicated for clinical staging of superficial cancer, we sought to determine if it accurately classifies tumor (T), regional nodal (N), and distant metastases (M), including distinguishing high-grade dysplasia (Tis) from invasive cancer (T1). METHODS: Fifty-eight superficial esophageal cancer patients had preoperative positron emission tomography, 53 (91%) fused with computed tomography. Tumor characteristics, esophagoscopy findings, and pTNM were compared with positron emission tomography cTNM. pT1 was subdivided into intramucosal cancers with lamina propria or muscularis mucosa invasion and submucosal cancers with inner or outer invasion. RESULTS: Fluorodeoxyglucose uptake increased with pT, from 5/11 (45%) for pTis to 11/16 (69%) for pT1 (outer submucosa), P=0.07, as it did for standardized uptake value, median 0 for pTis to 2.7 for pT1 (outer submucosa), P=0.06. Positron emission tomography could not differentiate Tis (5/11, 45%) from T1 (26/47, 55%; P=0.03). Regional nodal fluorodeoxyglucose uptake in three patients (standardized uptake value 2.8, 4.9, 11) was false positive; in six pN1 patients, it was false negative. Positron emission tomography had 0% sensitivity and positive predictive value for N1. There were no distant metastases; one patient developed a pulmonary metastasis 15 months postoperatively. Positron emission tomography detected three (5%) distant hypermetabolic sites, all synchronous tumors (papillary thyroid cancer, adrenal pheochromocytoma, rectal adenoma). Only increasing tumor length was related to greater fluorodeoxyglucose uptake (P=0.004) and higher standardized uptake value (P=0.001). CONCLUSIONS: Because positron emission tomography can neither differentiate pTis from T1 nor classify T, N, and M, it is not indicated in staging superficial esophageal cancer. Finding a synchronous primary tumor in approximately every 20th patient is its only benefit. Better, less expensive screening tools are available for common synchronous malignancies.     

A case of paraesophageal bronchogenic cyst with esophageal communication]

A case of mediastinal bronchogenic cyst communicating with the esophagus was reported. Previously, only 2 cases have been reported in the available literature. A 34-year-old man was admitted with a cystic mass communicating with the esophagus which was demonstrated on a barium study. Operation was performed with a suspect of esophageal diverticulum or congenital cyst with esophageal communication. At right thoracotomy, a mass measuring 6.0 x 5.0 cm with a well-defined patent communication to the esophagus was resected. It was a monolocular cyst containing a small amount of viscous mucus. Histologically, the cyst lined by a ciliated columnar epithelium, and it was diagnosed as a bronchogenic cyst because of the presence of the mucous glands, smooth muscle tissue and cartilage. This is the first case report of mediastinal bronchogenic cyst with esophageal communication appeared in the Japanese literature.     

Transthoracic Esophagectomy After Endoscopic Mucosal Resection in Patients with Early Esophageal Carcinoma

Introduction  For patients with esophageal carcinoma limited to the mucosa endoscopic mucosal resection (EMR) is the therapy of choice whereas surgical resection is advocated for submucosal tumors. Methods  This study analyzes the histopathologic results of patients with early esophageal carcinoma who underwent EMR prior to transthoracic esophagectomy. Sixteen patients with early esophageal carcinoma and EMR as first line treatment were included in this retrospective study. Ten patients underwent transthoracic esophagectomy because of submucosal infiltration combined incomplete tumor resection at the lateral/basal resection margin. In one patient each, surgical therapy was indicated due to submucosal infiltration or incomplete resection only. Three patients underwent surgical resection due to residual neoplasia within an esophageal stenosis following EMR. Surgical specimens were examined for pT and pN stage according to the UICC. Results  Three patients had a squamous cell carcinoma (SCC) and 13 patients an adenocarcinoma (AC), nine patients with a long segment Barrett’s esophagus. The distribution of the pT stages was as follows: 6× pT0 (no histopathologic evidence of residual tumor), 1× pT1m1, 1× pT1m2, 3× pT1m3, 1× pT1sm1, 1× pT1sm2, 1× pT2, and 2× pT3. Three of 16 patients (18.8%) with a pT1sm1, pT2, and pT3 stage had nodal metastases. In all three patients metastatic nodes were located in the mediastinum. In two patients, a second carcinoma was detected during histopathologic work-up (1× AC in the cardia and 1× SCC in the cervical esophagus). Conclusion  The data of this highly selected patients indicate that the boundary between the therapy of mucosal and submucosal tumors is not as clear as stated. Therefore, treatment of early esophageal carcinoma demands a close interdisciplinary cooperation.     

Amelanotic malignant melanoma of the esophagus. Report of a case

Primary malignant melanomas of the esophagus are rare neoplasms with aggressive behavior and tendency to lymphatic and hematogenous spread. We report on a patient affected with a primary amelanotic melanoma of the esophagus synchronous to a squamous cell carcinoma of the epiglottis and treated by subtotal esophagectomy. A 58-year-old woman presented with a three-month history of dysphagia, retrosternal pain and weight loss. An upper gastrointestinal endoscopy revealed a 3 cm, non pigmented, polypoid mass of the middle esophagus and biopsy was consistent with undifferentiated carcinoma. Fiberoptic bronchoscopy revealed a 0.5 cm, polypoid lesion of the right aspect of the epiglottis consistent with a squamous cell carcinoma. The esophageal neoplasm was treated by subtotal esophagectomy while the squamous cell carcinoma of the epiglottis was referred to radiotherapy 1 month after surgery. Microscopy showed diffuse proliferation of anaplastic cells with multiple mitotic figures, marked nuclei and multilobulated nucleoli. The neoplasm stained positive for HBM-45 antigen and S-100 protein. Tumor stage was pT1N0M0. Review of patient's medical history and exploration of skin and mucous membranes failed to reveal malignant lesions and definitive diagnosis was primary amelanotic malignant melanoma of the esophagus. The patient died 16 months after surgery of disseminated disease. In conclusion the present case confirms that primary malignant melanomas of the esophagus have a dismal outcome even in cases of early-stage lesions amenable to surgical resection.     

Metastasis of cancer to cancer: Report of a case of esophageal carcinoma metastasizing to early gastric cancer

A rare case of esophageal carcinoma metastasizing to early gastric cancer is reported herein. A 66 year old man who had experienced dysphagia for 8 months was preoperatively diagnosed as simultaneously having esophageal and gastric cancers. Thus, a lower esophagectomy and total gastrectomy with paraesophageal and paragastric lymph node dissection were performed. The surgical specimen revealed an ulcerative tumor in the lower esophagus and a slightly depressed lesion with a central elevation similar to that of early type IIc+IIa¹ gastric cancer in the upper part of the stomach. Microscopically, the esophageal tumor was revealed to be well differentiated squamous cell carcinoma while the gastric tumor was found to be early gastric cancer with a metastatic focus of esophageal cancer in the center. Though less than one hundred cases of metastasis of cancer to cancer have previously been reported, metastasis from cancer of one digestive organ to that of another digestive organ is very rare. To our knowledge, this report represents the first case of an esophageal carcinoma metastasizing to a gastric carcinoma.     

Three primary cancers of pulmonary cancer, malignant melanoma and esophageal cancer; report of a case

A 61-year-old man, who had medical history of hepatitis type C, surgery for malignant melanoma of the lower limb, endoscopic mucosal resection for esophageal cancer, was pointed out a pulmonary nodule in the right middle lobe by surveillance computed tomography after 5 years of surgery for melanoma. Pathology of esophageal cancer was squamous cell carcinoma limited in mucosa without lymphatic nor venous invasion. The nodule gradually enlarged and respiratory endoscopic examination could not establish pathological diagnosis. Thoracoscopy-assisted pulmonary biopsy revealed squamous cell carcinoma, and right middle lobectomy with mediastinal node dissection was performed. Histological examination showed moderately differentiated squamous cell carcinoma without lymph node involvement. The stage of lung cancer was T1N0M0, stage IA. Although 9 months have passed since surgery for lung cancer, recurrence of each malignancy has not been detected.     

A case report of a paraesophageal bronchogenic cyst and an esophageal cyst]

There are relatively few paraesophageal bronchogenic and esophageal cysts in mediastinal tumors. It is often difficult to distinguish between these cysts. Case 1: 11 year old, male with no symptoms. An abnormal tumor shadow was revealed by chest roentgenogram. Before operating, CT, MRI and other laboratory tests were suggested that the tumor was neurogenic. A cyst with a pedicle connected to the esophageal muscle layer was found during the operation. Pathological examination confirmed a bronchogenic cyst lined with cartilage. Case 2: 38 year old female with epigastralgia. Upper gastrointestinal series revealed that the thoracic esophagus was smoothly compressed from the outside. CT and MRI showed a well-defined cystic mass in the posterior mediastinum. The cyst bordered the esophagus, but there was no direct communication between them. The pathological findings showed the presence of a double layer of smooth muscle without cartilage which was diagnosed as an esophageal cyst.     

同时性多原发食管癌

目的 探讨同时性多原发食管癌的临床特点、诊断和治疗.方法 采用回顾性研究的方法,对收治的32例同时性多原发食管癌的临床资料进行总结、分析.结果 全组食管双原发灶30例,三原发灶2例,共66个病灶,其中位于颈段22个,胸上段10个,胸中段19个,胸下段15个.66个病灶中,鳞癌65个,腺癌1个.32例中术前确诊26例.32例均采用手术治疗,其中4例行探查手术,1例行姑息切除手术,余27例行完全性切除手术.术后病理食管残端阳性2例.术后出现并发症8例.术后随访28例,1、3和5年生存率分别为76.9％、43.3％和14.8％.结论 完善的术前检查可显著提高同时性多原发食管癌的确诊率,手术是其较好治疗方法.     

Eversion stripping of the esophagus with intraesophageal insufflation—A case report

IntroductionPatients with esophageal cancer frequently cannot tolerate thoracotomy due to their overall debilitated condition. Moreover, some patients have severe adhesions in the thoracic cavity. Eversion stripping of the esophagus is an option for resection in these patients.Presentation of caseA 64-year-old man was admitted to our institution with the chief complaint of epigastric pain. Endoscopic examination showed a protruding lesion 22 cm from the incisors, with a superficial and circumferential mucosal irregularity on the distal side of the lesion. Biopsy revealed squamous cell carcinoma. Clinical stage was T1b(sm)N0M0, cStage I. In addition to the poor pulmonary status of the patient, adhesions in the intrathoracic cavity were predicted. The decision was made to perform esophageal resection without a thoracotomy. In order to ensure complete invagination of the esophagus, the esophagus was insufflated prior to stripping. The stripping process was observed with a gastroscope. During the stripping, the esophagus did not bunch up, and stripping was smooth and with minimal resistance.DiscussionThe stripping resection of the esophagus is an important option for the esophageal surgeon. In this case report, we describe a new eversion stripping method of the esophagus. This easy and reliable stripping method incorporates intraesophageal insufflation.ConclusionThe indications for blunt esophageal dissection without thoracotomy have been decreasing. On the other hand, our method seems to be useful in optimal case of stripping of esophagus.     

胸、腹腔镜联合治疗食管癌2例报告

目的探讨胸、腹腔镜联合治疗食管癌的可行性和近期疗效。方法全麻。胸腔镜经4个trocar游离胸段食管并打开膈肌，留置引流管。腹腔镜同样经4个trocar游离胃。腹腔操作结束后，将食管从颈部切口提出，直视下切除病灶并吻合。留置鼻胃管和鼻空肠管。结果手术时间450、470min；术中出血量150、200ml，病灶彻底清除，切缘阴性。术后病理2例均为高分化鳞癌，T1N0M0。2例均随访4个月，无复发。结论胸、腹腔镜联合食管切除术可行，近期疗效满意。     

Metastasis of cancer to cancer: report of a case of esophageal carcinoma metastasizing to early gastric cancer.

A rare case of esophageal carcinoma metastasizing to early gastric cancer is reported herein. A 66 year old man who had experienced dysphagia for 8 months was preoperatively diagnosed as simultaneously having esophageal and gastric cancers. Thus, a lower esophagectomy and total gastrectomy with paraesophageal and paragastric lymph node dissection were performed. The surgical specimen revealed an ulcerative tumor in the lower esophagus and a slightly depressed lesion with a central elevation similar to that of early type IIc + IIa gastric cancer in the upper part of the stomach. Microscopically, the esophageal tumor was revealed to be well differentiated squamous cell carcinoma while the gastric tumor was found to be early gastric cancer with a metastatic focus of esophageal cancer in the center. Though less than one hundred cases of metastasis of cancer to cancer have previously been reported, metastasis from cancer of one digestive organ to that of another digestive organ is very rare. To our knowledge, this report represents the first case of an esophageal carcinoma metastasizing to a gastric carcinoma.     

Outcome of histologically node-negative esophageal squamous cell carcinoma

The outcome of node-negative esophageal carcinoma and the prognostic significance of lymph node micrometastasis remain unknown. The aim of this retrospective study was to clarify these two points. A series of 98 patients who underwent curative operation for histologically node-negative (pN0 in TNM classification) esophageal carcinoma were enrolled in the study. We reviewed the cause of death of these patients. The survival curves were calculated and compared after stratifications according to clinicopathologic parameters. Lymph node micrometastasis in the patients with recurrences was examined using immunohistochemical staining of cytokeratin. Their ages ranged from 45 to 83 years (mean 64.3 years). There were 83 men and 15 women. Altogether, 54 patients were still alive, and 44 had died. A total of 9 patients died from recurrence of their esophageal carcinoma, 33 died from other causes (pneumonia 11, extraesophageal carcinoma 7, and so on), and 2 died from unknown causes. Eight patients had locoregional recurrences, and two patients had distant recurrences. The overall survival rate for the 98 patients was 58.2%. The survival for patients with pT2 or pT3 tumors was significantly worse than for those with pTis or pT1 tumors (p = 0.02, log-rank test). Other clinicopathologic factors did not affect the prognosis. Immunohistochemical study found no lymph node micrometastasis in 365 lymph nodes resected from the patients with recurrences. Only the depth of tumor invasion affected the outcome of patients with node-negative esophageal carcinoma. Altogether, 75% of patients died of other causes without recurrence, with the two main causes of death being pulmonary complications and extraesophageal carcinoma in these patients. Lymph node micrometastasis was not associated with recurrence in this series.     

Extrathoracic esophagectomy in the treatment of esophageal cancer

Extrathoracic esophagectomy has the potential of improving the results of resectional therapy for carcinoma of the esophagus by eliminating the need for thoracotomy and decreasing postoperative pulmonary complications. This report compares the operative and functional results of blunt extrathoracic esophagectomy and substernal reversed gastric tube reconstruction in patients with esophageal cancer to results in 10 consecutive nonrandomized control patients treated by standard esophagogastrectomy. Extrathoracic esophagectomy was associated with greater pulmonary dysfunction than standard esophagogastrectomy. While there was no significant difference in survival in the two groups, three patients in the standard esophagogastrectomy group (mean survival 9.0 months) and none in the extrathoracic esophagectomy group (mean survival 7.4 months) developed anastomotic recurrence. Extrathoracic esophagectomy evidently does not afford patients with esophageal carcinoma better palliation than standard esophagogastrectomy.     

微创食管癌切除术后淋巴结转移规律及预后分析

目的淋巴结转移是食管癌转移的主要方式,对食管癌患者预后有重要影响,本文探讨食管癌胸腹二区淋巴结的转移规律。 方法选取2010年1月至2016年10月于山东大学齐鲁医院经微创食管癌切除术(minimally invasive esophagectomy, MIE)治疗的食管癌患者613例,参照日本食管肿瘤研究会(JEOG)淋巴结分区标准清扫淋巴结,统计各组淋巴结的转移率。对2010年1月至2013年10月行MIE治疗的203例食管癌患者进行生存分析。另外410例患者由于术后时间较短,随访数据未列入统计。 结果胸上段食管癌较多发生上纵隔淋巴结转移,其左、右喉返神经旁淋巴结转移率分别高达35.9%、40.7%,均显著高于胸中段和胸下段食管癌;胸中段食管癌既向上发生上纵隔淋巴结转移,又向下发生腹腔淋巴结转移;胸下段食管癌主要向胃周淋巴结转移,其中胃左动脉旁淋巴结转移率最高。单因素分析结果显示,病变长度、肿瘤分化程度、肿瘤浸润深度、淋巴结转移程度是影响食管癌患者预后的相关因素(P< 0.05)。COX多因素回归分析结果显示,肿瘤低分化和淋巴结转移是影响食管癌患者预后不良的独立危险因素(P< 0.05)。 结论手术治疗食管癌应重点清扫双侧喉返神经旁淋巴结和胃左动脉旁淋巴结。     

The management of treatment-related esophageal complications in children and adolescents with cancer

Background and Purpose

Serious treatment-induced esophageal strictures and tracheoesophageal fistulae are rare in the pediatric oncology population. This report details our experience with their management.

Methods

We retrospectively reviewed our experience with pediatric oncology patients treated for esophageal complications over a 23-year period. Serious complications were defined as development of strictures requiring dilatation or an esophageal fistula. Fifteen patients were identified, 5 of which had been previously reported.

Results

Thirteen patients developed esophageal stricture, and 2 progressed to tracheoesophageal fistulae. The remaining 2 patients developed tracheoesophageal fistulae without antecedent stricture. The median interval from cancer diagnosis until development of esophageal complications was 3.5 years (range, 0.4-11.8 years). Before development of esophageal complication, 14 patients (93%) were treated with mediastinal radiation and 7 (47%) for candidal esophagitis.Strictures were most commonly located in the distal esophagus (5), then midesophagus (3), cervical esophagus (3) and diffusely (2). A median of 5 dilatations (range, 1-50) were necessary before patients were able to resume a normal diet. The origin of tracheoesophageal fistulae was the midesophagus (3) and distal esophagus (1). All 4 patients with fistulae were treated with esophageal division and diversion followed by esophagocoloplasty.

Conclusions

Esophageal strictures and fistulae may occur because of cancer therapy in childhood. Prevention includes early treatment of esophagitis especially Candida mucositis, and minimization of radiation dose to the esophagus. Strictures usually respond to dilatation, but fistulae require esophageal diversion and secondary reconstruction.     

放射免疫显像在食管癌分期中的应用

目的 探讨放射免疫显像（RII）在食管癌分期的应用。方法 （1）LSAB法测定组织切片和抗人食管鳞癌单抗G9的反应;（2）^125I标记G9,在荷食管癌裸鼠腹腔注射^125I-G9后的连续3d内,测定各主要组织、器官的放射性;（3）食管鳞癌术前经纤维食管镜在原发灶周围黏膜下注射^131I-G9后行RII;（4）对清扫淋巴结行放射性测定。结果 （1）LSAB显示癌原发灶和转移淋巴结呈阳性,正常食管和淋巴结阴性;（2）^125I-G9在裸鼠体内分布显示,肿瘤组织的放射性计数均明显高于其它器官／组织;（3）镜下注药48h时RII在食管旁纵隔、贲门旁、胃小弯旁出现散在的细点状放射性浓集,浓集区域所清扫的淋巴结中,包含有转移淋巴结;无浓集区域,未发现转移淋巴结;（4）全部有转移淋巴结的放射性比活度均比无转移高,且均数高出两倍多。结论 （1）单抗G9能选择性定位于食管鳞癌细胞膜;（2）^125I-G9在荷食管癌裸鼠有肿瘤组织导向作用,显像效果良好;（3）用^131I-G9在食管鳞癌行RII,对转移淋巴结有定位作用,可作为cTNM分期的选择手段。     

Bilateral approach for thoracoscopic esophagectomy with lymph node dissection in the dorsal area of the thoracic aorta in patients with esophageal cancer: A report of two cases

IntroductionThe incidence of lymph node metastasis in the dorsal area of the thoracic aorta (DTA) is relatively low in patients with esophageal cancer. It is difficult to approach the DTA using surgical procedures, such as an open thoracotomy and thoracoscopy in the left decubitus position.Case presentationCase 1: A 70-year-old man with esophageal cancer underwent thoracoscopic esophagectomy with mediastinal lymph node dissection via a right thoracoscopic approach, followed by lymphadenectomy in the DTA via left thoracoscopy in the prone position. Microscopic findings revealed two metastatic lymph nodes in the DTA. The definitive diagnosis was squamous cell carcinoma of the esophagus, and the pathological stage was T2N3M0 (Union for International Cancer Control [UICC], 7th edition). The patient showed lung metastasis 8 months after the surgery. Case 2: A 72-year-old man with esophageal cancer underwent esophagectomy via a bilateral approach in the prone position, using a similar procedure as in case 1. The definitive diagnosis was squamous cell carcinoma of the esophagus, and the pathological stage was T3N2M0. The patient showed a metastatic mediastinal lymph node 4 months after the surgery.ConclusionBilateral thoracoscopic esophagectomy in the prone position can be safely performed, and it might be an alternative curative surgery for esophageal cancer. However, both our cases showed metastasis in the early postoperative period. The long-term outcome and significance of dissection of lymph nodes in the DTA in patients with esophageal cancer remains controversial. Further studies are required to establish the indications and efficacy of this therapeutic approach.     

Endoscopic and histopathological studies of experimental esophageal cancer in beagles

In order to obtain a reliable experimental model simulating human esophageal cancer, endoscopic and histopathological studies were undertaken in the esophageal cancer produced in the beagle dog. Thirty-seven dogs had been given a solution of N-Ethyl-N'-nitro-N-nitrosoguanidine (ENNG) at a concentration of 150 micrograms/ml for 3-9 months. Follow-up studies included serial endoscopy and biopsy, and almost all animals were eventually sacrificed for histological examination. The results were as follows: Squamous cell carcinoma was observed in 5 out of 22 female dogs, while none in male dogs at all. For the induction of squamous cell carcinoma in the esophagus, administration in the condition of 150 micrograms/ml (75mg/day) for 6-9 months was most suitable. Almost all of esophageal lesions were protruding and well-differentiated squamous cell carcinoma with invasion of the submucosa. The stages of hyperplasia, dysplasia and squamous cell carcinoma in the esophagus were chronologically followed. Carcinoma had been observed in the stomach about 4 months prior to the appearance of esophageal carcinoma. This experimental model was proved to be useful for studies on histogenesis of human esophageal cancer both light and electron microscopically.     

Changes and complication rate in surgery for thoracic esophageal carcinoma

AIM: In an analysis over 22 years it was investigated which parameters have changed in the operative treatment of thoracic esophageal carcinoma over time and in how far they have influenced complication rate. PATIENTS AND METHODS: Between 1978 and 1999 386 patients (350 men, 36 women) underwent resection for thoracic esophageal carcinoma (squamous cell carcinoma n=300, adenocarcinoma n=86). Cervical tumors were excluded from analysis. The time periods from 1978 to 1988 (n=242) and from 1989 to 1999 (n=144) were separately analyzed and compared with respect to age, sex, histological type, main tumor location, neoadjuvant therapy, method of operation, esophageal substitute and positioning of the substitute, R-status, pT/pN classification, UICC stage, number of dissected lymph nodes, complication rate, postoperative mortality and survival. RESULTS: Comparison of the two time periods showed a significant increase in adenocarcinomas and main tumor location in the lower thoracic third of the esophagus. Furthermore, significant changes concerning the indication of neoadjuvant chemoradiation, operative approach, esophageal substitute, R-status and number of dissected lymph nodes were observed. Tumor stage (pT/pN classification and UICC stage) significantly shifted towards earlier stages. Total complication rate dropped tendentially form 68.5 % to 59.0 % (p=0.061). Hospital mortality was significantly reduced from 24 % to 12.5 %, whereas anastomotic leakages and multiorgan failure remained on a constant level. Median survival of R0 resected patients was significantly prolonged from 19 months to 34 months. CONCLUSIONS: The increase of esophageal adenocarcinoma, a more strict patient selection (staging, functional status), standardization of operative technique as well as an optimized intensive care management are among the important changes in the operative management of thoracic esophageal carcinoma that have resulted in an improvement of prognosis of curatively resected patients. In spite of a more aggressive operative approach, i. e. lymph node dissection, operative mortality could be reduced by nearly 50 % in the face of a tendentially declining total complication rate.     

Surgical results of small sized (less than 3 cm) advanced lung cancer]

We studied the surgical results in 31 patients with small sized but advanced lung cancer. Twenty-two patients had mediastinal lymph node metastasis, 6 had pulmonary metastasis, 3 had pleural dissemination. Histological type were adenocarcinoma in 21 patients, large cell carcinoma in 5 patients, small cell carcinoma in 4 patients. The 5-year survival rate in patients with mediastinal lymph node metastasis (pT1N2) was 24.1%. The 5-year survival rate in patients (pT1N2) for clinical N0, N1 was 34.6%, but no patient with clinical N2 disease survived more than 2 years after the operation. In the patients with pulmonary metastasis or pleural dissemination none survived more than 5 years after the operation.