Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan

BACKGROUND: Surgery remains the mainstay of treatment for thymic epithelial tumors, and radiation and chemotherapy also have been applied widely as adjuvant and palliative procedures. METHODS: We compiled records of 1,320 patients with thymic epithelial tumors who were treated from 1990 to 1994 in 115 institutes certified as special institutes for general thoracic surgery by The Japanese Association for Chest Surgery. RESULTS: Patients with stage I thymoma were treated with only surgery, and patients with stage II and III thymoma and thymic carcinoid underwent surgery and additional radiotherapy. Patients with stage IV thymoma and thymic carcinoma were treated with radiation or chemotherapy. The Masaoka clinical stage is an excellent predictor of the prognosis of thymoma and thymic carcinoma, but not thymic carcinoid. In stage III and IV thymoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 93%, 64%, and 36%, respectively. On the other hand, in thymic carcinoma, the 5-year survival rates of total resection, subtotal resection, and inoperable groups were 67%, 30%, and 24%, respectively. Prophylactic mediastinal radiotherapy could not prevent local recurrences effectively in patients with totally resected stage II and III thymoma. Adjuvant therapy including radiation or chemotherapy did not improve the prognosis in patients with totally resected III and VI thymoma and thymic carcinoma. CONCLUSIONS: Total resection is the most important factor in the treatment of thymic epithelial tumors. There is value in debulking surgery in invasive thymoma, but not in thymic carcinoma. We doubt that adjuvant therapy is valuable for patients with totally resected invasive thymoma and thymic carcinoma.     

Synchronous B3 thymoma and lung bronchoalveolar carcinoma

The association between thymic tumors and other intrathoracic or extrathoracic neoplasms is relatively rare; the synchronous occurrence of thymoma and bronchoalveolar carcinoma of the lung has never been described so far. A huge B3 cystic thymoma was found at thoracotomy to be associated with stage IV bronchoalveolar carcinoma (intraparenchymal and pleural metastases). The thymic tumor was completely resected; lung cancer was biopsied only for diagnosis and staging purposes. After an uneventful postoperative course the patient underwent chemotherapy; she is still alive and well one year after surgery.     

Two cases of thymic carcinoma effectively treated by preoperative chemotherapy

A 67-year-old man was admitted with left pleural effusion on chest X-ray film. Chest CT scans showed an anterior mediastinal tumor, left pleural dissemination and pleural effusion. Percutaneous needle biopsy yielded a diagnosis of epitherial carcinoma. The patient underwent 3 courses of systemic chemotherapy (CDDP + ADM + VCR + CPA). At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. A 49-year-old woman was admitted our hospital with supraclavicular lymph nodes swelling. Chest CT scans showed an large mediastinal tumor. Percutaneous needle biopsy yielded a diagnosis of squamous cell carcinoma of thymus. The patient underwent 3 courses of systemic chemotherapy. At achievement of partial response, the tumor was completely resected. Examination of the resected tumor revealed partial response to chemotherapy. These cases indicate the usefulness of preoperative chemotherapy for advanced thymic carcinoma to reduce tumor size and to control local invasion, distant metastasis before operation.     

Three cases of small cell carcinoma of the urinary bladder: a case report

We report three cases of small cell carcinoma of the urinary bladder. Case 1: A 69-year-old man showed microscopic hematuria during follow up of prostate cancer of stage D2. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0. Complete remission was achieved by three courses of chemotherapy consisting of irinotecan and carboplatin. The patient was died by prostate cancer 16 months after the chemotherapy. Case 2: An 83-year-old woman presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage of pT2N0M0 and partial cystectomy was performed. The patient has been alive without any evidence of tumor recurrence at 6 months after surgery. Case 3: An 84-year-old man presented with macroscopic hematuria. The patient was diagnosed with small cell carcinoma of the urinary bladder at the stage ofcT3bN0M1 with multiple liver metastases. Complete remission was achieved by three courses of chemotherapy consisting of etoposide and carboplatin.     

Extragonadal germ cell tumor in the retrovesical region associated with Klinefelter's syndrome: a case report and review of the literature

We report a case of an extragonadal germ cell tumor from the retrovesical region associated with Klinefelter's syndrome. The patient presented with symptoms of macroscopic hematuria and micturition pain. An x-ray and digital examination were suspicious for prostatic carcinoma. However, needle biopsy of the tumor revealed embryonal cell carcinoma. Serum alpha-fetoprotein was 10,700 ng. per ml. Preoperatively, combined cytotoxic chemotherapy was administered and the antineoplastic effect was excellent. Serum alpha-fetoprotein rapidly returned to the normal range and the tumor volume decreased. Although the preoperative diagnosis was extragonadal germ cell tumor of the prostate, surgery revealed that the tumor originated from the retrovesical region. Orchiectomy and resection were performed. The resected tissue was mostly necrotic with a few viable cells of embryonal cell carcinoma, no metastatic lesions were detected in the lymph nodes and no masses were noted in the testes. Postoperatively, the patient was treated with cytotoxic chemotherapy. His condition has remained good with no clinical evidence of recurrence of the disease.     

Thymic basaloid carcinoma

We report a case of thymic basaloid carcinoma combined with multilocular thymic cyst (MTC). A 72-year-old man was found to have an abnormal shadow on a chest X-ray without pny symptoms. Chest computed tomography (CT) showed a smooth edged anterior mediastinum tumor projecting to the left lung field. After preoperative chemotherapy by irinotecan hydrochloride (CPT-11) and radiotherapy of 40 Gy, chest CT showed a large part of the tumor projecting to the left lung field had changed to a cyst. After the pericardium and upper lobe of the left lung to which the MTC adhered was partially resected via left thoracotomy, the tumor was resected with innominate vein via median sternotomy. The operation was followed by CPT-11 chemotherapy and radiotherapy of 20 Gy. The tumor was thymic basaloid carcinoma 3 x 2.5 x 2 cm in size combined with MTC 8.2 cm maximum in diameter. As he died of another disease 6 months after excision, sufficient postoperative observation was not obtained. Thymic basaloid carcinoma is rare and only 14 cases including the present case have been reported.     

Papillary adenocarcinoma developed in a thymic cyst

In this report, we describe a case of a thymic carcinoma that developed in a thymic cyst, which was resected by video-assisted thoracic surgery (VATS). Chest radiography of a 68-year-old Japanese woman revealed an abnormal shadow. She was asymptomatic with normal physical examination findings. Chest computed tomography demonstrated a well-confined cystic mass that measured 4 cm in diameter occupying the anterior mediastinum. Based on these findings, a thymic cyst was suspected. It was completely resected by VATS. The excised cyst was multiloculated with a partially thick wall. Microscopic examination revealed that the nodular excrescence of the wall to be limited to papillary adenocarcinoma and the cyst wall to be lined by cuboidal cells. On the basis of this diagnosis, we performed multidrug adjuvant chemotherapy. The patient was alive without any sign of recurrence 15 months after the operation.     

Successful long-term management of hepatic and lymph nodes metastases of ureteral cancer by multimodal treatment including radiofrequency ablation

A 56-year-old man presented with asymptomatic gross hematuria. Computed tomography (CT) scan revealed right hydronephrosis and a slightly enhanced invasive tumor in the right lower ureter, providing a diagnosis of ureteral cancer stage cT3NOM0. The patient underwent minimum incision endoscopic nephrouretectomy, and pathological examination of the resected specimen revealed urothelial carcinoma and squamous cell carcinoma with metastases to right obturator lymph nodes (pT3pN2). Ten months later, CT scan of the abdomen revealed two hepatic metastases. After three courses of combination chemotherapy consisting of gemcitabine and cisplatin (GC), one tumor completely disappeared and another achieved a partial response. The patient underwent radiofrequency ablation (RFA) for the residual followed by GC chemotherapy. However, eighteen months later, CT scan of the abdomen revealed two metastatic foci in other hepatic lesion. The patient underwent RFA again followed by GC chemotherapy and then all hepatic metastases have not revealed enlargement. More than three years after surgery, the patient has achieved a high quality of life.     

Thymic carcinoid in association with MEN syndromes.

Although carcinoid tumors in association with multiple endocrine neoplasia syndrome (MEN) has been well described, thymic carcinoid in association with MEN is extremely rare (only 23 cases in the world literature). A patient with thymic carcinoid and MEN-I was treated with surgical resection and postoperative radiation therapy, which was later followed by subtotal parathyroidectomy for hyperparathyroidism. Four years later, a symptomatic recurrence of his thymic carcinoid was resected from below his right clavicle. Six years after his original operation, the patient came to the hospital with pancreatitis, and a 5 cm, distal, pancreatic metastasis was resected. He now has symptomatic paraspinal and pleural metastases and is receiving somatostatin. Review of the world's literature shows that the majority of patients with thymic carcinoid and MEN-I are men with an average age of 37 years. Their clinical course is indolent, and surgery represents the only means of cure. Adjuvant chemotherapy and radiation therapy confer no survival advantage. The surgical decision making involved in treating a patient with thymic carcinoid and hyperparathyroidism associated with MEN is also discussed.     

Thymic large cell neuroendocrine carcinoma: report of a resected case - a case report

Thymic large cell neuroendocrine carcinomas (LCNECs) are very rare. We here describe a case in which the tumor could be completely resected. A 55-year-old male was admitted to our hospital for treatment of an anterior mediastinal tumor found at a regular health check-up. The patient underwent an extended thymectomy of an invasive thymoma of Masaoka's stage II that had been suspected preoperatively. The tumor was located in the right lobe of the thymus and was completely resected. Final pathological diagnosis of the surgical specimen was thymic LCNEC. The patient underwent adjuvant chemotherapy with irinotecan and cisplatin in accordance with the diagnosis of a lung LCNEC, and is alive without recurrence or metastasis 16 months after surgery.     

Primary small cell carcinoma of the esophagus: Report of a case

A case of esophageal small cell carcinoma successfully treated with combination therapy consisting of both pre- and postoperative chemotherapy as well as surgical resection is presented. A 74-year-old man presented with a small cell carcinoma measuring 11 cm in diameter in the lower half of his thoracic esophagus. After undergoing preoperative chemotherapy with cisplatin (25 mg, iv, days 1 through 5), the gross tumor completely regressed. However, a microscopic focus of residual cancer showing squamous cell carcinoma was found in the resected esophageal specimen. The patient received an additional two courses of postoperative chemotherapy with cisplatin (75 mg, iv monthly). He has since survived more than 9 years with no evidence of recurrent disease. We herein report a rare case of a patient with esophageal small cell carcinoma who demonstrated a complete cure.     

Surgical treatment of thymic carcinomas

Five cases of surgically treated thymic carcinoma are reported. The patients (4 men and a woman) ranged in age from 46 to 76 years old with a mean of 64.6. Four patients were asymptomatic and an abnormal shadow on X-ray films was noted. One remaining patient suffered from hoarseness. One patient had stage II disease and the others had stage III. Surgical tumor resection was performed in all cases. Only 1 patient among the 5 underwent a successful complete resection. Histological examinations of the resected specimens revealed squamous cell carcinoma of thymus. Four specimens were poorly differentiated and 1 is moderately differentiated carcinoma. All patients received radiation therapy post operatively. Three patients are alive without any recurrence 6, 8 and 109 months after the surgery. Thymic carcinomas are frequently invasive or metastatic at the time of diagnosis. But poorly differentiated group, in squamous cell carcinoma, mucoepidermoid carcinoma and besaloid carcinoma, are characterized by a low incidence of local recurrence and distant metastasis. They also have a good sensitivity for the radiation. Therefore complete surgical resection combined with postoperative radiation therapy should be a choice in treating thymic carcinomas. We considered that complete resection and postoperative radiation therapy is a curative therapy for thymic carcinomas.     

Complete resection of thymic carcinoma supported by cardiopulmonary bypass

We would like to report on a case of thymic carcinoma that could be completely resected supported by extracorporeal circulation. A 53-year-old female complaining of severe coughing and hoarseness was admitted to our hospital. Her chest X-ray film revealed an abnormal shadow in the upper mediastinum and an elevation of the left diaphragm. Chest CT and MRI showed an anterior mediastinal mass that invaded the main pulmonary artery. The preoperative histological diagnosis of thymoma was made by mediastinoscopic specimen. After 50 Gy irradiation, surgery was performed. During the operation, after resection of the left brachiocephalic vein and a part of the upper lobe of the left lung, the tumor was detached from the wall of the aorta and resected with the invaded part of the pulmonary artery supported by cardiopulmonary bypass. Reconstruction of the pulmonary wall defect was accomplished with Xenomedica. The final pathological diagnosis was thymic adenosquamous carcinoma. The postoperative course has been uneventful 24 months after surgery. Extracorporeal circulation is a useful technique in operations involving malignant diseases when complete resection is able to be accomplished.     

Which stages of thymoma benefit from adjuvant chemotherapy post-thymectomy?

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was 'Which stages of thymoma benefit from adjuvant chemotherapy post thymectomy?' Altogether more than 150 papers were found using the reported search, of which only eight represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated; these studies have mainly reported the survival and recurrence rates of post-thymectomy patients who received adjuvant radiotherapy or chemoradiotherapy, and adjuvant radiotherapy alone was only used in a small group of patients in these studies. We did not find any randomized controlled trials comparing adjuvant chemotherapy with chemo/radiotherapy and, due to a very small incidence of this tumour, it is unlikely to see any trials in future. Studies were mainly retrospective or institutional reports and showed that, despite the high sensitivity of this tumour to chemotherapy agents and the use of chemotherapy as one of the main treatment modalities in the advanced stages of thymoma, current data are not supporting postoperative chemotherapy as a sole adjuvant treatment in advanced stages of thymoma. We conclude that, in patients with thymoma, surgical resection with or without radiation therapy is the gold standard treatment for early-stage disease (I and II). Adjuvant radiotherapy/chemoradiotherapy should be considered for Masaoka stage III (A and B) or above, and it is also advised to add adjuvant therapy for all patients with cortical fenestration, even in stages I and II. But there is no evidence that chemotherapy alone improves the survival in patients with completely resected stage III and IV thymomas and thymic carcinoma. In patients with extra-radiation field disease, however, the use of chemotherapy can potentially improve survival but no follow-up data on this group of patients are available.     

Long-term outcome after multimodality treatment for stage III thymic tumors

BACKGROUND: Surgery remains the cornerstone of therapy for thymic tumors, but the optimal treatment for advanced, infiltrative lesions is still controversial. The introduction of multimodality protocols has substantially modified survival and recurrence rate. We reviewed our 13-year prospective experience with multimodality treatment of stage III thymoma and thymic carcinoma. METHODS: Since 1989 we have prospectively used a multimodality approach in 45 stage III thymic tumors. Sixteen patients (35%) had myasthenia gravis. Twenty-three patients (51%) had pure or predominantly cortical thymoma (group 1), 11 (24.5%) had well-differentiated thymic carcinoma (group 2), and 11 (24.5%) had thymic carcinoma (group 3). Tumors that were not considered radically resectable at preoperative workup underwent biopsy and induction chemotherapy (15 patients, 33%) followed by surgical resection; all patients were referred for adjuvant chemoradiotherapy. RESULTS: No operative mortality was recorded; 1 treatment-related death during adjuvant chemotherapy was observed in group 1. Complete resection was feasible in 91% of patients in groups 1 and 2 and 82% in group 3. The overall 10-year survival was 78%. Ten-year survival for groups 1 and 2 was 90% and 85%, respectively; 8-year survival for group 3 was 56%. During follow-up, tumor recurrence was noted in 3 patients (13%) from group 1, 3 (27%) from group 2, and 3 (27%) from group 3. CONCLUSIONS: Multimodality treatment with induction chemotherapy (when required) and adjuvant chemoradiotherapy offers encouraging results for stage III thymic tumors; the outcome is more favorable for cortical thymoma and well-differentiated thymic carcinoma.     

Clinicopathologic assessment of primary thymic carcinoma based on seven cases

In order to study clinicopathologic characteristics of thymic carcinomas, seven patients experienced in our department were reviewed in this paper; 6 patients underwent thoracotomy and one did not receive surgical treatment. Among 6 who received operation, the tumor was resected totally in 3, subtotally in one, partially in one. One patient underwent exploratory thoracotomy. There have been no distinctive clinical features including clinical symptoms and radiographical findings from invasive thymomas in 7 primary thymic carcinomas, however, in these malignant tumors there have been no tumor-associated disorders not infrequently observed in thymomas. Postoperatively, distant metastasis was common in patients with thymic carcinomas, even though the primary tumor was resected totally in the operation. However, one patient with squamous cell carcinoma of the thymus who underwent subtotal tumor resection followed by radiotherapy and chemotherapy are surviving over 6 years postoperatively. Intensive treatment including pre- and postoperative radiation, tumor resection and postoperative chemotherapy is absolutely necessary for thymic carcinoma. Histologically, there were 4 squamous cell carcinomas and 3 large cell carcinomas. One of 3 large cell carcinomas showed squamous cell differentiation histologically. Two of 4 squamous cell carcinomas demonstrated concomitant entity of residual thymus tissue as well as thymoma in one specimen. However, further studies are necessary to determine precise etiology and tumor characteristics of thymic carcinoma.     

Complete eradication of squamous cell carcinoma of the esophagus with combined chemotherapy and radiotherapy

Chemotherapy (with 5-fluorouracil and either mitomycin-C or cis-platinum) combined with radiotherapy was used either for palliation or as preoperative therapy in 67 patients with squamous cell carcinoma of the esophagus. In 25 patients having chemotherapy and 5000-6000 rads, good local palliation was obtained in 11 (49%) without surgery. In the remaining 25 patients, swallowing was restored with a variety of procedures (primarily Celestine tube or gastric bypass). The average survival time was seven months and two patients are still alive at 9 and 12.5 months. Of 42 patients receiving preoperative chemotherapy and radiotherapy, 35 had surgery. Of these, 13 (37%) had complete eradication of their tumors with no histologic evidence of carcinoma in the resected esophagus or associated lymph nodes. In another six (17%), the only evidence of tumor was small microscopic foci of cancer cells in the wall of the esophagus. The 6-, 12-, and 24-month survival rates for patients having surgery after the combined preoperative chemotherapy and radiotherapy were 83 per cent, 52 per cent, and 30 per cent, respectively. These results are far superior to those previously obtained.     

Long-term local intensive preoperative chemotherapy and joint-preserving conservative surgery for osteosarcoma around the knee

This study evaluated conservative joint-sparing surgery for patients with osteosarcoma around the knee. Of 23 patients with stage IIB osteosarcoma around the knee, 5 were treated with long-term (30-56 weeks) local intensive preoperative chemotherapy consisting of high-dose methotrexate, intra-arterial and intravenous cisplatinum, doxorubicin, and hyperthermic isolated regional perfusion. More conservative resection, sparing the knee joint, was performed with smaller sufficient surgical margin in these 5 patients, preserving good limb function. Excellent local effects were achieved in the resected specimens. These results suggest long-term local intensive preoperative chemotherapy, including intra-arterial cisplatin and hyperthermic isolated regional perfusion, help control local tumor and allow for more conservative surgery.     

A consultation between Andreas Vesalius and Ambroise Paré at the deathbed of Henri II, King of France, 15 July 1559

Fifteen patients (median age 55 years; range 23-69 years) with macroscopic invasive thymoma or thymic carcinoma were treated at Groote Schuur Hospital between 1969 and 1988. Stage 3 (macroscopically invasive) disease was present in 12 patients (80%) and stage 4 (metastatic disease) in 3 (20%). Ten of the patients with stage 3 disease were treated by combined surgery and full-dose mediastinal irradiation; in 2 resection was not possible and they were treated with irradiation alone. One of the patients with stage 3 disease developed progressive thymoma (median follow-up 74 months). This patient and 2 others died; 1 from mediastinitis after surgery for thymic carcinoma and 1 of unrelated disease. Both patients treated by irradiation alone were free of disease at follow-up. In the patients with stage 3 disease, the relapse rate was 8% (crude) and the 5-year disease-free survival rate 86% (life table). The patients with stage 4 disease received cisplatin-based combination chemotherapy, which was combined with further irradiation and debulking surgery in 2 of the 3 cases. These patients died of malignant disease at between 5 and 42 months, although 1 had a temporary response to chemotherapy. Tumour extent is the most important prognostic factor in these patients. A multidisciplinary approach to therapy is required.