High-dose chemotherapy with autologous PBSC transplantation for poor prognosis germ cell tumors: a retrospective monocenter analysis of 44 cases.

Germ cell cancer (GCC) is curable in metastatic stages. The International Germ Cell Cancer Collaborative Group (IGCCCG) reports a poor prognosis subgroup with a 5-year survival of 48%. High-dose chemotherapy with PBSC transplantation (HD-PBSCT) in these patients showed promising results in phase II, but failed to show significant advantage in randomized trials. We report our monocenter series of all poor and selected intermediate prognosis germ cell tumor patients treated with multiple-course HD-PBSCT and secondary surgery of remaining tissue. We performed a retrospective analysis of our complete series of 44 patients (40 poor prognosis and 4 intermediate prognosis) treated by HD-PBSCT as part of first-line therapy from 1999 to 2010. The CR rate after up to four cycles of HD-PBSCT and radical resection of residual manifestations was 73%. The 3-year survival rate was 79.5% (median follow-up of 51.5 months; range: 7-143 months). Disease-related death rate was 16%. HD-PBSCT-related death did not occur. One patient died postsurgery. Multiple courses of HD-PBSCT with radical secondary surgery is safe and effective in poor prognosis metastatic GCC. Despite disappointing phase III studies it is of high interest to further study this field.

[CT-guided cutting needle biopsies of thoracic lesions in patients with negative bronchoscopic findings]. / CT-gesteuerte Stanzbiopsien thorakaler Läsionen bei Patienten mit bronchoskopisch negativen Voruntersuchungen.

PURPOSE: The usefulness and the complication rate of CT-guided core biopsies for obtaining specimens for histopathological examinations in patients with uncertain thoracic lesions were evaluated. MATERIALS AND METHODS: Under local anesthesia CT-guided core biopsies were performed in 121 patients using tru-cut systems (14-18 gauge). Prior to CT all patients underwent bronchoscopy without obtaining sufficient material for a definite histopathological diagnosis. The following areas were punctured: lungs 84 (69%), pleura, chest-wall, ribs 24 (20%) and mediastinum 13 (11%). The diameter of the punctured lesion averaged 4.3 cm. RESULTS: Using CT-guided puncture techniques specimens could be obtained in 118 (97.5%) out of 121 patients. Of these 118 specimens 3 (2.5%) showed marked artifacts and necrosis, which obscured a definite histopathological opinion. In the end the biopsies from 115 (95.0%) out of 121 patients could be used whereby 84 (73.0%) were classified as malignant and 31 (27.0%) as benign. Due to further operations or bronchoscopic procedures in 35 patients additional material was obtained for histopathological tests. In 3 (8.6%) of those 35 patients newly malignant disease was diagnosed, therefore these specimens showed a relevant discrepancy as compared to the result of the CT-guided biopsy. Obviously the vital central part of the tumor was not biopsied due to poor delineation caused by peritumoral infiltration. A small pneumothorax or haemoptysis was seen in 17 (14.3%) out of 121 patients. CONCLUSIONS: Despite negative bronchoscopic findings CT-guided core biopsies will deliver sufficient specimens for histopathological tests in 95% of patients with uncertain thoracic lesions. Infiltrations surrounding the vital part of the tumor may obscure the correct targeting and lead to false negative results in a few patients. Severe complications were not seen in this study, although they might happen in rare cases according to reports in the literature. Therefore CT-guided core biopsies represent an efficient and safe procedure in patients with thoracic lesions.

Mucinous cystadenocarcinoma--an extremely rare tumor in a young patient.

We report on an extremely rare case of pulmonary mucinous cystadenocarcinoma. A 29-year-old male patient was admitted because of progressive enlargement of a right lower lobe mass over a period of 10 years. Right lower lobectomy was performed after a malignant mucinous cystadenocarcinoma was diagnosed by intraoperative frozen section. PET and CT scans did not detect metastatic disease. This case is the youngest patient reported so far with a malignant pulmonary mucinous cystadenocarcinoma and highlights the importance of close follow-up of indeterminate pulmonary nodules in patients with unremarkable history.

Cardiothoracic surgery after heart and heart-lung transplantation.

OBJECTIVE: We sought to examine our management and the outcomes of cardiothoracic procedures after heart and heart lung transplantation. METHODS: We performed a retrospective review of cardiothoracic surgical procedures carried out between 1990 and 2004 in patients who had previously undergone heart or heart-lung transplantation at our institution. RESULTS: Twenty-one out of 340 patients (6.2 %) were identified. Cardiothoracic surgery was performed 44.4 +/- 33 months (range 1 - 115 months) after transplantation. Predominant types of surgery were coronary artery bypass grafting due to allograft vasculopathy (n = 5), aortic surgery due to acute dissection (n = 3), biventricular assist device implantation due to acute rejection (n = 1), tricuspid valve repair (n = 1), multiple cardiac surgical procedures including coronary artery bypass grafting, retransplantation, and tricuspid valve replacement (n = 2), explantation of a functionless heterotopic transplanted heart (n = 1). Lung surgery was performed in six patients due to pneumonia (n = 2), primary lung carcinoma (n = 3), lung torsion following heart-lung transplantation (n = 1). All patients underwent either lobectomy or segmental lung resection. Single lung retransplantation (n = 2) after prior heart-lung transplantation due to bronchiolitis obliterans was performed. In one patient a pneumonectomy (n = 1) due to severe chronic rejection of the contralateral lung was performed. Six subsequent deaths after cardiothoracic procedures were recorded after 1, 4, 78, 163, 205, and 730 days, respectively. Causes of death were advanced carcinoma (n = 1), multi-organ failure due to sepsis (n = 2), sudden heart death (n = 2), and advanced heart failure (n = 1). Fifteen out of 21 patients having undergone cardiothoracic procedures (71.4 %) survived the observation period of 56.6 +/- 34 months (range 1 - 114). CONCLUSIONS: Reasons for cardiothoracic procedures after prior heart or heart-lung transplantation were allograft vasculopathy, aortic dissections years after transplantation, chronic rejection, and either lung infections or malignancies. Surgical repair can be performed with an acceptable operative risk and good long-term survival rates.

Plasma cell granuloma involving the brain and the lung.

BACKGROUND: Symptomatic plasma cell granulomas (PCG) of the central nervous system (CNS) are a rare entity, especially in association with an extracranial manifestation. CLINICAL PRESENTATION: A 13 years old boy was operated on for a symptomatic plasma cell granuloma of the lower lobe of the left lung. Four years later, he suffered his first generalized seizure. CT and MRI scans revealed a small hyperdense lesion, which was located in the right frontal lobe, adjacent to the motor strip. Intervention. Stereotactic guided surgery was performed. A plasma cell granuloma was found, which histopathologically resembled the intrapulmonary lesion, which had been removed four years ago. CONCLUSION: Histological findings, differential diagnosis and specific treatment are reviewed and discussed. Patients with PCG should be radiologically staged. Long term prognosis of PCG is good in cases surgically resectable. Nevertheless, patients require lifelong follow up.

[Primary Burkitt lymphoma of the heart--diagnosis and therapy]. / Primäres Burkitt-Lymphom des Herzens--Diagnose und Therapie.

An 85-year-old patient suffered from progressive deterioration (NYHA III) for several months. Cardiac disease was suspected. Echocardiography as well as a CT scan of the heart revealed a heart tumor to be the cause. Tumor staging was negative. After transvenous biopsy, the diagnosis of a Burkitt lymphoma could be established. Due to the advanced age of the patient, the intended surgical therapy was turned down and the patient was treated with 6 courses of a potentially therapeutic chemotherapy (CHOP scheme), which was well tolerated by the patient. The following CT scan showed a complete remission of the tumor. Six months after chemotherapy the patient is in NYHA stage I.

Coexistence of non-Hodgkin's lymphoma and non-small cell lung carcinoma: diagnosis and treatment.

Abstract. In this communication, we will present a very rare case of the coexistence of non-Hodgkin's lymphoma (NHL; low malignant lymphocytic lymphoma of the B-cell type) and a non-small-cell lung carcinoma (NSCLC). A patient with a 15-year history of NHL developed a generalized relapse of the lymphoma with an additional tumor mass in the left lower lobe of the lung. Bronchoscopy showed the evidence of the NHL. Due to non-responding chemotherapy on the lung tumor, the coexistence of a second malignancy was histologically proved in a second bronchoscopy. Resection of the lung tumor with complex lobectomy and lymphadenectomy was performed. After that, chemotherapy with four cycles of carboplatin supplemented with taxol was induced. The patient was discharged from the hospital with a stable remission of both tumor diseases. Restaging after six months showed no evidence of a tumor relapse. This is a very rare case of the coexistence of NHL and NSCLC; we will discuss the difficulty of diagnostic and treatment of both tumor diseases.

[Not Available]. / Primäres Burkitt-Lymphom des Herzens - Diagnose und Therapie.

An 85-year-old patient suffered from progressive deterioration (NYHA III) for several months. Cardiac disease was suspected. Echocardiography as well as a CT scan of the heart revealed a heart tumor to be the cause. Tumor staging was negative. After transvenous biopsy, the diagnosis of a Burkitt lymphoma could be established. Due to the advanced age of the patient, the intented surgical therapy was turned down and the patient was treated with 6 courses of a potentially therapeutic chemotherapy (CHOP scheme), which was well tolerated by the patient. The following CT scan showed a complete remission of the tumor. Six months after chemotherapy the patient is in NYHA stage I.

Leiomyosarcoma of the pulmonary artery--a diagnostic chameleon.

A 60-year-old woman suffered from right-sided pain in the back and dyspnea suspicious for chronic pulmonary thromboembolism. Since computed tomography demonstrated a progressive filling defect within the left pulmonary artery, a transvenous biopsy was taken, which demonstrated malignant sarcoma. The patient underwent left-sided pneumonectomy with the aid of cardiopulmonary bypass. In case of a suspected 'chronic' pulmonary embolism with occlusion of a main pulmonary artery, as may be seen with imaging techniques, a sarcomatous disease should be ruled out, especially if there are no coagulation disorders, and the tumor obliterations progress in serial CT scans despite effective anticoagulation.

Primary pigmented malignant schwannoma in the posterior mediastinum.

This paper describes a rare case of primary pigmented malignant schwannoma arising from the sympathetic trunk in the posterior mediastinum. A 30-year-old woman underwent a thoracoscopic tumor extirpation. A primary pigmented malignant schwannoma was diagnosed histologically. The tumor presented fascicles and whorls of pigmented plump spindle cells and positive immunoreactivity to S-100 protein, vimentin, and HMB-45. Postoperative radiotherapy of the mediastinum was performed. Our case demonstrates the successful thoracoscopic resection and postoperative radiation treatment of a malignant schwannoma.

Lung cancer surgery--preoperative risk assessment and patient selection.

Lung resection remains the therapy of choice offering the greatest potential for cure in non spread lung cancer. As these procedures have a significant rate of cardiopulmonary complications, risk assessment and evaluation of functional operability is essential for successful resectional surgery. The most valuable parameters for evaluation of lung function and risk assessment are FEV1, DLCO and VO2max as well as the calculation of predicted postoperative lung function. With preoperative preparatory physical therapy and treatment of comorbidities, also marginal patients may become operable for resectional surgery.

An epicardial cyst in a child.

An 8-year-old girl, without any previous medical history, presented with a first short syncope. Physical examination was unremarkable. Transthoracic echocardiography revealed a thin-walled, echo-free cystic structure adjacent to the posterior wall of the left ventricle, and compressing it moderately. Other echocardiographic findings were normal. Both computed tomography and magnetic resonance imaging suggested a simple pericardial cyst, but during surgery we found an epicardial cyst with partial involvement of the circumflex branch of the left coronary artery. Cardiopulmonary bypass was necessary for successful resection of the cyst, leaving behind only the small area in continuity with the coronary artery.

Diagnosis, treatment and outcome of patients with Askin-tumors.

Askin tumors are highly malignant small-round-cell tumors of the thoracopulmonary region, which occur rarely. Therefore, we report on our experiences with eight patients (5 male, 3 females), who were treated in our department between 11'94 and 10'97 (age: 9-40 years, mean age: 20.5 years). All Askin tumors were diagnosed by histological and immunohistochemical examinations as well as molecular genetic proof of characteristic translocations. In all patients, the tumor arose from the chest wall, infiltrating adjacent ribs and parts of the lung. At the time of first diagnosis, five patients did not reveal any metastases. One patient suffered from intrapulmonary metastases and two patients from an infiltration of the diaphragm and of adjacent vertebral bodies. Treatment consisted of a pre- and postoperative (radio-) chemotherapy according to the EVAIA protocol and a radical tumor resection in all patients. The postoperative course was uneventful in seven patients, one patient suffered from pneumonia after multiple wedge resections for intrapulmonary metastases. Four patients, in whom primary tumor resection was complete, are alive 14, 20, 35 and 84 months after first diagnosis - only one patient had to undergo a second operation for a local relapse 17 months after first diagnosis. The other 4 patients, who suffered from a very extensive primary tumor, expired 13, 17, 18 and 39 months after the diagnosis was made. Our data demonstrate that Askin tumors require an aggressive multimodality treatment consisting of pre- and postoperative chemotherapy, radical surgical resection and postoperative irradiation, which may be performed preoperatively in selected cases, too.

Small thymomas and myasthenia gravis: a poorly understood association.

Myasthenia gravis (MG) is associated with about 20% of all patients with thymomas, but the occurrence in patients with small thymomas is rare. The pathogenetic relevance of these small thymomas for MG is poorly understood until now. We report on the clinical course of a 39-year-old female patient suffering from MG and undergoing thymectomy for a small thymoma and discuss the pathogenetic importance of small thymomas for MG.

Recurrent genetic aberrations in thymoma and thymic carcinoma.

Apart from single reported aberrant karyotypes, genetic alterations in thymic epithelial neoplasms have not been investigated so far. In this study, 12 World Health Organization classification type A thymomas (medullary thymomas), 16 type B3 thymomas (well-differentiated thymic carcinomas), and nine type C thymomas, all of them primary thymic squamous cell carcinomas, were analyzed by comparative genomic hybridization and fluorescence in situ hybridization. With the exception of one single case, type A thymomas did not reveal chromosomal gains or losses in comparative genomic hybridization. In contrast, all type B3 thymomas showed chromosomal imbalances, with gain of 1q, loss of chromosome 6, and loss of 13q occurring in 11 (69%), six (38%), and five (31%) of 16 cases, respectively. In primary thymic squamous cell carcinoma, the most frequent chromosomal losses were observed for 16q (six of nine cases, 67%), 6 (4 of 9, 44%), and 3p and 17p (three of nine each, 33%), whereas recurrent gains of chromosomal material were gains of 1q (5 of 9, 56%), 17q, and 18 (three of nine each, 33%). This study shows that the distinct histological thymoma types A and B3 exhibit distinct genetic phenotypes, whereas type B3 thymoma and primary thymic squamous cell carcinoma partially share genetic aberrations. In addition to the possible tumorigenic role, the deletion in type B3 thymoma of chromosome 6, harboring the HLA locus, might play a role in the pathogenesis of paraneoplastic autoimmunity characteristic of thymoma.

Screening for asymptomatic early bronchogenic carcinoma with low dose CT of the chest.

BACKGROUND: Survival of patients with lung carcinoma is very poor, particularly for patients with advanced disease. There are no early clinical symptoms, and screening with chest radiography has not been recommended. Computed tomography (CT) is superior to radiography for detection of pulmonary nodules but usually is associated with relatively high radiation exposure. Recently, accuracy of low dose CT has been shown to be similar to conventional dose CT. The goal of the current study was to assess the findings of low dose CT of the chest in heavy smokers. METHODS: More than 700 heavy smokers (> 20 pack years; age: > 40 years) underwent unenhanced low dose CT of the chest. Detected nodules were classified according to their density (soft tissue, calcified, fat) and size (< 6 mm, 6-10 mm, > 10 mm). In nodules larger than 10 mm with no CT features to suggest a benign lesion, histology was obtained. RESULTS: In approximately 40% of smokers, nodules smaller than or equal to 10 mm were detected. None was resected. In less than 3% of individuals, lesions larger than 10 mm were detected; 8 were bronchogenic carcinoma. All eight carcinomas were resectable. Lesions for which no histology was obtained were followed with low dose CT. CONCLUSIONS: Low dose CT detected 8 bronchogenic carcinomas in more than 700 heavy smokers. All eight were resectable. Pulmonary nodules measuring up to 10 mm were found in 40% of smokers. The significance of these small lesions has remained unclear.

Ploidy, expression of erbB1, erbB2, P53 and amplification of erbB1, erbB2 and erbB3 in non-small cell lung cancer.

The aim of this study was to assess the prognostic value of deoxyribonucleic acid analysis, expression oferbB1, erbB2 and P53, and amplification levels of erbB1, erbB2 and erbB3 in non-small cell lung cancer (NSCLC). Consecutive patients with NSCLC who underwent treatment with curative intention (118) were included. In 108 cases, the cell cycle was analysed using flow cytometry and double-staining with propidium iodide and anticytokeratin. In another 108 cases, expression of erbB1, erbB2 and P53 was assessed immunhistochemically. Amplification of the erbB family was determined in the tumours of 53 patients using double-differential polymerase chain reaction. Of the tumours, 81% were aneuploid and 14% showed positive staining for erbB1, 18% for erbB2 and 41% for P53. There were normal mean gene copy numbers in 86% for erbB1, 94% for erbB2 and in 96% for erbB3. No significant correlations were noted between erbB1, erbB2 and P53 expression, ploidy status and tumour stage. In a Cox regression model, only tumour stage was shown to be prognostically significant. It seems that ploidy and expression status of erbB1, erbB2 and P53 are not prognostic parameters in non-small cell lung cancer. Amplification of the erbB family does not seem to be a frequent event in non-small cell lung cancer.

Impact of preoperative bimodality induction including twice-daily radiation on tumor regression and survival in stage III non-small-cell lung cancer.

PURPOSE: The objective of this prospective study was to assess the feasibility, toxicity, and efficacy of an intensive trimodality approach in stage III non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Fifty-four patients with NSCLC and biopsy-proven N2 nodes (IIIA; n = 25) or N3 nodes or T4 lesions (IIIB; n = 29) were administered two initial cycles of ifosfamide, carboplatin, and etoposide; subsequent radiotherapy (45 Gy, twice-daily 1.5 Gy) with concurrent carboplatin and vindesine; and surgery if the patient's disease was resectable or conventional radiotherapy (16 Gy, 2 Gy/d) if the patient's disease was not resectable or incompletely resectable. RESULTS: Thirty-seven patients (69%) responded to preoperative induction. Forty of 54 patients (74%) had disease that was resectable, with 34 (63%) complete resections (R0). A substantial pathologic response (tumor regression [TR] > 90%) was achieved in 27 of 54 patients (50%) and is revealed as an independent predictor for long-term survival after surgery. Five treatment-related deaths (9%) occurred. With a median follow-up period of 44 months, calculated survival rates at 3 years were 35% for patients with stage IIIA disease, 26% for patients with stage IIIB disease, and 56% for patients with R0 disease and TR > 90%. CONCLUSION: This trimodality approach is feasible and results in encouraging 3-year survival rates in prognostically unfavorable patients with stage III NSCLC. Patients experiencing a 90% degree of pathologic TR were most likely to achieve long-term survival.

Pectus excavatum: special surgical technique, perioperative management and long-term results.

BACKGROUND: It is generally accepted that pectus excavatum should be repaired in childhood if possible. The procedure could be performed conveniently even without implantation of any foreign material. In contrast there are several adult patients with aesthenic or marfanoid habitus and poor thorax cosmetics, who seek medical help especially surgical correction due to late awareness or cardiopulmonary dysfunction. METHODS: Between 1989 and 1997, 22 adult patients (mean age 26 years, 18 males and 4 females) underwent repair of the pectus excavatum in our institution. Patients data were analysed retrospectively. Indication was mainly for aesthetics or cardiopulmonary symptoms, in 3 patients for recurrence after primary repair elsewhere. The total surgical repair technique consisted of V-shape osteotomy of the ribs at the outer and inner limit of the funnel and transverse osteotomy of the sternum without displacement of the posterior cortical The sternal and chest wall stabilization in corrected position was performed with at least two metal struts installed transsternal and transversely. In most of our cases other diagonal struts on both sides were needed to achieve further stabilization of the lowest costal cartilages. The metal struts are removed 1 year after the procedure. RESULTS: All repairs were completed with a low complication rate. Chest radiographs and pulmonary function studies were performed routinely before and after corrective surgery. Good to satisfactory chest contour was achieved in 20 patients (91%), with a follow-up from 5 months to 8 years. CONCLUSIONS: Our current technique with perioperative management is successfully performed in adults and will be presented.