Heart dose exposure as prognostic marker after radiotherapy for resectable stage IIIA/B non-small-cell lung cancer: secondary analysis of a randomized trial.

Background: Heart exposure to ionizing irradiation can cause ischaemic heart disease. The partial heart volume receiving ≥5 Gy (heartV5) was supposed to be an independent prognostic factor for survival after radiochemotherapy for locally advanced non-small-cell lung cancer (NSCLC). But validation of the latter hypothesis is needed under the concurrent risks of lung cancer patients. Patients and methods: The ESPATUE phase III trial recruited patients with potentially operable IIIA(N2)/selected IIIB NSCLC between 01/2004 and 01/2013. Cisplatin/paclitaxel induction chemotherapy was given followed by neoadjuvant radiochemotherapy (RT/CT) to 45 Gy (1.5 Gy bid/concurrent cisplatin/vinorelbine). Operable patients were randomized to definitive RT/CT(arm A) or surgery (arm B) and therefore were treated at two different total dose levels of radiotherapy. HeartV5 and mean heart dose (MHD) were obtained from the 3D radiotherapy plans, the prognostic value was analysed using multivariable proportional hazard analysis. Results: A total of 161 patients were randomized in ESPATUE, heartV5 and MHD were obtained from the 3D radiotherapy plans for 155 of these [male/female:105/50, median age 58 (33-74) years, stage IIIA/IIIB: 54/101]. Power analysis revealed a power of 80% of this dataset to detect a prognostic value of heartV5 of the size found in RTOG 0617. Multivariable analysis did not identify heartV5 as an independent prognostic factor for survival adjusting for tumour and clinical characteristics with [hazard ratio 1.005 (0.995-1.015), P = 0.30] or without lower lobe tumour location [hazard ratio 0.999 (0.986-1.012), P = 0.83]. There was no influence of heartV5 on death without tumour progression. Tumour progression, and pneumonia were the leading causes of death representing 65% and 14% of the observed deaths. Conclusions: HeartV5 could not be validated as an independent prognostic factor for survival after neoadjuvant or definitive conformal radiochemotherapy. Tumour progression was the predominant cause of death. Register No: Z5 - 22461/2 - 2002-017 (German Federal Office for Radiation Protection).

[Functional Outcome after Chest Wall Stabilisation]. / Rippenosteosynthesen - funktionsverbessernd?

This overview reviews the current literature to compare the functional results after surgical and conservative treatment of patients with flail chest and multiple rib fractures. Regarding functional aspects, patients in the early phase after a thoracic trauma are those that benefit most from the stabilisation of the chest wall by internal fixation of the ribs. Patients recover faster from restrictive respiratory disorders, have less pain and return to the workplace earlier after an operation compared with those that receive conservative treatment. In the medium term, however, patients that are treated conservatively also achieve normal pulmonary function values and become free of pain. The period of convalescence after blunt thoracic trauma is generally underestimated. Future studies of the functional outcome after severe chest injuries should take this into account and the development of functional parameters should be monitored for at least 24 months. A prospective data collection of early and long-term surgical results in registries would be suitable to evaluate benefits and indications of chest wall stabilisation.

[Pulmonary Metastases of Colorectal Carcinoma]. / Pulmonale Metastasenchirurgie des kolorektalen Karzinoms.

Treatment strategies for patients with pulmonary metastases of colorectal carcinoma are continuously evolving. This applies mostly to new systemic therapeutic approaches. For carefully selected patients surgical removal of pulmonary metastases remains an important interdisciplinary therapeutic option and is recommended as first treatment option by the guidelines. Five-year survival rates of up to 60 % are reported following pulmonary metastasectomy. Parenchyma sparing resection has been well established in this setting with low morbidity and mortality. Prognostic factors are, among others, complete resection, thoracic lymph node involvement, the number of metastases and the disease free interval. Although data result mostly from retrospective studies, these factors currently help in patient selection.

Pulmonary adenocarcinoma occurring 5 years after resection of a primary pancreatic adenocarcinoma: a relevant differential diagnosis.

Ductal adenocarcinoma of the pancreas is a lethal disease. Surgical extirpation only offers the slim chance for long-term survival in localized disease. We report on a 73 year old female patient who initially underwent successful resection of pancreatic adenocarcinoma in May 2005. She was treated with adjuvant chemotherapy with gemcitabine. In October 2010 the patient noticed increasing dyspnea with haemoptysis. She was soon referred to our center. After the diagnosis of pulmonary adenocarcinoma with widespread metastasis, she was treated with systemic chemotherapy. For a period of next three years, she was treated with different chemotherapy regimens due to repeated episodes of tumor progression. To the best of our knowledge after reviewing the literature, this case represents an unusually clinical course with metachronous pulmonary adenocarcinoma arising after treatment of a primary pancreatic cancer after a long latency period.

Pulmonary leiomyosarcoma mimicking glomus tumor at first biopsy and surgically treated with isolated left main bronchus resection: rare clinical documentation.

Soft tissue tumors originating within the endobronchial tree are extremely rare and most of them correspond to lipomas or leiomyomas. We here report a rare clinical presentation of leiomyosarcoma mimicking glomus tumor at initial biopsy arising from the left main bronchial trunk leading to left lower lobe atelectasis. Primary leiomyosarcoma of the lung is an unusual malignancy. Among this entity, the endobronchial form is very rare and the preoperative diagnosis is extremely difficult. We documented two different presentations and outcomes of primary endobronchial leiomyosarcoma of the lung. In this clinical presentation, histological study and immunohistochemical stain of the surgical resection provided the final diagnosis. Through the following we present the diagnostic and therapeutic difficulties encountered with endobronchial leiomyosarcoma.

Pleural mesothelioma presenting as periumbilical metastasis: the first clinical documentation.

Introduction. Pleural mesothelioma with metastasis to the subcutaneous tissue of the abdominal wall at first diagnosis and without penetration into the peritoneum is an extremely rare clinical presentation. Methods. Patients with pleural mesothelioma have low survival rate. Usually, the disease at presentation is confined to its site of origin (most often the pleural cavity). A 55-year-old man was referred to our center due to increasing dyspnea and a painful periumbilical mass in the anterior abdominal wall. CT scan revealed both advanced mesothelioma of the pleura and a tumor mass confined to the subcutaneous fatty tissue without penetration through the peritoneum. Results. Video-assisted thoracoscopy confirmed the diagnosis of epithelioid pleural mesothelioma, which was also confirmed by a biopsy of the periumbilical mass. Systemic chemotherapy with cisplatin and pemetrexed was initiated. Under the ongoing systemic chemotherapy, the evaluation revealed partial remission of pleura mesothelioma and its subcutaneous manifestation of the abdominal wall. Conclusion. Mesothelioma of the pleura with a simultaneous metastasis to the subcutaneous fatty tissue of the abdominal wall at presentation without penetration of peritoneum is a rare clinical presentation of mesothelioma disease. The knowledge of its natural history is very limited. This is the first ever clinical documentation of a patient with pleura mesothelioma and simultaneous subcutaneous manifestation of abdominal wall.

Lung metastasis of primary alveolar soft-part sarcoma occurring 20 years after initial treatment.

A 30-year old woman was referred to our center because of suspicion of a primary lung tumor of the right upper lobe. Histological examination of the lung lesion revealed lung metastasis of a previously treated alveolar soft part sarcoma of the musculus vastus medialis of the right femur, which was resected 20 years ago. Alveolar soft-part sarcoma is a rare malignant tumor that occurs most often in the soft tissue of lower limbs. It is a slow-growing malignant soft tissue tumor arising in muscle tissue, usually in young adults. Due to pleural and extensive mediastinal infiltration with bilateral lung metastases, a systemic treatment with chemotherapy doxorubicin and ifosfamide was initiated. Late metastases from previously treated alveolar part sarcoma should be considered in patients with suspicious lung lesions even if surgical treatment was performed a long time ago.

Canine scent detection in the diagnosis of lung cancer: revisiting a puzzling phenomenon.

Patient prognosis in lung cancer largely depends on early diagnosis. The exhaled breath of patients may represent the ideal specimen for future lung cancer screening. However, the clinical applicability of current diagnostic sensor technologies based on signal pattern analysis remains incalculable due to their inability to identify a clear target. To test the robustness of the presence of a so far unknown volatile organic compound in the breath of patients with lung cancer, sniffer dogs were applied. Exhalation samples of 220 volunteers (healthy individuals, confirmed lung cancer or chronic obstructive pulmonary disease (COPD)) were presented to sniffer dogs following a rigid scientific protocol. Patient history, drug administration and clinicopathological data were analysed to identify potential bias or confounders. Lung cancer was identified with an overall sensitivity of 71% and a specificity of 93%. Lung cancer detection was independent from COPD and the presence of tobacco smoke and food odours. Logistic regression identified two drugs as potential confounders. It must be assumed that a robust and specific volatile organic compound (or pattern) is present in the breath of patients with lung cancer. Additional research efforts are required to overcome the current technical limitations of electronic sensor technologies to engineer a clinically applicable screening tool.

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia: 7-year follow-up of a rare clinicopathologic syndrome.

BACKGROUND: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare clinical pathological syndrome. There have been only 49 cases of DIPNECH reported in the literature so far. We report a case of a 69-year-old nonsmoking man with a 7-year follow-up. METHODS: The initial CT scan from December 2003 showed persistent nonspecific bilateral reticulonodular infiltrates. In January 2004, the patient underwent a video-assisted thoracoscopic wedge resection of his right lower lobe for further diagnostic workup. Pathology of the resected wedge of the right lower lobe revealed a diffuse idiopathic pulmonary cell hyperplasia (DIPNECH) highlighted by staining for the neuroendocrine typical carcinoid markers, such as marker CD 56. RESULTS: All the performed CT scans over a 7-year period showed no progression of the bilateral pulmonary lesion. The bilateral pulmonary nodules were stable in terms of size, number and form. The yearly control with chest CT scans will be continued. CONCLUSIONS: The neuroendocrine cell hyperplasia is confined to the airway mucosa without penetration through the basement membrane and appears in a diffuse pattern, generally in close association with obliterative bronchiolar fibrosis. DIPNECH is characterized by a mixed obstructive and/or restrictive ventilation pattern with bilateral reticulonodular infiltrates and a predilection for middle-aged women. Little is known about the clinical course and treatment for DIPNECH.

[Bronchial aspergillosis]. / Bronchiale Aspergillosen.

Bronchopulmonary aspergillosis is becoming more frequent, is often hard to diagnose and with today's antimycotics better to treat than before. It is therefore of current interest. This also concerns bronchial aspergillosis which is less common than pulmonary aspergillosis and the topic of this paper. A total of 39 patients with bronchial aspergillosis are presented: 1) 4 cases with endobronchial aspergilla, two which are visual bronchoscopically, 2) one case with chronic necrotising pulmonary aspergillosis (CNPA), where a bronchus has necrotised, 3) an invasive aspergillosis in the region of a bronchial anastomosis, 4) 7 cases with an Aspergillus invasion from endobronchial tumour tissue and 5) 26 cases with allergic bronchopulmonary aspergillosis (ABPA). 37 of the 39 cases are part of a single centre study with a total of 116 bronchopulmonary aspergilloses, which were collected over seven years. The focus of attention in this paper is on the bronchoscopic and radiological results.

Surgery of pulmonary aspergillomas in immunocompromised patients.

INTRODUCTION: Pulmonary aspergillosis is a devastating complication in immunocompromised patients. Timing of surgery is controversial and depends on the patients' general condition. METHODS: From 2000 to 2007, 16 patients (mean age 47 years, range 20-64) underwent surgery for pulmonary aspergillosis. All patients were receiving immunosuppressive drugs due to chemotherapy of hematological malignancies, ten with additional bone marrow or stem cell transplantation. Perioperatively, aspergillosis was treated with antifungal agents. If granulocyte numbers in the peripheral blood was below 1.0x10(9)/l, granulocyte stimulating factor and granulocyte transfusions were administered perioperatively. RESULTS: Four patients underwent lobectomy and wedge resections of the same lung, one patient bilobectomy, two patients lobectomy, eight patients wedge resections of one lung, and one patient wedge resections of both lungs. All patients survived surgery without major complications. Five patients were bone marrow or stem cell transplanted 1, 2, 3, 7 and 10 months after surgery. Three of them died due to recurrence of the underlying malignancy. All other patients are alive and free of fungal disease. CONCLUSIONS: Timing of surgery in the context of antifungal therapy and adequate numbers of granulocytes and platelets in the peripheral blood appear essential for successful surgical therapy and avoidance of major complications.

Distinct angiogenic and non-angiogenic growth patterns of lung metastases from renal cell carcinoma.

AIMS: We have recently evaluated a classification of non-small-cell lung cancer based upon the presence of an angiogenic or a non-angiogenic growth pattern. The aim of the present study was to test the hypothesis that lung metastases of clear cell renal cell carcinoma (RCC) can grow without eliciting angiogenesis and give rise to the same set of growth patterns. METHODS AND RESULTS: Tissue sections of 24 patients with lung metastases from clear cell RCC were analysed. Haematoxylin and eosin and reticulin staining were performed to evaluate growth pattern. Double-labelling with antibodies to CD34 and proliferating cell nuclear antigen (PCNA) was performed to determine the endothelial cell proliferation fraction (ECPF) and the microvessel density (MVD). Three growth patterns were observed. In the destructive growth pattern (54%), the architecture of the lung was not preserved. In the alveolar (33%) and interstitial growth patterns (13%), the normal lung parenchyma was preserved within the metastases. MVD was higher in the destructive than in the alveolar growth pattern (P = 0.009). ECPF was higher in the destructive (mean 31.1 +/- 22.7%, median 30.0) than in the alveolar growth pattern (mean 3.6 +/- 2.8%, median 3.2; P = 0.005). CONCLUSIONS: The present study demonstrates that highly angiogenic primary tumours can give rise to non-angiogenic metastases. This type of metastasis may be resistant to antiangiogenic therapy.

[Case studies of iatrogenic tracheal injury during intraoperative ventral positioning. Symptoms, diagnostics, and differential therapy]. / Iatrogene Trachealverletzung bei intraoperativer Bauchlagerung. Fallbeispiele mit Klinik, Diagnostik und Differenzialtherapie.

Two patients 16 and 21 years old developed tracheal rupture during elective surgery following trouble-free orotracheal intubation and intraoperative ventral positioning. The injuries remained undetected in both patients for more than 12 h. Diagnostic investigation after the onset of first symptoms indicated in each a tear in the posterior tracheal wall. Early operation prevented the development of serious complications in both patients. The casuistics indicate that tracheal injuries can emerge in minor elective surgery that may be carried out on an outpatient basis, and ventral positioning for surgery may represent a risk factor for their occurrence. Clinical symptoms, diagnostic procedure, findings, and therapy are discussed.

Impact of staging with 18F-FDG-PET on outcome of patients with stage III non-small cell lung cancer: PET identifies potential survivors.

PURPOSE: The aim of this study was to analyse the impact of FDG-PET staging on treatment results of neo-adjuvant radiochemotherapy in patients with advanced non-small cell lung cancer (NSCLC). We compared prospectively the outcome of two patient groups with stage III NSCLC undergoing the same neo-adjuvant radio-chemotherapy (NARCT). In one group, FDG-PET was part of the pretherapeutic staging, whereas in the other group, no PET scans were performed. METHODS: One hundred and eighty-eight patients with advanced stage III NSCLC were selected for a phase II trial of NARCT. The first 115 patients underwent conventional workup (CWU) and FDG-PET before inclusion (group I); the remaining 73 patients underwent CWU only (group II). All patients were followed up according to a standardised protocol for at least 11 months (up to 64 months). Overall survival and disease-free survival were used as parameters of therapeutic success and analysed statistically. RESULTS: After staging, 157/188 patients were included in the clinical trial. Thirty-one were excluded owing to the results of FDG-PET, in most cases because of the detection of previously unknown distant metastases. Overall survival and metastasis-free survival were significantly longer in patients of group I stratified by FDG-PET than in group II (p=0.006 and 0.02 respectively). Another significant factor for survival was complete tumour resection (p=0.02). Gender, histological tumour type, tumour grade and UICC stage had no significant influence. CONCLUSION: Pretherapeutic staging by FDG-PET significantly influences the results of NARCT and subsequent surgery by identifying patients not eligible for curative treatment.

Repeat 18F-FDG PET for monitoring neoadjuvant chemotherapy in patients with stage III non-small cell lung cancer.

PURPOSE: The relevance of (18)F-FDG PET for staging non-small cell lung cancer (NSCLC), in particular for the detection of lymph node or distant metastases, has been shown in several studies. The value of FDG-PET for therapy monitoring in NSCLC, in contrast, has not yet been sufficiently analysed. Aim of this study was to evaluate FDG-PET for monitoring treatment response during and after neoadjuvant radiochemotherapy (NARCT) in advanced NSCLC. METHODS: Sixty-five patients with histologically proven NSCLC stage III initially underwent three FDG-PET investigations, during NARCT prior to initiating radiation, and post-NARCT. Changes of FDG-uptake in the primary tumour at two time-points during NARCT were analysed concerning their impact on long-term survival. RESULTS: The mean maximum FDG uptake (standardized uptake value, SUVmax) of the whole group decreased significantly during NARCT (SUVmax PET 1: 14.9+/-4.0, SUVmax PET 3: 5.5+/-2.4, p=0.004). The difference between initial FDG uptake (PET 1) and uptake after induction chemotherapy (PET 2) was found to be highly predictive for long-term survival patients which had a greater than 60% decreases in their SUV change had a significantly longer survival than those below this threshold (5-year-survival 60% versus 15%, p=0.0007). Patients who had a lower than 25% decrease in their SUV change had a 5-years-survival lower than 5%. Furthermore, the difference between initial FDG uptake (PET 1) and uptake after completion of the whole NARCT (PET 3) was predictive for survival when 75% was applied as cut-off (p=0.02). However, the level of significance was considerably lower. CONCLUSION: FDG-PET is suitable for therapy monitoring in patients with stage III NSCLC. The decrease of FDG uptake during induction chemotherapy is highly predictive for patient outcome.

Is standardised (18)F-FDG uptake value an outcome predictor in patients with stage III non-small cell lung cancer?

PURPOSE: Recent studies have demonstrated the relevance of (18)F-FDG uptake as an independent prognostic factor for recurrence of operable non-small cell lung cancer (NSCLC). This corresponds with the experimental finding that FDG uptake correlates with the proliferative activity of tumour cells (Higashi et al., J Nucl Med 2000;41:85-92). On the basis of these observations, we studied the influence of FDG uptake on prognosis and occurrence of distant metastases in patients with advanced NSCLC. METHODS: One hundred and fifty-nine patients with NSCLC of UICC stage IIIA or IIIB were included in the study. In all patients, neoadjuvant treatment was planned to achieve operability. FDG PET was performed as an additional staging procedure prior to the initiation of therapy. Clinical outcome data in terms of overall survival, disease-free survival and incidence of distant metastases could be obtained for 137 patients and were correlated with the average standardised uptake value of the tumour (SUV(avg)). Furthermore, other factors influencing SUV(avg) and patient outcome (histological tumour type, grading, UICC stage, tumour size) were analysed. RESULTS: SUV(avg) was significantly influenced by tumour histology, UICC stage and tumour size. No significant difference could be shown for grading. In 38 out of the 159 patients (24%), FDG PET revealed previously unsuspected distant metastases. The incidence of distant metastases significantly correlated with SUV(avg). Overall survival tended to decrease with increasing SUV(avg); however, significance was only reached when a cut-off of 12.0 was applied (p=0.05). CONCLUSION: FDG uptake is an independent prognostic factor in patients with UICC stage III NSCLC, although less distinctively so than has been reported for stage I/II tumours.