Long-Term Follow-Up after Laser-Assisted Pulmonary Metastasectomy Shows Complete Lung Function Recovery.

Preserving maximum lung function is a fundamental goal of parenchymal-sparing pulmonary laser surgery. Long-term studies for follow-up of lung function after pulmonary laser metastasectomy are lacking. However, a sufficient postoperative lung function is essential for quality of life and reduces potential postoperative complications. In this study, we investigate the extent of loss in lung function following pulmonary laser resection after three, six, and twelve months. We conducted a retrospective analysis using a prospective database of 4595 patients, focusing on 126 patients who underwent unilateral pulmonary laser resection for lung metastases from 1996 to 2022 using a 1318 nm Nd:YAG laser or a high-power pure diode laser. Results show that from these patients, a median of three pulmonary nodules were removed, with 75% presenting central lung lesions and 25% peripheral lesions. The median preoperative FEV1 was 98% of the predicted value, decreasing to 71% postoperatively but improving to 90% after three months, 93% after six months, and 96% after twelve months. Statistical analysis using the Friedman test indicated no significant difference in FEV1 between preoperative levels and those at six and twelve months post-surgery. The findings confirm that pulmonary laser surgery effectively preserves lung function over time, with patients generally regaining their preoperative lung function within a year, regardless of the metastases' location.

CD31, EDNRB and TSPAN7 are promising prognostic markers in clear-cell renal cell carcinoma revealed by genome-wide expression analyses of primary tumors and metastases.

Currently used clinicopathological parameters are insufficient for a reliable prediction of metastatic risk and disease-free survival (DFS) of patients with clear-cell renal cell carcinoma (ccRCC). To identify prognostic genes, the expression profiles of primary ccRCC obtained from patients with different DFS--eight synchronously, nine metachronously and seven not metastasized tumors--were determined by genome-wide expression analyses. Synchronously and metachronously metastasized primary ccRCC differed in the expression of 167 genes. Thirty-six of these genes were also differentially expressed in synchronously vs. metachronously developed pulmonary metastases analyzed in a previous study. Because of their DFS-associated deregulation that is concordant in metastases and primary ccRCC, these genes are potentially functionally involved in metastatic tumor growth and are also prognostically useful. A prognostic impact was confirmed for the genes CD31, EDNRB and TSPAN7 at the mRNA level (n=86), and for TSPAN7 at the protein level (n=106). Patients with a higher gene expression of EDNRB or TSPAN7, or with TSPAN7-positive vessels in both cores investigated on tissue microarrays had a significantly longer DFS and tumor-specific survival (TSS). Patients with a higher CD31 gene expression showed a significantly longer TSS. EDNRB was an independent prognostic marker for the DFS. CD31, EDNRB and TSPAN7 had an independent impact on the TSS. In summary, comparative analysis of primary tumors and metastases is appropriate to identify independent prognostic markers in ccRCC. Gene expression of CD31 and EDNRB, and endothelial TSPAN7 protein level are potentially useful to improve outcome prediction because of their independent prognostic impact.

Farmer's lung in a case after bullectomy.

We present a case of farmer's lung (FL) with the primary presenting feature of a large bulla in the lung. A 70-year-old nonsmoking woman with dyspnea on exercise was referred for surgical resection of a large bulla in the lung. The postoperative evaluation of the lung tissue revealed a follicular lymphocytic alveolitis and loosely formed granulomas suspicious for hypersensitivity pneumonitis (HP). The patient had worked in farming since her youth. Dyspnea on exercise was the only symptom, but it was related to the large bulla. No other radiologic features of HP were shown in a high-resolution CT of the lung. Specific IgG antibodies against typical antigens of FL were detected, bronchoalveolar lavage demonstrated no lymphocytic alveolitis but an inhalative challenge with own hay was positive. A diagnosis of chronic FL was made. Despite lung emphysema being a possible reaction in FL, giant bullae as primary and single manifestation of this disease have not been reported before.

Pneumomediastinum as a primary manifestation of chronic hypersensitivity pneumonitis.

BACKGROUND: Patients with chronic hypersensitivity pneumonitis (HP) can present with an insidious onset of their disease without typical fluctuating flu-like symptoms, and there are only signs of chronic respiratory failure caused by the progressive fibrotic lung disease. CASE REPORT: A 45-year-old man with a pneumomediastinum and interstitial lung disease was referred for further investigations and therapy. No traumatic event or interventional procedure had occurred prior to referral. The patient had been working in farming for almost 20 years and was exposed in childhood by his father to pigeon breeding from childhood until 20 years ago. He reported dyspnea on exercise for the previous 2 years. High-resolution CT of the lung showed a pneumomediastinum and a fibrotic interstitial lung disease without dominating ground-glass opacities. Specific IgG antibodies were markedly elevated against molds and avian antigens. Bronchoalveolar lavage demonstrated a slightly lymphocytic and neutrophilic alveolitis. After recovering from the pneumomediastinum, an open lung biopsy was performed and a UIP-pattern was detected. An inhalative challenge with hay from the work-place was positive. A diagnosis of chronic farmer's lung was made. CONCLUSIONS: Pneumomediastinum has been described in other fibrotic lung diseases, but until now it has not been described as a primary manifestation of chronic fibrotic HP. Particularly in cases of concurrent antigen sources, an inhalative challenge could be done, even in a chronic course of HP.

Gene signatures of pulmonary metastases of renal cell carcinoma reflect the disease-free interval and the number of metastases per patient.

Our understanding of metastatic spread is limited and molecular mechanisms causing particular characteristics of metastasis are largely unknown. Herein, transcriptome-wide expression profiles of a unique cohort of 20 laser-resected pulmonary metastases (Mets) of 18 patients with clear-cell renal cell carcinoma (RCC) were analyzed to identify expression patterns associated with two important prognostic factors in RCC: the disease-free interval (DFI) after nephrectomy and the number of Mets per patient. Differentially expressed genes were identified by comparing early (DFI < or = 9 months) and late (DFI > or = 5 years) Mets, and Mets derived from patients with few (< or =8) and multiple (> or =16) Mets. Early and late Mets could be separated by the expression of genes involved in metastasis-associated processes, such as angiogenesis, cell migration and adhesion (e.g., PECAM1, KDR). Samples from patients with multiple Mets showed an elevated expression of genes associated with cell division and cell cycle (e.g., PBK, BIRC5, PTTG1) which indicates that a high number of Mets might result from an increased growth potential. Minimal sets of genes for the prediction of the DFI and the number of Mets per patient were identified. Microarray results were confirmed by quantitative PCR by including nine further pulmonary Mets of RCC. In summary, we showed that subgroups of Mets are distinguishable based on their expression profiles, which reflect the DFI and the number of Mets of a patient. To what extent the identified molecular factors contribute to the development of these characteristics of metastatic spread needs to be analyzed in further studies.

Increase in number of circulating disseminated epithelial cells after surgery for non-small cell lung cancer monitored by MAINTRAC(R) is a predictor for relapse: A preliminary report.

BACKGROUND: Lung cancer still remains one of the most commonly occurring solid tumors and even in stage Ia, surgery fails in 30% of patients who develop distant metastases. It is hypothesized that these must have developed from occult circulating tumor cells present at the time of surgery, or before. The aim of the present study was to detect such cells in the peripheral blood and to monitor these cells following surgery. METHODS: 30 patients treated for lung cancer with surgery were monitored for circulating epithelial cells (CEC) by taking peripheral blood samples before, 2 weeks and 5 months after surgery and/or radiotherapy (RT) chemotherapy (CT) or combined RT/CT using magnetic bead enrichment and laser scanning cytometry (MAINTRAC(R)) for quantification of these cells. RESULTS: In 86% of the patients CEC were detected before surgery and in 100% at 2 weeks and 5 months after surgery. In the control group, which consisted of 100 normal donors without cancer, 97 % were negative for CEC. A significantly higher number of CEC was found preoperatively in patients with squamous cell carcinoma than in those with adenocarcinoma. In correlation to the extent of parenchymal manipulation 2 weeks after surgery, an increase in numbers of CEC was observed with limited resections (18/21) whereas pneumonectomy led to a decrease (5/8) of CEC, 2 weeks after surgery. The third analysis done 5 months after surgery identified 3 groups of patients. In the group of 5 patients who received neo- or adjuvant chemo/radiotherapy there was evidence that monitoring of CEC can evaluate the effects of therapy. Another group of 7 patients who underwent surgery only showed a decrease of CEC and no signs of relapse. A third group of 11 patients who had surgery only, showed an increase of CEC (4 with an initial decrease after surgery and 7 with continuous increase). In the group with a continuous increase during the following 24 months, 2 early relapses in patients with stage Ia adenocarcinoma were observed. The increase of CEC preceded clinical detection by six months. CONCLUSION: We consider, therefore, that patients with adenocarcinoma and a continuous increase of CEC after complete resection for lung cancer are at an increased risk of early relapse.

Retrospective survival analysis of 237 consecutive patients with multiple pulmonary metastases from advanced renal cell carcinoma exclusively resected by a 1318-nm laser.

OBJECTIVES: Despite the introduction of new target drugs to treat pulmonary metastatic renal cell carcinoma (mRCC), complete surgical resection still generates significantly longer survival. We analysed the survival outcome for patients with pulmonary mRCC after extended laser metastasectomy with up to 110 metastases and systematic lymphadenectomy to assess the utility and value of laser resection in the respective patient groups even with high number of metastases. METHODS: Between 1996 and 2012, 237 patients (150 men, 87 women) underwent curative intended pulmonary laser metastasectomy of mRCC. A total of 2996 metastases (range: 1-110) were resected. Kaplan-Meier analysis was performed to assess overall survival in all 237 patients and for sub-groups. Multivariate analysis of prognostic factors was performed using Cox regression models. RESULTS: Two hundred and eight patients with R0-resection (88%) had 5-year overall survival rate and median overall survival of 54% and 69 months, respectively, significantly better than 7% and 19 months in those with incomplete resections (log-rank P < 0.00001). A mean of 13 metastases per patient were resected. Five-year survival for patients with 1, 2-5, 6-9, 10-29 or 30-110 metastases resected was 62, 59, 60, 43 and 40%, respectively. In multivariate Cox-regression of all 237 patients, only completeness of resection (P < 0.0001) and number of metastases (P = 0.0029) were independent factors. CONCLUSIONS: If complete resection is achieved, laser resection can remove even high numbers of metastases with considerable and comparable long-term survival known from previous reports. This tissue-saving technique allows repeated resections in case of recurrence.

Lobe-sparing resection of multiple pulmonary metastases with a new 1318-nm Nd:YAG laser--first 100 patients.

BACKGROUND: A new 1318-nm Nd:YAG laser has been developed to utilize the second wavelength (1318 nm; 40 watt) to more precisely cut, coagulate, and seal lung tissue adjacent to pulmonary nodules. This laser allows a precise intraparenchymal nodulectomy with a 5-mm rim of tissue destruction and subsequent lung parenchymal reapproximation to avoid lobar distortion. Resection of multiple, bilateral, and recurrent tumors in the lung is facilitated by this laser technique. METHODS: In 100 consecutive patients (53 men, mean age 60 years; 47 women, mean age 61 years) with various primaries (most commonly renal and colorectal), 155 laser resections were performed via anterolateral thoracotomy (staged 3 to 4 weeks, if bilateral) using a new 1318-nm Nd:YAG laser. All palpable and visible masses were removed with 2 to 3-mm visible tumor margins (plus a 5-mm rim of residual lung necrosis secondary to laser energy dispersal) if the tumor or residual lung ratio was judged favorable. No stapling devices or bioadhesives were used. RESULTS: Six hundred thirty-two metastases (6.3 per patient, range 1 to 124) were resected. Despite 41% centrally located metastases, tumor resections were possible in 95% of patients with only a 5% lobectomy rate. Of the 100 patients, 67 were considered "curative" with complete metastasectomy by inspection and palpation, and 23 were judged incomplete from too extensive tumor or residual lung, miliary lung spread, or pleural studding. There were no associated mortalities and two complications, including bleeding (1) and a prolonged airleak (1), both treated conservatively. Follow-up was complete in all patients for a median of 26.5 months with clinic visits and chest computed tomographic scan every 3 to 6 months. Nine recurrences were detected and underwent reoperation. Overall survival in the completely resected "curative" group was 85% at 1 year, 71% at 2 years, 69% at 3 years, 57% at 4 years, and 32% at 5 years; in the completely resected "palliative" group, they were 70% at 1 year, 36% at 2 years, 12% at 3 years, and 0 at 4 years; in the incomplete group, they were 56% at 1 year, 30% at 2 years, and 0 at 3 years. CONCLUSIONS: The new 1318-nm Nd:YAG laser is parenchyma-sparing, improves complete resection rates, and potentially improves survival with fewer required lobectomies.

Laser resection technique and results of multiple lung metastasectomies using a new 1,318 nm Nd:YAG laser system.

BACKGROUND AND OBJECTIVES: Advantages of a new 1,318 nm Nd:YAG laser based on multiple lung metastasectomies are shown. STUDY DESIGN/MATERIALS AND METHODS: Ninety-three percent of 328 patients with metastases (8/patient, range 1-124) had precision laser resections (lobectomy-rate reduced to 7%); this laser delivers 20 kW/cm(2) 1,318 nm power densities with 400 microm fibers, and a focussing handpiece. Absorption in water is tenfold higher. RESULTS AND CONCLUSIONS: Between 1/1996 and 12/2003 in 328 patients (164 males/females, 61 years) 3,267 nodules were removed. Pathologic examination revealed 2,546 metastases (range 3-80 mm) from kidney (n = 112), colorectal (n = 91), and breast cancers (n = 35). In 85% of patients where the complete resection was achieved the 5-year survival was 41%. For remaining 15% (incomplete resection) the 5-year survival was 7%. Five-year survival for patients with 10 (and more) metastases was 28%, for patients with 20 (and more) was 26%. No 30-day mortality was observed. CONCLUSION: This new laser system facilitates any kind of parenchymal lung resection in lobe-sparing manner and in case of complete resection improves significantly the survival.

Is surgery for multiple lung metastases reasonable? A total of 328 consecutive patients with multiple-laser metastasectomies with a new 1318-nm Nd:YAG laser.

OBJECTIVE: Our objective was to define the role of a new 1318-nm Nd:YAG laser for lobe- and parenchyma-saving resection of multiple lung metastases. PATIENTS AND METHODS: From January 1996 to December 2003, a total of 3267 nodules (10/patient) were removed from 328 patients (164 men/164 women, mean age 61 years). Criteria for eligibility were expanded to any primary tumors with no upper limit of metastases given. All parenchymal resections were performed with a new 1318-nm Nd:YAG laser whose effect on lung tissue differs significantly from that of the 1064-nm wavelength owing to a 10-fold higher absorption in water and one-third extinction in blood. In 93%, precision laser resection was achieved. The lobectomy rate was only 7%. RESULTS: Pathologic examination revealed 2546 metastases (8/patient) and lymph node disease in 19%. Complete resections (R0) were achieved in 93% of 177 patients undergoing unilateral procedures with a mean of 3 metastases (range 1%-29%) and 75% of 151 patients having bilateral operations with a mean of 13 metastases (range 2-124). The 5-year survival after R0 was 55% for solitary nodules, 41% for all patients, 28% for 10 metastases, and 26% for 20 or more metastases resected. Outcome was significantly poorer after incomplete resection (7%). No 30-day mortality was observed. Major postoperative complications included prolonged air leaks (n = 2), intrapleural bleeding (n = 2), and late pneumothorax (n = 2); all were treated successfully with a chest tube. CONCLUSION: This new 1318-nm Nd:YAG laser facilitates complete resection of multiple bilateral centrally located metastases and thus is lobe sparing. Resection of 20 or more metastases is reasonable because long-term survival was significantly better than that observed with incomplete resection.

Laser resection of lung metastasis.

Presentation of the laser resection technique for metastatic lung diseases: a new Nd:YAG 1.318 nm wavelength laser system enables the thoracic surgeon to extend indication and include a larger number of patients for pulmonary metastasectomy. This parenchyma-saving technique allows removal of a significantly higher number of lung nodules in comparison to conventional techniques (stapler, clamp resection). The novel laser system consisted of a high performance Nd:YAG laser emitting the 1318 nm wavelength exclusively up to a power of 40 W, thin flexible quartz fibers (400 µm) with low water content and a four-lens focusing handpiece. Description of laser system, the technique of laser resection, together with an overview of the literature is presented.