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Rich66 · 05-16-2010, 11:32 PM

(in research)

http://medicalphysicsweb.org/cws/article/research/39057

May 13, 2009
Microwave ablation best for lung tumours

Microwave ablation of lung tumours outperforms the more established radiofrequency (RF) ablation technique, according to a new animal study published in Radiology from the University of Wisconsin.
Analysis of gross pathology and CT images found that microwave ablation created larger, more uniform circular zones around ablated regions of normal porcine lungs, improving the chances that the targeted tumour and satellite tumour deposits just outside its periphery would be included in the ablated zone.
Thermal ablation is being used with increasing frequency for treating unresectable lung tumours, both as a primary treatment strategy and as an adjuvant to external radiation, wrote Christopher Brace and colleagues from the University of Wisconsin's Clinical Sciences Center in Madison, WI.
But RF ablation also comes with daunting technical deficiencies, particularly in the high-impedance path it creates in lung tissue inflated during treatment. The resulting lower energy deposition reduces the temperature to which the ablation zone can be successfully raised, increasing the chances of failed treatment - and the possibility that satellite tumour deposits just beyond the periphery will be left intact. The use of multipronged electrodes increases impedance in RF ablation, but it also increases the invasiveness of the procedure and the unpredictability of coverage.
In contrast, "microwave energy penetration is not limited by the lower electrical permittivity and conductivity of inflated lung, desiccated tissue, or charred tissue," wrote Brace and his team. "Unlike RF electrodes, microwave antennas do not require the placement of grounding pads, and multiple antennas can be operated simultaneously in close proximity without switching" (Radiology doi: 10.1148/radiol.2513081564).
Because the two techniques have not been compared, the study sought to evaluate the performance of equivalently sized radiofrequency and microwave ablation applicators in the lungs of eight pigs.
Brace, along with J Louis Hinshaw, Paul Laeseke and colleagues, performed a total of 18 ablations in vivo in the lungs of three female swine following sedation with tiletamine hydrochloride, zolazepam hydrochloride, and anaesthesia using 2% inhaled isoflurane.
RF and microwave ablation applicators were placed peripherally in normal porcine lungs by using CT fluoroscopic guidance (LightSpeed Plus, GE Healthcare, Chalfont St. Giles, UK). Applicators were used to prevent overlap of ablation zones and to avoid heat sinks (such as large vessels) that might alter the results. Three applicators of each energy type resulted in six ablations per animal.
Ablations were performed for 10 minutes by using either 125 W of microwave power or 200 W of RF power delivered with an impedance-based pulsing algorithm. CT images were acquired every minute during the procedures to monitor growth of the ablated areas.
The RF method was applied via a 17-gauge internally cooled electrode (Cool-tip, Valleylab, Boulder, CO) with 3-cm active length powered by a 200-W generator with impedance-based pulsing. The microwave ablation system consisted of a prototype 17-gauge water-cooled triaxial antenna delivering power from a 2.45-GHz generator with 125-W output (CoberMuegge, Norwalk, CT). The flow rate of the cooling water was approximately 100 mL/min in both systems.
After the experiment, the ablation zones were excised and sectioned transverse to the applicator in 5-mm increments, according to the authors. Measurements of the ablated zones included minimum and maximum diameter, cross-sectional area, length, and circularity from gross specimens and CT images, using a mixed-effects model to compare measurements.
According to the results, mean diameter of the ablated zone was 25% larger with microwave ablation, at 3.32 cm ± 0.19 (standard deviation), versus 2.70 cm ±0.23, p<0.001, with RF ablation. The mean cross-sectional area (8.25 cm² ±0.92 versus 5.45 cm² ±1.14, p<0.001) was 50% larger with microwave ablation than with RF ablation. With microwave ablation, the zones of ablation were also significantly more circular in cross section (mean circularity, 0.90 ±0.06 versus 0.82 ±0.09; p<0.05).
"Ablation zones achieved with microwave ablation also grew faster than those achieved with RF ablation," they wrote. "Three of nine ablation zones achieved with microwave ablation extended into the body wall, as noted by using attenuation changes on CT images."
All of the animals tolerated the procedure without complications. One small pneumothorax was found during RF ablation, but it stabilized without intervention.
"Our results indicate that microwave ablation by using a high-power generator and cooled-power delivery system outperforms RF ablation for increased ablation zone size and circularity in normal porcine lung," Brace and colleagues wrote. "Measurement variability was also slightly lower with microwave ablation, and this finding may indicate improved repeatability with the use of microwave energy."
The most likely reason for the superior performance of microwave energy is its ability to deliver power continuously over the target volume, they wrote. In contrast, RF power delivery is limited by the intrinsically high impedance of normal lung tissue due to its high air content, a problem that worsens during treatment when charred or desiccated tissue is present.
Based on previous experience showing that microwave ablation creates higher temperatures and a larger core of desiccation compared to RF ablation, and the authors' finding that microwave ablation created a larger zone of low attenuation at CT, "we hypothesize that this zone may relate to tissue desiccation that occurs at high temperatures," the group wrote. "More study is necessary to verify this theory."
The use of normal tissue was a limitation of the study, inasmuch as the properties of lung tumours are different from those of normal parenchyma. Inflated lung tissue has a high electrical impedance for RF energy, a factor that limits the power deposition of current RF systems.
"However, normal lung tissue often completely surrounds tumours and limits RF current flow in the same way as if the electrode were immersed in parenchyma," they wrote. "Therefore, we believe that the use of a normal model for this comparative study was warranted."
High-power microwave ablation using a 17-gauge triaxial antenna appears to create ablation zones that are larger and more circular than those produced by RF ablation systems using applicators of a similar diameter, the group concluded. More research is needed to compare multiple devices in the clinical setting "for a more complete characterization of the pulmonary ablation armamentarium," they wrote.

General Thoracic Surgery

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

Axel Rolle, MD, PhD^a^{, _*}, Arpad Pereszlenyi, MD, PhD^a, Rainer Koch, MD, PhD^b, Mathias Richard, MD^a, Barbara Baier^a ^a Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, University Medical Center, Coswig/Dresden, Germany
^b Department of Informatics, Carl Gustav Carus University, Dresden, Germany.
Received for publication June 20, 2005; revisions received November 17, 2005; accepted for publication November 28, 2005.
^_* Address for reprints: Axel Rolle, MD, PhD, Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, Affiliated to the Carl Gustav Carus University Dresden, Neucoswiger Straße 21, D-01640 Coswig/Dresden, Germany (Email: dr.rolle@fachkrankenhaus-coswig.de).

FREE TEXT

OBJECTIVE: Our objective was to define the role of a new 1318-nm Nd:YAGlaser for lobe- and parenchyma-saving resection of multiplelung 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 toany primary tumors with no upper limit of metastases given.All parenchymal resections were performed with a new 1318-nmNd:YAG laser whose effect on lung tissue differs significantlyfrom that of the 1064-nm wavelength owing to a 10-fold higherabsorption in water and one-third extinction in blood. In 93%,precision laser resection was achieved. The lobectomy rate wasonly 7%.

RESULTS: Pathologic examination revealed 2546 metastases (8/patient)and lymph node disease in 19%. Complete resections (R0) wereachieved in 93% of 177 patients undergoing unilateral procedureswith a mean of 3 metastases (range 1%-29%) and 75% of 151 patientshaving bilateral operations with a mean of 13 metastases (range2-124). The 5-year survival after R0 was 55% for solitary nodules,41% for all patients, 28% for 10 metastases, and 26% for 20or more metastases resected. Outcome was significantly poorerafter 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 resectionof multiple bilateral centrally located metastases and thusis lobe sparing. Resection of 20 or more metastases is reasonablebecause long-term survival was significantly better than thatobserved with incomplete resection.

Infez Med. 2010 Mar;18(1):39-42.
Differential diagnosis of lung nodules: breast cancer metastases and lung tuberculosis.

Endri M, Cartei G, Zustovich F, Serino FS, Fassina A.
Department of Medicine, Operative Unit of Medicine 2, Azienda Ospedaliera Santa Maria degli Angeli, Pordenone City Hospital, Pordenone, Italy.
Abstract

In a follow-up a 74-year-old woman with breast cancer (clinical stage T4N1M0 at onset, treatment by surgical resection and tamoxifen) presented a combination of two distinct diseases in the lung: breast cancer metastasis and tuberculosis. A CT scan showed multiple pulmonary nodular lesions and in only one lesion fine needle aspiration cytology (FNAC) diagnosed tuberculosis. After specific antibiotic therapy, isoniazide and rifampin, a CT scan highlighted disappearance of tubercular lesion. Because occurrence of tuberculosis during chemo or hormone therapy for metastatic breast cancer is rare, the present case is noteworthy. Indeed, it is worth pointing out the differential diagnosis of pulmonary nodular lesions in patients with cancer and the possible reactivation of tuberculosis even in patients without specific symptoms, without typical tubercular radiological features.

PMID: 20424525 [PubMed - indexed for MEDLINE]Free Article

http://www.wsoctv.com/health/19540065/detail.html

Treating Lung Metastases: Aerosolized Chemotherapy
When osteosarcoma metastasizes, 85 percent of the time it goes to the lungs. Chemotherapy may be given to control the growth and/or slow the spread of the cancer. But the treatment can have serious side effects, like hair loss, fatigue and an increased risk for infection. The side effects occur because the anti-cancer drugs have to travel through the body to get at the cancer site in the lungs, damaging healthy cells along the way.Researchers are now testing a new way to treat osteosarcoma lung metastases, by using inhaled chemotherapy. The treatment, delivered through an inhaler, uses GM-CSF (granulocyte macrophage colony stimulating factor), also known as LEUKINE® (sargramostim), to stimulate the production of white blood cells that fight the tumor. Pete Anderson, MD, PhD, Cancer Researcher with MD Anderson Cancer Center in Houston, says the drug is normally given as a shot under the skin. But as white blood cells numbers increase, patients can experience a significant amount of aches and bone pain. When the treatment is given in an inhaled form, the drug goes directly into the airways and only the lung cells are affected. Thus, patients don’t experience the painful side effects.The inhaled chemotherapy is combined with another treatment, an experimental drug called mifamurtide, or L-MTP-PE. This medication binds to white blood cells and boosts their activity. Although given intravenously, it readily travels to the lungs where it, hopefully, strengthens the ability of the white blood cells to fight the tumor. Anderson says MTP-PE can cause high fever and chills, so patients are usually pretreated with medications, like ibuprofen or acetaminophen, to prevent the side effects.

Science fiction? Aerosol delivery of an engineered virus halts lung cancer progression in mice

July 4, 11:29 AM

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Nasal sprays containing special viruses may revolutionize the field of pharmacology to correct a multitude of devastating genetic and sporadic human diseases including lung cancer. Lung cancer in conjunction with liver and pancreatic cancer are aggressive and common manifestations of this disease worldwide. Lung cancer tops the list with over 1.3 million deaths worldwide. Currently, the prognosis for lung cancer is extremely poor and multiple options for treatments include surgical removal of lung tumors, chemotherapy and radiation. Nowadays, scientists are relentlessly working to make gene therapy delivery to the lungs a viable alternative in order to correct a variety of pulmonary dysfunctions and illnesses which include cystic fibrosis, pulmonary fibrosis and lung cancer.
Different approaches for pulmonary gene delivery include intravenous injection, nasal or intratracheal instillation. On the other hand, aerosolized or intranasal gene delivery is a very attractive approach for treating lung cancer as it is a non-invasive, fast and an efficient delivery method with high a patient compliance rate.
So what are the current technologies that have been developed to make gene delivery possible to lungs in lung cancer patients?
Nowadays, biomedically engineered viruses are being used in certain academic and

Cryoelectron microscopy image of a
a lentivirus particle. Courtesy of the University
of Iowa Lentiviral Core Facility.
clinical institutions in small scale or large scale quantities to combat a variety of genetic diseases which include cystic fibrosis and hemophilia. Many classes of viruses have been used in the past by scientists to infect a variety of organs and tissues including adenoviruses, adeno-associated viruses, and retroviruses such as lentiviruses. Lentiviruses are the most promising for gene delivery therapies since this type of virus not only infects dividing cells but also infect non-dividing cells such as neurons. On the plus side, lentiviruses allow the long-term stable integration of their genes into the genome of target cells making it possible for researchers to correct congenital deficiencies in patients by using this technology. For instance, lentiviruses carrying a copy of the cystic fibrosis transmembrane receptor have successfully being used in mouse model of cystic fibrosis to correct this disease.

Lentiviruses is a genus of the Retroviridae family of whose members include the human immunodeficiency virus (AIDS virus), feline immunodeficiency virus (FIV), the causative agent of AIDS in cats, and the simian immunodeficiency virus (SIV), the causative virus of AIDS in chimps and monkeys. These viruses are used in small quantities to infect different mouse models of disease to test different hypothesis or used in large scale quantifies for clinical applications. Of course, there is the concern that these viruses may expose the researcher or patients to the risk of developing AIDS. However, academic and federal regulations obligate scientists to take necessary safety precautions and commercially lentiviruses are modified to make them non-pathogenic. The genomes of these viruses are modified to make them replication deficient and to only induce a single round of infection. For instance, modifications of lentiviruses include deletions of accessory genes (gag, env and pol) or the genome is cut into pieces and re-packaged in more than one vector. Thus in the inconvenient event of an accidental breach in the laboratory, these lentiviruses will not survive outside the laboratory and are replication deficient. To increase their infectivity to allow researchers to infect a whole variety of cell lines, the the vesicular stomatitis virus glycoprotein (VSVG) has been added to lentiviruses to allow them to infect but a whole range of tissues including brain.
One ground-breaking study have shown the validity and practical application of lentiviruses to correct lung cancer in mice.
In the June 15 edition of the American Journal of Respiratory and Critical Care Medicine, South Korean scientists have engineered a novel intranasal delivery of special viral particles that express a tumor suppressor gene to blunt cancer progression in mice. Tumors form due to an accumulation of mutations in several genes in the cell over time which aberrantly tip the balance of many signaling pathways in cells which lead to the slow progression of neoplasms (adenomas) into a malignant tumor, and ultimately form metastases. Dr. Cho and colleagues targeted the Akt (a protein kinase) signaling pathway. Akt is a master regulator of cell survival and cell proliferation and a persistent increase in the Akt signaling can lead to a transformation of normal cells into cancer cells in vitro and in vivo. In further support of this observation, a plethora of gene expression and proteomics profiling studies in lung and many other types of cancer have demonstrated that the Akt signaling pathway is up-regulated. Moreover, the Akt gene is amplified in many cancer cells just like the epidermal growth factor receptor is overexpressed in breast cancer. Relevant to lung cancer, it has been found that 90 percent of non-small cell lung carcinomas were associated with an aberrant activation of the Akt signaling pathway. Dr. Cho chose a commercial lentiviral vector for the same reasons that these type of viruses infect non-dividing cells and promote persistent and table genetic changes in cells. Dr. Cho and colleagues further modified the lentiviral vector to include a negative regulator of Akt signaling, carboxyl-terminal modulator protein (CTMP). This bioengineered CTMP lentiviral vector was repackaged with specific viral components and amplified by infecting a human renal cell line (ie., NIH 293 cells). The supernatant containing the virus was collected from the infected cells, concentrated, lyophilized, vaporized and contained in aerosol sprays.
The scientists then wanted to determine whether intranasal delivery of the CTMP lentivirus is able to suppress lung cancer progression in mice containing lung tumors. Thus by generating this lentivirus, Dr. Cho postulated that the progression of lung cancer may be halted by inhibiting the Akt signaling pathway in cancer cells by overexpressing CTMP in the lung.
Indeed, their results showed just that. Long-term repeated intranasal delivery of CTMP containing lentiviruses particles (twice a week for one month) effectively reduced tumor progression in the lungs at different stages of development in a mouse model of lung cancer (K-rasLA1 mice). Histopathological analyses showed a significant reduction in the number and size of lung tumors and led to a near complete absence of bronchoalveolar tumors. This is a very important piece of data because it shows that the progression of cancer is halted at the benign state (adenoma) and does not develop in the bronchioles.
So how does CTMP halt cancer progression? Using biochemical analysis to analyze the expression levels of certain proteins, scientist found that overexpression of CTMP shut down not only Akt signaling but also protein synthesis, proliferation, angiogenesis and cell cycle progression of lung cancer cells while normal cells were not affected. Not only was lung cancer progression halted in 9-week old mice but the authors of the study found that cancer cells died from apoptosis.
Unlike chemotherapy which preferentially affects cancer cells but still has deleterious consequences to normal tissue after prolonged treatment, lentiviral mediated gene therapy “surgically” targets tumor cells while sparing normal tissue.
Dr. Cho’s concluding remarks stated that "Repeated aerosol gene delivery may provide an effective noninvasive model of gene delivery and understanding the role of CTMP in the multistage lung tumorigenesis may be essential in developing effective therapeutics for lung cancer.” These results will open the door towards patenting and openly marketing this technology in the US. More importantly, the use of many different biomedically engineered lentiviruses to treat a variety of genetic and sporadic human illnesses and can attract venture capitalism for creating start-up companies in the US. Obviously, patenting this technology will have to undergo major scrutiny in the US through the conventional, protracted and painstaking process of FDA clinical trials before aerosolized or injectable lentiviral particles may be available for gene therapy.

For more information:
To read the original press release: www.eurekalert.org/pub_releases/2009-06/ats-vvv060809.php#

http://www.examiner.com/x-11432-Pittsburgh-Medical-Technology-Examiner~y2009m7d4-Science-fiction-Aerosol-delivery-of-an-engineered-virus-halts-lung-cancer-progression-in-mice

05-16-2010, 11:32 PM	#2
Rich66 Senior Member Join Date: Feb 2008 Location: South East Wisconsin Posts: 3,431	Re: Lung mets (in research) http://medicalphysicsweb.org/cws/article/research/39057 May 13, 2009 Microwave ablation best for lung tumours Microwave ablation of lung tumours outperforms the more established radiofrequency (RF) ablation technique, according to a new animal study published in Radiology from the University of Wisconsin. Analysis of gross pathology and CT images found that microwave ablation created larger, more uniform circular zones around ablated regions of normal porcine lungs, improving the chances that the targeted tumour and satellite tumour deposits just outside its periphery would be included in the ablated zone. Thermal ablation is being used with increasing frequency for treating unresectable lung tumours, both as a primary treatment strategy and as an adjuvant to external radiation, wrote Christopher Brace and colleagues from the University of Wisconsin's Clinical Sciences Center in Madison, WI. But RF ablation also comes with daunting technical deficiencies, particularly in the high-impedance path it creates in lung tissue inflated during treatment. The resulting lower energy deposition reduces the temperature to which the ablation zone can be successfully raised, increasing the chances of failed treatment - and the possibility that satellite tumour deposits just beyond the periphery will be left intact. The use of multipronged electrodes increases impedance in RF ablation, but it also increases the invasiveness of the procedure and the unpredictability of coverage. In contrast, "microwave energy penetration is not limited by the lower electrical permittivity and conductivity of inflated lung, desiccated tissue, or charred tissue," wrote Brace and his team. "Unlike RF electrodes, microwave antennas do not require the placement of grounding pads, and multiple antennas can be operated simultaneously in close proximity without switching" (Radiology doi: 10.1148/radiol.2513081564). Because the two techniques have not been compared, the study sought to evaluate the performance of equivalently sized radiofrequency and microwave ablation applicators in the lungs of eight pigs. Brace, along with J Louis Hinshaw, Paul Laeseke and colleagues, performed a total of 18 ablations in vivo in the lungs of three female swine following sedation with tiletamine hydrochloride, zolazepam hydrochloride, and anaesthesia using 2% inhaled isoflurane. RF and microwave ablation applicators were placed peripherally in normal porcine lungs by using CT fluoroscopic guidance (LightSpeed Plus, GE Healthcare, Chalfont St. Giles, UK). Applicators were used to prevent overlap of ablation zones and to avoid heat sinks (such as large vessels) that might alter the results. Three applicators of each energy type resulted in six ablations per animal. Ablations were performed for 10 minutes by using either 125 W of microwave power or 200 W of RF power delivered with an impedance-based pulsing algorithm. CT images were acquired every minute during the procedures to monitor growth of the ablated areas. The RF method was applied via a 17-gauge internally cooled electrode (Cool-tip, Valleylab, Boulder, CO) with 3-cm active length powered by a 200-W generator with impedance-based pulsing. The microwave ablation system consisted of a prototype 17-gauge water-cooled triaxial antenna delivering power from a 2.45-GHz generator with 125-W output (CoberMuegge, Norwalk, CT). The flow rate of the cooling water was approximately 100 mL/min in both systems. After the experiment, the ablation zones were excised and sectioned transverse to the applicator in 5-mm increments, according to the authors. Measurements of the ablated zones included minimum and maximum diameter, cross-sectional area, length, and circularity from gross specimens and CT images, using a mixed-effects model to compare measurements. According to the results, mean diameter of the ablated zone was 25% larger with microwave ablation, at 3.32 cm ± 0.19 (standard deviation), versus 2.70 cm ±0.23, p<0.001, with RF ablation. The mean cross-sectional area (8.25 cm² ±0.92 versus 5.45 cm² ±1.14, p<0.001) was 50% larger with microwave ablation than with RF ablation. With microwave ablation, the zones of ablation were also significantly more circular in cross section (mean circularity, 0.90 ±0.06 versus 0.82 ±0.09; p<0.05). "Ablation zones achieved with microwave ablation also grew faster than those achieved with RF ablation," they wrote. "Three of nine ablation zones achieved with microwave ablation extended into the body wall, as noted by using attenuation changes on CT images." All of the animals tolerated the procedure without complications. One small pneumothorax was found during RF ablation, but it stabilized without intervention. "Our results indicate that microwave ablation by using a high-power generator and cooled-power delivery system outperforms RF ablation for increased ablation zone size and circularity in normal porcine lung," Brace and colleagues wrote. "Measurement variability was also slightly lower with microwave ablation, and this finding may indicate improved repeatability with the use of microwave energy." The most likely reason for the superior performance of microwave energy is its ability to deliver power continuously over the target volume, they wrote. In contrast, RF power delivery is limited by the intrinsically high impedance of normal lung tissue due to its high air content, a problem that worsens during treatment when charred or desiccated tissue is present. Based on previous experience showing that microwave ablation creates higher temperatures and a larger core of desiccation compared to RF ablation, and the authors' finding that microwave ablation created a larger zone of low attenuation at CT, "we hypothesize that this zone may relate to tissue desiccation that occurs at high temperatures," the group wrote. "More study is necessary to verify this theory." The use of normal tissue was a limitation of the study, inasmuch as the properties of lung tumours are different from those of normal parenchyma. Inflated lung tissue has a high electrical impedance for RF energy, a factor that limits the power deposition of current RF systems. "However, normal lung tissue often completely surrounds tumours and limits RF current flow in the same way as if the electrode were immersed in parenchyma," they wrote. "Therefore, we believe that the use of a normal model for this comparative study was warranted." High-power microwave ablation using a 17-gauge triaxial antenna appears to create ablation zones that are larger and more circular than those produced by RF ablation systems using applicators of a similar diameter, the group concluded. More research is needed to compare multiple devices in the clinical setting "for a more complete characterization of the pulmonary ablation armamentarium," they wrote. General Thoracic Surgery 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 *Axel Rolle, MD, PhD^a^{, _}, Arpad Pereszlenyi, MD, PhD^a, Rainer Koch, MD, PhD^b, Mathias Richard, MD^a, Barbara Baier^a** ^a Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, University Medical Center, Coswig/Dresden, Germany ^b Department of Informatics, Carl Gustav Carus University, Dresden, Germany. Received for publication June 20, 2005; revisions received November 17, 2005; accepted for publication November 28, 2005. ^_* Address for reprints: Axel Rolle, MD, PhD, Department of Thoracic and Vascular Surgery, Coswig Specialised Hospital, Center for Pneumology and Thoracic Surgery, Affiliated to the Carl Gustav Carus University Dresden, Neucoswiger Straße 21, D-01640 Coswig/Dresden, Germany (Email: dr.rolle@fachkrankenhaus-coswig.de). FREE TEXT OBJECTIVE: Our objective was to define the role of a new 1318-nm Nd:YAGlaser for lobe- and parenchyma-saving resection of multiplelung 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 toany primary tumors with no upper limit of metastases given.All parenchymal resections were performed with a new 1318-nmNd:YAG laser whose effect on lung tissue differs significantlyfrom that of the 1064-nm wavelength owing to a 10-fold higherabsorption in water and one-third extinction in blood. In 93%,precision laser resection was achieved. The lobectomy rate wasonly 7%. RESULTS: Pathologic examination revealed 2546 metastases (8/patient)and lymph node disease in 19%. Complete resections (R0) wereachieved in 93% of 177 patients undergoing unilateral procedureswith a mean of 3 metastases (range 1%-29%) and 75% of 151 patientshaving bilateral operations with a mean of 13 metastases (range2-124). The 5-year survival after R0 was 55% for solitary nodules,41% for all patients, 28% for 10 metastases, and 26% for 20or more metastases resected. Outcome was significantly poorerafter 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 resectionof multiple bilateral centrally located metastases and thusis lobe sparing. Resection of 20 or more metastases is reasonablebecause long-term survival was significantly better than thatobserved with incomplete resection. Infez Med. 2010 Mar;18(1):39-42. Differential diagnosis of lung nodules: breast cancer metastases and lung tuberculosis. Endri M, Cartei G, Zustovich F, Serino FS, Fassina A. Department of Medicine, Operative Unit of Medicine 2, Azienda Ospedaliera Santa Maria degli Angeli, Pordenone City Hospital, Pordenone, Italy. Abstract In a follow-up a 74-year-old woman with breast cancer (clinical stage T4N1M0 at onset, treatment by surgical resection and tamoxifen) presented a combination of two distinct diseases in the lung: breast cancer metastasis and tuberculosis. A CT scan showed multiple pulmonary nodular lesions and in only one lesion fine needle aspiration cytology (FNAC) diagnosed tuberculosis. After specific antibiotic therapy, isoniazide and rifampin, a CT scan highlighted disappearance of tubercular lesion. Because occurrence of tuberculosis during chemo or hormone therapy for metastatic breast cancer is rare, the present case is noteworthy. Indeed, it is worth pointing out the differential diagnosis of pulmonary nodular lesions in patients with cancer and the possible reactivation of tuberculosis even in patients without specific symptoms, without typical tubercular radiological features. PMID: 20424525 [PubMed - indexed for MEDLINE]Free Article http://www.wsoctv.com/health/19540065/detail.html Treating Lung Metastases: Aerosolized Chemotherapy When osteosarcoma metastasizes, 85 percent of the time it goes to the lungs. Chemotherapy may be given to control the growth and/or slow the spread of the cancer. But the treatment can have serious side effects, like hair loss, fatigue and an increased risk for infection. The side effects occur because the anti-cancer drugs have to travel through the body to get at the cancer site in the lungs, damaging healthy cells along the way.Researchers are now testing a new way to treat osteosarcoma lung metastases, by using inhaled chemotherapy. The treatment, delivered through an inhaler, uses GM-CSF (granulocyte macrophage colony stimulating factor), also known as LEUKINE® (sargramostim), to stimulate the production of white blood cells that fight the tumor. Pete Anderson, MD, PhD, Cancer Researcher with MD Anderson Cancer Center in Houston, says the drug is normally given as a shot under the skin. But as white blood cells numbers increase, patients can experience a significant amount of aches and bone pain. When the treatment is given in an inhaled form, the drug goes directly into the airways and only the lung cells are affected. Thus, patients don’t experience the painful side effects.The inhaled chemotherapy is combined with another treatment, an experimental drug called mifamurtide, or L-MTP-PE. This medication binds to white blood cells and boosts their activity. Although given intravenously, it readily travels to the lungs where it, hopefully, strengthens the ability of the white blood cells to fight the tumor. Anderson says MTP-PE can cause high fever and chills, so patients are usually pretreated with medications, like ibuprofen or acetaminophen, to prevent the side effects. Science fiction? Aerosol delivery of an engineered virus halts lung cancer progression in mice July 4, 11:29 AM Comment ShareThisShareThis RSS Email Print Nasal sprays containing special viruses may revolutionize the field of pharmacology to correct a multitude of devastating genetic and sporadic human diseases including lung cancer. Lung cancer in conjunction with liver and pancreatic cancer are aggressive and common manifestations of this disease worldwide. Lung cancer tops the list with over 1.3 million deaths worldwide. Currently, the prognosis for lung cancer is extremely poor and multiple options for treatments include surgical removal of lung tumors, chemotherapy and radiation. Nowadays, scientists are relentlessly working to make gene therapy delivery to the lungs a viable alternative in order to correct a variety of pulmonary dysfunctions and illnesses which include cystic fibrosis, pulmonary fibrosis and lung cancer. Different approaches for pulmonary gene delivery include intravenous injection, nasal or intratracheal instillation. On the other hand, aerosolized or intranasal gene delivery is a very attractive approach for treating lung cancer as it is a non-invasive, fast and an efficient delivery method with high a patient compliance rate. So what are the current technologies that have been developed to make gene delivery possible to lungs in lung cancer patients? Nowadays, biomedically engineered viruses are being used in certain academic and Cryoelectron microscopy image of a a lentivirus particle. Courtesy of the University of Iowa Lentiviral Core Facility. clinical institutions in small scale or large scale quantities to combat a variety of genetic diseases which include cystic fibrosis and hemophilia. Many classes of viruses have been used in the past by scientists to infect a variety of organs and tissues including adenoviruses, adeno-associated viruses, and retroviruses such as lentiviruses. Lentiviruses are the most promising for gene delivery therapies since this type of virus not only infects dividing cells but also infect non-dividing cells such as neurons. On the plus side, lentiviruses allow the long-term stable integration of their genes into the genome of target cells making it possible for researchers to correct congenital deficiencies in patients by using this technology. For instance, lentiviruses carrying a copy of the cystic fibrosis transmembrane receptor have successfully being used in mouse model of cystic fibrosis to correct this disease. Lentiviruses is a genus of the Retroviridae family of whose members include the human immunodeficiency virus (AIDS virus), feline immunodeficiency virus (FIV), the causative agent of AIDS in cats, and the simian immunodeficiency virus (SIV), the causative virus of AIDS in chimps and monkeys. These viruses are used in small quantities to infect different mouse models of disease to test different hypothesis or used in large scale quantifies for clinical applications. Of course, there is the concern that these viruses may expose the researcher or patients to the risk of developing AIDS. However, academic and federal regulations obligate scientists to take necessary safety precautions and commercially lentiviruses are modified to make them non-pathogenic. The genomes of these viruses are modified to make them replication deficient and to only induce a single round of infection. For instance, modifications of lentiviruses include deletions of accessory genes (gag, env and pol) or the genome is cut into pieces and re-packaged in more than one vector. Thus in the inconvenient event of an accidental breach in the laboratory, these lentiviruses will not survive outside the laboratory and are replication deficient. To increase their infectivity to allow researchers to infect a whole variety of cell lines, the the vesicular stomatitis virus glycoprotein (VSVG) has been added to lentiviruses to allow them to infect but a whole range of tissues including brain. One ground-breaking study have shown the validity and practical application of lentiviruses to correct lung cancer in mice. In the June 15 edition of the American Journal of Respiratory and Critical Care Medicine, South Korean scientists have engineered a novel intranasal delivery of special viral particles that express a tumor suppressor gene to blunt cancer progression in mice. Tumors form due to an accumulation of mutations in several genes in the cell over time which aberrantly tip the balance of many signaling pathways in cells which lead to the slow progression of neoplasms (adenomas) into a malignant tumor, and ultimately form metastases. Dr. Cho and colleagues targeted the Akt (a protein kinase) signaling pathway. Akt is a master regulator of cell survival and cell proliferation and a persistent increase in the Akt signaling can lead to a transformation of normal cells into cancer cells in vitro and in vivo. In further support of this observation, a plethora of gene expression and proteomics profiling studies in lung and many other types of cancer have demonstrated that the Akt signaling pathway is up-regulated. Moreover, the Akt gene is amplified in many cancer cells just like the epidermal growth factor receptor is overexpressed in breast cancer. Relevant to lung cancer, it has been found that 90 percent of non-small cell lung carcinomas were associated with an aberrant activation of the Akt signaling pathway. Dr. Cho chose a commercial lentiviral vector for the same reasons that these type of viruses infect non-dividing cells and promote persistent and table genetic changes in cells. Dr. Cho and colleagues further modified the lentiviral vector to include a negative regulator of Akt signaling, carboxyl-terminal modulator protein (CTMP). This bioengineered CTMP lentiviral vector was repackaged with specific viral components and amplified by infecting a human renal cell line (ie., NIH 293 cells). The supernatant containing the virus was collected from the infected cells, concentrated, lyophilized, vaporized and contained in aerosol sprays. The scientists then wanted to determine whether intranasal delivery of the CTMP lentivirus is able to suppress lung cancer progression in mice containing lung tumors. Thus by generating this lentivirus, Dr. Cho postulated that the progression of lung cancer may be halted by inhibiting the Akt signaling pathway in cancer cells by overexpressing CTMP in the lung. Indeed, their results showed just that. Long-term repeated intranasal delivery of CTMP containing lentiviruses particles (twice a week for one month) effectively reduced tumor progression in the lungs at different stages of development in a mouse model of lung cancer (K-rasLA1 mice). Histopathological analyses showed a significant reduction in the number and size of lung tumors and led to a near complete absence of bronchoalveolar tumors. This is a very important piece of data because it shows that the progression of cancer is halted at the benign state (adenoma) and does not develop in the bronchioles. So how does CTMP halt cancer progression? Using biochemical analysis to analyze the expression levels of certain proteins, scientist found that overexpression of CTMP shut down not only Akt signaling but also protein synthesis, proliferation, angiogenesis and cell cycle progression of lung cancer cells while normal cells were not affected. Not only was lung cancer progression halted in 9-week old mice but the authors of the study found that cancer cells died from apoptosis. Unlike chemotherapy which preferentially affects cancer cells but still has deleterious consequences to normal tissue after prolonged treatment, lentiviral mediated gene therapy “surgically” targets tumor cells while sparing normal tissue. Dr. Cho’s concluding remarks stated that "Repeated aerosol gene delivery may provide an effective noninvasive model of gene delivery and understanding the role of CTMP in the multistage lung tumorigenesis may be essential in developing effective therapeutics for lung cancer.” These results will open the door towards patenting and openly marketing this technology in the US. More importantly, the use of many different biomedically engineered lentiviruses to treat a variety of genetic and sporadic human illnesses and can attract venture capitalism for creating start-up companies in the US. Obviously, patenting this technology will have to undergo major scrutiny in the US through the conventional, protracted and painstaking process of FDA clinical trials before aerosolized or injectable lentiviral particles may be available for gene therapy. For more information: To read the original press release: www.eurekalert.org/pub_releases/2009-06/ats-vvv060809.php# http://www.examiner.com/x-11432-Pittsburgh-Medical-Technology-Examiner~y2009m7d4-Science-fiction-Aerosol-delivery-of-an-engineered-virus-halts-lung-cancer-progression-in-mice __________________ Mom's treatment history (link)