We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appe... more We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appendectomy for mucinous cystadenocarcinoma with pseudomyxomatous peritonei. He underwent bilateral staged metastatectomies for metastases 7 years after the diagnosis and further metastasectomy after a recent recurrence. This is a rare case of recurrent pulmonary metastatic mucinous cystadenocarcinoma, and despite poor prognosis and nondefinitive initial treatment, this patient remains alive and well 20 years later.
Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in pa... more Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appe... more We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appendectomy for mucinous cystadenocarcinoma with pseudomyxomatous peritonei. He underwent bilateral staged metastatectomies for metastases 7 years after the diagnosis and further metastasectomy after a recent recurrence. This is a rare case of recurrent pulmonary metastatic mucinous cystadenocarcinoma, and despite poor prognosis and nondefinitive initial treatment, this patient remains alive and well 20 years later.
Objectives: Prolonged alveolar air leak is the most common complication after pulmonary surgery. ... more Objectives: Prolonged alveolar air leak is the most common complication after pulmonary surgery. We conducted an investigator-led randomized trial to evaluate the effectiveness of CoSeal W surgical sealant (Cohesion Technologies Inc.; manufactured and distributed by Baxter Healthcare) for the closure of alveolar air leak after anatomical pulmonary resection. Methods: Patients undergoing primary open lobectomy, bilobectomy, or sublobar resection with a demonstrable air leak on intra-operative testing were randomized to either standard care or standard care plus application of CoSeal W surgical sealant to areas of air leak. A second application of CoSeal W was used in the treatment group if air leak persisted. Patients were allocated at the point of entry to the trial by unbiased allocation with minimization to ensure balance between the two arms with respect to age, sex, surgeon, number of segments resected, preoperative forced expiratory volume in 1 s (FEV 1 ), and grade of air leak. Kaplan-Meier analysis of air-leak duration and a log rank test were performed on an intention-to-treat basis, with observations censored at death, transfer to the intensive care unit, or discharge. Results: Of the 200 patients, who entered the trial over a 24-month period, 121 with demonstrable intra-operative air leak were randomly allocated to the two groups. Data were missing for one patient in the CoSeal W group. In 57%, the air leak was stopped at the first application; a quarter continued to leak after the second. At 24 h, there was no difference in air leak and fewer patients in the control group were leaking at 48 h postoperatively. By log rank test, the difference was not significant ( p = 0.09). Conclusions: Patients treated with CoSeal W in this study had, as a group, a longer duration of air leak and hence we cannot recommend its routine use. #
Journal of Thoracic and Cardiovascular Surgery, 2010
within the same tumor. 2 It is generally accepted that these tumors originate as a primary epithe... more within the same tumor. 2 It is generally accepted that these tumors originate as a primary epithelial malignancy from which a subset of cells then undergoes dedifferentiation into sarcomatous cells. 1,2 This theory is supported by the frequent finding of a transition zone between the 2 cell populations. 2,4 Previous theories of 2 simultaneously occurring malignancies (collision tumor) or a common origin from a single pleomorphic cell population have fallen out of favor. 2 The epithelial component is usually squamous cell carcinoma, but adenocarcinoma can also occur. 4 Fibrosarcoma is the most common sarcomatous component, although rhabdomyosarcoma, chondrosarcoma, and osteosarcoma (as occurred in our patient) have also been described. 2,4 The sarcomatous cells stain for vimentin, whereas the epithelial cells stain for cytokeratin, 4 although it has been reported that the sarcomatous cells might stain for cytokeratin and the epithelial cells for vimentin. 4 Importantly, results of S-100 protein staining are negative, thus differentiating carcinosarcoma from stromal tumor and an important diagnostic consideration. 3 Clinically, carcinosarcomas are characterized by short doubling time (around 2 months) and rapid growth. 1 They are typically large at presentation (mean, 6-7 cm) and polypoid. 2 Oat cell carcinoma, squamous cell carcinoma, and adenocarcinoma might also present as bulky polypoid tumors of the esophagus, although much more rarely. 5 Endoscopic biopsy specimens show only the epithelial component in close to two thirds of cases. 2 In spite of their propensity to cause symptoms earlier because of their large size and the fact that more than 80% of tumors are limited to the submucosa or muscularis propria at presentation, 2,4,5 these tumors might behave aggressively, and thus radical resection in the form of esophagectomy is advocated. 1,2 Local resection through an esophagotomy has been described in frail patients thought to represent a high operative risk, with occasional long-term survival. 2 Chemotherapy and radiotherapy have rarely been reported, and their efficacy is unclear. 2 Long-term prognosis is thought to be similar to that of pure squamous cell carcinoma of the esophagus. 5
Aim: To report our experience with a multi-modality regimen involving pleurectomy/decortication, ... more Aim: To report our experience with a multi-modality regimen involving pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Method: Prospective study of all patients receiving this multimodality regimen at Guy's & St Thomas' hospital between September 2004 and August 2010. All patients had pleurectomy/ decortication through thoracotomy, received prophylactic radiotherapy postoperatively (21 Gy in 3 fractions) and completed adjuvant chemotherapy (pemetrexed and cisplatin). Nine patients underwent extended resection involving diaphragm (n = 4), lobectomy (n = 3), segmentectomy (n = 2) or SVC (n = 1). All were followed up in the clinic at 1, 6 months and then 6 monthly. Result: Thirty-nine patients completed the multimodality therapy (100%). Thirty day mortality was nil. Ten patients (25.6%) experienced complications: persistent air leak (n = 6, 15%), chylothorax (n = 4, 10%), ARDS (n = 1, 2.5%). Sixteen patients died and 23 patients are still alive at follow-up. Median survival is 29.5 months (CI 19.7 39.2 months), one-year survival is 91.8 % and 2-year survival 65.5%. Macroscopically complete resection (R0-R1) is significantly associated with longer survival versus non-radical resection (R2) (median survival 45.1 months versus 21.1 months, p = 0.005). Patients with epithelioid histology (n = 27) tend to have longer survival than patients with biphasic/sarcomatoid histology (n = 12) (median survival 42.1 months versus 22.8 months, p = 0.069). Conclusion: Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy is a well tolerated multi-modality regimen associated with low mortality and morbidity. This therapeutic plan compares favourably with other regimens including extrapleural pneumonectomy and radical radiotherapy.
Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in pa... more Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in mali... more The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a randomized controlled trial if this radical surgery is to be regarded as the standard of care. The question was whether randomization to surgery versus no surgery would be possible. The Mesothelioma and Radical Surgery trial was planned to randomize 50 patients to test feasibility. There was a two-stage consent process. At first consent, the patients who were possible candidates for radical surgery were registered into the trial for completion of assessment and staging. All received platinum-based chemotherapy. If still eligible, they completed a second consent to be randomized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care. Patients were recruited through 11 collaborating centers in the United Kingdom. One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy. One died, 27 progressed, five were inoperable, four were treated off trial, and 18 withdrew either during or after chemotherapy but before final review. Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew. The remaining 50 were randomized; 24 to EPP and 26 to continued best care. In this study, 50/112 (45%) of patients entering the evaluation and induction phase of the trial went on to be randomized. We have shown that this randomization between surgery and no surgery is feasible. This was the primary aim of the Mesothelioma and Radical Surgery trial.
Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surger... more Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surgery. Recent studies have suggested a neuroprotective effect of polyunsaturated fatty acids against cerebral ischemia. We investigated the effect of linolenic acid (LIN) in a rat model of spinal cord ischemia.Rats were subjected to cross-clamping of the aortic arch and left subclavian artery for 14 minutes. Groups were as follows: sham operation (n = 15); ischemia (n = 15), receiving only vehicle; LIN A (n = 15), receiving LIN before clamping; and LIN B (n = 15), receiving LIN at onset of reperfusion. Neurologic status was assessed daily for 7 days. Spinal cords were harvested for histopathologic analysis, TUNEL staining, and immunohistochemistry for Bax, heat shock protein 70 (HSP70), and nuclear factor–κB.Ischemic rats had severe and definitive paraplegia. LIN-treated rats had significantly better neurologic function. Histopathologic analysis disclosed severe neuronal necrosis in the lumbar gray matter of ischemic rats, whereas most of the LIN-treated rats sustained mild to moderate injury. LIN reduced the loss of motor neurons at 7 days (LIN A, 17 ± 6, and LIN B, 15 ± 7, versus ischemia, 6 ± 2 per section; P < .05). LIN prevented apoptotic neuronal cell death, Bax immunoreactivity of the pro-apoptotic protein Bax, and the nuclear transcription factor NF-κB. Nuclear HSP70 immunoreactivity was noted exclusively in motor neurons from LIN-treated rats and not in motor neurons from ischemic rats.These results suggest that LIN can induce protection against ischemia in the spinal cord, thereby preventing both necrosis and apoptosis of motor neurons.
The effects of tyrosine protein kinases (TK) on the L-type Ca(2+) current (I(Ca)) were examined i... more The effects of tyrosine protein kinases (TK) on the L-type Ca(2+) current (I(Ca)) were examined in whole cell patch-clamped human atrial myocytes. The TK inhibitors genistein (50 microM), lavendustin A (50 microM), and tyrphostin 23 (50 microM) stimulated I(Ca) by 132 +/- 18% (P &lt; 0.001), 116 +/- 18% (P &lt; 0.05), and 60 +/- 6% (P &lt; 0.001), respectively. After I(Ca) stimulation by genistein, external application of isoproterenol (1 microM) caused an additional increase in I(Ca). Dialyzing the cells with a protein kinase A inhibitor suppressed the effect of isoproterenol on I(Ca) but not that of genistein. Inhibition of protein kinase C (PKC) by pretreatment of cells with 100 nM staurosporine or 100 nM calphostin C prevented the effects of genistein on I(Ca). The PKC activator phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 +/- 17%, P &lt; 0.05), decreased I(Ca) (-36 +/- 5%, P &lt; 0.001). Once the inhibitory effect of PMA on I(Ca) had stabilized, genistein strongly stimulated the current (323 +/- 25%, P &lt; 0.05). Pretreating myocytes with genistein reduced the inhibitory effect of PMA on I(Ca). We conclude that, in human atrial myocytes, TK inhibit I(Ca) via a mechanism that involves PKC.
Objective: Recent studies con®rmed the deleterious role of glutamate in the pathophysiology of sp... more Objective: Recent studies con®rmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. Materials and methods: Spinal cord ischemia was induced in normothermia for 14 min in Sprague±Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n 15), control (n 15) receiving only vehicle, riluzole (n 15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n 3), control (n 5), and riluzole (n 5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n 5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. Results: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and de®nitive paraplegia. Riluzole-treated rats had signi®cantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into < 180 multiples of base pairs. Conclusions: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during`high risk' surgical procedures on the thoracoabdominal aorta. q
Intrathoracic extramedullary hematopoiesis is a rare entity, mostly observed in patients with hem... more Intrathoracic extramedullary hematopoiesis is a rare entity, mostly observed in patients with hematologic disorders. Extramedullary hematopoiesis is usually asymptomatic and is often located in the lower paravertebral sulci and rarely in the pleura. We report the case of a 54-year-old man without hematologic disorder or pleural malignancy who had a massive bilateral chylothorax develop due to primary pleural extramedullary hematopoiesis. He was successfully treated by bilateral video thoracoscopic talc pleurodesis and low-dose radiotherapy.
Surgery 124 Predictive prognostic factors of surgically treated intra-pulmonary metastases from c... more Surgery 124 Predictive prognostic factors of surgically treated intra-pulmonary metastases from colorectal carcinomas: a 30 years retrospective analysis
A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found t... more A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found tightly adherent to the esophageal wall and right lower lobe of the lung. Histological examination showed a solid tumor composed of closely packed nests of cells with clear and eosinophilic cytoplasm, which were strongly and diffusely positive for S100 protein but negative for HMB45 and Melan-A. The diagnosis of clear cell sarcoma was supported by demonstrating the presence of an EWS gene rearrangement by fluorescence in situ hybridization. There was no evidence that this lesion represented metastatic disease. To the best of our knowledge, primary mediastinal clear cell sarcoma has not been previously reported in the literature. We present the case and discuss the differential diagnosis.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disord... more Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder with less than 50 reported cases in the literature. DIPNECH belongs to the group of preinvasive lesions defined by the 1999 World Health Organization classification, ...
Surgery may offer a long-term survival benefit to a small proportion of patients with operable no... more Surgery may offer a long-term survival benefit to a small proportion of patients with operable non-small cell lung cancer (NSCLC) and solitary adrenal metastasis. Several approaches to lung resection with a separate open or laparoscopic adrenalectomy have been advocated. We describe a technique that allows a single incision, single operation through a transdiaphragmatic approach to the ipsilateral adrenal gland following a standard lung resection through a postero-lateral thoracotomy. By using this approach, along with the harmonic scalpel to aid adrenal dissection, both lobectomy and adrenalectomy can be carried out safely and effectively with minimal perioperative and postoperative morbidity.
We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appe... more We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appendectomy for mucinous cystadenocarcinoma with pseudomyxomatous peritonei. He underwent bilateral staged metastatectomies for metastases 7 years after the diagnosis and further metastasectomy after a recent recurrence. This is a rare case of recurrent pulmonary metastatic mucinous cystadenocarcinoma, and despite poor prognosis and nondefinitive initial treatment, this patient remains alive and well 20 years later.
Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in pa... more Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appe... more We report a 65-year-old man presenting with recurrent pulmonary metastases 20 years after an appendectomy for mucinous cystadenocarcinoma with pseudomyxomatous peritonei. He underwent bilateral staged metastatectomies for metastases 7 years after the diagnosis and further metastasectomy after a recent recurrence. This is a rare case of recurrent pulmonary metastatic mucinous cystadenocarcinoma, and despite poor prognosis and nondefinitive initial treatment, this patient remains alive and well 20 years later.
Objectives: Prolonged alveolar air leak is the most common complication after pulmonary surgery. ... more Objectives: Prolonged alveolar air leak is the most common complication after pulmonary surgery. We conducted an investigator-led randomized trial to evaluate the effectiveness of CoSeal W surgical sealant (Cohesion Technologies Inc.; manufactured and distributed by Baxter Healthcare) for the closure of alveolar air leak after anatomical pulmonary resection. Methods: Patients undergoing primary open lobectomy, bilobectomy, or sublobar resection with a demonstrable air leak on intra-operative testing were randomized to either standard care or standard care plus application of CoSeal W surgical sealant to areas of air leak. A second application of CoSeal W was used in the treatment group if air leak persisted. Patients were allocated at the point of entry to the trial by unbiased allocation with minimization to ensure balance between the two arms with respect to age, sex, surgeon, number of segments resected, preoperative forced expiratory volume in 1 s (FEV 1 ), and grade of air leak. Kaplan-Meier analysis of air-leak duration and a log rank test were performed on an intention-to-treat basis, with observations censored at death, transfer to the intensive care unit, or discharge. Results: Of the 200 patients, who entered the trial over a 24-month period, 121 with demonstrable intra-operative air leak were randomly allocated to the two groups. Data were missing for one patient in the CoSeal W group. In 57%, the air leak was stopped at the first application; a quarter continued to leak after the second. At 24 h, there was no difference in air leak and fewer patients in the control group were leaking at 48 h postoperatively. By log rank test, the difference was not significant ( p = 0.09). Conclusions: Patients treated with CoSeal W in this study had, as a group, a longer duration of air leak and hence we cannot recommend its routine use. #
Journal of Thoracic and Cardiovascular Surgery, 2010
within the same tumor. 2 It is generally accepted that these tumors originate as a primary epithe... more within the same tumor. 2 It is generally accepted that these tumors originate as a primary epithelial malignancy from which a subset of cells then undergoes dedifferentiation into sarcomatous cells. 1,2 This theory is supported by the frequent finding of a transition zone between the 2 cell populations. 2,4 Previous theories of 2 simultaneously occurring malignancies (collision tumor) or a common origin from a single pleomorphic cell population have fallen out of favor. 2 The epithelial component is usually squamous cell carcinoma, but adenocarcinoma can also occur. 4 Fibrosarcoma is the most common sarcomatous component, although rhabdomyosarcoma, chondrosarcoma, and osteosarcoma (as occurred in our patient) have also been described. 2,4 The sarcomatous cells stain for vimentin, whereas the epithelial cells stain for cytokeratin, 4 although it has been reported that the sarcomatous cells might stain for cytokeratin and the epithelial cells for vimentin. 4 Importantly, results of S-100 protein staining are negative, thus differentiating carcinosarcoma from stromal tumor and an important diagnostic consideration. 3 Clinically, carcinosarcomas are characterized by short doubling time (around 2 months) and rapid growth. 1 They are typically large at presentation (mean, 6-7 cm) and polypoid. 2 Oat cell carcinoma, squamous cell carcinoma, and adenocarcinoma might also present as bulky polypoid tumors of the esophagus, although much more rarely. 5 Endoscopic biopsy specimens show only the epithelial component in close to two thirds of cases. 2 In spite of their propensity to cause symptoms earlier because of their large size and the fact that more than 80% of tumors are limited to the submucosa or muscularis propria at presentation, 2,4,5 these tumors might behave aggressively, and thus radical resection in the form of esophagectomy is advocated. 1,2 Local resection through an esophagotomy has been described in frail patients thought to represent a high operative risk, with occasional long-term survival. 2 Chemotherapy and radiotherapy have rarely been reported, and their efficacy is unclear. 2 Long-term prognosis is thought to be similar to that of pure squamous cell carcinoma of the esophagus. 5
Aim: To report our experience with a multi-modality regimen involving pleurectomy/decortication, ... more Aim: To report our experience with a multi-modality regimen involving pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy in patients with malignant pleural mesothelioma. Method: Prospective study of all patients receiving this multimodality regimen at Guy's & St Thomas' hospital between September 2004 and August 2010. All patients had pleurectomy/ decortication through thoracotomy, received prophylactic radiotherapy postoperatively (21 Gy in 3 fractions) and completed adjuvant chemotherapy (pemetrexed and cisplatin). Nine patients underwent extended resection involving diaphragm (n = 4), lobectomy (n = 3), segmentectomy (n = 2) or SVC (n = 1). All were followed up in the clinic at 1, 6 months and then 6 monthly. Result: Thirty-nine patients completed the multimodality therapy (100%). Thirty day mortality was nil. Ten patients (25.6%) experienced complications: persistent air leak (n = 6, 15%), chylothorax (n = 4, 10%), ARDS (n = 1, 2.5%). Sixteen patients died and 23 patients are still alive at follow-up. Median survival is 29.5 months (CI 19.7 39.2 months), one-year survival is 91.8 % and 2-year survival 65.5%. Macroscopically complete resection (R0-R1) is significantly associated with longer survival versus non-radical resection (R2) (median survival 45.1 months versus 21.1 months, p = 0.005). Patients with epithelioid histology (n = 27) tend to have longer survival than patients with biphasic/sarcomatoid histology (n = 12) (median survival 42.1 months versus 22.8 months, p = 0.069). Conclusion: Pleurectomy/decortication, hyperthermic pleural lavage with povidone-iodine and adjuvant chemotherapy is a well tolerated multi-modality regimen associated with low mortality and morbidity. This therapeutic plan compares favourably with other regimens including extrapleural pneumonectomy and radical radiotherapy.
Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in pa... more Background-The effects of extra-pleural pneumonectomy (EPP) on survival and quality of life in patients with malignant pleural mesothelioma have, to our knowledge, not been assessed in a randomised trial. We aimed to assess the clinical outcomes of patients who were randomly assigned to EPP or no EPP in the context of trimodal therapy in the Mesothelioma and Radical Surgery (MARS) feasibility study.
The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in mali... more The effectiveness of extrapleural pneumonectomy (EPP) to extend quality-adjusted survival in malignant pleural mesothelioma within multimodality treatment should be proven in a randomized controlled trial if this radical surgery is to be regarded as the standard of care. The question was whether randomization to surgery versus no surgery would be possible. The Mesothelioma and Radical Surgery trial was planned to randomize 50 patients to test feasibility. There was a two-stage consent process. At first consent, the patients who were possible candidates for radical surgery were registered into the trial for completion of assessment and staging. All received platinum-based chemotherapy. If still eligible, they completed a second consent to be randomized to have either EPP followed by radical hemithorax radiotherapy or to have continued best care. Patients were recruited through 11 collaborating centers in the United Kingdom. One hundred twelve potentially eligible patients gave informed consent to enter the registration phase and undergo chemotherapy. One died, 27 progressed, five were inoperable, four were treated off trial, and 18 withdrew either during or after chemotherapy but before final review. Additionally six were deemed inoperable at review after completing chemotherapy and one more patient withdrew. The remaining 50 were randomized; 24 to EPP and 26 to continued best care. In this study, 50/112 (45%) of patients entering the evaluation and induction phase of the trial went on to be randomized. We have shown that this randomization between surgery and no surgery is feasible. This was the primary aim of the Mesothelioma and Radical Surgery trial.
Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surger... more Spinal cord ischemia is a devastating complication of thoracic and thoracoabdominal aortic surgery. Recent studies have suggested a neuroprotective effect of polyunsaturated fatty acids against cerebral ischemia. We investigated the effect of linolenic acid (LIN) in a rat model of spinal cord ischemia.Rats were subjected to cross-clamping of the aortic arch and left subclavian artery for 14 minutes. Groups were as follows: sham operation (n = 15); ischemia (n = 15), receiving only vehicle; LIN A (n = 15), receiving LIN before clamping; and LIN B (n = 15), receiving LIN at onset of reperfusion. Neurologic status was assessed daily for 7 days. Spinal cords were harvested for histopathologic analysis, TUNEL staining, and immunohistochemistry for Bax, heat shock protein 70 (HSP70), and nuclear factor–κB.Ischemic rats had severe and definitive paraplegia. LIN-treated rats had significantly better neurologic function. Histopathologic analysis disclosed severe neuronal necrosis in the lumbar gray matter of ischemic rats, whereas most of the LIN-treated rats sustained mild to moderate injury. LIN reduced the loss of motor neurons at 7 days (LIN A, 17 ± 6, and LIN B, 15 ± 7, versus ischemia, 6 ± 2 per section; P < .05). LIN prevented apoptotic neuronal cell death, Bax immunoreactivity of the pro-apoptotic protein Bax, and the nuclear transcription factor NF-κB. Nuclear HSP70 immunoreactivity was noted exclusively in motor neurons from LIN-treated rats and not in motor neurons from ischemic rats.These results suggest that LIN can induce protection against ischemia in the spinal cord, thereby preventing both necrosis and apoptosis of motor neurons.
The effects of tyrosine protein kinases (TK) on the L-type Ca(2+) current (I(Ca)) were examined i... more The effects of tyrosine protein kinases (TK) on the L-type Ca(2+) current (I(Ca)) were examined in whole cell patch-clamped human atrial myocytes. The TK inhibitors genistein (50 microM), lavendustin A (50 microM), and tyrphostin 23 (50 microM) stimulated I(Ca) by 132 +/- 18% (P &lt; 0.001), 116 +/- 18% (P &lt; 0.05), and 60 +/- 6% (P &lt; 0.001), respectively. After I(Ca) stimulation by genistein, external application of isoproterenol (1 microM) caused an additional increase in I(Ca). Dialyzing the cells with a protein kinase A inhibitor suppressed the effect of isoproterenol on I(Ca) but not that of genistein. Inhibition of protein kinase C (PKC) by pretreatment of cells with 100 nM staurosporine or 100 nM calphostin C prevented the effects of genistein on I(Ca). The PKC activator phorbol 12-myristate 13-acetate (PMA), after an initial stimulation (75 +/- 17%, P &lt; 0.05), decreased I(Ca) (-36 +/- 5%, P &lt; 0.001). Once the inhibitory effect of PMA on I(Ca) had stabilized, genistein strongly stimulated the current (323 +/- 25%, P &lt; 0.05). Pretreating myocytes with genistein reduced the inhibitory effect of PMA on I(Ca). We conclude that, in human atrial myocytes, TK inhibit I(Ca) via a mechanism that involves PKC.
Objective: Recent studies con®rmed the deleterious role of glutamate in the pathophysiology of sp... more Objective: Recent studies con®rmed the deleterious role of glutamate in the pathophysiology of spinal cord ischemia induced by aortic cross-clamping. We investigated the effect of riluzole, an anti-glutamate drug, in a rat model of spinal cord ischemia. Materials and methods: Spinal cord ischemia was induced in normothermia for 14 min in Sprague±Dawley rats using direct aortic arch plus left subclavian artery cross-clamping through a limited thoracotomy. Experimental groups were as follows: sham-operation (n 15), control (n 15) receiving only vehicle, riluzole (n 15) receiving riluzole (4 mg/kg) before clamping and at the onset of reperfusion. Separate animals were used for monitoring physiologic parameters in the sham-operation (n 3), control (n 5), and riluzole (n 5) groups. Neurologic status was assessed at 6, 24 h, and then daily up to 96 h. Rats were randomly killed at 24, 48, or 96 h (n 5 for each time). Spinal cords were harvested for histopathology, immunohistochemistry for microtubule-associated protein 2 (MAP-2), TUNEL staining, and analysis of DNA fragmentation by agarose gel electrophoresis. Results: All sham-operated rats had a normal neurologic outcome, whereas all control rats suffered severe and de®nitive paraplegia. Riluzole-treated rats had signi®cantly better neurologic function compared to the control. Histopathology disclosed severe neuronal necrosis in the lumbar gray matter of control rats, whereas riluzole-treated rats suffered usually mild to moderate injury. Riluzole particularly prevented motor neurons injury. MAP-2 immunoreactivity was completely lost in control rats, whereas it was preserved either completely or partly in riluzole-treated rats. TUNEL staining revealed numerous apoptotic neurons scattered within the whole gray matter of control rats. Riluzole prevented or dramatically attenuated apoptotic neuronal death in treated rats. DNA extracted from lumbar spinal cords of sham-operated and riluzole-treated rats exhibited no laddering, whereas spinal cords from control rats showed DNA laddering with fragmentation into < 180 multiples of base pairs. Conclusions: Riluzole may protect the spinal cord in a setting of severe ischemia by preventing neuronal necrosis and apoptosis. This drug may therefore be considered for clinical use during`high risk' surgical procedures on the thoracoabdominal aorta. q
Intrathoracic extramedullary hematopoiesis is a rare entity, mostly observed in patients with hem... more Intrathoracic extramedullary hematopoiesis is a rare entity, mostly observed in patients with hematologic disorders. Extramedullary hematopoiesis is usually asymptomatic and is often located in the lower paravertebral sulci and rarely in the pleura. We report the case of a 54-year-old man without hematologic disorder or pleural malignancy who had a massive bilateral chylothorax develop due to primary pleural extramedullary hematopoiesis. He was successfully treated by bilateral video thoracoscopic talc pleurodesis and low-dose radiotherapy.
Surgery 124 Predictive prognostic factors of surgically treated intra-pulmonary metastases from c... more Surgery 124 Predictive prognostic factors of surgically treated intra-pulmonary metastases from colorectal carcinomas: a 30 years retrospective analysis
A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found t... more A 59-year-old woman presented with a large mediastinal mass. At thoracotomy, the mass was found tightly adherent to the esophageal wall and right lower lobe of the lung. Histological examination showed a solid tumor composed of closely packed nests of cells with clear and eosinophilic cytoplasm, which were strongly and diffusely positive for S100 protein but negative for HMB45 and Melan-A. The diagnosis of clear cell sarcoma was supported by demonstrating the presence of an EWS gene rearrangement by fluorescence in situ hybridization. There was no evidence that this lesion represented metastatic disease. To the best of our knowledge, primary mediastinal clear cell sarcoma has not been previously reported in the literature. We present the case and discuss the differential diagnosis.
Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disord... more Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is a rare pulmonary disorder with less than 50 reported cases in the literature. DIPNECH belongs to the group of preinvasive lesions defined by the 1999 World Health Organization classification, ...
Surgery may offer a long-term survival benefit to a small proportion of patients with operable no... more Surgery may offer a long-term survival benefit to a small proportion of patients with operable non-small cell lung cancer (NSCLC) and solitary adrenal metastasis. Several approaches to lung resection with a separate open or laparoscopic adrenalectomy have been advocated. We describe a technique that allows a single incision, single operation through a transdiaphragmatic approach to the ipsilateral adrenal gland following a standard lung resection through a postero-lateral thoracotomy. By using this approach, along with the harmonic scalpel to aid adrenal dissection, both lobectomy and adrenalectomy can be carried out safely and effectively with minimal perioperative and postoperative morbidity.
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