Pleural recurrence after transthoracic needle lung biopsy in stage I lung cancer: a systematic review and individual patient-level meta-analysis.

INTRODUCTION: Conflicting results exist regarding whether preoperative transthoracic biopsy increases the risk of pleural recurrence in early lung cancer. We conducted a systematic, patient-level meta-analysis to evaluate the risk of pleural recurrence in stage I lung cancer after percutaneous transthoracic lung biopsy. METHODS: A systematic search of OVID-MEDLINE, Embase and the Cochrane Database of Systematic Reviews was performed through October 2018. Eligible studies were original articles on the risk of pleural recurrence in stage I lung cancer after transthoracic biopsy. We contacted the corresponding authors of eligible studies to obtain individual patient-level data. We used the Fine-Gray model for time to recurrence and lung cancer-specific survival and a Cox proportional hazards model for overall survival. RESULTS: We analysed 2394 individual patient data from 6 out of 10 eligible studies. Compared with other diagnostic procedures, transthoracic biopsy was associated with a higher risk for ipsilateral pleural recurrence, which manifested solely (subdistribution HR (sHR), 2.58; 95% CI 1.15 to 5.78) and concomitantly with other metastases (sHR 1.99; 95% CI 1.14 to 3.48). In the analysis of secondary outcomes considering a significant interaction between diagnostic procedures and age groups, reductions of time to recurrence (sHR, 2.01; 95% CI 1.11 to 3.64), lung cancer-specific survival (sHR 2.53; 95% CI 1.06 to 6.05) and overall survival (HR 2.08; 95% CI 1.12 to 3.87) were observed in patients younger than 55 years, whereas such associations were not observed in other age groups. DISCUSSION: Preoperative transthoracic lung biopsy was associated with increased pleural recurrence in stage I lung cancer and reduced survival in patients younger than 55 years.

Generation of ventilation/perfusion ratio map in surgical patients by dual-energy CT after xenon inhalation and intravenous contrast media.

BACKGROUND: While many studies have evaluated the change in lung volume before and after lung resection and correlated this with pulmonary function test results, there is very little evidence on the changes in ventilation perfusion ratio (V/Q) before versus after lung resection. In the present pilot study, we evaluated if V/Q mapping can be constructed using dual energy CT images. METHODS: Thirty-one lung cancer patients planned for pulmonary resection were included in this study. To evaluate ventilation, Xenon-enhanced CT was performed. This was immediately followed by perfusion CT. The two images were registered manually as well as using dedicated softwares, and division between ventilation pixels and perfusion pixels were done to produce the V/Q map. Also, in order to characterize the distribution of the V/Q, the following numerical indices were calculated; mean, median, mode, standard deviation (SD), coefficient of variation (CV), skewness, kurtosis, and fractal dimension (FD). Pulmonary function tests and blood gas parameters were measured using standard institutional procedures. RESULTS: In the whole group, VC, %VC, and FEV1 decreased significantly after resection. FEV1.0% was increased significantly after resection. No significant changes were seen in PaO2, PaCO2, and DLCO/VA before and after resection. The mean, median, mode, SD, skewness, kurtosis and FD of the V/Q did not change significantly before and after resection. A marginal but significant decrease in CV was seen before versus after resection. CONCLUSIONS: Overall, it was considered that the V/Q maps could be adequately generated in this study. With further accumulation of data, V/Q map generated by dual energy CT may become one of the potentially useful tools for functional lung imaging. TRIAL REGISTRATION: This trial was registered in University Medical Information Network in Japan ( UMIN000010023 ) on 13Feb2013.

Acute 40% exchange-transfusion with hemoglobin-vesicles in a mouse pneumonectomy model.

OBJECTIVES: Hemoglobin vesicles (HbVs) function as a red blood cell (RBC) substitute and are composed of purified hemoglobin encapsulated in a phospholipid bilayer membrane. The performance of HbVs as a substitute for RBC transfusions was examined in a mouse model of pneumonectomy following acute 40% exchange-transfusion with HbVs. METHODS: Before performing left pneumonectomies, 40% of the blood volume of mice was replaced with a) lactated Ringer's solution (control), b) 5% recombinant human serum albumin (rHSA), c) mouse RBCs shed in rHSA (mRBCs/rHSA), or d) HbV suspended in rHSA (HbV/rHSA). We compared postoperative a) survival, b) functional recovery, and c) histopathological, immunohistochemical, and inflammatory responses among the study groups. RESULTS: In the HbV/rHSA and mRBC/rHSA groups, all mice survived ≥7 days after pneumonectomy, whereas 100% of the control mice died within a few h and 50% of mice in the rHSA group died within 24 h after pneumonectomy. Immunohistochemical staining for hypoxia-inducible factor-1α showed that hepatic and renal hypoxic injuries were prominently mitigated by HbV and mRBCs. CONCLUSIONS: The oxygen-carrying performance of HbV was similar to that of mRBCs, even with impaired lung functions following pneumonectomy. HbV infusion did not interfere with the recovery from surgical injury. In the near future, HbVs could be used clinically as a substitute for the perioperative transfusion of RBCs, when or where donated RBCs are not immediately available.

Optimized magnitude of cryosurgery facilitating anti-tumor immunoreaction in a mouse model of Lewis lung cancer.

BACKGROUND: Cryosurgery has reemerged as a less invasive local treatment with possible immune-regulatory effects. However, the optimal magnitude of cryosurgery for achieving immune-regulatory responses at abscopal tumor sites remains unclear. We aimed to investigate appropriate magnitude of cryosurgery for this goal using a mouse model. METHODS: C57BL/6J mice were inoculated with Lewis lung carcinoma cells or B16 melanoma cells in bilateral flanks. The left-sided tumor was cryoablated with repeated freeze/thaw cycles either once, twice, or thrice. The peritumoral injections of LPS were performed. Abscopal tumor volumes were measured, immunohistochemistry was performed for CD4, CD8, Foxp3, and Ki-67, and proinflammatory cytokines were measured in lavage fluid of cryoablated tumor. RESULTS: The growth rate of the abscopal tumor was slowest in the Cryosurgery ×2 group among the five experimental groups. The proportions of CD4(+) T cells and CD8(+) T cells in the abscopal tumor were also significantly higher in the Cryosurgery ×2 group. The levels of IL-1ß, IL-2, IL-6, IL-12ß, IFN-γ, and TNF-α in the peritumoral lavage fluid in Cryosurgery ×2 + LPS group were significantly increased compared with the other groups. CONCLUSIONS: This study suggested that achievement of approximately 73 % damaged area in the cryoablated tumor by two cycles of cryosurgery generates the most favorable immune-regulatory response for abscopal tumors via activation of anti-tumor immune cells as well as increased secretion of proinflammatory cytokines.

Total absence of the pericardium incidentally found during surgery for spontaneous pneumothorax.

Congenital absence of the pericardium is a rare malformation which is often found incidentally. We report a case of pericardial absence which was found during surgery for spontaneous pneumothorax. Image analyses suggested that the pericardial absence was bilateral and total. These findings were overlooked on CT, preoperatively. Although rare, the possibility of asymptomatic pericardial absence should be kept in mind when observing the chest images before performing thoracic interventions.

A case of pulmonary sarcoma with significant extension into the right lung.

A female patient in her 30s was referred to us with a mass approximately 8 centimeters in diameter in right lung segment 6. Bronchoscopy was done, and a tumorous lesion obstructing right B6 was found. Biopsy of this lesion supported suspicions of sarcoma or spindle cell carcinoma. Contrast-enhanced CT showed that the mass extended to and obstructed the right main pulmonary artery. A skip lesion was also suspected in the periphery of pulmonary artery trunk. The tumor was removed by right pneumonectomy accompanied by resection of the main and left pulmonary arteries under cardiopulmonary bypass. The pulmonary artery trunk and the left pulmonary artery were reconstructed with a vascular graft. Collectively, intimal sarcoma originating from the right main pulmonary artery with extension into the right lung was diagnosed. Significant extension of pulmonary artery sarcoma into the lung, as was observed in the present case, is considered to be rare, and to our knowledge this is the first report in which the primary lesion was biopsied by bronchoscopy.

Partial anomalous pulmonary venous connection associated with lung cancer in the same lobe: report of a case.

A 64-year-old man with primary lung cancer (cT1aN0M0) was diagnosed as having partial anomalous pulmonary venous connection (PAPVC) in the same lobe by preoperative chest computed tomography (CT). The anomalous vein originated from left upper lobe pulmonary vein and flowed into the left brachiocephalic vein. Although the patient was asymptomatic, cardiac catheterization revealed that pulmonary-systemic blood flow ratio (Qp/Qs ratio) was 2.0, and his pulmonary arterial pressure was marginally elevated (60/18 mmHg). We performed left upper lobectomy as the definitive treatment for both lung cancer and PAPVC. His pulmonary arterial pressure decreased after lobectomy (33/16 mmHg). He is living well without relapse of lung cancer 56 months after surgery. Although PAPVC is detectable on computed tomography, out of 7 previous reports of PAPVC associated with lung cancer, only 2 cases were diagnosed preoperatively. The presence of PAPVC should be kept in mind before major lung resections.

Coadministration of erlotinib and curcumin augmentatively reduces cell viability in lung cancer cells.

Resistance to erlotinib in lung cancer cases includes T790M mutant epidermal growth factor receptor and c-Met gene amplification, but other unknown mechanisms account for about 30% of the resistance. Activation of the nuclear factor kappa B (NFkappaB)-related pathways in association with the reduction in ikappaB level may be one of such potential mechanisms. It is known that curcumin inhibits the inducible activation of NFkappaB at least in part by sustaining ikappaB expression level. Therefore, we evaluated the effects of coadministration of erlotinib and curcumin on lung cancer cells. We found that erlotinib and curcumin augmentatively reduced cell viability. Studies in PC9 cells showed that induction of apoptosis was involved. Expression of ikappaB was elevated in PC9 cells by curcumin administration, and pretreatment with siRNAs for ikappaB significantly attenuated the reduction in cell viability after coadministration of erlotinib and curcumin. Furthermore, coadministration of erlotinib and/or curcumin augmentatively attenuated the growth of PC9 tumors in mice. These results suggested the existence of an augmentative tumor growth inhibitory effect between erlotinib and curcumin, and this effect was at least in part mediated by the increase in the expression of ikappaB induced by curcumin.

Airway administration of vascular endothelial growth factor siRNAs induces transient airspace enlargement in mice.

PURPOSE: Reduction in the level of vascular endothelial growth factor (VEGF) has been implicated in the pathogenesis of pulmonary emphysema. To this end, pharmacological VEGF receptor blockade, and the Cre-lox system models have been utilized to study the effects of VEGF depletion in the lung. These models generally reproduce air space enlargement resembling clinical emphysema. Here we report a potentially more readily available model of lung targeted VEGF depletion by airway administration of VEGF small inhibitory RNA oligonucleotides (siRNAs) in mice. METHODS: Airway administration of VEGF siRNAs were done in C57BL/6 mice. The lungs were removed for histology and protein analysis 2, and 4 days later. Airspace enlargement was evaluated by lung volume measurement, and histological analyses. VEGF levels were analyzed by western blot and immunohistochemistry. RESULTS: Airway administration of VEGF siRNAs induced transient air space enlargement in the mouse lung morphologically resembling the previously reported models of pulmonary emphysema. VEGF expression was significantly reduced in the lung, particularly in the alveolar septal cells. We also found that in this particular model, sequential airway administration of recombinant VEGF protein attenuated this air space enlargement. Additionally, we found that airway administration of DCI, a combination of dexamethasone, 3'-5'-cyclic adenosine monophosphate, and isobutylmethylxanthine attenuated the air space enlargement in this particular model, at least in part through the recovery of lung VEGF expression. CONCLUSIONS: The pathogenesis of pulmonary emphysema is likely to be multifaceted, but the present mouse model may be useful in dissecting the involvement of VEGF in pulmonary emphysema.

Lewis lung carcinoma progression is facilitated by TIG-3 fibroblast cells.

BACKGROUND: The interactions of tumor cells with stromal fibroblasts influence tumor biology, but the exact mechanisms involved are still unclear. In the present study, we evaluated the effects of a human lung fibroblast cell line, TIG-3, on Lewis lung carcinoma (LLC) cells both in vitro and in vivo. MATERIALS AND METHODS: LLC and TIG-3 cells were co-cultured/co-implanted in vitro and in vivo. Cell invasion was assayed. Local tumor growth, as well as lung metastasis, were evaluated after subcutaneous cell co-implantation into NOD/SCID/γ-null (NOG) mice. LLC, and TIG-3 cells were pre-treated with either SB431542, a small molecule TGF-ß receptor antagonist, or siRNA for transforming growth factor (TGF)-ß before co-culture or co-implantation, and the effects of pre-treatments were compared both in cell culture and in mice. RESULTS: Subcutaneous LLC tumor growth (L group) in NOG mice was significantly increased by co-implantation of TIG-3 cells (L+T group) at four weeks. The number of macroscopic lung metastases was also significantly increased in the L+T group in comparison to the L group. In vitro cell invasion was significantly increased in the L+T group in comparison to the L group. In vitro expression of phosphorylated-SMAD3 was significantly increased in the L+T group in comparison to the L group. Furthermore, pre-treatment with either SB431542 or siRNA for TGF-ß reduced the invasiveness both in culture and in mice. CONCLUSION: This study suggested that in vitro as well as in vivo progression of LLC was facilitated by co-culture/co-implantation with TIG-3 cells, and that this process was at least in part dependent on TGF-ß-mediated interactions.

Anterior mediastinal lymphoma arising after resection of an invasive thymoma and immunosuppressive therapy for complicated myasthenia gravis.

We present the case of a 56-year-old woman with an anterior mediastinal tumor who has past history of myasthenia gravis and invasive thymoma. Furthermore, she had superior vena cava syndrome that was caused by a rapidly growing tumor. A biopsy proved diffuse large B-cell lymphoma. After 8 courses of chemotherapy, remission of the lymphoma was achieved. Because a second primary malignancy, including lymphoma, can occur in patients with thymoma, a biopsy is necessary for tumors located in the anterior mediastinum, particularly in patients with a history of treatment for thymoma, to distinguish between recurrence and a second primary malignancy.

Hepatoblastoma metastasis confined to the pulmonary artery: report of a case.

Here, we report a case of hepatoblastoma metastasis to the left pulmonary artery which was resected by left lingular segmentectomy plus left lower lobectomy in 5-year-old girl. She had previously undertaken right upper lobectomy and multiple lung partial resections on bilateral lungs as hepatoblastoma metastatectomies. Prediction of postoperative pulmonary function based on perfusion scan merged with CT image and the measurement by CT volumetry, showed that left lingular segmentectomy plus left lower lobectomy could preserve 78% of the preoperative functional values and resection was done. Three weeks after the operation, her condition recovered to the preoperative level. Pathological examination showed that the metastasis was tumor embolism of hepatoblastoma which extended into the pulmonary arterial wall, which to our knowledge, has not been previously reported.

Complete laceration of the middle lobe bronchus caused by blunt trauma.

Bronchial ruptures due to blunt trauma are rarely encountered injuries. A previously healthy 42-year-old man fell from heights of 8 meters. A prompt chest tube-drainage for suspected right sided tension pneumothorax and a tracheal intubation were performed. Massive air leak and pneumothorax of the right lung continued. Laceration of the tracheobronchial tree was suspected. Operation was performed 20 hours after patient's arrival. The complete avulsion of the middle lobe bronchus was identified during operation, and a middle lobectomy was performed. The patient was transferred to a rehabilitation hospital on 20th post-operative day without complication. Early decision making for surgery resulted in a good outcome. When a complete atelectasis of the whole right lung and a massive air leakage continues despite appropriate chest-tube drainage in a blunt trauma patient, laceration of the tracheobronchial tree should be suspected.

Prediction of the critical thermal zone during pulmonary cryoablation on computed tomography from correlated experimental and clinical findings.

OBJECTIVE: During cryoablation, cells are destroyed at temperatures less than -20°C. The determining factors for local cancer control in pulmonary cryoablation were assessed using computed tomography (CT), isothermal curves, and histologic findings in pigs. Experimental findings were compared with clinical CT findings and were extrapolated to local cancer control outcomes. METHODS: Cryoablation was performed with thermal monitoring, and the ablated areas were divided into 3 zones: less than -20°C, -20°C to 0°C, and greater than 0°C and were compared with histologic findings. CT findings with multiplanar reconstruction in 36 nodules were compared with the porcine histologic findings. The relationship between CT findings and 3-year local cancer control was evaluated in 98 nodules. RESULTS: The 3 concentric thermal zones correlated with histologic findings as follows: less than -20°C zone, complete tissue destruction (zone D); -20°C to 0°C zone (which surrounded zone D), hemorrhage with air trapping and maintenance of alveolar structures (zone H); and greater than 0°C zone (outermost), edema with sustained alveolar structures (zone E). The CT findings in 36 nodules showed a central solid zone, a surrounding air-containing zone, and an outside solid zone, corresponding to zones D, H, and E, respectively. Local cancer control at 3 years in 80 nodules contained within the central solid zone was significantly greater compared with the 18 nodules that were not (82% vs 33%, P = .0002). CONCLUSIONS: Pulmonary cryoablation should be performed such that tumors are contained within the central solid zone on CT, which represents the less than -20°C zone.

Successful surgical resection of leiomyoma obstructing the trachea.

We report a case of 51-year-old woman with a severely airway-obstructing leiomyoma who underwent successful tracheal resection. A preoperative tumor biopsy was avoided not to cause any risk of suffocation. At surgery, an endotracheal intubation distal to the tumor was achieved with a bronchoscopic guidance. A segmental resection of the trachea with a primary end-to-end anastomosis was performed via a half-splitting median sternotomy. Negative surgical margins for tumor were confirmed intraoperatively. Final pathological diagnosis was a primary tracheal leiomyoma. Definitive surgical resection is a treatment of choice for such airway-obstructing, wide-based leiomyoma. Although a bronchoscopic removal of the tumor is an alternative choice, the risks of suffocation, positive surgical margins, and perforation of the trachea need to be carefully discussed if it is considered.

Incidence of pleural recurrence after computed tomography-guided needle biopsy in stage I lung cancer.

OBJECTIVE: A risk of tumor seeding after percutaneous needle biopsy has been reported in various organs, including the lung. This study retrospectively evaluated the proportion of ipsilateral pleural recurrence after computed tomography-guided needle biopsy (CTNB) in p-stage I lung cancer patients. METHODS: Of the 321 patients diagnosed with p-stage I lung cancer, 124 underwent CTNB before surgery, while 197 underwent non-CTNB procedures, including bronchoscopic biopsy in 188 patients and thoracoscopic wedge resection in 9. These patients were retrospectively analyzed. RESULTS: While the tumor size was significantly larger in the non-CTNB group (25 ± 9 mm) in comparison to the CTNB group (19 ± 9 mm) (p<0.001), percentage of pleural, vascular, or lymphatic invasions were comparable between the two groups. Eight patients developed ipsilateral pleural recurrences, one (1%) in the CTNB group, and 7 (4%) in the non-CTNB group. Of these, 3 patients developed pleural recurrence only at first, 1 (1%) in the CTNB group, and 2 (1%) in the non-CTNB group. The differences in the proportions of these pleural recurrences between the 2 groups were not significant. Subgroup analyses by baseline characteristics such as tumor size, pT stage, or microscopic pleural invasion, showed that proportions of pleural recurrences in CTNB group were not high compared with non-CTNB group in each subgroup. Analysis of progression-free survival showed that recurrences in CTNB were not high compared with non-CTNB. CONCLUSIONS: The pleural recurrence was not significantly increased after CTNB in p-stage I lung cancer patients in this particular study.

Computed tomographic appearance of lung tumors treated with percutaneous cryoablation.

PURPOSE: To describe the computed tomographic (CT) appearance of lung tumors treated with cryoablation to establish a reliable reference profile. MATERIALS AND METHODS: CT images of 56 patients who underwent follow-up CT for at least 1 year for treatment with cryoablation of 79 tumors from 2003 to 2010 were retrospectively reviewed. Patients had a follow-up CT scan immediately after the procedure; 1 day, 1 week (two-phase dynamic CT), and 1 month later; and then at 3-month intervals. The appearance of ablation zones on CT images was classified into five patterns, and bidimensional diameters and other imaging features were evaluated. RESULTS: Seventy-eight percent of ablation zones (62 of 79) showed transformation similar to the following: a consolidation or nodular pattern was seen within the 1-week follow-up, involution and a "stripe" pattern was shown at 1 month or later, and zones later became indistinct. Eighty percent of cases of local progression (eight of 10) arose from the stripe pattern on follow-up CT 6 months or later, after the ablation zones showed a transformation opposite the aforementioned pattern. Ice balls could not always be visualized exactly because of dense peritumoral hemorrhage. Internal and marginal enhancement of the ablation zone within the 3-month follow-up did not show a direct relationship with local progression. In total, cavitation and peritumoral ground-glass opacity were seen in 35% (n = 28) and 85% (n = 66) of ablation zones, respectively. CONCLUSIONS: The reference profile of CT appearance, which is mandatory for follow-up, has been established. No single indicator of complete ablation was proven throughout this study. Careful long-term follow-up with CT is indispensable.

Salvage surgery for a super-responder by gefitinib therapy for advanced lung cancer.

Salvage surgery after gefitinib therapy in a 66-year-old female with cT4N1M1a lung adenocarcinoma in the right middle lobe, which had gene mutation of epidermal growth factor receptor, is presented. The patient had bulky hilar lymph nodes, pleural dissemination, and pulmonary metastases in the ipsilateral lobes. After 3 courses of chemotherapy, the patient was treated with gefitinib, resulting in partial response, i.e. only the primary tumor and the middle lobe atelectasis remained. We performed the middle lobe lobectomy aimed at local control and pathological confirmation of the remaining tumor. Because the hilum of the middle lobe was occupied with scar tissue, its pulmonary vein had to be cut within the pericardium and its pulmonary artery and bronchus had to be transected simultaneously with a stapler. Pathological stage was yp-T2aN0N0 with Ef 2. For salvage surgery after good response to gefitinib therapy, it should be taken care to expose pulmonary vessels.

Simplified rat lung transplantation using a new cuff technique.

We introduce a new procedure for orthotopic left lung transplantation in rats. First, cuffs are attached to vessels or bronchi in both donors and recipients. Next, the cuffs are anastomosed by interposing pieces of the donor's descending aorta. Anastomosis time is markedly reduced to approximately 10 minutes. Transplantations were completed in 8 rats without technical errors. This rat lung transplantation technique is a straightforward method any surgeon can perform.