Rib resection using a pneumatic high-speed power drill system for lung cancer with chest wall invasion: our clinical experience.

Rib resection for chest wall tumors, including lung cancer with chest wall invasion, is usually performed through open thoracotomy. Resection of part of the external rib cage requires an elongated or additional incision depending on the location and extension of the tumor, eventually becoming more invasive to patients. We recently introduced a technique of rib resection using a pneumatic high-speed power drill system known as "air tome". This novel technique is easy to perform through a small incision or even via video-assisted thoracoscopic surgery (VATS) in selected patients. We present our clinical experience and discuss the usefulness of this technique for rib resection in patients with lung cancer and chest wall invasion.

Preoperative Evaluation of the Right Upper Lobe Pulmonary Artery by 3D-CT Pulmonary Angiography vs. Thin-Section Multiplanar Reconstruction Images Obtained by Contrast-Enhanced Multidetector-Row CT.

We compared the effectiveness of 3-dimensional computed tomography pulmonary angiography (3D-CTPA) and thin-section multiplanar reconstruction (MPR) images obtained using contrast-enhanced multidetector row CT (MDCT), in the evaluation of pulmonary artery (PA) branches of the right upper lobe. We studied 127 patients suspected of having lung cancer of the right upper lobe who underwent contrast-enhanced MDCT scans and a right upper lobectomy. We compared the intraoperative findings of the PA branches of the right upper lobe obtained with 3D-CTPA and thin-section MPR images. In 125 (97.7%) patients, one or more PA branches arose from arteries other than the superior trunk. Among 10 (7.9%) patients, a PA branch arose from the middle lobe in one patient and from the superior segment of the lower lobe in the other 9 patients. According to the intraoperative findings, 97.2% and 99.7% of the PA branches were identified by 3D-CTPA and thin-section MPR images, respectively (p ＜ 0.03). The single branch missed by both imaging modalities was 1.0mm in dia. The 8 branches missed only by 3D-CTPA were ＜ 1.4mm in dia. Both the 3D-CTPA and thin-section MPR images provided precise preoperative information regarding PA branches of the right upper lobe. However, the thin-section MPR images appeared to contribute more to the evaluation of smaller PA branches.

Novel therapeutic approach for pulmonary emphysema using gelatin microspheres releasing basic fibroblast growth factor in a canine model.

PURPOSES: The prognosis of patients with emphysema is poor as there is no truly effective treatment. Our previous study showed that the alveolar space was smaller and the microvessel density was higher in a canine emphysema model after the intrapulmonary arterial administration of gelatin microspheres slowly releasing basic fibroblast growth factor (bFGF-GMS). In the present study, we evaluated the functional effect of injecting bFGF-GMS via the pulmonary artery in this canine pulmonary emphysema model. METHODS: Using the porcine pancreatic elastase (PPE)-induced total emphysema model, we approximated the value of lung compliance with a Power Lab System, and performed blood gas analysis in a control group, a total emphysema group, and a bFGF group in which bFGF-GMS were injected toward the whole pulmonary artery via the femoral vein. Each group comprised five dogs. RESULTS: Lung compliance was higher in the total emphysema group than in the control group (p = 0.031), and the bFGF group showed no significant improvement of lung compliance vs. the total emphysema group (p = 0.112). PaO2 (partial pressure of oxygen in arterial blood) was improved by administering bFGF-GMS in the total emphysema model (p = 0.027). CONCLUSION: In the canine total emphysema model, blood gas parameters were improved by the whole pulmonary arterial administration of bFGF-GMS. This method has the potential to be an effective novel therapy for pulmonary emphysema.

A newly developed surgeon-controlled suction device in robotic-assisted thoracoscopic surgery.

INTRODUCTION: Assistant surgeons usually clean the surgical field with a suction cannula in robotic-assisted surgery. This manipulation requires skill and experience to avoid interfering with the operation of the console surgeon. Recently, we created a new suction device that a console surgeon can manipulate with the robotic arms. MATERIALS AND SURGICAL TECHNIQUE: A small metal suction tip with as a lumen and small side pores for suction and can be connected to a silicone tube connected to wall suction. The tip of the silicone tube can be grasped with robotic forceps and used for organ retraction as well as suction. The suction device has been used in eight lung lobectomy cases and four lung segmentectomy cases to date. There were no major difficulties related to the new suction device except for metal tip disconnection and blood clots clogging. DISCUSSION: Our newly developed surgeon-controlled suction device is inexpensive, easy to handle, and useful for suction, blunt dissection, and organ retraction in robotic-assisted thoracoscopic surgery, especially when performing lymph node dissection.

Association between oxygen consumption and stepping exercise standardized with a triaxial accelerometer.

OBJECTIVE: According to the current American College of Chest Physicians (ACCP) guideline, a cardiopulmonary exercise test (CPET) is indicated in patients with lung cancer being considered for lung surgery. The measurement of maximum oxygen consumption ([Formula: see text] max) is not sufficiently prevalent because it requires special technical equipment. Considering that stepping is a simple and common exercise, we aimed to establish a simple and reproducible test with standardization of exercise intensity using a triaxial accelerometer. METHODS: Twenty healthy volunteers (10 male, 10 female) were included in the study. The subjects were obliged to step on the same spot at the rate of 80 and 110 counts for 1 min each and then step as quickly as possible for the last minute. Oxygen consumption ([Formula: see text]) (mL/kg/min) for every breath was continuously measured during the exercise. A triaxial accelerometer was attached to the hip of test subjects whereby metabolic equivalents (METs) at each test level were measured. RESULTS: The mean age of the study subjects was 42.9 ± 11.4 (mean ± SD). The mean value of [Formula: see text] at each level increased linearly along with the stepping level in each individual but varied among subjects. Using METs instead of step counts minimized the difference in regression lines among subjects. A receiver operating characteristic analysis revealed the possibility of [Formula: see text] prediction for the critical values of 10 and 20 mL/kg/min using METs. CONCLUSION: A simple and reproducible stepping test was suggested as applicable to standardizing the intensity of exercise using a triaxial accelerometer.

Mechanism of action of DSP-7888 (adegramotide/nelatimotide) Emulsion, a peptide-based therapeutic cancer vaccine with the potential to turn up the heat on non-immunoreactive tumors.

BACKGROUND: Wilms' tumor 1 (WT1) is highly expressed in various solid tumors and hematologic malignancies. DSP-7888 (adegramotide/nelatimotide) Emulsion is an investigational therapeutic cancer vaccine comprising three synthetic epitopes derived from WT1. We evaluated the mechanism of action of DSP-7888 Emulsion, which is hypothesized to induce WT1-specific cytotoxic T lymphocytes (CTLs) and helper T lymphocytes (HTLs). METHODS: The ability of nelatimotide and adegramotide to induce WT1-specific CD8+ T cells and CD4+ T cells was assessed in human peripheral blood mononuclear cells (PBMCs). The ability of DSP-7888 Emulsion to induce WT1-specific CTLs in vivo was assessed using human leukocyte antigen-I (HLA-I) transgenic mice. To assess how adegramotide, the helper peptide in DSP-7888 Emulsion, enhances WT1-specific CTLs, HLA-I transgenic mice were administered DSP-7888 or nelatimotide-only Emulsion. Interferon-gamma secretion under antigen stimulation by splenocytes co-cultured with or without tumor cells was then quantified. The effects of combination treatment with DSP-7888 Emulsion and an anti-programmed cell death protein 1 (PD-1) antibody on tumor volume and the frequency of tumor-infiltrating WT1-specific T cells were assessed in HLA-I transgenic mice implanted with WT1 antigen-positive tumors. RESULTS: The peptides in DSP-7888 Emulsion were shown to induce WT1-specific CTLs and HTLs in both human PBMCs and HLA-I transgenic mice. Unlike splenocytes from nelatimotide-only Emulsion-treated mice, splenocytes from DSP-7888 Emulsion-treated mice exhibited high levels of interferon-gamma secretion, including when co-cultured with tumor cells; interferon-gamma secretion was further enhanced by concomitant treatment with anti-PD-1. HLA-I transgenic mice administered DSP-7888 Emulsion plus anti-PD-1 experienced significantly greater reductions in tumor size than mice treated with either agent alone. This reduction in tumor volume was accompanied by increased numbers of tumor-infiltrating WT1-specific CTLs. CONCLUSIONS: DSP-7888 Emulsion can promote both cytotoxic and helper T-cell-mediated immune responses against WT1-positive tumors. Adegramotide enhances CTL numbers, and the CTLs induced by treatment with both nelatimotide and adegramotide are capable of functioning within the immunosuppressive tumor microenvironment. The ability of anti-PD-1 to enhance the antitumor activity of DSP-7888 Emulsion in mice implanted with WT1-positive tumors suggests the potential for synergy.

Thoracic composite hemangioendothelioma with neuroendocrine marker expression.

BACKGROUND: Composite hemangioendothelioma is an extraordinarily rare form of vascular neoplasm which develops predominantly in the skins and soft tissues of the adults. Neuroendocrine marker expression in composite hemangioendothelioma is considered as specifically relevant to the more aggressive behavior. CASE PRESENTATION: The patient was a 71-year-old man complaining continuous back pain. Computed tomography (CT) showed that 10 cm of contrast-enhanced soft tissue mass was occurring on the right posterior chest wall and developing adjacent to the spinal canal. Via the laminectomy, the tumor end was identified and separated from the dura mater. Then, via the posterolateral thoracotomy, the en bloc resection was achieved by separating the tumor from the diaphragm and vertebras. Histologic examination showed a complex combination of epithelioid and retiform hemangioendothelioma areas which were positive for anti-synaptophysin staining. At 12-month follow-up, there were no signs of tumor recurrence on CT, and the patient had no symptom. CONCLUSIONS: We achieved the complete resection of a huge thoracic neuroendocrine composite hemangioendothelioma developing adjacent to the spinal canal. The combination of the posterior lumbar laminectomy and the following posterior thoracotomy is a viable approach to radically resect a thoracic neuroendocrine composite hemangioendothelioma involving chest wall.

Thoracoscopic rib resection and reconstruction of chest wall: Our clinical experience.

Chest wall resection is traditionally performed via open thoracotomy, a procedure that increases surgical morbidity and reduces postoperative quality of life. Conversely, thoracoscopic chest wall resection may minimize invasiveness but the optimal procedure remains uncertain. We previously reported rib resection using a pneumatic high-speed power drill during video-assisted thoracoscopic surgery for selected lung cancer patients. In this report, we present two cases of chest wall tumor resected using the drill via the thoracoscopic approach. We also report thoracoscopic chest wall reconstruction in one patient using a patch sheet.

Association between values of preoperative 6-min walk test and surgical outcomes in lung cancer patients with decreased predicted postoperative pulmonary function.

OBJECTIVE: We retrospectively investigated the possibility that the 6-min walk test (6MWT) could predict surgical outcomes in lung cancer patients with decreased predicted postoperative (ppo) lung function. METHODS: Patients were enrolled based on their preoperative spirometry: <60% of the ppo forced expiratory volume in 1 s (FEV1.0) or < 60% of the ppo lung carbon monoxide diffusion capacity (DLco). Morbidity, oxygen inhalation required > 10 days, home oxygen therapy (HOT) requirement, unexpected readmission within 90 days, and 90-day mortality were included as surgical outcomes. The correlations with walking distance and the minimum SpO2 (SpO2min) and maximum decrease in SpO2 (ΔSpO2) during the 6MWT were analyzed using logistic regression analysis, adjusting for age, sex, and surgical procedure. RESULTS: Altogether, 121 patients were analyzed. Logistic regression analysis revealed that higher ΔSpO2 and lower SpO2min were significantly correlated with a higher risk of prolonged need for oxygen inhalation and HOT, surgical morbidity, and 90-day mortality. Cut-off values of > 4% for ΔSpO2 were significant for prolonged oxygen inhalation and surgical morbidity. Cut-off values of < 89-91% for SpO2min were also significant for the need for prolonged oxygen inhalation, surgical morbidity, and HOT requirement. There were no significant correlations between walking distance and each surgical outcome. CONCLUSIONS: Oxygen desaturation during 6MWT was a good predictor for poor surgical outcomes in lung cancer patients with decreased ppo pulmonary function.

Clinical Experience of Thoracoscopic Sleeve Lobectomy Using a Novel Needle Holder.

Thoracoscopic bronchoplasty requires high technique to control stitching during bronchial reconstruction. Improved quality of suturing instrument may contribute to overcome this difficulty of bronchial anastomosis. Recently, a unique and expected articulated instrument for suturing has been launched on endoscopic surgery. We have successfully performed two cases of thoracoscopic sleeve lobectomy using this instrument.

En bloc partial vertebrectomy for lung cancer invading the spine after induction chemoradiotherapy.

OBJECTIVE: The optimal surgical treatment for non-small cell lung cancer (NSCLC) with vertebral body invasion remains both controversial and challenging. We reviewed our experiences of NSCLC with vertebral body invasion, in which we have performed induction chemoradiotherapy followed by lung resection with en bloc partial vertebrectomy. METHODS: Six NSCLC patients with vertebral invasion underwent an operation following chemoradiotherapy from January 2001 to July 2006. Vertebral invasion was evaluated by the chest CT and MRI findings. Either carboplatin-paclitaxel (n=3) or carboplatin-docetaxel (n=3) was used. Two cycles of chemotherapy were performed with concurrent radiation (50 Gy) treatment. RESULTS: In all of the six cases, a complete resection with en bloc partial vertebrectomy was performed with no operative mortality. The histological complete response rate and major response rate were 16.7% (1/6) and 83.3% (5/6), respectively. The 5-year overall survival rate was 67.7%. In addition, no local failure was observed after surgery. CONCLUSIONS: Surgery after chemoradiotherapy (carboplatin/paclitaxel or docetaxel and 50 Gy radiation) for NSCLC with vertebral invasion could thus be performed with acceptable morbidity.

Intra-thoracic fibrous tissue induction by polylactic acid and epsilon-caprolactone copolymer cubes, with or without slow release of basic fibroblast growth factor.

OBJECTIVE: We investigated whether implantation of polylactic acid and epsilon-caprolactone copolymer (PLAC) cubes with or without basic fibroblast growth factor (b-FGF) released slowly from gelatin microspheres was able to induce fibrous tissue in the dead space remaining after pneumonectomy in the thoracic cavity. METHODS: Left pneumonectomy was performed in Japanese white rabbits. In the control group (n=6), the left thoracic cavity was closed without any treatment. In the FGF group (n=6), gelatin microspheres that released 100 microg of b-FGF were implanted into the left thoracic cavity. In the PLAC group (n=6), PLAC cubes were implanted into the left thoracic cavity. In the PLAC/FGF group (n=6), both PLAC cubes and gelatin microspheres releasing 100 microg of b-FGF were implanted into the left thoracic cavity. RESULTS: In the control and FGF groups, herniation of the heart, mediastinal shift, and overinflation of the right lung were observed. No granular tissue formation was observed. In the PLAC and PLAC/FGF groups, a dense area of newly formed soft tissue was observed, and only a mild mediastinal shift was observed during the 3-month follow-up period. Pathological examination revealed induction of fibrous and granular tissue in the left thoracic cavity. The foreign-body reaction induced by PLAC was very mild. CONCLUSIONS: Implantation of PLAC cubes with or without gelatin microspheres releasing 100 microg of b-FGF is able to induce fibrous tissue in the post-pneumonectomy dead space.

A surgical case of primary lung cancer with peripheral intrapulmonary lymph node metastasis.

We report on a case of a patient with lung adenocarcinoma and peripheral intrapulmonary lymph node (IPLN) metastasis who was misdiagnosed as having intrapulmonary metastasis. A subpleural nodular shadow visualized by radiography was diagnosed as an intrapulmonary metastasis originating from primary lung cancer. Preoperative evaluation indicated that this case was a clinical T4N1 lung adenocarcinoma with metastasis in the same lobe. However, postoperative evaluation showed that it was a peripheral IPLN metastasis, and this was actually a case of pathologic T2N1 adenocarcinoma. It may have been possible to treat this case non-surgically with the possibility of radical cure. This case suggests that a nodule is present in the same lobe with lung cancer, and it must be borne in mind that IPLN metastasis may be misdiagnosed as intrapulmonary metastasis.

Thoracoscopic partial resection without using a stapler. (complete republication).

Thoracoscopic partial pulmonary resection for small peripheral nodules without using a stapler has been introduced to our hospital. After partial resection was performed with electrocautery, two different methods of surface sealing were used: a coagulation method (C method) with Soft Coagulation alone, and a coagulation-suturing method (CS method) with Soft Coagulation combined with continuous suturing. The clinical outcomes of the two methods were retrospectively compared in this study. The C method was used in 19 lesions of 18 cases, and the CS method was used in 20 lesions of 19 cases. Primary lung cancer was the most frequent diagnosis (22 lesions of 21 cases). There were no differences between the two groups in the size and depth of the lesions. Operative time was longer with the CS method than with the C method. Postoperative air leakage was a complication in 4 cases with the C method, and one of them required re-do surgery, whereas only one case with the CS method had temporary air leakage. Postoperative computed tomography showed cavitation in 3 C method cases and 5 CS method cases, all without related symptoms. There were no local recurrences at resected sites. In conclusion, the C method was technically easy to perform, but air leakage may be prolonged after surgery. The CS method may have the advantage of causing less air leakage than the C method, but mastering the technique is important to shorten operative time.

Computed tomography (CT) and positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET) images of pulmonary cryptococcosis mimicking lung cancer.

BACKGROUND: The objective of this study was to clarify the clinical features of pulmonary cryptococcosis using chest computed tomography (CT) and positron emission tomography with [18F]fluoro-2-deoxy-D-glucose (FDG-PET), with a view to developing appropriate treatment. METHODS: We analyzed the clinical features, and chest CT and FDG-PET characteristics of six cases of pulmonary cryptococcosis that were treated by surgery. The patients comprised four males and two females, ranging in age from 28 to 79 years. RESULTS: All the patients were asymptomatic and had no extrapulmonary involvement. In all cases, chest CT showed nodular shadows. Spiculation and convergence of peripheral vessels were demonstrated in three cases, and pleural indentation in two cases. FDG-PET was performed in four of the cases, and showed accumulation of FDG in all of them. The standard uptake value (SUV) ranged from 0.93 to 4.85. Chest CT findings and accumulation of FDG made it difficult to distinguish pulmonary cryptococcosis from malignancies. Segmentectomy or wedge resection was performed in all cases for pathological diagnosis, and this revealed Cryptococcus fungal bodies. After surgical resection, no sign of relapse has been seen in any of the patients. CONCLUSIONS: Surgical resection is recommended for both diagnosis and treatment of pulmonary cryptococcosis.

Regeneration of canine tracheal cartilage by slow release of basic fibroblast growth factor from gelatin sponge.

We investigated the efficiency of basic fibroblast growth factor (b-FGF) released from a gelatin sponge in the regeneration of tracheal cartilage. A 1-cm gap was made in the midventral portion of each of 10 consecutive cervical tracheal cartilages (rings 4 to 13) in 15 experimental dogs. In the control group (n = 5), the resulting gap was left blank. In the gelatin group (n = 5), a gelatin sponge alone was implanted in the gap. In the b-FGF group (n = 5), a gelatin sponge containing 100 mug b-FGF solution was implanted in the gap. We euthanatized one of the five dogs in each group at 1 month after implantation and one at 3 months and examined the implant sites macroscopically and microscopically. In the control and gelatin groups, no regenerated cartilage was observed in the tracheal cartilage gap at 1 or 3 months. The distances between the cartilage stumps had shrunk. In the b-FGF group, fibrous cartilage had started to regenerate from both host cartilage stumps at 1 month. At 3 months, regenerated fibrous cartilage filled the gap and had connected each of the stumps. The regenerated cartilage was covered with regenerated perichondrium originating from the host perichondrium. Shrinkage of the distance between the host cartilage stumps was not observed in the b-FGF group. We succeeded in inducing cartilage regeneration in the gaps in canine tracheal cartilage rings by using the slow release of b-FGF from a gelatin sponge. The regenerated cartilage induced by b-FGF was fibrous cartilage.

Prognostic value of body mass index and change in body weight in postoperative outcomes of lung cancer surgery.

OBJECTIVES: Nutritional status is associated with an effect on oncological outcomes. However, the effect of nutritional status on postoperative survival in lung cancer has not been well studied. We retrospectively analysed and evaluated the effect of preoperative body mass index (BMI) and changes in body weight on postoperative outcomes of lung cancer surgery. METHODS: A total of 1311 patients with non-small-cell lung cancer who underwent surgery between January 2001 and December 2011 were included in this study. Preoperative body weight at 4-12 weeks prior to surgery was obtained in 737 patients and the ratio of change in body weight was calculated. RESULTS: The patients were classified into four groups as follows: underweight (BMI < 18.5), normal weight (BMI from ≥18.5 to <25), overweight (BMI from ≥25 to <30) and obese (BMI ≥ 30). Postoperative survival curves of the BMI groups showed that the underweight group had a poorer prognosis than the other groups, especially for disease-free survival (DFS) (P = 0.03). Univariate and adjusted survival analyses using Cox's proportional hazards regression model showed that low BMI was a significantly poor prognostic factor in overall survival (OS) (P = 0.03 and P = 0.02, respectively) and DFS (P < 0.01 and P < 0.01, respectively). Among the BMI groups, the underweight group had a significant worse prognosis than the other groups for DFS in univariate and adjusted analyses (P = 0.04 and P < 0.01, respectively). With regard to changes in body weight, patients with a body weight loss of 3.7% or greater had a significantly poorer prognosis for OS and DFS in univariate analysis and for DFS in adjusted analyses compared with the other patients. Regarding short-term outcomes, the weight loss group had a significantly longer postoperative hospital stay than the non-weight loss group (P = 0.02) and postoperative 90-day mortality was significantly lower in the normal weight group than in the underweight group (P = 0.03). CONCLUSIONS: Low BMI and significant body weight loss before surgery have a negative effect on surgical outcomes for patients with non-small-cell lung cancer.

Real time imaging and quantitative evaluation of the emphysematous lung by infrared thoracoscopy in experimental dogs.

To accurately excise emphysematous lung tissue in volume reduction surgery, we projected a digitally analyzed excision line on the real time image obtained by infrared thoracoscopy (IRT) with indocyanine green (ICG) intravenous injection. Emphysema was created in the canine lung by intrabronchial injection of elastase. We examined the emphysematous lung by IRT after intravenous injection of ICG. A digitized static image was obtained and analyzed in real time during the surgery. The color densities on the image were measured and the color density ratios (CDRs) calculated. We resected lung areas where the CDR was 1.0 or less. Resected and residual lung areas were examined microscopically. Microscopically, areas displayed as white by IRT with intravenous injection of ICG were emphysematous, and areas displayed as blue were normal. Areas with a CDR of 1.0 or less were emphysematous, and we were able to determine an appropriate excision line by connecting sample points with a CDR of 1.0. Use of digital image analysis combined with IRT after ICG injection enabled us to remove emphysematous regions accurately.

Pulmonary rehabilitation during induction chemoradiotherapy for lung cancer improves pulmonary function.

OBJECTIVE: Chemoradiotherapy for non-small cell lung cancer can impair pulmonary function, particularly when it is followed by surgery. This study aimed to document the changes in respiratory function as a result of a perioperative intensive pulmonary rehabilitation program in patients with non-small cell lung cancer who underwent induction chemoradiotherapy. METHODS: A total of 82 consecutive patients underwent pulmonary resection after undergoing induction chemoradiotherapy. A pulmonary rehabilitation program was started at the same time as the induction chemoradiotherapy. Standard respiratory function tests were performed before and after induction chemoradiotherapy. Treatment-related mortality and the incidence of postoperative respiratory complications were investigated. The Wilcoxon signed-rank test was used to analyze the differences in spirometric changes. RESULTS: All patients underwent a pulmonary rehabilitation program for an average of 10 weeks. Significant increases were observed in forced vital capacity (+6.4%, P = .0096) and forced expiratory volume in 1 second (+10.4%, P < .0001). Diffusing capacity of the lung for carbon monoxide decreased (-14.0%, P < .0001). Patients with respiratory impairment (forced vital capacity <80% predicted or forced expiratory volume in 1 second/forced vital capacity <70%) showed significant improvements in forced vital capacity (+13.9%, P = .0025) and forced expiratory volume in 1 second (+22.5%, P < .0001). Significant increases were observed in forced vital capacity (+7.0%, P = .0042) and forced expiratory volume in 1 second (+10.8%, P = .0001) in patients with a smoking history. There was no mortality, and postoperative respiratory morbidity was 6.1%. CONCLUSIONS: A pulmonary rehabilitation program for patients with non-small cell lung cancer undergoing induction chemoradiotherapy seems to improve respiratory function. It is particularly recommended for smokers and patients with respiratory impairment.