Tadayuki Oka

Video-assisted thoracic surgery lobectomy reduces the morbidity after surgery for stage I non-small cell lung cancer

OBJECTIVE We conducted this study to evaluate the surgical invasiveness and the safety of video-assisted thoracic surgery lobectomy for stage I lung cancer. METHODS Video-assisted thoracic surgery lobectomies were performed on 43 patients with clinical stage IA non-small cell lung cancer. We compared the surgical invasiveness parameters with 42 patients who underwent lobectomy by conventional thoracotomy. RESULTS Intraoperative blood loss was significantly less than that in the conventional thoracotomy group (151+/-149 vs. 362+/-321 g, p<0.01). Chest tube duration (3.0+/-2.1 vs. 3.9+/-1.9 days) was significantly shorter than those in the conventional thoracotomy group (p<0.05). The visual analog scale which was evaluated as postoperative pain level on postoperative day 7, maximum white blood count and C-reactive protein level were significantly lower than those in the conventional thoracotomy group (p<0.05). The morbidity rate was significantly lower than that in the conventional thoracotomy group (25.6% vs. 47.6%, p<0.05). Sputum retention and arrhythmia were significantly less frequent than in the conventional thoracotomy group (p<0.05). We experienced no operative deaths in both groups. CONCLUSION We conclude that video-assisted thoracic surgery lobectomy for stage I non-small cell lung cancer patients is a less invasive and safer procedure with a lower morbidity rate compared with lobectomy by thoracotomy.

Low-potassium UW solution for lung preservation. Comparison with regular UW, LPD, and Euro-Collins solutions.

University of Wisconsin solution has been used successfully in clinical kidney and liver preservation. The object of this study was to determine if low-potassium UW (LPUW) solution could be applied to pulmonary preservation. Rabbit lungs were stored after hypothermic pulmonary artery (PA) flush with four different solutions (group 1: low-potassium dextran (LPD) solution, group 2: high-potassium UW (HPUW) solution, group 3: LPUW solution, group 4: modified Euro-Collins (E-C) solution). The lungs were preserved at 10°C for 30 hr and evaluated in an ex vivo ventilation/perfusion apparatus using fresh pooled venous rabbit blood. Mean PA flush pressures (MFP) during harvesting were significantly lower in groups 1 and 3 (8.1±1.0 mmHg and 7.3±0.6 mmHg, respectively; mean ± SEM) than in groups 2 and 4 (15.5±1.7 mmHg and 12.3±0.9 mmHg, respectively). Lungs in groups 1 and 3 showed significantly higher PaO2 (103.5±8.0 mmHg and 89.3±7.2 mmHg) than groups 2 and 4 (48.3±7.7 mmHg, 66.7±4.7 mmHg). Groups 1 and 3 showed significantly lower wet/ dry weight (W/D) ratios after reperfusion (6.21±0.15 and 6.39±0.23) than groups 2 and 4 (7.70±0.57 and 7.13±0.21, respectively). There were no significant differences in MFP, PaO2, PaCO2, mean pulmonary artery pressure, or W/D ratio between groups 1 and 3. These results suggest that LPUW solution may be as beneficial as LPD solution for pulmonary arterial flush and lung preservation.

The Effect Of Pge1 And Temperature On Lung Function Following Preservation

We studied the effect of a vasodilator (prostaglandin E1) as well as flush (F) and storage (S) temperatures (4°C or 10°C) on lung preservation in an isolated rabbit lung perfusion model. Low-potassium dextran (LPD) or Euro-Collins (E-C) solution was used as flush solution. Six groups of six animals were studied: group 1 (LPD, 4°C F-S), group 2 (LPD with PGE, 4°C F-S), group 3 (E-C with PGE, 4°C F-S), group 4 (LPD, 10°C F-S), group 5 (LPD with PGE1, 10°C F-S), group 6 (E-C with PGE1, 10°C F-S). After 18-hr preservation, left lungs alone were ventilated, and reperfused with fresh venous blood. PaO2, PaCO2, pulmonary artery pressure (PAP), tracheal pressure (P1) during reperfusion, and wet/dry weight (W/D) ratios were measured. PaO2 after LPD with or without PGE1 was significantly higher than after E-C with PGEi at 4°C (95.8±11.5 mmHg in group 1 or 102.7±8.6 in group 2 vs. 41.8±10.5 in group 3, P>0.01) and at 10°C (119.3±2.3 in group 4 or 131.1± 6.2 in group 5 vs. 54.6±5.2 in group 6, P>0.01). PaCO2, PAP, P1, and W/D ratios in the LPD groups were lower than in the E-C groups. LPD/PGE1 and LPD alone produced similar pulmonary preservation. PaO2 of lungs flushed with LPD and preserved at 10°C was higher than that of lungs stored at 4°C. We conclude that LPD solution is superior to E-C solution in this ex vivo rabbit lung preservation model, even when PGE1 is used. A moderate dose of PGE1 did not improve the performance of LPD as a flush solution. Pulmonary preservation with LPD at 10°C is superior to preservation at 4°C.

The Importance of Peripheral Blood Leukocytes and Macrophage Infiltration on Bronchial Wall Wound Healing in Rats Treated Preoperatively with Anticancer Agents

Abstract Preoperative chemotherapy is commonly used for small cell lung cancer or advanced non-small cell lung cancer. This study was conducted to investigate the effects of preoperative antineoplastic agents on the postoperative would healing of bronchial anastomoses in a rat model. Cisplatin (CDDP), doxorubicin (ADM), or cyclophosphamide (CPA) was administered either 3 days preoperatively (experiment 1) or 7 days preoperatively (experiment 2). Wound healing was assessed on postoperative days (POD) 3, 5, and 7 after anastomosis of the bronchus, by examining the bursting strength and hydroxyproline tissue content. In experiment 1, significant impairment of wound healing was seen on POD 3 in the CPA-treated rats, but no significant changes were seen in the other groups. Severe leukopenia and marked reduction of macrophage infiltration into the wound were also observed in the CPA-treated rats. The impairment of wound healing coincided with the time of leukopenia and reduced macrophage infiltration into the wounds. In experiment 2, induction chemotherapy did not impair wound healing. Our experimental results suggest that preoperative chemotherapy producing mild leukopenia, or when followed by a sufficient interval to allow for the recovery of myelosuppression, did not impair wound healing of the bronchial anastomoses. The findings of this study also showed that the depletion of macrophages at the anastomotic site is one of the most important causes of impaired wound healing.

Surgical Treatment for Lung Cancer in Octogenarians

PurposeWe conducted this study in order to determine how we should perform the surgical treatment for clinical stage I non-small cell lung cancer (NSCLC) in octogenarians.MethodsThirty-three octogenarians with clinical stage I NSCLC participated in this study. They were retrospectively divided into two groups: one group of 11 patients who underwent a lymph node dissection (ND group), and one group of 22 patients who did not undergo this procedure (ND0 group). We analyzed the surgical invasiveness, morbidity, mortality, and survival in both groups.ResultsThe morbidity rate in the ND group (45%) was higher than that in the ND0 group (23%); however, the difference was no statistically significant (P = 0.1805). There was no significant difference in the overall survival rates of the two groups (P = 0.1647), and the median survival time of the ND0 group (76 months) was slightly longer than that of the ND group (26 months). There was no significant difference in local recurrence rate between the two groups (9.1% vs 4.5%, P = 0.6059).ConclusionWe thus conclude that a limited operation without lymph node dissection might be the best surgical treatment for carefully selected octogenarians with clinical stage I NSCLC.

Tumor necrosis factor inhibitor gene transfer ameliorates lung graft ischemia-reperfusion injury.

OBJECTIVE Tumor necrosis factor is an important mediator of lung transplant ischemia-reperfusion injury, and soluble type I tumor necrosis factor receptor binds to tumor necrosis factor and works as a tumor necrosis factor inhibitor. The objectives of this study were to demonstrate that gene transfer of type I tumor necrosis factor receptor-IgG fusion protein reduces lung isograft ischemia-reperfusion injury and to compare donor endobronchial versus recipient intramuscular transfection strategies. METHODS Three donor groups of Fischer rats (n = 6/group) underwent endobronchial transfection with either saline, 2 x 10(7) plaque-forming units of control adenovirus encoding beta-galactosidase, or 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein. Left lungs were harvested 24 hours later. Two recipient groups (n = 6/group) underwent intramuscular transfection with 2 x 10(7) plaque-forming units or 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein 24 hours before transplantation. All donor lung grafts were stored for 18 hours before orthotopic lung transplantation. Graft function was assessed 24 hours after reperfusion. Transgene expression was evaluated by means of enzyme-linked immunosorbent assay and immunohistochemistry of type I tumor necrosis factor receptor. RESULTS Endobronchial transfection of donor lung grafts with 2 x 10(7) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein significantly improved arterial oxygenation compared with the saline and beta-galactosidase donor groups (366.6 +/- 137.9 vs 138.8 +/- 159.9 and 140.6 +/- 131.4 mm Hg, P =.009 and.010, respectively). Recipient intramuscular transfection with 1 x 10(10) plaque-forming units of adenovirus encoding type I tumor necrosis factor receptor-IgG fusion protein improved lung graft oxygenation compared with that seen in the low-dose intramuscular group (2 x 10(7); 320.3 +/- 188.6 vs 143.6 +/- 20.2 mm Hg, P =.038). Type I tumor necrosis factor receptor-IgG fusion protein was expressed in endobronchial transfected grafts. In addition, intramuscular type I tumor necrosis factor receptor-IgG fusion protein expression was dose dependent. CONCLUSIONS Donor endobronchial and recipient intramuscular adenovirus-mediated gene transfer of type I tumor necrosis factor receptor-IgG fusion protein improved experimental lung graft oxygenation after prolonged ischemia. However, donor endobronchial transfection required 500-fold less vector. Furthermore, at low vector doses, it does not create significant graft inflammation.

Thoracoscopic drainage with wound edge protector for descending necrotizing mediastinitis

It has recently been found that wide recognition of descending necrotizing mediastinitis (DNM) and its resultant early diagnosis can reduce the high mortality rate associated with this disease by allowing for rapid surgical intervention. Nevertheless, thoracotomy remains controversial as a treatment for DNM. We report a successful case of DNM in which the mediastinitis had spread below the carina and which was treated by drainage through cervicotomy and by thoracoscopic drainage with mini-thoracotomy using the newly available wound edge protector called a Lap-protector.

Extended resection for lung cancer invading mediastinal organs

We analyzed 49 patients with non-small-cell lung cancer invading mediastinal organs such as the left atrium (15), superior vena cava (13), trachea (11), aorta (5), thoracic vertebral body (4) and esophagus (1). Lung resection included lobectomy (37), pneumonectomy (8) and limited resection (4). Twenty-seven patients underwent carina- or bronchoplasty. Complete resection was possible in 35 patients. Operative mortality was 12% and overall 5-year survival was 13%. Median survival time was 519 days. Factors significantly affecting survival were the completeness of resection, node status, and histological type. Five-year survival was 18% with complete resection and 0% with incomplete resection (p < 0.0001). Five-year survival for patients with squamous cell carcinoma was 36% and for those with other types of lung cancer, 0% (p < 0.02). Five-year survival for patients classified pathologically as N0 or N1 was 36% and, for those classified as N2 or N3, 0% (p < 0.05). We concluded that aggressive resection for lung cancer invading the mediastinal organs involves a high mortality rate, making selectivity important. Patients undergoing complete resection, classified as N0 or N1, and having squamouse cell carcinoma may benefit most from surgery.

Chromosome 8 numerical aberrations in stage II invasive ductal carcinoma: correlation with patient outcome and poor prognosis.

Aberrations in chromosome 8 are common in breast cancer. However, the relationship between numerical aberrations of chromosome 8 and clinical behavior (especially prognosis) in breast cancer is not well understood. In this study, a total of 40 specimens of stage II invasive ductal carcinomas (IDCs) was analyzed by fluorescence in situ hybridization (FISH) with a chromosome 8 centromere-specific probe and DNA flow cytometry (stage IIA: 20 cases; stage IIB: 20 cases). All cases were followed for at least 5.7 yr (mean: 7.5 yr; median: 7.7 yr) after surgery or until death. Single (loss), double, and triple or more signals (gain) of chromosome 8 were found in 7.6±3.5% (range: 2–16%; median: 7%), 53.7±13.2% (range: 25–81%, median: 53%), and 38.7±13.2% (range: 17–65%, median: 38%), respectively, of tumors. The frequencies of chromosome 8 gain and disomy correlated with patient outcome (respectively p<0.05 and p<0.01). When median ratios of chromosome 8 loss, disomy, and gain were used as the cutoff values, the survival curves revealed that patients in the low-frequency group survived significantly longer than those in the high-frequency group for chromosome 8 gain (p<0.05), and patients in the high-frequency group survived significantly longer than those in the low-frequency group for chromosome 8 disomy (p<0.05). Poor prognosis was not associated with age, tumor size, lymph node metastasis, histologic type, TNM stage, estrogen-receptor status, progesterone-receptor status, or DNA ploidy. Our results suggest that the frequencies of chromosome 8 gain and disomy is a potentially useful parameter for predicting prognosis of stage II IDCs.

Postoperative Complications of Pulmonary Resection After Platinum-Based Induction Chemotherapy for Primary Lung Cancer

Abstract.Purpose: We investigated the postoperative complications that developed in patients who underwent surgery after induction chemotherapy (IC) for primary lung cancer. Methods: Twenty-seven patients underwent surgery after receiving IC; for advanced non-small cell lung cancer in 16, and for small cell lung cancer in 11. All patients were given the platinum-based chemotherapy regimen. Results: Lobectomies were performed for 18 patients, bilobectomies for 4, pneumonectomies for 2, and partial resections or segmentectomies for 3. There were two postoperative deaths; one caused by adult respiratory distress syndrome (ARDS) and one caused by respiratory failure, resulting in a mortality rate of 7.4%. The postoperative complications included sputum retention in six patients, ARDS in two, anastomotic dehiscence after bronchoplasty in one, and pneumonia in one, resulting in 44.4% morbidity. The morbidity of patients who had received IC (IC group) was higher than that of a comparative group of 560 who underwent lung resection without IC during the same period (non-IC group), but the difference was not significant (44.4% vs 22.6%; P = 0.16). Both ARDS and bronchial insufficiency occurred more frequently in the IC group than in the non-IC group, but the differences were not significant (P = 0.25). Conclusions: These findings indicate the feasibility of treating primary lung cancer with IC followed by surgery as long as a cautious operative procedure is used and careful postoperative management is given, paying particular attention to the risk of ARDS and bronchial complications.