Hiroyasu Kinoshita

The Long-Term Outcomes of Induction Chemoradiotherapy Followed by Surgery for Locally Advanced Non-Small Cell Lung Cancer

Background: Although the concept of induction therapy followed by surgical resection for locally advanced non-small cell lung cancer (LA-NSCLC) has found general acceptance, the appropriate indications and the strategy for this treatment are still controversial. Methods: From 2000 through 2008, 36 patients received concurrent chemoradiotherapy followed by surgery. We retrospectively reviewed these cases, analyzed the outcomes and examined the prognosis. Results: The median radiation dose given was 60 Gy. Chemotherapy included a platinum agent in all cases; cisplatin-based chemotherapy was administered to 9 cases, and a carboplatin-based chemotherapy regimen was administered to 27. A complete resection was performed in 94% of the patients. Seventeen (47.2%) patients exhibited a complete pathological response, and downstaging was induced in 26 (72%) cases. The morbidity and 30-day mortality rates were 11.1 and 0%, respectively. The 5-year overall survival rate in the patients with complete resection (n = 33) was 83.3%. Conclusions: Induction chemoradiotherapy followed by surgery for LA-NSCLC provided a favorable prognosis for selected patients. A complete pathological response was found in about half of cases. This strategy is feasible and was associated with low morbidity and high resectability rates, suggesting that it contributed to improving the treatment results.

Routine genetic testing of lung cancer specimens derived from surgery, bronchoscopy and fluid aspiration by next generation sequencing

After the development of EGFR tyrosine kinase inhibitors (TKIs), genetic testing of EGFR became required for effective treatment of lung cancer. Initially, the testing was conducted separately for each mutated region. However, many EGFR mutations have since been identified that determine the efficacy of EGFR-TKIs. Therefore, genetic testing of EGFR by next generation sequencing (NGS) may be a suitable strategy for lung cancer. Here we examined the applicability of the NGS method in regard to sensitivity, time and cost. A total of 939 specimens were obtained from 686 lung cancer patients at our hospital. DNA and RNA were simultaneously extracted from specimens derived from surgery, bronchoscopy, and fluid aspiration. Specimens included cerebrospinal fluid, pleural effusion, abdominal fluid, and pericardial effusion. From RNA, target regions (EGFR, KRAS, ALK fusion and RET fusion) were enriched by RT-PCR and sequenced with MiSeq. From DNA, PCR or PCR-RFLP conventional methods were performed. NGS and conventional methods were carried out routinely per week. Among the total 939 specimens, 38 specimens could not be examined with NGS. Among these, 34 specimens were analyzed by conventional testing with simultaneously extracted DNA. The remaining four specimens could not be tested with either method. Compared with the conventional method, the concordance rate of mutations was 99% (892/901), excluding specimens with NGS failure. The time period required from processing of specimens to results was 4 days, and the cost per sample was sufficiently low. In conclusion, the genetic testing with NGS method was useful for lung cancer treatment. The cost, sensitivity and time were able to tolerate routine examinations.

Targeted Gene Delivery to Selected Liver Segments Via Isolated Hepatic Perfusion

BACKGROUND Development of targeted gene transfer technologies is essential for in vivo gene therapy. In this study, we examined the feasibility of physically targeting an adenoviral vector to selected liver segments in rats by isolating the hepatic perfusion (IHSP) and clamping the portal vein between the upper and lower segments. MATERIALS AND METHODS The rats were divided into two groups: IHSP group and the inferior vena cava (IVC) group. The adenoviral vector, which harbored the beta-galactosidase (beta-gal) gene, was administered via the portal vein, after which unbound vector particles were washed out with phosphate-buffered saline (PBS) and removed via the cannulated inferior vena cava (IVC) in IHSP group, while the IVC group received the transgene directly via the IVC without isolation of the hepatic perfusion. RESULTS With this configuration (IHSP group), >99% of the beta-gal activity was limited to the targeted hepatic lobes, findings which were confirmed by histochemical staining with X-gal. We also found there to be significant differences in transgene expression among the hepatic lobes in the IVC group. CONCLUSIONS Taken together, these results indicate that the IHSP technique is useful for local gene delivery to selected liver segments, and that when evaluating the efficacy of IHSP in the treatment of liver disease (e.g., nonresectable tumors), interlobar differences must be given careful consideration to ensure that sufficient drug or vector is delivered to all targeted hepatic lobes.

Surgical Treatment of Superior Sulcus Tumors

PurposeTo access the clinical outcome of patients with superior sulcus tumor.MethodsWe reviewed the records of 16 patients who underwent surgery for a superior sulcus tumor between 1988 and 2003, focusing on the type of surgery.ResultsAll 16 patients underwent en bloc lung and chest wall resection, which was done as pneumonectomy in 1 patient and lobectomy in 15. Complete resection was achieved in 11 patients, but incomplete resection was done in 5 patients because microscopic examination revealed positive surgical margins. Eight patients underwent partial vertebrectomy and 1 patient had combined resection of the subclavian artery. There was no postoperative mortality. All patients received pre- or postoperative adjuvant therapy, or both. The overall 5-year survival rate was 31.0%. The 5-year survival rate was higher after complete resection than after incomplete resection (59.3% vs 0%, P = 0.08). Patients who underwent complete resection for vertebral invasion and those who did not had 5-year survival rates of 66.7% and 0%, respectively (P = 0.17). Patients who underwent preoperative induction therapy followed by complete resection and those who did not had 5-year survival rates of 80% and 0%, respectively (P = 0.009).ConclusionAlthough superior sulcus tumors are still complex, preoperative induction therapy followed by complete resection seemed effective for prolonging survival.

The importance of determining surgical indications in cases of lung cancer and interstitial pneumonia with multiple intrapulmonary lymph nodes

Highlights • It is difficult to determine whether surgery is indicated in patients with lung cancer with multiple nodular shadows in multiple lung lobes.• Physicians are reluctant to perform surgery for patients with lung cancer and interstitial pneumonia.• However, surgery is the only treatment method that is expected to achieve cure of lung cancer with interstitial pneumonia.• ∼10-mm nodular shadows located near the pleura may represent an intrapulmonary lymph node.• Even for patients with lung cancer with interstitial pneumonia, a biopsy should be actively performed to determine the indication for surgery.

Case report of two patients having successful surgery for lung cancer after treatment for Grade 2 radiation pneumonitis

Introduction Surgery for locally advanced lung cancer is carried out following chemoradiotherapy. However, there are no reports clarifying what the effects on the subsequent prognosis are when surgery is carried out in cases with radiation pneumonitis. In this paper, we report on 2 cases of non-small cell lung cancer with Grade 2 radiation pneumonitis after induction chemoradiotherapy, in which we were able to safely perform radical surgery subsequent to the treatment for pneumonia. Presentation of cases Case 1 was a 68-year-old male with a diagnosis of squamous cell lung cancer cT2aN2M0, Stage IIIA. Sixty days after completion of the radiotherapy, Grade 2 radiation pneumonitis was diagnosed. After administration of predonine, and upon checking that the radiation pneumonitis had improved, radical surgery was performed. Case 2 was a 63-year-old male. He was diagnosed with squamous cell lung cancer cT2bN1M0, Stage IIB. One hundred and twenty days after completion of the radiotherapy, he was diagnosed with Grade 2 radiation pneumonitis. After administration of predonine, the symptoms disappeared, and radical surgery was performed. In both cases, the postoperative course was favorable, without complications, and the patients were discharged. Conclusion Surgery for lung cancer on patients with Grade 2 radiation pneumonitis should be deferred until the patients complete steroid therapy, and the clinical pneumonitis is cured. Moreover, it is believed that it is important to remove the resolved radiation pneumonitis without leaving any residual areas and not to cut into any areas of active radiation pneumonitis as much as possible.

Easy Diagnosis of Aortic Invasion in Patients with Lung Cancer Using Cine Magnetic Resonance Imaging

Selecting the proper treatment strategy for locally advanced lung cancer, such as T4 tumors, is difficult. Therefore, obtaining an accurate diagnosis of T4 tumors is required. It can be difficult to determine whether the tumor invades adjacent structures. We describe the case of a patient easily diagnosed to be without aortic invasion using cine magnetic resonance imaging (MRI). We herein report the case of an 80-year-old male who presented a lung tumor. The transbronchial lung washing cytology findings were consistent with those of adenocarcinoma. In addition, the computed tomography findings indicated suspected aortic invasion of the lung tumor, as the mass girdled the descending aorta beyond 120° adjoining at a length of 10 cm. However, cine MRI display clearly demonstrated a clear area of isolation between the aorta and lung tissue based on differences in the heart rhythm from the patients respiratory movements. Therefore, the lesion was clinically diagnosed as a stage IIB (T3N0M0) tumor. Radiation was administered due to the patients advanced age and comorbidities such as chronic obstructive pulmonary disease. He remains alive without disease progression 6 months after the therapy. Our findings, therefore, indicate the usefulness of easily diagnosing the absence of aortic invasion in patients with lung cancer using cine MRI without the need for a special software program.

A case of incomplete Carney’s triad

A 62-year-old woman, who had multiple pulmonary nodules noted 6 years earlier, and surgery for a gastrointestinal stromal tumor 2 years earlier, was found to have enlargement of her pulmonary nodules. Surgery was selected to make a definite diagnosis. Thoracoscopic segmentectomy of right segments 9 and 10 was performed, and pulmonary chondroma was diagnosed. Carney designated the combination of 3 rare soft tissue tumors (gastric leiomyosarcoma, pulmonary chondroma, and extraadrenal paraganglioma) as a syndrome. This patient may have had an incomplete type of Carney’s triad with 2 lesions in the stomach and lung.

An extremely rare case report of surgery of lung cancer with the absence of azygos vein

In thoracic surgery, we occasionally encounter vessel anomalies. We herein report an extremely rare surgical case with the absence of the azygos vein. Mediastinal vascular abnormalities are said to be rare. The etiology of vascular abnormalities of the whole body, including the chest is known gene mutations, hormone abnormalities, infection, and trauma. But, many causes have been unknown. In thoracic surgery field, there is some reports and literature about pulmonary arteriovenous malformation, pulmonary sequestration, and partial anomalous pulmonary venous return. But reports about absence of azygos vein are not much. It is considered that it is less likely to become a problem in clinical. As we discussed in the paper, it will be more interesting if the association with PLSVC reveals from more cases. A 58-year-old man was admitted to our hospital in order to undergo operation for the treatment of lung cancer. We detected absence of the azygos vein by preoperative computed tomography (CT). Furthermore, three-dimensional angiography (3D-angiography) showed that the right superior intercostal vein and hemiazygos vein in the left thoracic cavity were more developed than usual. Then, we discuss the key points during surgery and suggest the potential association between the absence of the azygos vein and a persistent left superior vena cava (PLSVC).

Surgical Treatment for Pulmonary Metastasis of Head and Neck Cancer: Study of 58 Cases

PURPOSE Although the number of surgeries performed for pulmonary metastasis of head and neck cancer has been increasing, there have been few reports of the surgical effectiveness. We collected the data of surgeries performed in our facility in order to discuss the surgical performance and indication. METHODS We retrospectively examined the prognosis and predictors for 58 patients with pulmonary metastasis of head and neck cancer who underwent a surgery in our facility during the 15-year period, from January 2000 to December 2015. RESULTS The 3-year and 5-year survival rates were 54.2% and 35.7%, respectively, and the median survival time was 42.2 months. The disease-free interval (DFI) was less than 24 months and patients with oral cavity cancer were poor prognostic factors. CONCLUSION The effectiveness of surgical treatment for pulmonary metastasis of head and neck cancer was suggested.