A randomized controlled trial comparing paravertebral block via the surgical field with thoracic epidural block using ropivacaine for post-thoracotomy pain relief.

PURPOSE: We conducted a comparative study to evaluate analgesic efficacy between paravertebral block via the surgical field (PVB-sf), in which the catheter was inserted into the ventral side of the sympathetic trunk in the paravertebral space by a thoracic surgeon under thoracoscopic visualization, and epidural block (Epi) using ropivacaine for post-thoracotomy pain relief. METHODS: Lung cancer patients scheduled for lobectomy via thoracotomy were randomly allocated to receive either PVB-sf or Epi (n = 36 per group). Before thoracotomy closure, 0.375% ropivacaine was administered as a bolus (PVB-sf, 20 mL; Epi, 5 mL), followed by a 300-mL continuous infusion of 0.2% ropivacaine at 5 mL/h. Postoperative pain was assessed using a visual analog scale (VAS) score at various time points, including the primary endpoint of 2 h after ropivacaine bolus injection. Sensory block area, vital signs, serum ropivacaine concentrations, and side effects were also evaluated. RESULTS: The Epi group showed significantly lower VAS scores and blood pressure and a wider sensory block area than the PVB-sf group at all evaluation time points. While the mean serum ropivacaine concentration in the PVB-sf group was significantly higher than that in the Epi group until 1 h after injection of the ropivacaine bolus, there was no significant difference at any subsequent assessment point. The incidence of side effects was similar between the groups. CONCLUSION: The Epi was superior to PVB-sf for the management of post-thoracotomy pain in this patient cohort. The number of dermatomes anaesthetized by Epi was greater than that anaesthetized by PVB-sf. No difference in complication rates was observed between the two groups.

Pulmonary inflammatory myofibroblastic tumor harboring EML4-ALK fusion gene.

Inflammatory myofibroblastic tumor is a rare tumor deriving from mesenchymal tissue. Approximately 50% of inflammatory myofibroblastic tumors harbor an anaplastic lymphoma kinase fusion gene. Pulmonary inflammatory myofibroblastic tumors harboring tropomyosin3-anaplastic lymphoma kinase or protein tyrosine phosphatase receptor-type F polypeptide-interacting protein-binding protein 1-anaplastic lymphoma kinase have been reported previously. However, it has not been reported that inflammatory myofibroblastic tumors harbor echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene which is considered to be very specific to lung cancers. A few tumors harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene other than lung cancers have been reported and the tumors were all carcinomas. A 67-year-old man had been followed up for a benign tumor for approximately 3 years before the tumor demonstrated malignant transformation. Lobectomy and autopsy revealed that an inflammatory myofibroblastic tumor harboring echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion gene had transformed into an undifferentiated sarcoma. This case suggests that echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion is an oncogenic event in not only carcinomas but also sarcomas originating from stromal cells.

A prospective multi-institutional study to verify the non-inferiority of postoperative pain in robot-assisted thoracic surgery in comparison with video-assisted thoracoscopic surgery for lung cancer: The Japanese RATS interest group 01 (J-RATSIG 01).

OBJECTIVES: We sought to compare the latest data on postoperative pain between robot-assisted thoracic surgery (RATS) and video-assisted thoracoscopic surgery (VATS), and to clarify the relationship between the number or placement of ports and postoperative pain in patients with lung cancer. METHODS: Patients who underwent anatomical lung resection by RATS or VATS and whose chest tube was removed within 7 days were enrolled. The primary endpoint was the percentage of patients with a numeric rating scale (NRS) score ≤ 3 on postoperative day 30 (POD30). The target sample size was 400 patients. RESULTS: Four hundred five patients (RATS, n = 196; VATS, n = 209) managed at 12 institutions were included. Ninety-nine patients in the VATS group underwent a uniport procedure. Significant differences were observed between the RATS and VATS groups in the mean number of inserted ports (5.0 vs. 2.2), number of injured intercostal sites (2.9 vs. 1.9), largest wound size (3.4 vs. 3.7 cm), operation time (202 vs. 165 min), and use of epidural anesthesia or continuous nerve block (45 vs. 31 %). In the RATS and VATS groups, the rates of NRS≤3 on POD30 were 82.0 % and 94.7 % (95 %CI: -19.0 to -6.6 %), respectively, which could not prove noninferiority. However, in a multivariable analysis, the RATS approach was not proven to be a significant risk factor. CONCLUSION: In the current status of minimally invasive thoracic surgery in Japan, RATS involves a greater number of ports, longer operation time, and higher frequency of local anesthesia than VATS and may be inferior in terms of postoperative pain.

Paravertebral block via the surgical field versus epidural block for patients undergoing thoracotomy: a randomized clinical trial.

PURPOSE: A paravertebral block (PVB) given via the surgical field can be safer and technically simpler than an epidural block (EP) for postoperative pain control. We conducted this clinical trial to confirm the effectiveness of PVB after thoracotomy. METHODS: In this non-inferiority trial, patients were randomly assigned to receive PVB (n = 35) or EP (n = 35). The primary endpoint was the pain assessed using the visual analog scale (VAS) at rest, 2, 24, and 48 h after thoracotomy, with the non-inferiority margin set at 15 mm. The secondary end points were the pain assessed using the VAS on exercising and on coughing, 2, 24, and 48 h after surgery, respectively, and the complications and need for additional analgesic agents. RESULTS: This trial revealed that PVB was not inferior to EP with respect to the primary end point: The mean VAS scores at rest, 2, 24, and 48 h after thoracotomy were 26.3, 10.8, and 8.3 mm in the PVB group and 23.6, 12.4, and 12.6 mm in the EP group, respectively (P < 0.01 for non-inferiority at all points). There were no significant differences between the groups in the incidence of complications or the need for additional analgesic agents. CONCLUSION: PVB may replace EP for postoperative pain control because of its technical simplicity and safety.

Pathologically confirmed spontaneous regression of small cell lung cancer after computed tomography-guided percutaneous transthoracic needle biopsy followed by surgery.

BACKGROUND: Spontaneous regression of malignant tumors is a rare phenomenon, especially in primary lung cancer. The underlying mechanisms remain unclear, but they may often involve immunological mechanisms. CASE PRESENTATION: In January 2020, a 78-year-old female underwent examination during follow-up of interstitial pneumonia. Chest X-ray and computed tomography (CT) scan revealed a 1.2 × 1.2 cm nodule in the left lower lobe. Based on CT-guided percutaneous transthoracic needle biopsy (PTNB), it was diagnosed as small cell lung cancer (SCLC). Immunohistochemical staining showed that tumor cells were positive for CD56, synaptophysin, and chromogranin A. Twenty-three days after the CT-guided PTNB, repeat CT scan showed that the tumor size regressed to 0.6 × 0.6 cm. The tumor showed positive uptake in fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT. The maximum standardized uptake value of the nodule was 2.24. PET-CT and enhanced magnetic resonance imaging of the brain showed no distant or lymph node metastasis. The patient's preoperative disease was diagnosed as cT1aN0M0, stageIA1, SCLC. In March 2020, she underwent left lower lobectomy and mediastinal lymph node dissection. Pathological examination of the resected specimen showed that the small tumor cells were dense with a high nucleus to cytoplasm ratio, and the morphological diagnosis was small cell carcinoma. The resected tumor size regressed to 0.05 × 0.02 cm, and no lymph node metastasis was observed. Because it was extremely small, immunohistochemical staining could not be conducted. Active fibrosis and inflammation were present around the tumor. Finally, the patient was pathologically diagnosed as SCLC pT1miN0M0, stage IA1. The patient is alive without recurrence 23 months after surgery with no adjuvant therapy. CONCLUSIONS: We present a rare surgical case of pathologically confirmed spontaneous regression of SCLC after CT-guided PTNB. Although spontaneous regression is extremely rare, we should recognize this phenomenon.

Polyglycolic acid sheet covering to prevent recurrence after surgery for spontaneous pneumothorax: a meta-analysis.

The coverage technique using absorbable mesh was first described in a European guideline published in 2015 as a preventive method for the recurrence of spontaneous pneumothorax. We performed a meta-analysis based on a literature search of primary studies that compared the postoperative recurrence rate of primary spontaneous pneumothorax between the use and nonuse of polyglycolic acid sheet coverage. Two reviewers independently selected and evaluated the quality of the relevant studies. The risk ratio in each study was calculated in a random-effect meta-analysis. Statistical heterogeneity among the included studies was quantitatively evaluated using the I2 index, and publication bias was assessed using a funnel plot. A total of 19 retrospective cohort studies were analyzed: 1524 patients who underwent wedge resection alone (the control group) and 1579 who received additional sheet coverage. Polyglycolic acid sheet coverage was associated with a lower recurrence rate than that in the control group (risk ratio: 0.27, 95% confidence interval 0.20-0.37, P < 0.001; I2 0%). The funnel plot suggested possible publication bias. The covering technique reduced the recurrence rate of pneumothorax after thoracoscopic surgery to one-fourth.

Lobectomy with bronchoplasty and pulmonary arterial angioplasty for lung cancer after correction of contralateral partial anomalous pulmonary venous connection.

BACKGROUND: There have been few reports on surgically treated primary lung cancer accompanied by contralateral partial anomalous pulmonary venous connection (PAPVC). In such cases, repair of the PAPVC might be necessary to avoid postoperative right-heart failure due to the increased flow of the left-to-right shunt. CASE PRESENTATION: We herein report a case of lung adenocarcinoma treated by left-upper lobectomy with bronchoplasty and pulmonary arterial angioplasty after induction chemoradiation therapy followed by surgical correction of the PAPVC in the right-upper lobe. The patient is alive without recurrence of lung cancer or any symptoms of heart failure 17 months after pulmonary resection. CONCLUSION: When considering performing major pulmonary resection for lung tumor, thoracic surgeons should pay close attention to the presence of a PAPVC not only on the ipsilateral side of the lung tumor, but also the contralateral side, although it is a rare phenomenon.

Impact of the preoperative body mass index on the postoperative outcomes in patients with completely resected non-small cell lung cancer: A retrospective analysis of 16,503 cases in a Japanese Lung Cancer Registry Study.

OBJECTIVES: The aim of this study was to evaluate the impact of the preoperative body mass index (BMI) on the postoperative outcomes in patients with completely resected non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: The data of patients with NSCLC in whom R0 resection was achieved were extracted from the database of NSCLC samples accumulated by the Japanese Joint Committee of Lung Cancer Registry in the year 2010, and the surgical outcomes including postoperative morbidity, mortality and the prognosis, were evaluated. RESULTS: Among 18,978 registered lung cancer cases, 16,509 patients (9996 men and 6513 women) were extracted. The median of age was 69 years old, and the histologic types included adenocarcinoma (n = 12,029), squamous cell carcinoma (n = 3286), large-cell carcinoma (n = 488) and others. The patients were divided into three groups according to their BMI: normal (BMI 18.5 to <25), underweight (BMI < 18.5) and overweight (BMI ≥ 25). Multivariate logistic regression analyses of factors associated with postoperative morbidity and mortality showed no significant differences among the three groups. In comparison to the normal group, the overall survival (OS) of the underweight group was significantly worse (p < 0.001) while that of the overweight group was marginally better (p = 0.075). A multivariate analysis of factors associated with OS showed that in addition to the age, sex and clinical stage, the preoperative BMI (underweight group vs. normal group: hazard ratio [HR] 1.417 [95% confidence interval {CI}: 1.278-1.572, p < 0.001], overweight group vs. normal group: HR 0.883 [95% CI: 0.806-0.967, p = 0.007]) was an independent prognostic factor. A multivariate analysis for the disease-free survival (DFS) also showed the preoperative BMI to be an independent significant prognostic factor. CONCLUSIONS: The preoperative BMI is an independent prognostic factor in patients with completely resected NSCLC. A low preoperative BMI was associated with significantly poor survival in Japan.

Preoperative evaluation of the depth of chest wall invasion and the extent of combined resections in lung cancer patients.

The optimal extent of a combined resection in patients with lung cancer invading the chest wall remains controversial. To assess whether specific preoperative findings could lead to the precise evaluation of the depth of chest wall invasion and evade en-bloc resection of the chest wall in cases of tumor invasion limited to the parietal pleura, 132 patients with resected lung cancer involving the chest wall were retrospectively surveyed for the preoperative findings, surgical procedures, pathological results, and survival. A pathological examination of the resected specimens showed that 58 tumors had invaded only to the parietal pleura (shallow invasion) and 74 had involved the soft tissue or ribs (deep invasion). A multivariate analysis showed that preoperative CT findings of obvious tumor invasion beyond the parietal pleura (p = 0.005) and complaints of chest pain (p = 0.015) were independent indicators of deep invasion. In patients with lung cancer involving the chest wall, chest pain and/or invading on chest CT suggested that an en-bloc resection was a suitable surgical procedure, because 79% of those patients had deep invasion. On the other hand, in patients without chest pain and invasion on chest CT, an extrapleural approach was recommended at first based on the fact that 63% of them had shallow invasion. In practice, an extrapleural resection was performed in 40 cases and an en-bloc resection in 10 patients with shallow invasion. There was no significant difference in the survival between the two surgical procedures. Therefore, the CT findings of obvious tumor invasion beyond the parietal pleura and/or the presence of chest pain indicate the need to perform an en-bloc resection in patients with lung cancer involving the chest wall. However, in patients without these findings, an extrapleural approach could be initially attempted for chest wall resection, because an en-bloc resection had no survival benefit for patients with shallow invasion.

Comparison of the analgesic effects of modified continuous intercostal block and paravertebral block under surgeon's direct vision after video-assisted thoracic surgery: a randomized clinical trial.

OBJECTIVE: Clinical evidence comparing paravertebral (PVB) and continuous intercostal nerve (ICB) blocks for pain management post video-assisted thoracic surgery (VATS) is limited. This study confirms the analgesic effect of ICB using two catheters is not inferior to that of PVB under direct vision. METHODS: Fifty patients who underwent VATS lobectomy from July 2015 to March 2016 were prospectively recruited and randomly assigned to PVB and ICB groups. Postoperative pain was assessed using the visual analog scale (VAS). VAS score at rest at 24 h was the primary endpoint. Data on time required for catheter insertion, adverse effects, and frequency of additional analgesics as secondary endpoints were also collected. Noninferiority was assessed by adding a VAS margin of 15 mm to the PVB group. RESULTS: No significant differences were observed between the VAS scores of the two groups except at 48 h after surgery, with a margin noted for the PVB group. No significant differences were detected in the frequency of additional analgesics and occurrence of adverse effects. CONCLUSIONS: Our results could not clearly establish noninferiority of ICB to PVB. Improvements in ICB may be necessary for it to be used as an alternative method to PVB.

Microbial Community Analysis of Colored Snow from an Alpine Snowfield in Northern Japan Reveals the Prevalence of Betaproteobacteria with Snow Algae.

Psychrophilic algae blooms can be observed coloring the snow during the melt season in alpine snowfields. These algae are important primary producers on the snow surface environment, supporting the microbial community that coexists with algae, which includes heterotrophic bacteria and fungi. In this study, we analyzed the microbial community of green and red-colored snow containing algae from Mount Asahi, Japan. We found that Chloromonas spp. are the dominant algae in all samples analyzed, and Chlamydomonas is the second-most abundant genus in the red snow. For the bacterial community profile, species belonging to the subphylum Betaproteobacteria were frequently detected in both green and red snow, while members of the phylum Bacteroidetes were also prominent in red snow. Furthermore, multiple independently obtained strains of Chloromonas sp. from inoculates of red snow resulted in the growth of Betaproteobacteria with the alga and the presence of bacteria appears to support growth of the xenic algal cultures under laboratory conditions. The dominance of Betaproteobacteria in algae-containing snow in combination with the detection of Chloromonas sp. with Betaproteobacteria strains suggest that these bacteria can utilize the available carbon source in algae-rich environments and may in turn promote algal growth.

A prospective, multi-institutional phase II study of induction chemoradiotherapy followed by surgery in patients with non-small cell lung cancer involving the chest wall (CJLSG0801).

OBJECTIVES: The standard therapy for patients with T3N0-1M0 non-small cell lung cancer (NSCLC) involving the chest wall is considered surgical resection and adjuvant therapy. However, the compliance of adjuvant therapy is relatively low, and the prognosis for those patients has been unsatisfactory. Therefore, we conducted a phase II study of induction chemoradiotherapy followed by surgery with the aim of improving the survival. PATIENTS AND METHODS: This treatment strategy consisted of induction chemotherapy (two cycles of cisplatin at 80mg/m2 on Day 1 and vinorelbine at 20mg/m2 on Days 1 and 8) concurrent with radiotherapy (40Gy in 20 fractions) followed by surgery. The inclusion criteria were patients with resectable T3N0-1M0 NSCLC involving the chest wall who were 20-70 years of age. The primary end point was the 3-year survival, assuming an expected rate of 67%. RESULTS: From January 2009 to November 2012, 51 eligible patients were enrolled. Induction therapy was completed as planned in 49 (96%) patients without treatment-related death, and 25 (51%) had a partial response. Complete resection combined with the involved chest wall was achieved in 46 (92%) patients, and a pathologic complete response was seen in 13 (26%) patients. Five patients experienced major postoperative complications, and 1 patient died of acute exacerbation of interstitial pneumonia. With a median follow-up period of 42 months, the 3- and 5-year overall survivals of all registered patients were 77% and 63%, respectively. There was a significant difference in the survival rate between patients with a pathologic complete response and those with a residual tumor (p=0.039). CONCLUSION: The mature results of this study in a multi-institutional setting showed the treatment strategy to be safe and effective with a high rate of pathologic response for patients with NSCLC involving the chest wall.

Mutations of the epidermal growth factor receptor gene predict prolonged survival after gefitinib treatment in patients with non-small-cell lung cancer with postoperative recurrence.

PURPOSE: To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection. PATIENTS AND METHODS: We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels. RESULTS: EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053). CONCLUSION: EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.

Clinical aspects of multimodality therapy for resectable locoregional esophageal cancer.

Radical resection has been considered the only possible way to save the lives of patients with esophageal cancer. Therefore, tremendous efforts have been made in order to improve the surgical results for resectable locoregional esophageal cancer. Various surgical approaches have been developed. Combination therapies such as neoadjuvant, adjuvant chemotherapy, and neoadjuvant chemoradiation have been extensively investigated in numerous randomized clinical trials. Due to insufficient surgical results and high postoperative mortality rates, definitive chemoradiation has been studied as alternative treatment in selected patients, based on the concept that combined-modality therapy allows simultaneous treatment of locoregional disease and systemic micrometastases. Chemoradiation has shown survival rates equivalent to surgery in some non-randomized comparative studies. Presently, concerns appear to be shifting to the question of whether definitive chemoradiation could be an alternative to surgery in the primary treatment of resectable locoregional esophageal cancer. Recently, 2 randomized trials, comparing definitive chemoradiation with chemoradiation and surgery were published. These trials seem to show at first glance that definitive chemoradiation can achieve results comparable to surgery with neoadjuvant chemoradiation. More sophisticated trials should be conducted as treatment modalities used in these trials are far from routine.

Krüppel-like factor 6 is frequently down-regulated and induces apoptosis in non-small cell lung cancer cells.

Krüppel-like factor 6 (KLF6) is a ubiquitously expressed zinc finger transcriptional factor, which has been suggested to be a candidate tumor suppressor gene in prostate cancer and astrocytic glioma. Because KLF6 is located at chromosome 10p15, where non-small cell lung cancers (NSCLCs) also exhibit frequent allelic loss, we hypothesized that the inactivation of KLF6 is also involved in the development of NSCLC. To determine this, we performed mutational analysis for 105 NSCLCs, including 9 cell lines and 96 primary tumors, and Northern blot analysis for 74 NSCLCs, including the 9 cell lines and 65 primary tumors. Although somatic mutations were not detected in the coding sequence of KLF6, expression of KLF6 mRNA was down-regulated in the 9 cell lines and in 55 (85%) of the 65 primary tumors compared with normal lung tissue. Treatment of two cell lines expressing KLF6 at low levels with 5-azacytidine did not induce KLF6 expression, suggesting that KLF6 down-regulation is not due to promoter hypermethylation. We also performed loss of heterozygosity (LOH) analysis using the laser capture microdissection technique, and found that 21 of 62 (34%) informative samples had LOH in the KLF6 gene locus. Comparing the LOH status with mRNA expression of KLF6, we found that 14 of the 14 (100%) samples with LOH showed KLF6 down-regulation, and that even 23 of 31 (74%) samples without LOH also showed this down-regulation. We also studied the expression of the WAF1 gene, a possible downstream gene of KLF6, and detected simultaneous down-regulation of WAF1 and KLF6 mRNA in 6 of 9 (67%) cell lines and 48 of the 55 (87%) primary tumors, although there was not a significant association between loss of KLF6 and WAF1 expression. Furthermore, colony formation assay of two NSCLC cell lines (NCI-H1299 and NCI-H2009) induced a markedly reduced colony formation by KLF6 transfection, and Annexin V staining and terminal deoxynucleotidyl transferase-mediated nick end labeling assays revealed that KLF6 induced apoptosis. Our present studies demonstrated that KLF6 is frequently down-regulated in NSCLC and suppresses tumor growth via induction of apoptosis in NSCLC, which may suggest that KLF6 is a tumor suppressor for NSCLC.

Frequent inactivation of RASSF1A, BLU, and SEMA3B on 3p21.3 by promoter hypermethylation and allele loss in non-small cell lung cancer.

Non-small cell lung cancer frequently shows loss of heterozygosity of the chromosome 3p21.3 region and several genes such as RASSF1A, BLU, and SEMA3B have been identified as candidate tumor suppressor genes at this region since their downregulation and hypermethylation at their promoter regions were frequently detected in lung cancer. To determine whether these three genes are simultaneously inactivated during lung cancer development, we studied 138 primary non-small cell lung cancers for the promoter methylation status of these genes and allelic loss of the chromosome 3p21.3 region. We found promoter hypermethylation at 32% in RASSF1A, 30% in BLU, and 47% in SEMA3B. Allelic loss of 3p21.3 was detected in 54 (58%) of 93 informative tumors. Despite the weak association of methylation status among these three genes, there was no correlation between the methylation status of each gene and loss of heterozygosity. We also studied possible genes downstream of RASSF1A in 16 primary non-small cell lung cancers and found that the expressions of SM22 and SPARC were significantly downregulated in RASSF1A-hypermethylated tumors. Our results showed that, while candidate tumor suppressor genes at this locus can be simultaneously inactivated by epigenetic alterations, loss of heterozygosity without any hypermethylation of the three genes can also occur in some cases, suggesting that just one allelic loss might also be sufficient for the inactivation of any of these genes for lung cancer development.

Primary lung adenocarcinoma with heterotopic bone formation.

A 46-year-old man was referred to our hospital for the treatment of lung cancer. Computed tomography showed a well-defined tumor mass that was 50x45 mm in size and contained a trabecular pattern of calcification. Since he was diagnosed as having a primary lung adenocarcinoma (clinical stage IB), a left upper lobectomy with mediastinal lymph node dissection was performed. Histologically, the tumor was a poorly differentiated adenocarcinoma with rich fibrous stroma, in which there were island-shaped bone formation lesions. An immunohistochemical examination showed the expression of bone morphogenic protein-2 within tumor cells, which induce and stimulate bone formation. This finding may elucidate a possible mechanism of heterotopic bone formation.

[Carney triad; report of a case].

We report a case of Carney triad which is very rare disease composed of gastrointestinal stromal tumor (GIST), pulmonary chondroma and paraganglioma. A 15-year-old girl was reffered for treatment with multiple tumors in the left lung. At the age of 13, she underwent total gastrestomy for GIST. At that time multiple pulmonary tumors have already developed and made a diagnosis of chondroma. Progressive enlargement of their size and persistent bloody sputum made her received operation. Finally she underwent left pneumonectomy. In general all 3 tumors have manifested for a long time. Gastric tumors and paragangliomas are often lethal. This shows the necessity of intensive and long-term follow-up.

Establishment of a large cell lung cancer cell line (Y-ML-1B) producing granulocyte colony-stimulating factor.

We established a new lung cancer cell line, designated Y-ML-1B, from a lung cancer of a 70-year-old Japanese man with leukocytosis and thrombocytosis. Before surgical resection, the white blood cell and platelet counts were elevated to 34,400/mm3 and 668,000/mm3, respectively, and the granulocyte colony-stimulating factor (G-CSF) level in the serum was increased at 141 pg/mL. The primary tumor showed an undifferentiated morphology with large cells and induced extensive thickening of the pleura in the right hemithorax. The Y-ML-1B cells grow as a monolayer, with a doubling time of 19 hours, and are tumorigenic in nude mice, which showed a morphology similar to the primary tumor in xenografts. Analysis of the supernatant of cell culture medium of Y-ML-1B showed elevated levels of G-CSF and other cytokines such as interleukin (IL)-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF), consistent with the high levels detected in the patient's serum. Cytogenetic analysis revealed aneuploidy of greater than 56 in metaphases with many structural abnormalities. Mutation analysis of the tumor suppressor genes showed that Y-ML-1B is inactivated in TP53 and RASSF1A, but not in p14(ARF), p16(INK4A), or RB. Neither activating mutations of KRAS or NRAS nor amplification of MYC or MDM2 were detected. Y-ML-1B expressed N-cadherin but not E-cadherin. This newly established cell line might serve as a useful model for studying the molecular pathogenesis for large cell cancers of the lung which express high levels of cytokines.

Trimodality therapy for lung cancer with chest wall invasion: initial results of a phase II study.

BACKGROUND: The chest wall is the most common neighboring structure involved by locally advanced lung cancers. However, the optimal treatment strategy for such tumors has not been established. This phase II trial was therefore conducted with the aim of evaluating whether induction chemoradiotherapy followed by surgery improves the survival of patients with T3N0 or T3N1 lung cancer involving the chest wall. METHODS: Patients with resectable T3N0 or T3N1 non-small cell lung cancer involving the chest wall were candidates for this study. Induction therapy consisted of two cycles of cisplatin and vinorelbine chemotherapy concurrent with 40 Gy of radiation. Surgical resection was performed 3 to 6 weeks after the last day of chemotherapy. RESULTS: From January 2009 to November 2012, 51 eligible patients (40 stage IIB and 11 stage IIIA tumors) were entered in this study. Induction therapy was completed as planned in 49 (96%) patients, and 25 (51%) had a partial response revealed on computed tomography. Forty-eight patients underwent pulmonary resection combined with chest wall resection, and 44 (92%) underwent a complete resection. Pathologic examinations of the resected specimens revealed no viable tumor cells in 12 (25%) cases and minimal residual disease in 31 (65%) cases. Five patients experienced major postoperative complications, and 1 patient died of postoperative exacerbation of interstitial pneumonia. CONCLUSIONS: The initial results of this study showed the treatment regimen to be safe and feasible with a high rate of a pathologic response for patients with lung cancer involving the chest wall in a multiinstitutional setting.