口蓋扁桃転移を来した原発性肺癌例とその臨床的特徴

Micro-RNAs are approximately 21-25-nucleotide-long noncoding RNAs that regulate gene expression primarily at the post-transcriptional level in animals. Here, we report that micro-RNA-1 (miR-1), abundant in the cardiac and smooth muscles, is expressed in the lung and is down-regulated in human primary lung cancer tissues and cell lines. In situ hybridization demonstrated localization of miR-1 in bronchial epithelial cells. The tumor suppressor C/EBPalpha, frequently suppressed in lung cancer, reactivated miR-1 expression in the lung cancer cells. Repressed miR-1 was also activated in lung cancer cells upon treatment with a histone deacetylase inhibitor. These observations led us to examine the antitumorigenic potential of miR-1 in lung cancer cells. Expression of miR-1 in nonexpressing A549 and H1299 cells reversed their tumorigenic properties, such as growth, replication potential, motility/migration, clonogenic survival, and tumor formation in nude mice. Exogenous miR-1 significantly reduced expression of oncogenic targets, such as MET, a receptor tyrosine kinase, and Pim-1, a Ser/Thr kinase, frequently up-regulated in lung cancer. Similarly, the levels of two additional targets, FoxP1, a transcription factor with oncogeneic property, and HDAC4 that represses differentiation-promoting genes, were reduced in miR-1-expressing cells. Conversely, depletion of miR-1 facilitated N417 cell growth with concomitant elevation of these targets. Further, ectopic miR-1 induced apoptosis in A549 cells in response to the potent anticancer drug doxorubicin. Enhanced activation of caspases 3 and 7, cleavage of their substrate PARP-1, and depletion of anti-apoptotic Mcl-1 contributed to the sensitivity of miR-1-expressing cells to doxorubicin. Thus, miR-1 has potential therapeutic application against lung cancers.

Informing Patient Surveillance for the Growing Number of Survivors of Lung Cancer

Commentary: Postrecurrence survival in patients with lung cancer after curative surgery warrants systematic investigation to optimize management strategies

The European Society of Thoracic Surgeons (ESTS) registry was created 10 years ago and represents an international database collecting thoracic surgery procedures from European contributors. The purpose of the present report was to offer an overview of baseline and surgical characteristics and outcomes of patients submitted to lung resections for malignant lung disease as derived from the ESTS registry. We retrieved data about all lung resections from 2007 to 2016 performed for primary and metastatic (secondary) lung cancer. We evaluated the baseline characteristics and the surgical management of this population. Within the subgroup of patients affected by primary lung cancer, we described the preoperative mediastinal staging management and the final pathological stage of disease. Finally, we analysed the morbidity and mortality rates for the cohort of patients submitted to anatomic lung resections for primary or secondary lung cancer. Outcomes were also evaluated in relation to several risk factors: type of resection, age, comorbidity, predicted postoperative forced expiratory volume in 1 s and surgical approach. We selected 62 774 patients submitted to lung resections (male 66.5%, median age 64 years). For the entire population, median predicted postoperative forced expiratory volume in 1 s was 73.3% (interquartile range: 59, 87.6), 33.8% of patients had cardiac comorbidities and 17.3% had other comorbidities. Among the patients with primary lung cancer (51 931 patients), 50.8% had Stage I disease and 23.2% Stage II disease; preoperative invasive mediastinal staging was performed in 70.3% of patients with computed tomography scan nodal enlargement and positron emission tomography scan nodal uptake. After anatomical lung resection (51 756 patients), overall morbidity was 18.5% and mortality (30 days or in-hospital) was 2.6%. Extent of resection, age ≥75 years, presence of cardiac comorbidity, predicted postoperative forced expiratory volume in 1 s <70% and open approach instead of video-assisted thoracic surgery were associated with worse outcomes. The results of the present report represent reliable European benchmarks for comparing the activities and outcomes of single institutions and surgeons at an international level.

SC02.01 Multiple Primary Lung Cancers Versus Lung Metastases: Pathological Differential Diagnosis

MULTIDISCIPLINARY APPROACH TO RECURRENCE AFTER RESECTION OF PRIMARY LUNG CANCER

Lung cancer with gastrointestinal metastasis is uncommon; however, when such metastasis occurs, the small bowel is the most common metastatic site. There are few case reports of colonic metastasis developing from a primary lung adenocarcinoma. We report a case of metastatic adenocarcinoma in the colon, complicated by bowel obstruction and hydropneumothorax, in a 67-year-old woman. The primary cancer was highly suspected to have originated from the lung, based on immunohistochemistry assessments. Immunohistochemistry was positive for thyroid transcription factor-1 and cytokeratin 7, but negative for cytokeratin 20. The published literature, focusing on the differential diagnosis of the origin of the primary malignancy using immunohistochemistry, was reviewed.

Primary lung cancer is the fourth most frequently diagnosed cancer, but gastric metastasis from lung cancer is extremely rare. Little is known about its clinicopathological features, prognosis and optimal treatment strategy. The present study reports a case of primary lung cancer that metastasized to the stomach and to the best of our knowledge, is the first to identify discordance in epidermal growth factor receptor (EGFR) mutation status between the primary tumor and gastric metastasis. The study also systematically searched the Medline database for similar cases to provide a literature review. Data concerning the clinicopathological features, treatment strategies and outcomes were extracted and analyzed. In total, 22 eligible cases were identified from 16 studies. The average age at presentation was 67.3 years and there was a male predominance of 90.9%. Epigastric pain (45.5%) was the most common chief complaint, followed by melena (22.7%), nausea/vomiting (13.6%) and hematemesis (9.1%). Three patients were asymptomatic. Five patients sought the initial consultation for gastrointestinal symptoms. The median time between the primary lung cancer diagnosis and the confirmation of gastric metastasis was five months. Endoscopically, gastric lesions were described as polypoid masses or volcano-like ulcers, mostly involving the gastric corpus, which were identified in 62.5% of the 16 cases in which information regarding the site of metastasis was available. Gastric metastases were reported from adenocarcinoma, squamous cell carcinoma, small cell lung cancer and pleomorphic carcinoma of the lung. The median survival following comprehensive treatment strategies was four months, and the one-year post-metastasis survival rate was 35.3%. In conclusion, although primary lung cancer metastasis to the stomach is rare, clinicians should be aware of the possibility of its occurrence. Comprehensive and personalized treatment may be beneficial to patients. EGFR tyrosine-kinase inhibitor therapy may be the treatment of choice for non-small cell lung carcinoma patients harboring an activating EGFR mutation in the metastatic lesion.

Metachronous lung cancer: the role of improved postoperative surveillance

There are few reports of resected cases of second primary lung cancer in post-treatment survivors of small-cell lung cancer. Here, we report a surgical case of a 62-year-old female with second primary lung adenocarcinoma after chemoradiotherapy against small-cell lung cancer. She had been treated for small-cell lung cancer 2 years earlier, and achieved complete response after the treatment. A new nodular lesion was detected at a different segment in the right lower lobe. We performed a right lower lobectomy accompanied with systemic mediastinal nodal dissection. Histopathological findings revealed that the new nodular lesion was a second primary lung adenocarcinoma. No metastatic tumor was seen in the dissected lymph node; the initial tumor had disappeared completely. The postoperative course was uneventful, and she was discharged on day 10 after the operation. Ten months after the operation, she was free of recurrent tumor.

背景与目的肺癌是我国最常见的恶性肿瘤之一，在治疗中给患者带来了巨大的躯体病痛和情绪障碍，本实验旨在研究疏肝肺积方结合心理干预对原发性肺癌患者抑郁情绪和焦虑情绪的影响，并进一步探讨患者抑郁和焦虑之间的相互关系。方法将118例原发性非小细胞肺癌患者随机分为两组：疏肝肺积方结合心理干预加化疗组（联合治疗组57例）和单纯化疗组（61例）。联合治疗组采用疏肝肺积方和心理干预与化疗的联合应用；单纯化疗组仅接受化疗，共完成两次化疗，为一个总疗程。采用ZUNG抑郁自评量表和ZUNG焦虑自评量表测定心理状况。结果联合治疗组的抑郁、焦虑评分治疗后较治疗前下降（P < 0.01）；单纯化疗组的抑郁、焦虑评分治疗后较治疗前上升（P < 0.01）；联合治疗组的抑郁、焦虑评分比单纯化疗组患者明显下降（P < 0.01）；患者抑郁与焦虑指数呈正相关（P < 0.01）。结论疏肝肺积方结合心理干预能缓解并改善肺癌患者的抑郁情绪和焦虑情绪，具有较好的临床疗效。

Impact of Low-Dose Computed Tomography Screening for Primary Lung Cancer on Subsequent Risk of Brain Metastasis

Synchronous double primary lung cancers are difficult to distinguish from intrapulmonary metastasis histopathologically. The differential diagnosis is a critical point that is of therapeutic importance. If the lesions are diagnosed as double primary lung cancers, the patient would mainly undergo curative treatment. By contrast, if intrapulmonary metastasis is found present, the patient would be more likely to benefit from systemic treatment modalities such as chemotherapy or targeted therapy. With the widespread launch of large-scale cancer screening projects equipped with low dose CT scan, multiple lung nodules are detected increasingly. Therefore, there is a need for a diagnostic workup that effectively distinguishes double primary lung cancers from intrapulmonary metastasis. However, current tumor staging system, which largely rely on histological and pathological features, lacks the standard criteria for the diagnosis of multiple primary lung cancers. This situation at times leads to equivocal cases, in which the lung nodules are histologically and pathologically the same or highly similar. Herein, we present a case, in which genomic alteration patterns revealed by next-generation sequencing (NGS) facilitated the differential diagnosis between double primary lung cancer and intrapulmonary metastasis. A 57-year-old male presented with two separate lesions in both upper lobes of the lung, which were histopathologically determined as T1cN0M0 adenocarcinoma in right upper lobe and T1cN3M0 adenocarcinoma in left upper lobe. NGS identified an EGFR exon 19 deletion in the right upper lobe lesion and an EGFR L858R in the other one, suggestive of double primary malignancies. The patient underwent concurrent chemoradiotherapy for the left upper lung cancer and fractionated stereotactic radiotherapy for the right upper lung cancer. He had a disease-free survival of 18 months and the left upper lung cancer began to increase in size. The patient received gefitinib treatment and achieved a stable disease with a progression-free survival of three years. Then he underwent cytotoxic chemotherapies and an immunotherapy. Owing to the heterogeneity of cancer, it is also difficult to select the optimal therapeutic strategy for patients with multiple primary lung cancer. Our case provides evidence for utility of NGS in facilitating diagnosis and treatment decisions of primary lung cancer diagnosis.

THREE METACHRONOUS PRIMARY LUNG CANCERS IN A CHRONIC SMOKER: A CASE REPORT

Primary and secondary lung cancers are the most common clinical conditions that thoracic surgeons have to deal with: primary lung cancer, in fact, is one of the most frequently diagnosed cancers and is the leading cause of cancer-related death worldwide [...].