[Current Status and Prospects of Lung Cancer Screening].

The prognosis for advanced lung cancer is still poor, even though various therapeutic methods such as molecular targeted therapeutics and immunotherapy have become available. Early detection is still important in the treatment of lung cancer, and the role of lung cancer screening is very essential. The current lung cancer screening system in Japan has many problems. Although low-dose chest computed tomography (CT) screening has appeared as a new screening modality, there are still many things to be studied and improved. In this article, the outline of the current system of lung cancer screening in Japan is presented, and then the problems in the system and future prospects are described.

[Acute Megakaryoblastic Leukemia Developed after the Surgical Treatment of Mediastinal Malignant Germ Cell Tumor].

A 26-year-old man was admitted to our hospital for an examination of a mediastinal tumor. Chest computed tomography(CT) showed a giant anterior mediastinal tumor narrowing the trachea and right main bronchus. Although needle biopsy could not be done because of patient respiratory condition, non-seminomatous mediastinal germ cell malignant tumor was strongly suspected by high level of serum AFP without no abnormal finding in his testis. After 1 cycle of chemotherapy by cisplatin, etoposide and bleomycin, the mediastinal tumor decreased in size. Percutaneous biopsy was challenged, however, definite diagnosis could not be established and the surgical resection was performed. The tumor was pathologically diagnosed as mature teratoma with elements of a yolk-sac tumor and some sort of sarcoma. Sudden onset of back pain and thrombocytopenia were encountered 5 months after the operation. Hematologic examination confirmed acute megakaryoblastic leukemia, and remission-induction therapy and allogeneic hematopoietic stem cell transplantation were performed. Twelve months after the operation, the patient is well without recurrence of either disease.

[Pericardial Fenestration and Multidisciplinary Treatment to Improve the Prognosis of the Malignant Pericarditis Due to Lung Cancer].

We experienced 3 cases in whom multidisciplinary treatment with pericardial fenestration was effective for malignant pericardial effusion associated with lung cancer. Case 1:Right upper lobectomy for lung adenocarcinoma, EGFR (-) and ALK (-) had been performed. After 34 months, malignant pericarditis occurred and left pericardial fenestration was performed. After fenestration, anticancer drugs and immune checkpoint inhibitor( ICI) were administered. He died of lung cancer in 53 months after fenestration. Case 2:Thirty-three months after left upper lobectomy for lung adenocarcinoma [EGFR (+) and ALK (-)], malignant pleuritis and pericarditis occurred and right pericardial fenestration was performed. After fenestration, anticancer drugs, EGFR-TKI and ICI were administered. He died of lung cancer in 35 months after fenestration. Case 3:Pericardial fenestration was performed for malignant pericarditis due to lung adenocarcinoma with EGFR (-), ALK (-) and PD-L1 [tumor propotion score (TPS) 0%]. After fenestration, anticancer drugs and ICI were administered. The patient died of lung cancer in 15 months after fenestration. Pericardial fenestration for malignant pericarditis is possibly useful for the management of patients, which in turns is also useful in continuing the medical treatment to prolong the prognosis.

[Clinical Efficacy of Monotherapy with Immune Checkpoint Inhibitors for Advanced Non-Small Cell Lung Cancer].

OBJECTIVE: To retrospectively assess data on immune checkpoint inhibitors(ICIs)in an actual clinical setting, examine the factors that contribute to response and survival using real-world data, and compare the effectiveness of the 3 types of ICIs for patients with non-small cell lung cancer(NSCLC). METHODS: A retrospective analysis of 127 patients with NSCLC treated with ICIs at our hospital was conducted. RESULTS: Nivolumab(56 patients)showed a 3-year survival rate of 21.6% and a disease control rate of 57.1%. These results are consistent with the clinical trials of Nivolumab. Pembrolizumab(36 patients) showed a 2-year survival rate of 60.3%, a response rate of 50.0%, and a disease control rate of 63.9%. Atezolizumab(35 patients)displayed a particularly low response rate with a 1-year survival rate of 58.4%, response rate of 8.6%, and disease control rate of 25.7%. The treatment results for recurrence after surgery for lung cancer were comparable to those for unresectable lung cancer. CONCLUSION: Anti-PD-1 antibody displayed better therapeutic results than anti-PD-L1 antibody. The efficacy of ICI administration for postoperative recurrent lung cancer was also shown in this study.

A population-based cohort study to evaluate the effectiveness of lung cancer screening using low-dose CT in Hitachi city, Japan.

OBJECTIVES: To evaluate the effectiveness of lung cancer screening using low-dose computed tomography for the general population, we conducted a retrospective cohort study of screening for participants among Hitachi residents. MATERIALS AND METHODS: Citizens aged 50-74 who underwent low-dose computed tomography screening at least once during 1998-2006 were defined as the computed tomography group, and those who underwent X-ray screening at least once during the same period, but did not receive low-dose computed tomography screening throughout the follow-up period, were defined as the XP group. We investigated the lung cancer incidence rate, mortality rate and all-cause mortality rate for both groups from the first lung cancer screening to the end of 2012. RESULTS: In the computed tomography group (17 935 residents; 9790 males and 8145 females), 273 cases of lung cancer (1.5%), 72 cases of lung cancer death (0.4%), and 885 cases of all-cause death (4.9%) were observed. On the other hand, 164 cases (1.1%) of lung cancer, 80 cases (0.5%) of lung cancer death and 1188 cases (7.6%) of all-cause death were observed in the XP group (15 548 residents; 6526 males and 9022 females). The hazard ratios of the computed tomography group to the XP group adjusted for gender, age and smoking history were 1.23 for lung cancer incidence rate, 0.49 for lung cancer mortality rate and 0.57 for all-cause mortality rate. Non-smokers and light smokers (<30 pack-years) had a significantly lower lung cancer mortality (0.41 and 0.21, respectively). CONCLUSION: low-dose computed tomography screening for a population including non-smokers and light smokers may be effective.

[Association Between Juvenile Spontaneous Pneumothorax and Smoking].

We assessed the relation between smoking and pneumothorax in patients aged <40. Of 526 patients who underwent surgery for pneumothorax in 2011~2015, 311 were under the age of 40 and they were included in this study. Of 311, 54 cases( 17.4%) were diagnosed with spontaneous pneumothorax associated with emphysematous change by pathological assessment. By the multivariate analysis, 2 parameters exhibited significance for the risk of these spontaneous pneumothorax:a Brinkmann index of ≥165 and a smoking period of ≥9.5 years. It was suggested that smoking is strongly related to the onset of spontaneous pneumothorax even in the younger population less than 40 years of age.

[Bronchial Artery Aneurysm with Hoarseness;Report of a Case].

The patient was a 72-year-old man with a history of bronchiectasis. He was admitted to our hospital for an examination of hoarseness. Chest computed tomography (CT) showed bronchiectasis in the bilateral lungs and bronchial artery aneurysm in the mediastinum. To prevent rupture of the aneurysm, we imaged the bronchial artery aneurysm by selective bronchial artery angiography and performed bronchial artery embolization (BAE) with 19 platinum coils. Three months after successful BAE, his hoarseness had improved, and the bronchial artery aneurysm was reduced in size after 12 months. To our knowledge, this is the 1st report of BAE improving hoarseness due to bronchial artery aneurysm.

[Clinical Assessment of Fourteen Cases of Thoracic Endometriosis].

We retrospectively assessed the clinical and pathological features of 14 patients with thoracic endometriosis who were treated at our hospital from 2007 to 2017. Thirteen patients presented pneumothorax and 1 patient presented bloody sputum. All were treated surgically. Pneumothorax occurs on the right side in all 13 cases and bloody sputum was from left side lesion. Ten patients presented symptoms closely related with their menstrual cycle (days -2 to 5). At surgery, dark red or dark brown spots, small hiatus and scar-like findings on the surface of the visceral pleura or diaphragm were identified in all cases. Pathological or immunohistochemical examinations of diaphragm or lung tissue specimens revealed endometrial tissue in 6 cases of pneumothorax and a case of bloody sputum. Nine patients received hormonal therapy(8:pneumothorax, 1:bloody sputum). Pleurodesis was performed for 1 pneumothorax patient with recurrent pneumothorax after hormonal therapy. In case of young female with repeated pneumothorax, catamenial pneumothorax must be kept in mind as a differential diagnosis and appropriate timing for surgical treatment should be considered to establish pathologically correct diagnosis.

Efficacy of low-dose computed tomography screening for lung cancer: the current state of evidence of mortality reduction.

The interim and final results of randomized controlled trials on the efficacy of lung cancer computed tomography (CT) screening have been reported recently from Western countries. The outcome of the National Lung Screening Trial (NLST) demonstrated the efficacy of low-dose thoracic CT screening for heavy smokers; however, other studies have found no apparent reduction in the mortality rate, and the outcome of the NELSON study is awaited. To date, a few studies have reported on the efficacy of lung cancer CT screening for non-/light smokers. A report from the Hitachi district, which is an ecological/time series study where non-/light smokers account for approximately half of the CT screening examinees, was published in 2012, with an outcome suggesting efficacy. Currently, a randomized controlled trial (JECS Study) is underway in Japan with non-/light smokers as the subjects, and this trial is very important in terms of cancer prevention.

The Japanese Guidelines for Breast Cancer Screening.

OBJECTIVE: The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported age-standardized rate of 63.6 per 100 000 women. METHODS: The Japanese guidelines for breast cancer screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for population-based and opportunistic screenings were formulated. RESULTS: Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. CONCLUSIONS: Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness.

A survey about further work-up for cases with positive sputum cytology during lung cancer mass screening in Ishikawa Prefecture, Japan: a retrospective analysis about quality assurance of lung cancer screening.

OBJECTIVE: In cancer screening programs, performing appropriate further work-up is essential. In order to elucidate whether the further work-up for the subjects with positive screening results by sputum cytology was performed appropriately, the present study was conducted as the first large-scale thorough survey in Japan. METHODS: All of the lung cancer screening records from 2007 to 2012 in Ishikawa Prefecture were reviewed. Additional investigations about the further work-up were performed. RESULTS: In total, 2 234 984 people were invited to undergo lung cancer screening, and 494 424 people participated in the screening. Of these, 25 264 people underwent sputum cytology, and 68 positive cases were identified. Three of these 68 cases did not undergo further work-up, and another three cases had already been diagnosed to have lung cancer. Forty-five of the remaining 62 cases did not have suspicious chest shadows, and bronchoscopic examinations were performed in 36 cases. Seventeen of these 36 cases were diagnosed as having cancer, whereas none of the nine cases who did not receive the examination was diagnosed (P = 0.038). A bronchoscopic examination was not performed due to other medical conditions in three cases, due to the patient's refusal in another three cases and in the remaining three cases, the reasons were unknown. CONCLUSION: The participation rate for further work-up was very high. However, there are some issues to be resolved regarding the transmission of information. With our new registered hospital system, the quality assurance of our screening program will be improved.

A phantom study investigating the relationship between ground-glass opacity visibility and physical detectability index in low-dose chest computed tomography.

In this study, the relationship between ground-glass opacity (GGO) visibility and physical detectability index in low-dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of -630 Hounsfield units (HU; high attenuation GGO: HGGO) and -800 HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices (CTDI(vol)) varied over 1.0-5.0 mm and 0.85-3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one another's observations, evaluated GGO visibility using a five-point scoring system. The physical detectability index correlated reasonably well with the GGO visibility (R² = 0.709, p < 0.01 for 6 mm HGGO and R² = 0.646, p < 0.01 for 10 mm LGGO), and was nearly proportional to the CTDI(vol). Consequently, the CTDI(vol) also correlated reasonably well with the GGO visibility (R² = 0.701, p < 0.01 for 6 mm HGGO and R² = 0.680, p < 0.01 for 10 mm LGGO). As a result, the CTDI(vol) was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study.

Postoperative drainage with one chest tube is appropriate for pulmonary lobectomy: a randomized trial.

To expand postoperative residual lungs after pulmonary lobectomy, thoracic drainage with two chest tubes has been recommended. Several studies recently demonstrated that postoperative drainage with one chest tube (PD1) was as safe as that with two chest tubes (PD2). However, most of the patients in those studies underwent lobectomy by standard thoracotomy. Although the number of pulmonary lobectomies by video-assisted thoracic surgery (VATS) has been increasing in recent years, there have been no reports that compared PD1 with PD2 after pulmonary lobectomy, including that by VATS. To elucidate whether postoperative management with PD1 is as safe as that with PD2, we conducted a randomized controlled trial. Lung cancer patients who underwent lobectomies with mediastinal nodal dissection in our hospital were assigned to one of two groups: one chest tube placed in PD1 group and two chest tubes placed in PD2 group. A total of 108 patients were registered in the study. There were no significant differences in the age, gender, pathological stage or histological type between two groups. Since the residual lung expansion was good in both groups, there were no patients who needed thoracentesis. There were no significant differences in the number of cases with pleurodesis, the amount/duration of drainage or the pain of the patients between two groups. In conclusion, since PD1 has advantages in saving cost and time and in low risk of transcutaneous infection, PD1 is appropriate after pulmonary lobectomy by VATS and by open thoracotomy.

Efficacy of durvalumab plus chemotherapy in small-cell lung cancer with Lambert-Eaton myasthenic syndrome.

Lambert-Eaton myasthenic syndrome (LEMS) is a rare disease but is often associated with small-cell lung cancer (SCLC). We discuss the case of a 65-year-old man diagnosed with SCLC-LEMS and treated with carboplatin, etoposide, and durvalumab. Lower extremity weakness and high anti-P/Q voltage-gated calcium channel (VGCC) antibody levels were diagnostic and helpful. The patient showed a reduction in neurological symptoms with treatment for SCLC, including an immune checkpoint inhibitor (ICI), without standard treatment for LEMS. This treatment may be a treatment option, although the recurrence of LEMS as an immune-related adverse events (irAEs) should be noted.

Advantages of diffusion-weighted imaging over positron emission tomography-computed tomography in assessment of hilar and mediastinal lymph node in lung cancer.

BACKGROUND: The significance of diffusion-weighted imaging (DWI) is uncertain for the diagnosis of nodal involvement. The purpose of this study was to examine diagnostic capability of DWI compared with PET-CT for nodal involvement of lung cancer. METHODS: A total of 160 lung cancers (114 adenocarcinomas, 36 squamous cell carcinomas, and 10 other cell types) were analyzed in this study. DWI and PET-CT were performed preoperatively. RESULTS: The optimal cutoff values to diagnose metastatic lymph nodes were 1.70 × 10(-3) mm(2)/s for ADC value and 4.45 for SUVmax. DWI correctly diagnosed N staging in 144 carcinomas (90 %) but incorrectly diagnosed N staging in 16 (10 %) [3 (1.9 %) had overstaging, 13 (8.1 %) had understaging]. PET-CT correctly diagnosed N staging in 133 carcinomas (83.1 %) but incorrectly diagnosed N staging in 27 (16.8 %) [4 (2.5 %) had overstaging, 23 (14.4 %) had understaging]. Sensitivity, accuracy, and negative predictive value for N staging by DWI were significantly higher than those by PET-CT. Of the 705 lymph node stations examined, 61 had metastases, and 644 did not. The maximum diameter of metastatic lesions in lymph nodes were 3.0 ± 0.9 mm in 21 lymph node stations not detected by either DWI or PET-CT: 7.2 ± 4.1 mm in 39 detected by DWI, and 11.9 ± 4.1 mm in 24 detected by PET-CT. There were significant differences among them. The sensitivity (63.9 %) for metastatic lymph node stations by DWI was significantly higher than that (39.3 %) by PET-CT. The accuracy (96.2 %) for all lymph node stations by DWI was significantly higher than that (94.3 %) by PET-CT. CONCLUSIONS: DWI has advantages over PET-CT in diagnosing malignant from benign lymph nodes of lung cancers.

[Efficacy of low-dose erlotinib against gefitinib-induced hepatotoxicity in a patient with lung adenocarcinoma harboring EGFR mutations].

We report a case of a female in her 80s who was diagnosed with recurrent lung adenocarcinoma after primary surgery. She was treated with a systemic chemotherapy regimen consisting of carboplatin plus paclitaxel until the disease showed progression. On detection of epidermal growth factor receptor(EGFR)mutations, we administered gefitinib, an EGFR tyrosine kinase inhibitor, at a dosage of 250 mg daily. After 6 months of gefitinib therapy, laboratory findings revealed elevated serum aspartate aminotransferase(AST)and alanine aminotransferase(ALT)levels(grade 2), indicative of hepatotoxicity. Gefitinib was discontinued and erlotinib was initiated at a dosage of 50 mg daily. She continued the therapy for 3 years, during which her disease stabilized without any further complications or hepatotoxicity. Thus, low-dose erlotinib may be effective and well tolerated by patients with non-small cell lung cancer harboring EGFR mutations who are intolerant to gefitinib.

Detection of Mycobacterium avium-intracellulare Complex (MAC) by Bronchial Lavage and the Relationship with Titers of Anti-Glycopeptidolipid-Core IgA Antibodies to MAC in Patients with Pulmonary MAC Disease.

Background: Higher rates of diagnosis of pulmonary Mycobacterium avium-intracellulare complex (MAC) disease by bronchoscopy (BS) in patients who could not diagnose by sputum cultures have been suggested, but the detailed utility of BS, especially in combination with anti-glycopeptidolipid-core IgA antibodies (anti-MAC Ab), is still unclear. Methods: A total of 111 patients at our hospital with suspected MAC who underwent BS because they were sputum-negative from April 2018 to March 2022 were analyzed prospectively. These patients were also divided into two groups, anti-MAC Ab-positive and anti-MAC Ab-negative, and compared. Results: A total of 111 patients underwent BS, though 95 (38.0%) of 250 enrolled patients were sputum smear/culture-positive. The age of the 111 patients was 69.14 (31.0-89.0) years, and 90 (81.0%) were female; 69 (62.2%) of 111 patients were either smear-positive (n = 42, 37.8%) or culture-positive (n = 27, 24.3%) by BS. Of the total 111 patients, 69 (62.2%) were anti-MAC Ab-positive and 57 (82.6%) of 69 patients were also positive by BS. In contrast, only 12 (28.6%) of the 42 anti-MAC Ab-negative patients were positive by BS. The sensitivity and specificity of anti-MAC Ab for positive by BS were 82.6% and 71.4%, respectively, and the area under the curve (AUC) on receiver-operating characteristic (ROC) curve analysis was 0.807. Conclusion: BS and anti-MAC Ab showed similar usefulness to confirm the diagnosis in patients who could not be diagnosed by sputum examination, but pulmonary MAC disease was strongly suspected based on chest radiography/CT findings. These two examinations were correlated, and their combination appeared to provide more accurate diagnosis and earlier therapy.

First case report of erlotinib plus ramucirumab treatment for lung carcinosarcoma with EGFR L858R mutation.

Lung carcinosarcoma is acknowledged as a rare form of lung cancer. Due to its rarity, the inability to conduct large-scale clinical trials and interventions is currently carried out based on empirical evidence. In this study, we report the case of a 73-year-old female patient diagnosed with postoperative recurrence of lung carcinosarcoma. The resected tumor was diagnosed as lung carcinosarcoma, and genetic testing revealed the presence of the epidermal growth factor receptor (EGFR) exon21 L858R. Approximately 2 years postoperatively, the tumor recurred and the patient was treated with erlotinib plus ramucirumab, which were effective in controlling metastatic disease. Erlotinib plus ramucirumab is therefore a treatment option for EGFR mutation-positive lung carcinosarcoma.

Novel Algorithm for the Estimation of Cancer Incidence Using Claims Data in Japan: A Feasibility Study.

PURPOSE: We developed algorithms to identify patients with newly diagnosed cancer from a Japanese claims database to identify the patients with newly diagnosed cancer of the sample population, which were compared with the nationwide cancer incidence in Japan to assess the validity of the novel algorithms. METHODS: We developed two algorithms to identify patients with stomach, lung, colorectal, breast, and cervical cancers: diagnosis only (algorithm 1), and combining diagnosis, treatments, and medicines (algorithm 2). Patients with newly diagnosed cancer were identified from an anonymized commercial claims database (JMDC Claims Database) in 2017 with two inclusions/exclusion criteria: selecting all patients with cancer (extract 1) and excluding patients who had received cancer treatments in 2015 or 2016 (extract 2). We estimated the cancer incidence of the five cancer sites and compared it with the Japan National Cancer Registry incidence (calculated standardized incidence ratio with 95% CIs). RESULTS: The number of patients with newly diagnosed cancer ranged from 219 to 17,840 by the sites, algorithms, and exclusion criteria. Standardized incidence ratios were significantly higher in the JMDC Claims Database than in the national registry data for extract 1 and algorithm 1, extract 1 and algorithm 2, and extract 2 and algorithm 1. In extract 2 and algorithm 2, colorectal cancer in male and stomach, lung, and cervical cancers in females showed similar cancer incidence in the JMDC and national registry data. CONCLUSION: The novel algorithms are effective for extracting information about patients with cancer from claims data by using the combined information on diagnosis, procedures, and medicines (algorithm 2), with 2-year cancer-treatment history as an exclusion criterion (extract 2).

A randomized controlled trial on the efficacy of thoracic CT screening for lung cancer in non-smokers and smokers of <30 pack-years aged 50-64 years (JECS study): research design.

In order to assess the efficacy of lung cancer screening using low-dose thoracic computed tomography, compared with chest roentgenography, in people aged 50-64 years with a smoking history of <30 pack-years, a randomized controlled trial is being conducted in Japan. The screening methods are randomly assigned individually. The duration of this trial is 10 years. In the intervention arm, low-dose thoracic computed tomography is performed for each participant in the first and the sixth years. In the control arm, chest roentgenography is performed for each participant in the first year. The participants in both arms are also encouraged to receive routine lung cancer screening using chest roentgenography annually. The interpretation of radiological findings and the follow-up of undiagnosed nodules are to be carried out according to the guidelines published in Japan. The required sample size is calculated to be 17 500 subjects for each arm.