Clinicopathological features of intraoperative pleural lavage cytology for non-small cell lung cancer.

OBJECTIVE: The significance of clinicopathological features of pre- and post-resection pleural lavage cytology (PLC) for non-small cell lung carcinoma (NSCLC) currently remains unknown. METHODS: Between January 2010 and December 2012, pre- and post-resection PLC were performed for NSCLC in 565 patients at Tohoku University, Miyagi Cancer Center, or Sendai Medical Center. The relationship between the clinicopathological features and patient outcomes was analyzed. RESULTS: Twenty-two patients (3.9%) had positive findings from pre- or post-resection PLC. Both PLC were correlated with pT and pl factors, while only post-resection PLC was correlated with pN factor (p < 0.005). The 5-year disease-free survival (DFS) rate of the positive pre-resection PLC was significantly poorer than that of negative (26.7% vs. 76.9%, p < 0.0001). In addition, the 5-year DFS of the positive post-resection PLC was also poorer than that of negative (14.3% vs. 76.0%, p < 0.0001). Multivariate analyses revealed that both PLC were not independent prognostic factors in our study. CONCLUSIONS: A significant association of post-resection PLC with N factor is considered to be characteristics of post-resection PLC different from pre-resection PLC. A prognostic impact of post-resection PLC and its detailed difference from pre-resection PLC should be clarified by further investigations.

[Vacuum-assisted Closure Therapy for Residual Space after Open Window Thoracotomy for Pleural Empyema due to Bronchopleural Fistula].

A 73-year-old man underwent right middle-lower bilobectomy for lung adenocarcinoma. He suffered from pneumonia followed by empyema due to bronchopleural fistula. On day 19 after the operation, an open window thoracostomy was created. Then the pleural space was treated conservatively with saline irrigation and petrolatum gauze packing. Progressive formation of healthy granulation tissue was observed around the bronchopleural fistula and the adjacent pulmonary artery, resulting in a complete closure of the bronchopleural fistula. And then we applied vacuum-assisted closure (VAC) therapy to the residual pleural cavity. At 4 weeks after the initiation of VAC therapy, the pleural cavity was completely filled with granulation tissue and re-expanded residual lung. In conclusion, VAC therapy is a safe and effective treatment for residual space after open window thoracostomy for empyema due to bronchopleural fistula, if it is applied after closure of bronchopleural fistula and adequate granulation tissue formation on the great vessels.

Inter-rater agreement of sputum cytology for lung cancer screening in Japan.

BACKGROUND: To compare lung cancer detection rate by sputum cytology, we need some assurance that the estimates do not vary widely if different observers evaluate the same specimens. The aim of this study was to determine inter-rater agreement of sputum cytology diagnoses. METHODS: Slides of sputum cytology from 150 subjects were selected from a pool of slides held by six of the laboratories that had participated in a population-based lung cancer screening program over the last ten years in Japan. The cytotechnologists in these laboratories had considerable experience with sputum cytology. Each case was re-evaluated six times. Cases that were diagnosed as the same category by all six laboratories were selected as consensus cases to serve as standardized sputum cytology cases. Thirty-seven cytotechnologists with various levels of experience in sputum cytology then re-evaluated these consensus cases. Inter-rater agreement was calculated by kappa statistics including Fleiss' kappa. RESULTS: All pairs of interlaboratory agreement for the 150 cases showed statistically significant kappa values, most pairs showing substantial agreement. Fleiss' kappa value across the six laboratories was 0.5. Fourteen cases were identified as the consensus cases, and the agreement among observers with less experience of sputum cytology showed significantly lower than the agreement among those with considerable experience (Fleiss' kappa value 0.27 vs. 0.45, P < 0.05). Moreover, cytotechnologists with less experience under-diagnosed the slides significantly more often than those with considerable experience. CONCLUSION: When the observers have considerable experience with sputum cytology, inter-observer agreement is good.

[A case of benign metastasizing leiomyoma medicating for 14 years].

We report a case of benign metastasizing leiomyoma medicated for 14 years after the diagnosis. A 47-year-old woman, who had undergone hysterectomy for uterine myoma at age 40 in 1989, was readmitted in 1996 because of abnormal shadows found on a chest X-ray film. Computed tomography (CT) and further chest X-ray films showed multiple nodules in bilateral lung fields. Open lung biopsy revealed leiomyomatous nodules histologically similar to those found at age 40. Tests for both estrogen and progesterone receptors in the biopsied specimen were positive. We diagnosed the lung nodules as benign metastasizing leiomyoma (BML) and gave her progesterone. Apart from 2 occasions when the patient elected to stop receiving medication, we obtained decreases in the size and number of tumors for 10 years from the start of treatment. However, despite continued administration of progesterone, the tumors continued to grow slowly during the next 4 years. We believe that the effectiveness of progesterone may have gradually decreased in this case, and thus are considering a change in treatment. BML is rare, and it must be carefully followed up long-term in post-menopausal patients.

Cytological characteristics of pulmonary pleomorphic and giant cell carcinomas.

OBJECTIVE: To establish cytological features of pulmonary pleomorphic carcinoma (PC) or giant cell carcinoma (GC), we evaluated the cytological characteristics of these tumors using a multidisciplinary approach. STUDY DESIGN: Samples from 13 surgically resected and histologically confirmed PC or GC patients were collected from our institutes. Eight cases without prior chemotherapy before surgery were selected, and cytological features were analyzed. RESULTS: The background contained numerous lymphocytes and neutrophils. The tumor cells were arranged in flat loose clusters, but some were in fascicles. The shape of the tumor cell was spindle or pleomorphic, and the sizes of the tumor cells varied by more than 5-fold. The tumor cells had an abundant, thick and well-demarcated cytoplasm. The location of the nucleus was centrifugal, and the nucleus was oval or irregularly shaped. Multinucleated giant cells were frequently observed. The size of the nucleus was more than 5 times that of normal lymphocytes, and its size also varied by more than 5-fold. The nuclear membrane was thin, and nuclear chromatin was coarsely granular, while the nucleolus was single and round. CONCLUSION: PC or GC has characteristic cytological features, however, spindle cells tended to be hardly observed in cytological specimens in some cases.

[The fluorodeoxyglucose-positron emission tomography (FDG-PET) findings and surgical strategy for pulmonary sclerosing hemangioma].

The pulmonary sclerosing hemangioma is a comparatively rare lung tumor. We operated on 7 patients of the pulmonary sclerosing hemangioma during January, 2009 from December, 2001. We collected the information such as preoperative image findings, surgical methods, and the postoperative course. FDG-PET was performed in 4 patients preoperatively, and there was FDG uptake in 2 patients, and no FDG uptake in 2 patients. In 2 cases with FDG uptake, there was a tendency to increase the tumor diameter during preoperative follow-up. Among 7 patients, 1 patient underwent tumor enucleation, 2 patients underwent partial resection, and 2 patients underwent thoracoscopic lobectomy. Lung biopsy was performed in remaining 2 cases. Because a tumor was located in pulmonary hilum in 1 case, we underwent lung needle biopsy under thoracoscopy. Because another case was a multiple case, and the resection of all lesions was impossibile, we performed lung biopsy (partial resection). In all cases, the recurrence or exacerbation of the tumor was not detected postoperatively. We thought that the findings of FDG-PET reflected proliferation potency of the pulmonary sclerosing hemangioma. The clinical features of the pulmonary sclerosing hemangioma are various. Therefore, the surgical treatment should be determined in each case carefully while considering the FDG-PET findings.

Results of long-term follow-up of photodynamic therapy for roentgenographically occult bronchogenic squamous cell carcinoma.

BACKGROUND: Photodynamic therapy (PDT) is considered a useful and minimally invasive modality for treating centrally located early lung cancer. To date, there has been limited information on the long-term outcome of patients treated with PDT, especially those who are medically operable. METHODS: Beginning in 1994, patients with roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC) who met our criteria underwent PDT at Tohoku University Hospital and were followed up through 2006. Our criteria were as follows: (1) ROSCC without distant metastasis; (2) medically operable by means of lobectomy or further resection; (3) longitudinal tumor length of

Immunocytochemical evaluation of large cell neuroendocrine carcinoma of the lung.

OBJECTIVE: To examine whether immunocytochemistry can distinguish pulmonary large cell neuroendocrine carcinoma (LCNEC) among non-small cell lung cancers (NSCLCs). STUDY DESIGN: Tumor touch imprint cytologic specimens of 109 lung cancers were studied. Immunocytochemistry was done using a total of 8 primary antibodies: chromogranin A, synaptophysin, neural cell adhesion molecule, neuron specific enolase, CK34betaE12, thyroid transcription factor-1, cytokeratin 18 and E-cadherin. RESULTS: If 2 or 3 antibodies of chromogranin A, synaptophysin and neural cell adhesion molecule were stained positive and CK34betaE12 was not stained, pulmonary LCNEC can be selected accurately among other NSCLCs with 100% sensitivity and 100% specificity. CONCLUSION: This study reveals that immunocytochemistry can help distinguish LCNEC of the lung from other NSCLCs.

Four years experience of the survey on quality control of lung cancer screening system in Japan.

Although quality control is essential in mass screening system for early detection of cancer, no global method for quality control has not been established, because the mass screening system in each country is quite different from each other. At present, we have to find appropriate method for each cancer and for each country. In 2000, The Lung Cancer Screening Division (LCSD) of the Miyagi Prefectural Committee for Management of the Cancer Screening System (Miyagi PCMCSS) decided to evaluate annually whether the local governments had appropriate information to evaluate the quality of lung cancer screening systems, announcing that the results would be informed to residents. On the basis of the manual developed by the Ministry of Health, Labor and Welfare, 45 items were selected as indicators for the survey, which could be obtained easily when the screening had been conducted according to the standard method. LCSD of Miyagi PCMCSS sent a questionnaire including the 45 items to the municipalities. According to the reply to the questionnaire, LCSD rated each municipality using a 5-rank classification depend on the number of insufficient items: A: 0; B: 1-4; C: 5-8; D: 9 or more; E: no reply. As the results, 58, 3, 6, 3, and 0 municipalities were categorized in 2002 as A, B, C, D, and E, respectively. In 2003, the number of municipalities changed to 60, 7, 2, 1, and 0. In 2005, the distribution improved more, such as 68, 2, 0, 0, and 0. The detection rate of lung cancer also improved. It is possible for PCMCSS to annually conduct surveys to determine whether the local government has appropriate information to evaluate the quality of lung cancer screening systems. Such surveys improve the distribution of response to better direction.

Cytological characteristics of pulmonary large cell neuroendocrine carcinoma.

To establish cytological features of pulmonary large cell neuroendocrine carcinoma (LCNEC), we evaluated the cytological characteristics of LCNEC. Samples from 25 histologically confirmed LCNECs (14 touch imprint (TI) and 11 curettage) were analyzed. The findings were compared with those for seven small cell lung carcinomas. Cytological findings of TIs were as follows: Tumor cells were medium- to large-sized, round or polygonal, and nuclear polymorphism was observed. Some of the tumor cells had clearly identified cytoplasms, but naked nuclei were frequently observed. Nuclei were round, oval, or polygonal, and possessed thin and smooth nuclear membranes. The nuclear chromatin pattern was finely or coarsely granular. One or two nucleoli were observed in the nuclei, but were inconspicuous in some cases. Tumor cells appeared in clusters, and rosette formation was observed, but single cells were frequently observed also. Necrotic background and nuclear streaking were frequently observed. In brush or curettage specimens, the number of cells observed on a glass was small, but the findings were almost the same as those for the TI samples. TI samples have characteristic features, such as a neuroendocrine morphologic pattern, large cell size, abundant cytoplasm, finely or coarsely granular chromatin of the nucleus, and prominent nucleoli, and the diagnosis of LCNEC is possible. In brush or curettage specimen, the LCNEC diagnosis may be possible if a sufficient number of tumor cells are obtained.

The natural history of radiographically occult bronchogenic squamous cell carcinoma: a retrospective study of overdiagnosis bias.

OBJECTIVE: An overdiagnosis bias occurs with the diagnosis of a disease that does not produce signs or symptoms before the patient dies from other causes. We sought to determine whether overdiagnosis bias is a factor when screening for squamous cell carcinoma of the lung. DESIGN: Retrospective study of the Miyagi Population-Based Lung Cancer Screening Registry for high-risk patients who were seen between January 1, 1982 (when sputum cytology tests were added for men with long smoking histories), and December 31, 1996. SETTING: Miyagi Prefecture, Japan. PATIENTS: A total of 251 patients (all men) who had sputum cytology test results that were positive for squamous cell carcinoma but had normal radiograph findings, 44 of whom declined cancer treatment (mean age, 70 years) and 207 of whom were treated with resection within 12 weeks of diagnosis (mean age, 65.5 year). END POINTS: Five-year and 10-year survival rates from primary lung cancer in both groups as of August 15, 2001. RESULTS: Among the 44 untreated patients, 15 (34%) remained asymptomatic. The survival rate due to primary lung cancer death in the untreated group was 53.2% at 5 years and 33.5% at 10 years. The survival rate among treated patients was 96.7% at 5 years and 94.9% at 10 years. Of the 125 treated patients who died, 14 (11.2%) died from primary lung cancer. CONCLUSION: Given that the two thirds of the untreated patients with squamous cell carcinoma of the bronchus died from lung cancer within 10 years, overdiagnosis bias does not appear to be a factor in screening for this disease. Thus, we recommend that patients with radiographically occult squamous cell carcinoma of the bronchus undergo tumor treatment after localization.

The efficacy of lung cancer screening conducted in 1990s: four case-control studies in Japan.

The efficacy of lung cancer screening is still controversial. In order to evaluate efficacy of mass screening for lung cancer in 1990s, the Japanese Ministry of Health and Welfare planned to conduct four independent case-control studies in four different regions; Miyagi, Gunma, Niigata, and Okayama Prefecture. The study design of all the four studies was a matched case-control study in which the decedents from lung cancer were defined as cases. In Gunma Prefecture, a screening examination is annual miniature chest X-ray only, whereas sputum cytology is added for high-risk screenees in others. Matching conditions were gender, year of birth, smoking histories (except Okayama), and municipality. Smoking adjusted odds ratio (OR) of dying from lung cancer for those screened within 12 months before case diagnosis compared with those not screened ranged 0.40-0.68. Three of four studies revealed statistically significant reduction of the risk for lung cancer death. OR of pooled analysis, where all sets were combined and analyzed, was 0.56 (95% confidence interval: 0.48-0.65). Recent mass screening program for lung cancer in Japan could reduce the risk for lung cancer death. However, the possibility exists that some confounding factors affected the results. In order to elucidate whether the results can be applied to Western countries, further studies will be required.

The efficacy of sputum cytology in mass screening program for early detection of lung cancer.

BACKGROUND: In order to evaluate the efficacy of sputum cytology in lung cancer screening, we re-analyzed the data obtained in our previous case-control study. MATERIALS AND METHODS: The source population was defined as the previous screenees for reducing self-selection bias. Matching conditions were: gender, year of birth, municipality and smoking history. RESULTS: Smoking adjusted odds ratio (SAOR) of dying from lung cancer for those screened by chest roentgenogram (CXp) only vs. not screened was 0.47, and that for those screened by sputum cytology (SpC) & CXp vs. not screened was 0.36, which was approximately three-fourths of the former. In another analysis, SAOR for those screened by SpC & CXp vs. those screened by CXp only was 0.63. CONCLUSION: Although statistical significance was not obtained, there might be some possibility that the risk of lung cancer death in smokers would decrease by additional SpC, compared with CXp only.

A randomized trial of postoperative UFT therapy in p stage I, II non-small cell lung cancer: North-east Japan Study Group for Lung Cancer Surgery.

OBJECTIVE: A prospective randomized trial was performed to investigate the prognostic advantage of postoperative adjuvant chemotherapy in patients with resected stage I-II non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: From March 1992 to December 1994, 221 patients with completely resected stage I-II primary NSCLC were enrolled and randomly assigned to two groups, as follows: 2-year oral administration of Uracil plus Tegafur (UFT) (adjuvant group, 109 patients), and surgical treatment alone (control group, 110 patients). RESULTS: The overall 5-year survival rates were 79% for the adjuvant group and 75% for the control group, and there was no statistical significance. The 5-year disease-free survival rates were 78% for the adjuvant group and 71% for the control group, and there was also no statistical significance. There have been seen no severe complications in the adjuvant group. The mean total dosages of UFT were about 75% of maximum basic amount. CONCLUSIONS: The UFT regimen was feasible. However, we have not observed any survival benefit in the adjuvant group. Larger trials are needed to confirm the effect of UFT to patients with resected NSCLC.

[Lung cancer screening--its efficacy and limitations].

Although the purpose of cancer screening is to decrease the number of cancer deaths, the efficacy of some cancer screening programs has not been proved. This article describes the authorized method for the lung cancer screening system in Japan, and introduces papers reporting the efficacy of lung cancer screening. The problems in the present lung cancer screening system in Japan are also discussed.