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Sun glint contamination on unmanned aerial vehicles (UAV) imagery is a ubiquitous problem and poses a significant impediment in the retrieval of water quality parameters for coastal monitoring applications. Previous studies using near-infrared (NIR) and regression-based sun glint corrections have shown overcorrection at turbid regions as water-leaving NIR radiance is non-negligible. A spatial shift in the band channels would also result in suboptimal correction in the visible spectrum. Recent total variation (TV) methods show promise in reducing spectral variation associated with glint-affected regions and achieve effective correction of sun glint while leaving non-glint regions largely unaltered. To that end, this study proposes an open-source Sun Glint-Aware Restoration (SUGAR) algorithm that bridges principles in NIR and TV methods for the effective correction of sun glint in multispectral and hyperspectral UAV imagery. The present study shows that SUGAR achieves the best sun glint correction performance among existing regression and pixel-based sun glint correction methods when applied on UAV imagery of turbid and shallow regions. Around 40-80% of the total variation at glint-affected regions have been reduced while preserving features in non-glint regions. Validation of SUGAR with in situ UAV flight surveys and turbidity measurements in the coastal region of Singapore demonstrated significant improvement in turbidity retrieval, with root-mean-squared error (RMSE) reducing from 0.464 to 0.183 FNU and 0.551 to 0.285 FNU for multispectral and hyperspectral imagery, respectively., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Purpose: In the modern era of precision medicine, next-generation sequencing (NGS) is employed for a variety of clinical purposes. The aim of this study was to investigate the trends and clinical characteristics of NGS testing in South Korea., Materials and Methods: This nationwide, population-based, retrospective cohort study examined National Health Insurance Service claims data from 2017 to 2021 for NGS and from 2008 to 2021 for gene-targeted anticancer drugs., Results: Among the total 98,748 claims, there were 51,407 (52.1%) solid cancer panels, 30,173 (30.5%) hereditary disease panels, and 17,168 (17.4%) hematolymphoid cancer panels. The number of annual claims showed a persistent upward trend, exhibiting a 5.4-fold increase, from 5,436 in 2017 to 29,557 in 2021. In the solid cancer panel, colorectal cancer was the most common (19.2%), followed by lung cancer (18.8%). The annual claims for targeted cancer drugs have increased 25.7-fold, from 3,932 in 2008 to 101,211 in 2020. Drugs for the treatment of lung cancer accounted for 488,819 (71.9%) claims. The number of patients who received non-hereditary NGS testing has substantially increased, and among them, the count of patients prescribed targeted anticancer drugs consistently rose from 508 (13.9%) in 2017 to 2,245 (12.3%) in 2020., Conclusion: This study highlights the rising nationwide demand for comprehensive genetic testing for disease diagnosis and treatment following NGS reimbursement by the National Health Insurance in South Korea, in addition to the need for greater utilization of targeted anticancer drugs.

The adoption of Unmanned Aerial Vehicle (UAV) remote sensing for the regulatory monitoring of turbidity plumes induced by land reclamation operations remains a difficult task. Compared to UAV remote sensing on ambient turbidity in estuaries and rivers, such monitoring of construction-induced turbidity plumes requires significantly higher spatial resolutions and accuracy as well as wider turbidity ranges with nonlinear reflectance. In this study, a pilot-scale deployment of UAV-based hyperspectral sensing is carried out for this objective, with specific new elements developed to overcome the challenges and minimise the uncertainties involved. In particular, Machine learning (ML) models for the turbidity determination were trained by the large dataset collected to better capture the non-linearity of the relationship between the water leaving reflectance and turbidity level. The models achieve a good accuracy with a R 2 score of 0.75 that is deemed acceptable in view of the uncertainties associated with construction and land reclamation work., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

This study aimed to investigate the risk of developing major depressive disorder (MDD) in women with polycystic ovary syndrome (PCOS). As a population-based retrospective cohort study based on the Korean National Health Insurance Claims Database and National Health Information Database, newly diagnosed 26,251 women with PCOS with age matched 131,480 women without PCOS from 2007 to 2010 were followed longitudinally and the subsequent occurrence of newly onset MDD was evaluated. The risk of developing MDD in women with PCOS after adjusting for various confounding variables was higher compared to women without PCOS (hazard ratio [HR]1.34, 95% confidence intervals [CI] 1.29-1.40, p <.0001). Stratified by the body mass index, the risk of being admitted to the hospital due to MDD was the highest in the overweight PCOS (HR 2.53, 95% CI 1.71-3.76, p <.0001). The risk of developing MDD was higher in women with PCOS compared to women without PCOS. Maintenance of the appropriate body weight should be emphasised as the hazard ratio of developing MDD was higher in overweight women with PCOS.Impact statement What is already known on this subject? PCOS is a multisystem disorder associated with various comorbidities including diabetes mellitus, infertility and endometrial cancer. What do the results of this study add? Women with PCOS showed a higher risk of developing MDD compared to age matched women without PCOS in this multivariate analysis after adjusting for body-mass-index, smoking habit, socio-economic status, residential area, blood glucose, and blood cholesterol. The risk of being admitted to hospital due to MDD was the highest in PCOS with BMI ≥ 25. What are the implications of these findings for clinical practice and/or further research? PCOS should not be considered as a condition confined to ovulatory dysfunction and dermatologic problems, but the higher risk of developing MDD should be recognised. The importance of maintaining an appropriate BMI should be emphasised, as the risk of being admitted to the hospital due to MDD increased in overweight and obese women with PCOS.

Land use plays a significant role in determining the spatial patterns of water quality in the Johor River Basin (JRB), Malaysia. In the recent years, there have been several occurrences of pollution in these rivers, which has generated concerns over the long-term sustainability of the water resources in the JRB. Specifically, this water resource is a shared commodity between two states, namely, Johor state of Malaysia and Singapore, a neighbouring country adjacent to Malaysia. Prior to this study, few research on the influence of land use configuration on water quality have been conducted in Johor. In addition, it is also unclear how water quality varies under different seasonality in the presence of point sources. In this study, we investigated the influence of land use and point sources from wastewater treatment plants (WWTPs) on the water quality in the JRB. Two statistical techniques - Multivariate Linear Regression (MLR) and Redundancy Analysis (RA) were undertaken to analyse the relationships between river water quality and land use configuration, as well as point sources from WWTPs under different seasonality. Water samples were collected from 49 sites within the JRB from March to December in 2019. Results showed that influence from WWTPs on water quality was greater during the dry season and less significant during the wet season. In particular, point source was highly positively correlated with ammoniacal‑nitrogen (NH 3 -N). On the other hand, land use influence was greater than point source influence during the wet season. Residential and urban land use were important predictors for nutrients and organic matter (chemical oxygen demand); and forest land use were important sinks for heavy metals but a significant source of manganese., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Water quality monitoring is a pillar in water resource management, but it can be resource intensive, especially for developing countries with limited resources. As such, Water Quality Indices (WQI) are developed to summarise general water quality, but efforts to assess the utility, flexibility, and practicality of WQI have been limited. In this study, we introduced an additional step to the traditional WQI development framework by introducing an adjusted form of WQI (WQI ADJUSTED ) to handle missing values, and capitalise on the remaining available information for the development of a WQI. A Sub-WQI was also developed to address local water quality conditions. WQI results (weighted and non-weighted) developed using different parameter optimisation methods, namely Multivariate Linear Regression and Principal Component Analysis were compared. To build upon the current framework, a new procedure was developed to assess the adequacy of WQI based on the sensitivity analysis of parameters and uncertainties associated with each parameter's missing values distribution. The number of observations needed for the development of a robust WQI was optimised with respect to user-defined acceptable change in WQI, based on Monte Carlo probabilistic simulation. The Johor River Basin (JRB), Malaysia is used as a case-study for the application of this new framework. The JRB serves as an important resource for Johor, one of the most populous state in Malaysia, and Singapore, a country south of Johor. WQI MLR performed better in explaining the general water quality than WQI PCA for weighted water quality parameters. Optimisation of sampling frequency revealed that around 130 samples will be required if a 2% change in WQI can be tolerated. The results (specific to the JRB) also revealed that total coliform is the most sensitivity parameter to missing values, and the distribution of sensitive parameters are similar for both WQI NON-ADJUSTED and WQI ADJUSTED ., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background and Purpose: Previous studies have reported conflicting results about the prevalence of seizures in Alzheimer's disease (AD). There are few epidemiological studies on this topic in Asia. Thus, the objective of this study was to examine demographic and clinical characteristics as well as incidence for seizures in AD patients compared to non-AD patients in a prospective, longitudinal, community-based cohort with a long follow-up., Methods: Data were collected from National Health Insurance Service-National Elderly Cohort (NHIS-elderly) Database to define patients with AD from 2004-2006 using Korean Classification Diseases codes G30 and F00. We performed a 1:5 case-control propensity score matching based on age, sex, and household income. We conducted Cox proportional hazards regression analysis to estimate the risk of epilepsy in AD patients., Results: In the cohort study, patients with AD had higher risk for epilepsy than those without AD, with hazard ratio of 2.773 (95% confidence interval [CI], 2.515-3.057). This study also showed that male gender and comorbidities such as hypertension, hyperlipidemia, diabetes, and chronic kidney disease increased the risk of developing epilepsy. Patients with AD had 1.527 (95% CI, 1.375-1.695) times higher mortality rate than those in the control group., Conclusions: AD patients have significantly higher risk of developing epilepsy than non-AD patients., Competing Interests: Conflict of Interest: The authors have no financial conflicts of interest.

Objective: To investigate the demographic features of labial adhesion (LA) in South Korea., Design: A population-based nationwide study., Setting: Census population of South Korea., Participants: With the entire population of South Korea (n=47 990 761), patients under age 7 who were newly diagnosed with LA from January 2010 to December 2014 were included., Main Outcome Measure: The average incidence and the peak age of LA occurrence were estimated., Results: A total of 4934 newly diagnosed LAs were analysed. The incidence of LA has constantly increased since 2008, the year that the Korean Developmental Screening Test for InfantsandChildren registry began. The average incidence of LA was 55.0 cases/100 000 person-years (95% CI 53.5 to 56.6). The highest incidence was 183.6 cases/100 000 person-years (95% CI 175.8 to 191.6) in the age group of13 to 24 months. The relative risk of acquiring LA in the age group of 13 to 24 months was 1.481 (95% CI 1.381 to 1.587) compared with the age group of 0 to 12 months., Conclusions: The demographic characteristics of LA including the average incidence and the highest incidence age group in South Korea were revealed in this nationwide, population-based study including a total of 4934 newly developed LA cases. Further studies are needed to reveal the natural disease course and the significance of diagnosing asymptomatic LA cases., Competing Interests: Competing interests: None declared.

Background: The purpose of this study was to evaluate whether performing an assessment of myocardial deformation using speckle tracking imaging during the recovery period after dobutamine stress echocardiography (DSE) allows detection of significant coronary artery disease (CAD) in patients with chest discomfort., Methods: DSE and coronary angiography were performed in 44 patients with chest discomfort. The mean global longitudinal peak systolic strain (GLS) was measured at rest, at low stress (dobutamine infusion rate of 10 µg/kg/min) and at recovery (5 min after cessation of dobutamine infusion) of DSE using automated function imaging with apical views. Fractional flow reserve (FFR) was also performed in patients with intermediate coronary stenosis. CAD was defined as having a ≥ 70% diameter stenosis on coronary angiography or as having a FFR < 0.8. Patients were divided two groups based on the absence or presence of CAD [CAD (-) group vs. CAD (+) group]., Results: There were no significant differences in the clinical characteristics and results of conventional echocardiography between the two groups. GLS at recovery was lower in the CAD (+) group than in the CAD (-) group (-18.0 ± 3.4% vs. -21.0 ± 1.9%, p = 0.003). The optimal cutoff of GLS at recovery for detection of CAD was -19% (sensitivity of 70.6%, specificity of 83.3%)., Conclusion: Assessment of GLS at recovery of DSE is a reliable and objective method for detection of CAD. This finding may suggest that systolic myocardial stunning remains even after recovery of wall motion abnormalities in patients with CAD.

A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[alpha]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean +/- standard deviation [SD], 3.77 +/- 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean +/- SD, 6.48 +/- 3.6). These differences are significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Rapid-stain cytologic evaluation of needle aspirates are a recent adjunct to diagnosis and staging of lung neoplasms. The benefits of this approach include ease of sampling from deep and remote lesions and the fact that the results are generally available within 10 minutes. In the past 2 years, we did 187 needle aspirations for cytopathological evaluation in 70 patients at 51 thoracotomies and 21 mediastinoscopies. The cytologic findings from aspirates of lymph nodes, mediastinal masses, and intrapulmonary lesions were compared with diagnosis obtained by histopathological techniques. Quick-stain cytopathological evaluation discriminated cancer among all 55 lung masses from which aspirates were taken; specific diagnosis as to the type of neoplasm, lymphoproliferative disorder, or infection was achieved in 60 of 70 patients (85%). We conclude that intraoperative needle aspirations for cytologic evaluation facilitates the practice of modern general thoracic surgery.

Research on early human lung cancer is difficult; we have sought a canine correlate. Regimens included endobronchial submucosal injections and topical focal applications of benzo[a]pyrene, nitrosomethylurea, dimethylbenzanthracene, and methylcholanthrene, singly or in combinations. Sustained-release discs were placed into lung parenchyma or sutured into major bronchi. Tracheal segments were isolated as cervical pedicle grafts. Gross and histological evolution was reproducible. Columnar and basal hyperplasia and squamous metaplasia were early changes. Atypia occurred within 6 weeks and was found in all dogs within 16 to 18 weeks. Invasive cancers occurred within 8 to 65 months. No tracheal graft developed cancer. Of 15 dogs with parenchymal sustained-release implants, 1 to date has developed cancer in 8 months. Four endobronchial regimens have produced 16 cancers in 56 lungs at risk for 18 to 65 months. No cancers developed in 23 lungs at risk from eight other regimens. Of 10 dogs at risk for unilateral endobronchial cancer, 5 have had cancer. Of 23 dogs with both lungs at risk, 9 developed cancer. We have shown focal carcinogenesis with well-defined pathogenesis and an extended preneoplastic period at predictable sites in a lung cancer model.

Hepatic metastases occur rarely in epithelial ovarian carcinoma and also appear to be unusual in malignant stromal tumors of the ovary (granulosa cell tumors). Recently two patients with extensive hepatic metastasis from this primary tumor, were treated. Review of the experience at the City of Hope National Medical Center provided three additional patients with a confirmed diagnosis of granulosa cell tumor of the ovary, one of whom is alive and disease-free. A review of clinical and pathologic data revealed that both of the other patients died of their disease and had hepatic metastases proven at autopsy. Hemorrhagic events complicating the clinical course of these patients were frequent. It is believed that the frequency of hepatic metastasis in granulosa cell tumor of the ovary may be higher than has been appreciated in the past, and that the cystic-hemorrhagic nature of these lesions contributes to the morbidity and mortality associated with granulosa cell tumors of the ovary.

A canine model of squamous cell lung cancer has been developed through studies with 110 dogs exposed by 11 focal endobronchial regimens to chemical carcinogens: benzo(a)pyrene, nitrosomethylurea, methylcholanthrene, and dimethylbenzanthracene. A combination of nitrosomethylurea and benzo(a)pyrene caused the first invasive cancer after 5.5 years. Toxic side-effects resulted from either nitrosomethylurea or high-dose dimethylbenzanthracene given by bronchial submucosal injection and from adjuvant immunosuppression with azathioprine and corticosteroids. Four regimens in 58 dogs caused 31 cancers, including five T1-2 N0 M0 cancers, 17 metastasizing carcinomas, and nine carcinomas of lesser stages. The following regimens caused cancers: sequential benzo(a)pyrene, nitrosomethylurea, and yttrium 91; benzo(a)pyrene and topical nitrosomethylurea; low-dose dimethylbenzanthracene; high-dose methylcholanthrene. The most suitable regimen to date has been 30 mg of methylcholanthrene given by submucosal injection every 2 to 3 weeks; this produced cancers at preselected sites within 2 years of first exposure in eight of 10 dogs. The neoplastic continuum has followed a predictable, reproducible sequence that regularly began with epithelial hyperplasia. Squamous metaplasia occurred in 6 to 18 weeks; it was followed by progressive squamous atypia. The interval until invasive cancer developed varied with the regimen employed; it was about 20 months with methylcholanthrene. Serial cytologic specimens, studied by image analysis, revealed progressive increase in mean total cellular deoxyribonucleic acid content from diploid in normal cells to greater than tetraploid in cancer cells (p less than 0.01). We have recently been successful with serial passage of four canine lung cancers from four to twelve transplant generations in nude mice. There is now a predictable large animal model of squamous cell lung carcinoma at preselected site(s) that closely resembles human lung cancer. The preneoplastic period is short enough to be fiscally defensible, but long enough to permit study of the biologic changes during endobronchial carcinogenesis.

Comparative DNA measurements in human and canine preneoplastic and neoplastic tracheobronchial cells were made with the application of computerized image analysis. Canine studies demonstrated that the sequence of cellular events that precede epidermoid lung cancer simulates precisely the progression observed in humans. DNA studies concomitantly confirmed that there is a stepwise increase in DNA content with advancing nuclear atypia in metaplastic respiratory cells in both species. All carcinomas, regardless of histologic type, were significantly hyperploid to aneuploid (4c to 6c). Small-cell carcinoma exhibited a narrow modal distribution in the 4c region. The uniformity of the cytologic and quantitative DNA changes among these disparate species tends to confirm that humans and canines share biologic characteristics in bronchogenic carcinogenesis. The quantitative DNA measurements provide an objective cellular marker and may be used clinically for diagnostic purposes.

A description is made of the application of image analysis to quantitative deoxyribonucleic acid (DNA) determinations in a variety of cells. Optical density of the video signal from Feulgen-stained material was integrated across the area of the nucleus and values obtained related to values derived from known diploid cells. Analysis was performed on three classes of material: (1) biological material with known haploid, diploid and tetraploid nuclear DNA (standards), (2) metaplasias of the bronchial epithelium and (3) bronchogenic carcinomas. Results obtained with image analysis corresponded with expected data for the biologic standards and with microspectrophotometric data obtained for metaplasia and epidermoid carcinoma of the bronchial system. Application of this and other quantitative methods to cancer screening and biology is discussed.

The sarcoid-like granulomas encountered in lymph nodes, spleens, and hepatic biopsy specimens removed from patients being "staged" in the course of Hodgkin's disease and, in lower incidence, in non-Hodgkin's lymphomas may, at least in part, be due to reactions to the oily radiographic contrast medium used in lymphangiography. They are seen more often following lymphangiography than when no contrast medium is used. The granulomas in patients who have not undergone lymphangiographic procedures are attributed to the many agents inciting pseudosarcoid lesions. It is speculated that the granulomas seen in Hodgkin's disease after lymphangiography may be the result of a combination of lipogranulomatous reaction and the effects of an immune adjuvant.

A clinicopathologic analysis of 15 patients with glassy cell carcinoma confirmed that this is a rare disease, having an incidence of 1.2%. It is a rapidly progressive and biologically aggressive disease with early extrapelvic metastasis. The five-year survival and the median survival in our series were 28% and 14 months, respectively. The majority of patients (87%) were understaged, which may have played a role in the poor prognosis. Four of 12 patients (33%) were initially diagnosed as having a benign disease (false-negatives). Defining of cytologic characteristics and differential features of this tumor may facilitate an early and more accurate diagnosis to improve prognosis.

The progression of preneoplasia into lung cancer can be serially studied in a new canine model that is simpler and more cost effective than previously reported methods of orthotopic endobronchial carcinogenesis. Short segments of bronchus, obtained by pneumonectomy, were placed on the back of 10 dogs in the form of subcutaneous bronchial autografts. These autografts (12 to 14 per dog) became vascularized and lined with normal respiratory epithelium. Four to 12 weeks after autograft implantation, 10% methylcholanthrene in crystalline form was put into 57 autografts and 10% methylcholanthrene in a silicone polymer sustained-release implant was placed into 54 autografts. Ten autografts without carcinogen (one per dog) served as controls. Serial samplings of each autograft during 9 to 97 weeks of carcinogen exposure showed the neoplastic progression from normal bronchial cells to invasive cancer through stages such as atypical squamous metaplasia and carcinoma in situ. To date, cancers have been histologically proved in 60 autografts; 36 were induced by implants and 24 by the crystalline form. Thirty-nine cancers were epidermoid, and the remainder were either adenocarcinomas (n = 3) or poorly differentiated spindle cell cancers (n = 18). The sustained-release implant method resulted in larger autografts with a greater tendency to progress to cancer than the crystalline carcinogens (p greater than 0.025). Therefore, the sustained-release implant is now considered the preferred method. Measurement of nuclear deoxyribonucleic acid by image analysis of nine histologic cancers demonstrated hyperploidy. Deoxyribonucleic acid from the L1 repeated sequence family was demonstrably hypomethylated in spindle cell tumors. Curettement of individual autografts yielded sheets of respiratory epithelium from which 43.5 to 409.5 micrograms of deoxyribonucleic acid was isolated. For the first time, deoxyribonucleic acid from each stage of the neoplastic progression in non-small cell lung cancer is available in adequate quantities for serial biochemical and therapeutic analysis.

Cutaneous metastases from various visceral organs were studied in 43 patients. The morphologic diagnosis in each case was established by fine-needle aspiration cytodiagnosis. There were 28 males and 15 females, with median ages of 62 and 61 yr, respectively. The most common primary tumor in men was carcinoma of the lung (35%), followed by malignant melanoma (21%) and carcinoma of the oropharynx (14%). In women, the most frequent primary cancers were carcinoma of the colon (59%) and lung (20%). Metastatic cutaneous lesions were more frequent in the back (23%), upper extremities (21%), and scalp (12%). Median survival from onset of cutaneous metastasis was shortest in primary lung cancer at 3 mo followed by colon at 5 mo and oropharynx at 5.5 mo. Our study confirms that cutaneous metastasis represents a terminal manifestation of the disease due to either hematogenous or lymphatic spread. This study also reiterates the clinical usefulness of needle aspiration biopsy as an alternative diagnostic tool in establishing the presence of cutaneous metastasis.

Fifty-two consecutive patients ranging in age from 22 to 90 years underwent percutaneous transthoracic fine needle aspiration biopsy under fluoroscopic guidance. A quick staining and rapid interpretation technique was used on samples from the 37 most recent cases. Rapid staining was accomplished within five minutes, and interpretation was available less than 15 minutes after obtaining the specimen. Successful diagnosis was obtained in 36 of 37 patients (97%). Standard methods utilizing a single aspiration sample yielded a successful diagnosis in 13 of 15 patients (86%). The improved rate of successful diagnosis following the rapid stain technique reflects the advantage of being able to determine the adequacy of specimens before releasing patients from the procedure room.

Short bronchial segments obtained by pneumonectomy were implanted, 9-12 per dog, in the subcutaneous tissues of the back of seven dogs. These subcutaneous bronchial autografts (SBA) became vascularized, and they contained viable, histologically normal respiratory epithelium 4 wk after implantation. From 1-3 mo after implantation, 10% methylcholanthrene in steroid suspension medium was instilled into 21 SBAs, and 10% methylcholanthrene in a silicone polymer sustained release implant was placed in 22 SBAs. Ten SBAs were left carcinogen free as controls. SBA contents were examined cytologically at 3-mo intervals. Biopsies were done from 2-32 mo after carcinogen implantation. Progressive preneoplastic changes were noted in all five dogs which received carcinogen. Curetments of five SBAs after 14-mo exposure to methylcholanthrene yielded 10(4)-10(5) cells from each SBA; 40-70% of the cells obtained were at the same stage of atypical squamous metaplasia. At least one SBA in each dog yielded cancer cells by cytological criteria by 19-29 mo after instillation. Biopsy of a grossly abnormal SBA revealed well-differentiated epidermoid carcinoma at 32 mo. The multiple SBA method provides isolated portions of canine respiratory epithelium for the study of chemical carcinogenesis and for the production of sizable preneoplastic cell populations.

During the course of induction of bronchogenic carcinoma in a colony of standard-bred beagles, serial cytologic and biopsy material was obtained under direct bronchoscopy. Cytological changes followed the sequence from metaplasia to carcinoma, closely simulating those features observed in humans, but with subtle differences characterized as species variations. Quantitative DNA done by image analysis correlated directly with the severity of cytologic atypia and also corresponded well with data obtained from humans. Equivalent studies in human bronchogenic carcinoma have shown similar results and strongly suggest that graded hyperploidy accurately reflects atypia in the lung and qualifies as an interspecies tumor marker.

Typical and atypical carcinoids constitute less than 5% of lung tumors. They and small cell undifferentiated lung cancers (SCLC) belong to the same family of apudomas arising from bronchopulmonary Kulchitzky cells. To reflect the overlap among these cancers, the authors suggest calling them Kulchitzky cell carcinomas (KCC); to indicate their spectrum of aggressiveness, the authors suggest calling typical carcinoids KCC-I, atypical carcinoids KCC-II, and small cell cancers KCC-III. One hundred fifty-six KCCs were reviewed: 115 were KCC-I and 41 were KCC-II. The ratio of women to men equals 2:1. At time of initial diagnosis, all patients with KCC-I, except one patient, were in Stage I. Among patients with KCC-II, 16 (39%) were in Stages II or III at time of presentation. The incidence of carcinoid syndrome was 1.9%. Treatment was lobectomy in 112 (72%) of patients, the remainder having lesser resections or pneumonectomy in approximately equal distribution. Our data cannot support the use of radical resection in the treatment of KCC because none of the patients died of local recurrence. The mean diameters of KCC-I and -II tumors were 1.5 and 2.8 cm, respectively. Increased mitotic activity and tumor necrosis were reliable criteria for diagnosing KCC-II. Electron microscopic examination did not help in differentiating KCC-I and KCC-II. Thorough sampling of the entire tumor was found to be mandatory for precise diagnosis and for differentiation from KCC-III (SCLC). Measurement of nuclear DNA was done using integrated optical density (IOD) by image analysis. The IODs of KCC-I, -II and -III were 1.36, 1.55 and 1.94, respectively. These significant differences (P less than 0.001) correlated with the aggressiveness of the cancers. Of patients with KCC-I, 1.7% succumbed to KCC; this included one patient reported to have died of KCC-III (SCLC). Of 41 patients with KCC-II, 11 (27%) died of KCC; this includes at least 3 deaths from KCC-III.

The cytologic diagnosis of a thymoma by transthoracic fine needle aspiration is described. A 64-year-old female was found toi have a left hilar mass following an episode of hemoptysis. Fine needle aspiration of the lesion demonstrated an intimate admixture of two cell types: epithelial and lymphoid. On the basis of the biphasic cytomorphology, the diagnosis of thymoma was suggested; this was confirmed by light and electron microscopic examination of tissue obtained at thoracotomy. Because of the paucity of cytologic descriptions of thymoma in the literature, pertinent morphologic features are emphasized, differential diagnostic possibilities are discussed, and the value of ultrastructural studies is confirmed.

A case of granulocytic sarcoma involving the uterine cervix as primary manifestation without evidence of leukemia is presented. It was followed by neurological symptoms 19 months later and a right breast mass 26 months after the initial cervical lesion, but still with no evidence of leukemia. Two years and four months after onset, soft tissue and skin nodules developed and rare blastic cells appeared on peripheral blood smear. The patient terminally developed acute granulocytic leukemia with a rapidly downhill course. The differential diagnosis of granulocytic sarcoma and histiocytic lymphoma is discussed. The literature is reviewed with emphasis on the clinical and pathological problems that arise when the tumor presents in an unusual location without peripheral blood manifestation of leukemia.

The efficacy of surgical judgments in the management of thoracic lymphoma was studied through review of 34 patients with primary mediastinal lymphomas, 30 patients who needed one or more thoracic operations after treatment of extrathoracic lymphomas, and 5 patients with primary lymphocytic infiltrates (PLI) of the lung. In all patients with primary lymphocytic infiltrates of the lung, thoracotomies were required in order to establish the correct diagnosis. Patients with primary mediastinal lymphoma required 74 surgical procedures (2.2 per patient) to establish the correct diagnosis. In retrospect, 40 operations were not beneficial. The procedures that provided diagnostic samples were 15 anterior mediastinotomies, 8 full thoracotomies, 3 median sternotomies, and 8 lesser procedures such as mediastinoscopy. Patients who needed thoracic procedures after treatment of extrathoracic lymphomas had 41 thoracic operations (1.37 per patient). Five operations were needed to manage complications of thoracic lymphoma or its therapy. To evaluate new radiographic findings, there were 35 operations (1.3 per patient) at a mean interval of 5.0 years following initial treatment; the findings were recurrent lymphoma in 62% and new lesions in 38% of patients. Among new lesions, there were 2 bronchogenic cancers; 9 enlarging mediastinal-pleural masses were not caused by lymphoma. The accurate diagnosis of thoracic lymphoma or new thoracic lesions in patients with lymphomas usually requires enough tissue for immunophenotyping. Providing adequate tissue samples and treating new lesions that are not lymphomas often require major thoracomediastinotomies for immunophenotyping.