Machine learning to identify lymph node metastasis from thyroid cancer in patients undergoing contrast-enhanced CT studies.

INTRODUCTION: We compared the diagnostic performance of morphological methods such as the major axis, the minor axis, the volume and sphericity and of machine learning with texture analysis in the identification of lymph node metastasis in patients with thyroid cancer who had undergone contrast-enhanced CT studies. METHODS: We sampled 772 lymph nodes with histology defined tissue types (84 metastatic and 688 benign lymph nodes) that were visualised on CT images of 117 patients. A support vector machine (SVM), free programming software (Python), and the scikit-learn machine learning library were used to discriminate metastatic-from benign lymph nodes. We assessed 96 texture and 4 morphological features (major axis, minor axis, volume, sphericity) that were reported useful for the differentiation between metastatic and benign lymph nodes on CT images. The area under the curve (AUC) obtained by receiver operating characteristic analysis of univariate logistic regression and SVM classifiers were calculated for the training and testing datasets. RESULTS: The AUC for all classifiers in training and testing datasets was 0.96 and 0.86, at the SVM for machine learning. When we applied conventional methods to the training and testing datasets, the AUCs were 0.63 and 0.48 for the major axis, 0.70 and 0.44 for the minor axis, 0.66 and 0.43 for the volume, and 0.69 and 0.54 for sphericity, respectively. The SVM using texture features yielded significantly higher AUCs than univariate logistic regression models using morphological features (p = 0.001). CONCLUSION: For the identification of metastatic lymph nodes from thyroid cancer on contrast-enhanced CT images, machine learning combined with texture analysis was superior to conventional diagnostic methods with the morphological parameters. IMPLICATIONS FOR PRACTICE: Our findings suggest that in patients with thyroid cancer and suspected lymph node metastasis who undergo contrast-enhanced CT studies, machine learning using texture analysis is high diagnostic value for the identification of metastatic lymph nodes.

Automated computer-based CT stratification as a predictor of outcome in hypersensitivity pneumonitis.

BACKGROUND: Hypersensitivity pneumonitis (HP) has a variable clinical course. Modelling of quantitative CALIPER-derived CT data can identify distinct disease phenotypes. Mortality prediction using CALIPER analysis was compared to the interstitial lung disease gender, age, physiology (ILD-GAP) outcome model. METHODS: CALIPER CT analysis of parenchymal patterns in 98 consecutive HP patients was compared to visual CT scoring by two radiologists. Functional indices including forced vital capacity (FVC) and diffusion capacity for carbon monoxide (DLco) in univariate and multivariate Cox mortality models. Automated stratification of CALIPER scores was evaluated against outcome models. RESULTS: Univariate predictors of mortality included visual and CALIPER CT fibrotic patterns, and all functional indices. Multivariate analyses identified only two independent predictors of mortality: CALIPER reticular pattern (p = 0.001) and DLco (p < 0.0001). Automated stratification distinguished three distinct HP groups (log-rank test p < 0.0001). Substitution of automated stratified groups for FVC and DLco in the ILD-GAP model demonstrated no loss of model strength (C-Index = 0.73 for both models). Model strength improved when automated stratified groups were combined with the ILD-GAP model (C-Index = 0.77). CONCLUSIONS: CALIPER-derived variables are the strongest CT predictors of mortality in HP. Automated CT stratification is equivalent to functional indices in the ILD-GAP model for predicting outcome in HP. KEY POINTS: • Computer CT analysis better predicts mortality than visual CT analysis in HP. • Quantitative CT analysis is equivalent to functional indices for prognostication in HP. • Prognostication using the ILD-GAP model improves when combined with quantitative CT analysis.

Percutaneous microwave coagulation therapy for primary or recurrent hepatocellular carcinoma: long-term results.

BACKGROUND/AIMS: To clarify the indication of percutaneous microwave coagulation therapy for hepatocellular carcinoma. METHODOLOGY: Thirty-three hepatocellular carcinoma patients who underwent percutaneous microwave coagulation therapy were enrolled in this study, including 18 primary and 15 recurrent hepatocellular carcinoma patients. We examined the local recurrence rates and the long-term results after the treatment. RESULTS: The overall survival rates of the primary group at 1, 2, 3, 4 and 5 years were 94.4%, 77.8%, 77.8%, 77.8% and 48.6%, respectively, whereas those of the recurrent group were 100%, 85.7%, 66.7% and 50.0% at 1, 2, 3 and 4 years, respectively. Local recurrence after percutaneous microwave coagulation therapy was found in about 50% of patients in both groups. Seventeen of the 27 patients (63.0%) with a moderately or poorly differentiated hepatocellular carcinoma tumor had local recurrence, while none of the 6 patients with a well-differentiated hepatocellular carcinoma tumor did (P = 0.005). CONCLUSIONS: Irrespective of primary or recurrent hepatocellular carcinoma, the indication of percutaneous microwave coagulation therapy as an alternative to hepatic resection should be limited to cases of a well-differentiated hepatocellular carcinoma tumor smaller than 2 cm in diameter.

Hürthle cell tumor of the thyroid: analysis of 188 cases.

We reviewed 188 cases of Hürthle cell tumor of the thyroid (HCT) between 1982 and 1996. There were 160 women and 28 men with a mean age of 51.8 years. Thirty-one of the patients had cancer, and the others had adenoma. Age, size of the primary tumor, and preoperative thyroglobulin level were not significantly different in the cancer and adenoma patients. The gender ratio, however, was significantly different (p < 0.05). Recurrent HCT was observed in three patients with adenoma. Two patients had subcutaneous recurrence (suspected implantation), and the other patient had recurrence in the residual thyroid gland. All patients with recurrence of adenoma underwent partial lobectomy at the initial operation. Three cancer patients had recurrent disease. Locoregional recurrence was observed in one patient and distant metastases in two patients (lung in one, lung and bone in one). One of the patients with distant metastasis died from the disease, and the other is alive with the disease. Tumor implantation was observed in patients with adenoma, so intraoperative handling of the tumor requires care. It also means that this tumor, even though benign, is aggressive in terms of proliferative activity. All patients with Hürthle cell tumor should be treated by total lobectomy at least. The outcome of the cancer patients was not as poor as in previous reports.

Reaction of beta-alkannin (shikonin) with reactive oxygen species: detection of beta-alkannin free radicals.

beta-Alkannin (shikonin), a compound isolated from the root of Lithospermum erythrorhizon Siebold Zucc., has been used as a purple dye in ancient Japan and is known to exert an anti-inflammatory activity. This study aimed to understand the biological activity in terms of physico-chemical characteristics of beta-alkannin. Several physico-chemical properties including proton dissociation constants, half-wave potentials and molecular orbital energy of beta-alkannin were elucidated. This compound shows highly efficient antioxidative activities against several types of reactive oxygen species (ROS), such as singlet oxygen ((1)O2). superoxide anion radical (.O2), hydroxyl radical (.OH) and tert-butyl peroxyl radical (BuOO.) as well as iron-dependent microsomal lipid peroxidation. During the reactions of beta-alkannin with 1O2, .O2- and BuOO., intermediate organic radicals due to beta-alkannin were detectable by ESR spectrometry. Compared with the radicals due to naphthazarin, the structural skeleton of beta-alkannin, the beta-alkannin radical observed as an intermediate in the reactions with (1)O2, and .O2- was concluded to be a semiquinone radical. On the other hand, during the reactions of beta-alkannin and naphthazarin with BuOO., ESR spectra different from the semiquinone radical were observed, and proposed to result from the abstraction of hydrogen atoms from phenolic hydroxyl groups of beta-alkannin by BuOO.. Based on the ROS-scavenging abilities of beta-alkannin, the compound was concluded to react directly with ROS and exhibits antioxidative activity, which in turn exerts anti-inflammatory activity.

Study on eight patients with malignant tumors after renal transplantation.

The high incidence of cancer after renal transplantation is now a critical concern since the graft survival rate has been improved extensively. We experienced 9 malignancies in 8 patients out of 168 recipients up to December 31, 1999 in our hospital, consisting of a case of gastric plasmacytoma and cases of cancer in the liver (2), thyroid (2), prostate (1), breast (1), sigmoid colon (1) and gall-bladder (1). Two patients were diagnosed as having tumors within 3 months after transplantation, suggesting post-transplant acceleration of growth of the latent tumors. The other patients were diagnosed at an average of 128 months, ranging from 84 to 263 months after transplant. Two patients died of gastro-intestinal bleeding and acute heart failure. Four patients died directly of progressive neoplasm within 3 months after diagnosis. These results suggest that the course of malignancies developing in post-transplant recipients is more aggressive than that expected in non-transplant patients, and it is very important to intensively follow long-term surviving cases to detect the malignant tumors as early as possible.

[Familial nonmedullary thyroid cancer].

Familial occurrence of nonmedullary thyroid carcinoma is rare but this has been increasingly recognized over the recent years. Epidemiological studies showed that relatives of thyroid cancer cases were at increased risk of the same site. Surveying published familial cases, there were two groups of familial thyroid carcinoma; groups related to other familial diseases(familial adenomatous polyposis FAP, Gardner's syndrome, Cowden's disease) and another independent of accompanying disease. Familial thyroid carcinomas independent of accompanying disease were reported aggressive features and several authors recommended aggressive treatments. Genetic bases has not been clearly elucidated identification of genetic defects should undoubtedly aid an understanding of pathogenesis of sporadic cases.

PCNA and Ki-67 as prognostic markers in human parathyroid carcinomas.

BACKGROUND: It is widely accepted that histological diagnosis of parathyroid tumors is established with great difficulty. Carcinomas cannot be reliably separated from adenomas by histology alone. In this study, immunohistochemical staining for proliferating cell nuclear antigen (PCNA) and Ki-67 was determined in 10 cases of parathyroid carcinomas, labeling indices (LIs) were calculated, and the results were correlated with the clinical outcomes. METHODS: Ten cases of formalin-fixed, paraffin-embedded tissue with surgically resected parathyroid carcinoma were used. Immunohistochemical staining for PCNA and Ki-67 was performed and the LIs were calculated. We also examined whether LI could become a useful marker for parathyroid carcinomas. RESULTS: Although nine patients with minimally invasive growth without recurrence of the tumor showed a low LI for both markers, one patient with a widely invasive neoplasm, and who died, had a high LI. CONCLUSIONS: These results suggested that the LI of PCNA and Ki-67, in addition to the histological appearance, may be markers of the biological behavior of parathyroid carcinomas. However, this study was on a small scale, so it may be valuable to repeat these studies in a larger group of patients with better defined histological criteria.

Is there a place for the late cardioversion of atrial fibrillation? A long-term follow-up study of patients with post-thyrotoxic atrial fibrillation.

AIMS: As atrial fibrillation is associated with significant mortality and morbidity, restoration of sinus rhythm is desirable. However, previous data suggest that cardioversion should be restricted to patients in whom the fibrillation is of limited duration (<1-2 years) because of high relapse rates. It may be the frequent association with cardiac disease, rather than the duration of fibrillation itself, which determined the high relapse of earlier studies. The aim of this study was to investigate rates of cardioversion, maintenance of sinus rhythm and predictors of subsequent relapse in a homogeneous group of patients without evidence of any co-existent cardiac disease. METHODS AND RESULTS: We report on a retrospective series of 106 patients with thyrotoxicosis-induced fibrillation but no other heart disease: 87% had been in atrial fibrillation for >12 months (median duration 28.5, interquartile range 15-47 months). Cardioversion was attempted using disopyramide and then electric shock. Ninety-eight patients were successfully cardioverted: at late follow-up, 80.6+/-37 months (mean+/-SD), 67% were in sinus rhythm. CONCLUSION: Although a relationship between the duration of fibrillation and maintenance of sinus rhythm was found, the high proportion remaining in sinus rhythm, compared with other series, suggests this influence may be less important than the presence or absence of structural heart disease.

Immediate causes of death in thyroid carcinoma: clinicopathological analysis of 161 fatal cases.

Most patients with thyroid carcinoma have a good prognosis. Due to the small number of fatal cases, it has not been clarified what conditions result in death for patients with thyroid carcinoma. To provide appropriate management for advanced thyroid carcinoma patients, we analyzed causes of death in 161 fatal cases. Clinical characteristics and immediate (final) causes of death based on pathological conditions were analyzed in 62 anaplastic carcinomas and 99 fatal differentiated carcinomas. Single fatal conditions could not be specified in 55 patients. In the remaining 106 patients, respiratory insufficiency (43%) was the most common specific fatal condition, followed by circulatory failure (15%), hemorrhage (15%), and airway obstruction (13%). Respiratory insufficiency due to remarkable pulmonary metastasis replacing lung tissue, massive hemorrhage and airway obstruction due to uncontrolled local tumors, and circulatory failure resulting from compression of the vena cava by extensive mediastinal or sternal metastases were found to be the most important immediate causes of death. Based on this knowledge, several palliative procedures may be worth considering to improve survival and quality of life in patients with advanced thyroid carcinoma.

Postoperative changes in thyrotropin-binding inhibitory immunoglobulin level in patients with Graves' disease: is subtotal thyroidectomy a suitable therapeutic option for patients of childbearing age with Graves' disease?

Thyroid-stimulating hormone (TSH)-binding inhibitory immunoglobulin (TBII) is thought to be one of the essential causes of Graves' disease, and most cases of neonatal hyperthyroidism can be explained by transplacental passage of TBII. Because surgery is often indicated for patients of childbearing age, it is important to elucidate how surgery reduces TBII levels. Between 1988 and 1991 a total of 946 female patients with Graves' disease underwent subtotal thyroidectomy. Follow-up examination was undertaken at 1, 2, 3, and 4 to 5 years after surgery. At 4 to 5 years after surgery, 76.8% of patients without recurrent overt hyperthyroidism had TBII < 20%. In patients with recurrent hyperthyroidism, TBII increased gradually during follow-up, and they had higher TBII levels than nonrecurrence patients. There were a few euthyroid and hypothyroid patients who had TBII > 60%, and the number of such patients decreased annually. In most of the patients, immunologic remission was obtained by subtotal thyroidectomy except for their having recurrent hyperthyroidism. To acquire immunologic remission, hormonal remission, at least, would be necessary. Because no definite factor other than the size of the thyroid remnant related to postoperative thyroid function was elucidated, near-total thyroidectomy rather than subtotal thyroidectomy is expected to be induced not only hormonal remission but also immunologic remission. It should be noted that a few patients achieved hormonal remission but not immunologic remission.

Granular cell tumor of the breast: report of a case.

A case of granular cell tumor of the breast in a 43-year-old woman is described. The patient presented with a painless mass in the upper-outer quadrant of her right breast. Mammography showed a spiculated tumor and ultrasonography demonstrated a hypoechoic mass with an irregular border. Magnetic resonance (MR) mammography revealed a homogeneous enhanced mass in T1-weighted images using Gd-DTPA and a ringed high-intensity area around the mass in T2-weighted images. Fine-needle aspiration cytology failed to show any malignant cells. A partial resection of the breast was performed and histological examination revealed a granular cell tumor. Granular cell tumors are generally always benign, but they may be misdiagnosed as malignant tumors because of their mammographic and ultrasonographic findings. MR mammography did not reveal a typical breast cancer in either T1- or T2-weighted images in the present case. This case illustrates the need for care in preoperative examinations in order to avoid overdiagnosis of breast cancer.

A patient with a large hepatocellular carcinoma alive 13 years after repeated transcatheter arterial chemoembolization and hepatectomy.

We describe a rare case of a large hepatocellular carcinoma (HCC) in a patient who survived 13 years after repeated transcatheter arterial chemoembolization (TAE) and hepatectomy. The patient was a 41-year-old woman found in March 1985 to have a large HCC, measuring 14 x 12 cm in diameter and associated with obstruction of the main portal trunk. She underwent TAE 8 times over a period of 1 year. The serum alpha-fetoprotein level decreased from 18342 to 1871 ng/ml. The patient subsequently underwent left hepatectomy on October 9, 1986. Thirteen years after hepatectomy, the patient is being followed up on an outpatient basis and has had no evidence of recurrence.

Anaplastic transformation of papillary thyroid carcinoma in recurrent disease in regional lymph nodes: a histologic and immunohistochemical study.

BACKGROUND AND OBJECTIVES: Although the prognosis of papillary thyroid carcinoma is favorable in most cases, recurrent disease in the regional lymph nodes is not uncommon, and some patients die of recurrent disease that ultimately becomes unresectable. We studied the proliferative activity of cancer cells in recurrent foci in lymph nodes to see whether repeated recurrences might result in anaplastic transformation of papillary thyroid carcinoma. METHODS: Fourteen patients with papillary thyroid carcinoma who underwent reoperation for recurrent disease in the regional lymph nodes more than once were the subjects of the study. The histologic findings and proliferative activity of carcinoma foci at each recurrence were studied histologically and immunohistochemically. RESULTS: There were higher incidences of histologic features of poorly differentiated thyroid carcinoma in the metastatic foci in the lymph nodes as it recurred repeatedly, and the labeling indexes of proliferating cell nuclear antigen (PCNA) and nuclear antigen Ki-67 (MIB-1) increased. CONCLUSIONS: These observations suggest that papillary thyroid carcinoma may become more malignant, even undergo transformation to an anaplastic variety, as metastatic disease in the regional lymph nodes recurs repeatedly.

Simultaneous Determination of Different Classes of Lipid Hydroperoxides by High-Performance Liquid Chromatography with Post Column Detection by a Ferrous/Xylenol Orange Reagent.

A novel high-performance liquid chromatographic (HPLC) method with post-column detection was developed to simultaneously analyze the lipid hydroperoxides of polar and nonpolar lipids. The HPLC method uses a reversed-phase column (octyl-bonded silica) and a mobile phase of water/acetonitrile/methanol. Hydroperoxides were detected at 592 nm by using a ferrous (II)/xylenol orange (FeXO) reagent. This method enabled the separation of fatty acid hydroperoxides, phosphatidylcholine hydroperoxides, and hydroperoxides of neutral lipids, including triacylglycerol hydroperoxides and cholesterol ester hydroperoxides, by chromatography. These hydroperoxides could be quantified in a range between 40 pmol and 2 nmol. This new method was applied to estimate the lipid hydroperoxides formed during the photosensitized oxidation of rat plasma.

Factors affecting postoperative prognosis in the solitary-nodule type of hepatocellular carcinoma: experience of 132 cases in our institute.

A retrospective analysis of clinical and pathological factors was performed on 132 surgical cases with solitary-nodule type HCC in our hospital. The overall cancer-free survival rates after 1, 3 and 5 years were 82.2%, 42.3% and 26.5%, respectively. With univariate analysis, the significant prognostic factors for survival were tumor size, cancer cell infiltration of the fibrous capsule of the tumor (fc-inf), invasion into portal vein (vp), and intrahepatic metastasis (im), while significant prognostic factors for non-recurrence were tumor size, fc-inf, vp, im, Edmondson-Steiner's classification and perioperative blood transfusion. With multivariate analysis for recurrence, significant factors were vp, clinical stage (CS), and perioperative blood transfusion. Therefore, prognostic factors for long-term survival in surgical cases of HCC are thought to be good hepatic function, absence of portal invasion, and avoidance of perioperative blood transfusion if possible.

Papillary microcarcinoma of the thyroid.

Papillary microcarcinoma of the thyroid has been often detected by aspiration biopsy cytology performed with ultrasonographic guidance. Autopsy studies also have often revealed small thyroid carcinomas, and it was concluded that most small thyroid carcinomas should not be regarded as a clinical matter. In this study, 112 patients with papillary microcarcinoma 10 mm or less in size treated between 1992 and 1995 were analyzed. There were 104 females and 8 males, with a mean age of 46.0 years. Diagnosis of papillary carcinoma was made preoperatively in 100 of these patients (89.3%), and 77 patients underwent aspiration biopsy cytology under ultrasound guidance. Seventy of these patients underwent modified neck dissection, and 63.8% of these patients had lymph node metastases. The number of lymph node metastasis increased as primary tumor size increased. There was no clear border or clinical differences between primary tumors 10 mm or less and tumors more than 10 mm. One patient had lymph node recurrence after surgery and another patient had recurrent nerve palsy at the first visit. Based on these findings, papillary microcarcinoma should be treated surgically.

Malignant phyllodes tumor of the breast with hypoglycemia: report of a case.

A surgically resected case of giant malignant phyllodes tumor of the breast associated with a hypoglycemic attack is reported. A 54-year-old woman was referred to our hospital with loss of consciousness and a huge chest wall tumor. She was diagnosed as having a malignant phyllodes tumor by core needle biopsy and underwent palliative simple mastectomy because lung metastasis was detected on computed tomography and by other imaging modalities on admission. The preoperative laboratory data revealed a very low fasting blood sugar level of 37 mg/dl. After removal of the tumor, the blood sugar level gradually normalized (90-100 mg/dl) and the plasma insulin-like growth factor-II (IGF-II) level promptly decreased. The IGF-II level of tumor extracts was high (2500 ng/g wet weight) and the majority of atypical cells stained positively for IGF-II immunohistochemically. These findings suggested that the patient's hypoglycemia was associated with IGF-II produced by a giant malignant phyllodes tumor that consumed glucose.

A case of abdominal aortic aneurysm associated with systemic lupus erythematosus.

A case of abdominal aortic aneurysm associated with systemic lupus erythematosus (SLE) is reported. A 45-year-old woman with a 18-year history of SLE was admitted with severe lumbago radiating to the bilateral inguinal region. CT and DSA showed a dumbbell shaped true aneurysm of the abdominal aorta. An aorto-biiliac Y shaped graft replacements was performed. SLE is rarely associated with aneurysm of the great arteries. We could find only 4 reports of abdominal aneurysm associated with SLE. Common features were the young age of the patient, the long term of the systemic disease, and administration of corticosteroid therapy for a relatively long period of time. We speculate that atherosclerosis, hypertension, and corticosteroid may all work in concert, possibly together with aortic wall involvement or vasculitic damage, to produce the rare abdominal aneurysm in SLE.