Prehospital diagnostic algorithm for acute coronary syndrome using machine learning: a prospective observational study.

Rapid and precise prehospital recognition of acute coronary syndrome (ACS) is key to improving clinical outcomes. The aim of this study was to investigate a predictive power for predicting ACS using the machine learning-based prehospital algorithm. We conducted a multicenter observational prospective study that included 10 participating facilities in an urban area of Japan. The data from consecutive adult patients, identified by emergency medical service personnel with suspected ACS, were analyzed. In this study, we used nested cross-validation to evaluate the predictive performance of the model. The primary outcomes were binary classification models for ACS prediction based on the nine machine learning algorithms. The voting classifier model for ACS using 43 features had the highest area under the receiver operating curve (AUC) (0.861 [95% CI 0.775-0.832]) in the test score. After validating the accuracy of the model using the external cohort, we repeated the analysis with a limited number of selected features. The performance of the algorithms using 17 features remained high AUC (voting classifier, 0.864 [95% CI 0.830-0.898], support vector machine (radial basis function), 0.864 [95% CI 0.829-0.887]) in the test score. We found that the machine learning-based prehospital algorithms showed a high predictive power for predicting ACS.

Prognostic impact of Schlafen 11 in bladder cancer patients treated with platinum-based chemotherapy.

The utility of Schlafen 11 (SLFN11) expression as a predictive biomarker for platinum-based chemotherapy has been established for cancers from different histologies. However, the therapeutic relevance of SLFN11 in bladder cancer (BC) is unknown. Here, we examined the clinicopathologic significance of SLFN11 expression across 120 BC cases by immunohistochemistry. We divided the cases into two cohorts, one including 50 patients who received adjuvant or neoadjuvant platinum-based chemotherapy, and the other including 70 BC patients treated by surgical resection without chemotherapy. In the cohort of 50 BC cases treated with platinum-based chemotherapy, the SLFN11-positive group (n = 25) showed significantly better overall survival than the SLFN11-negative group (n = 25, P = .012). Schlafen 11 expression correlated significantly with the expression of luminal subtype marker GATA3. Multivariate analyses identified SLFN11 expression as an independent prognostic predictor (odds ratio, 0.32; 95% confidence interval, 0.11-0.91; P = .033). Conversely, in the cohort of 70 BC cases not receiving platinum-based chemotherapy, the SLFN11-positive group (n = 29) showed significantly worse overall survival than the SLFN11-negative group (n = 41, P = .034). In vitro analyses using multiple BC cell lines confirmed that SLFN11 KO rendered cells resistant to cisplatin. The epigenetic modifying drugs 5-azacytidine and entinostat restored SLFN11 expression and resensitized cells to cisplatin and carboplatin in SLFN11-negative BC cell lines. We conclude that SLFN11 is a predictive biomarker for BC patients who undergo platinum-based chemotherapy and that the combination of epigenetic modifiers could rescue refractory BC patients to platinum derivatives by reactivating SLFN11 expression.

Papillary thyroid carcinoma with heterotopic ossification is a special subtype with extensive progression.

An immunohistochemical study was conducted of 108 papillary carcinoma cases, including 48 cases with intratumoral heterotopic ossification (IHO). In 48 cases, papillary carcinoma with IHO was accompanied by nodular fibrosis. Cases of papillary carcinoma with IHO or nodular fibrosis showed higher incidences of lymph node metastasis, multifocal lesions, and extrathyroidal invasion than those without IHO and nodular fibrosis. A higher number of stromal myofibroblasts was observed in papillary carcinoma with IHO or nodular fibrosis than in that without fibrosis. Expression of both basic fibroblast growth factor (bFGF) and bone morphogenetic protein (BMP)-2 was the highest in papillary carcinoma with IHO. Papillary carcinoma with IHO showed higher vascular invasion and higher numbers of capillaries expressing nestin, which is associated with high expression of vascular endothelial growth factor (VEGF). Papillary carcinoma with IHO is a unique subtype with extensive progression including frequent lymph node metastasis, multifocality, and invasive behavior. Papillary carcinoma with IHO was correlated with expression of bFGF, BMP-2, and VEGF in the carcinoma cells, leading to neovascularization.

Usefulness and pitfall of Narrow band imaging combined with magnifying endoscopy for detecting an unknown head and neck primary site with cervical lymph node metastasis.

OBJECTIVE: Cervical nodal metastasis from clinically undetectable primary squamous cell carcinoma (SCC) accounts for 1-2% of head and neck malignancies. We retrospectively evaluate the ability of Narrow band imaging combined with magnifying endoscopy (NBI-ME) to detect the primary sites of superficial SCC in the head and neck region. METHODS: This was a report of 11 patients. We performed with NBI-ME to detect unknown primary sites in the head and neck. RESULTS: Among 11 patients, primary sites were detected in eight. Primary sites were detected in the head and neck in 6 (54.5%) of 11 patients on NBI-ME, all 6 primary lesions were a flat lesion. Two patients in whom primary lesions could not be detected on NBI-ME, one had submucosal tumor like lesion, the other featured by a detectable primary lesion 19 months after neck dissection. CONCLUSION: NBI-ME can be recommended as an essential procedure for the detection of primary lesions in patients with primary unknown cervical lymph node metastasis.

Inverted epiglottis: a postoperative complication of supracricoid laryngectomy with cricohyoidoepiglottopexy.

OBJECTIVES: Among the 50 laryngeal cancer patients who received SCL-CHEP between 1997 and 2008, we experienced three patients with complete epiglottis prolapse, which obstructed the neoglottis. By defining this complication as "Inverted epiglottis" and presenting the clinical features, we intend to elucidate the mechanism, risk factors, and management of this complication. METHODS: Details of the clinical features are presented. We conducted the following analyses: (1) distance from anterior commissure to the upper resected end of the surgical specimen was grossly measured. (2) Based on the analysis of sagittal cut CT images, the level of vallecula was identified and compared with the level of hyoid bone. (3) Distance between hyoid bone and cricoid arch (cricohyoid gap) after SCL-CHEP was measured using sagittal cut CT images. RESULTS: Prolonged edema of the neoglottis and delayed stomal closure were the main symptoms. In patients with the vallecula lower than the hyoid bone, excessive resection of the epiglottic petiole (anterior commissure-upper edge>25 mm) might be a risk factor. CONCLUSIONS: We reported a post-SCL-CHEP complication "Inverted epiglottis". Extensive excision of the epiglottic petiole, patients with a low vallecula profile, and incorrect suturing of epiglottic petiole during pexis are the three factors most related. Inverted epiglottis was treatable and most of the laryngeal function could be retrieved.

Clinicopathological analyses of fifty supracricoid laryngectomized specimens: evidence base supporting minimal margins.

OBJECTIVES: Supracricoid laryngectomy (SCL) is a reliable laryngeal preservation surgery. However, close surgical margins are often inevitable. Based on clinicopathological analyses of supracricoid laryngectomized specimens, we evaluated the evidence base supporting minimal margins. METHODS: The distance between tumor edge and resected margin was measured macro- and microscopically at the anterior, posterior, superior and inferior edges, using 50 surgical specimens. The margins were correlated with pathological T staging and the prognoses. RESULTS: The anterior and posterior margins were the shortest, and the superior margin was the longest. The inferior margin was the only edge at which a positive margin was encountered. Cancer extending 10 mm below the glottal free edge significantly decreased the inferior margin. CONCLUSIONS: The surgical potential of SCL with cricohyoidoepiglottopexy was confirmed to be able to cope with tumor extensions showing margins of a few millimeters at the anterior, posterior and superior ends. Accurate assessment and management at the inferior margin is the key to stable local control.

[Clinical review of supracricoid laryngectomy with CHEP and CHP: 50 patients treated in 11 years].

An analysis of clinical data on 50 patients undergoing supracricoid laryngectomy (SCL) between 1997 and 2008 i.e., cricohyoidoepiglottopexy (CHEP) in 47 and cricohyoidopexy (CHP) in 3 cases showed that the number of SCL cases operated on within a year surpassed that of Total Laryngectomy after 2003. Selection criteria included performance status 0-1 and blood gas PO2>80 torr, especially in those patients over 70-years-old. Postoperative wound infection occurred in 16 patients (32%), with four requiring additional surgical intervention (two ruptured pexis and two chondritis induced by C3-C4 osteophytes). A history of radiotherapy and systemic complications, i.e., diabetes and renal failure, added to the risk of wound infection. Introducing a clinical pathway shortened hospitalization. Vocal function was achieved in 96% and swallowing function in 89% of patients. Five-year crude survival in CHEP was 69% and in TL 51%. Laryngeal preservation was 70%, increasing to 89% after the introduction of SCL. SCL-CHEP is thus indicated for unfavorable T2 (ASCO 2006), well-selected T3, T4, and rT1-4 (radiation failures). Effort should emphasize a good balance in prognosis and function in organ preservation for laryngeal cancer.

Narrow band imaging in the diagnosis of intra-epithelial and invasive laryngeal squamous cell carcinoma: a preliminary report of two cases.

Narrow band imaging (NBI) is a novel optical technique that enhances the diagnostic capability of the gastrointestinal endoscope (GIE) by illuminating the intraepithelial papillary capillary loop (IPCL) using narrow bandwidth filters in a red-green-blue sequential illumination system (CV-260SL processor and CLV-260SL light source, Olympus Optical Co. Ltd, Tokyo, Japan). The NBI filter sets (415 nm and 540 nm) are selected to obtain fine images of the microvascular structure. Because 415 nm is the hemoglobin absorption band, capillaries on the mucosal surface can be seen most clearly at this wavelength. NBI is able to represent more clearly both capillary patterns and the boundary between different types of tissue, which are necessary for diagnosing a tumor in its early stage (Gono K, Yamazaki K, Doguchi N, Nonami T, Obi T, Yamaguchi M, et al. Endoscopic observation of tissue by narrow band illumination. Opt Rev 2003;10:211-215, Gono K, Obi T, Yamaguchi M, Ohyama N, Machida H, Sano Y, et al. Appearance of enhanced tissue feature in narrow-band endoscopic imaging. J Biomed Opt 2004;9:568-577). We present two patients with laryngeal squamous cell carcinoma in whom the spread and the depth of invasion was evaluated with transnasal GIE equipped with NBI. Based on our results, the vascular neoplastic changes of carcinoma in situ of the larynx could be similar to carcinoma in situ of the esophagus.

Narrow band imaging for detecting metachronous superficial oropharyngeal and hypopharyngeal squamous cell carcinomas after chemoradiotherapy for head and neck cancers.

We present two cases of metachronous superficial squamous cell carcinomas at oropharyngeal and hypopharyngeal mucosal sites after chemoradiotherapy for head and neck cancers. These were detected by narrow band imaging combined with a magnifying gastrointestinal endoscopy. In one case, we successfully removed the tumor using endoscopic submucosal dissection. Narrow band imaging combined with magnifying gastrointestinal endoscopy illustrated well-demarcated brownish area and scattered foci of microvascular proliferation. Thus, it may serve as an ideal surveillance mode after chemoradiotherapy for head and neck cancers.

Supracricoid laryngectomy with cricohyoidoepiglotto-pexy or cricohyoido-pexy: experience on 32 patients.

OBJECTIVE: Supracricoid laryngectomy (SCL) with Cricohyoidoepiglotto-pexy (CHEP) or Cricohyoido-pexy (CHP) is an organ preservation surgery indicated for early and selected advanced laryngeal cancers. To verify the clinical usefulness of supracricoid laryngectomy versus total laryngectomy, a retrospective review was conducted. METHODS: We summarized the clinical and postoperative data of 32 patients who received SCL over the past 9 years (1997-2005). Five-year survival rate of the SCL patient group (29 cases) was compared with that of the patient group receiving total laryngectomy (35 cases) within the same period. RESULTS: Wound infection was detected in 12 patients (38%). Those with severe infection, which required surgical intervention, included two cases of ruptured pexis and two cases showing cricoid cartilage necrosis induced by Forestier disease. There were two T4 cases that resulted in extensive excision. In one case, excision involved the posterior part of the cricoid cartilage resulting in insufficient closure of the neoglottis; the patient received total laryngectomy 30 months after SCL-CHEP because of persistent aspiration of liquid diet. In the other T4 case, the tumor invaded the thyroid and arytenoid cartilages but not the cricoid cartilage. Reposition of the remaining corniculate cartilage resulted in sufficient closure of the neoglottis; this patient subsequently acquired satisfactory laryngeal function. The 5-year overall survival rate was 86% for SCL group and 61% for the total laryngectomy group (limited to Stages III and IV glottic cancers). The causes of the four deaths were distant metastasis, neck metastasis, and intercurrent disease, respectively. Two patients are alive with distant disease. CONCLUSION: Through our experience in this series, the functional and oncological results of SCL showed certain advantages over those of total laryngectomy. Particularly, the clinical impact of SCL-CHEP was impressive; this technique needs is recommended to both head and neck surgeons and patients.

[Change of reactive small round cell infiltration in the stroma after pre-operative 8 Gy irradiation using treatment to maxillary sinus carcinoma with Kitasato method and prognosis according to the change].

PURPOSE: In this paper, we report the results of studying the degree of reactive small round cell infiltration in the stroma as a prognostic indicator of maxillary sinus carcinoma treated with the Kitasato method and the effect of preoperative irradiation at 8 Gy on infiltration in the stroma. SUBJECTS: Out of 74 patients who had been treated with this method in the 27 years from 1976 to 2002, the following patients were enrolled in this study: (1) 17 patients from whom tissue specimens could be obtained with biopsies or probe antrotomies before preoperative irradiation, and (2) 40 patients from whom tissue specimens could be obtained after preoperative irradiation including those who survived five years and who died of a specific cause. METHOD: We classified the pattern of distribution of small round cell infiltration in the stroma into three degrees. (1) Stromal infiltration was compared before and after the operation to recognize the prognosis for each patient based on the pattern of distribution of small round cell infiltration in the stroma. (2) The correlation between the degree of stromal infiltration and prognosis was studied statistically. RESULTS: (1) Both the patients with increased stromal infiltration and those postoperatively preserving a preoperative score of 2+ with irradiation at 8 Gy had a good prognosis. (2) The five-year survival rate for patients was significantly higher in those with a score of 2+ for their tissue specimens. CONCLUSION: The Kitasato treatment method is effective and improves the QOL of patients with maxillary sinus carcinoma. The prognosis was good in the patients with increased or preserved stromal infiltration. The low-dose irradiation and chemotherapy used in combination seemed to be biological response modifiers.