Application of machine learning methods to guide patient management by predicting the risk of malignancy of Bethesda III-V thyroid nodules.

OBJECTIVE: Indeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN. DESIGN: Multi-centric diagnostic retrospective cohort study conducted between 2010 and 2020. METHODS: Adult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms. RESULTS: There were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively. CONCLUSIONS: Our ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries.

Predictive factors and prognosis of microscopic residual disease in non-small-cell lung cancer surgery.

OBJECTIVES: We described patients with microscopic residual disease (R1) operated on for non-small-cell lung cancer (NSCLC) and investigated predictive factors for R1. We also examined prognostic factors for overall survival in these patients. METHODS: From June 2003 to December 2019, a total of 2595 patients benefited from an anatomical resection operation for NSCLC in our department. All preoperative data were prospectively collected in Epithor, the French thoracic surgery national database. All pre-, per- and postoperative care followed the current recommendations. Tumours were classified by experienced pathologists according to the TNM classification and the resection status R. Survival information was collected retrospectively using the French national death register. RESULTS: A total of 94 R1 patients (3.6%) and 2255 R0 patients (86.9%) were identified. R1 patients showed significant differences: They were older (p = 0.02), with a high rate of pneumonectomy(p < 0.001), more squamous cell carcinomas (p < 0.001) and more cases of advanced-stage disease (p < 0.001). We proved that incomplete resection was a poor and independent prognostic factor whereas complete resection had a significant impact on overall survival (HR: 4.66 [3.46-6.27]). Thus, we identified high clinical T status (odds ratio [OR]: 8.82 [5.00-15.56]), high clinical N status (OR: 3.54 [2.13-5.87), squamous cell carcinoma (OR: 3.86 [2.33-6.42]), obesity (OR 1.91 [1.04-3.52]) and low forced expiratory volume in 1 s (OR: 3.62 [1.70-7.68]) as risk factors for R1. No statistical differences were found according to the location of positive resection margin or treatment, whether adjuvant or neoadjuvant. CONCLUSIONS: Incomplete resection was a poor prognostic factor for overall survival of patients operated on for NSCLC, particularly in the advanced stages of the disease. Identification of different predictive factors should help to avoid this situation.subj collection: 152.

Mass spectrometry-based proteomic analysis of parathyroid adenomas reveals PTH as a new human hormone-derived amyloid fibril protein.

BACKGROUND: Congo red-positive material was described in normal and diseased parathyroids (adenoma and hyperplasia) 50 years ago. However, the incidence and the clinical significance of such observation are unknown, and the causal fibril protein has never been convincingly demonstrated. METHODS: We conducted the present study including an exceptional case report accompanied with a retrospective study of 105 parathyroid adenomas. We used histopathological, immunohistochemical, ultrastructural, mass spectrometry-based proteomic analysis of parathyroid adenoma tissue samples, and genetic analysis. RESULTS: We describe a 57-year-old man with mild hypercalcemia and elevated parathyroid hormone (PTH) level for whom histopathological analysis revealed a parathyroid adenoma associated with nodular typical amyloid deposits. Tandem mass spectrometry after laser microdissection (LMD-MS) of amyloid adenoma identified PTH as the fibril protein, and no germline mutation in the PTH gene was detected. Congo red-positive PTH-deposits were further observed in 6.6% of the parathyroid adenomas analyzed, and were associated with complete/incomplete or absent universal amyloid signature, but with fibrillar morphology at ultrastructural level. CONCLUSIONS: Inappropriate PTH production leads to progressive disease-amyloid aggregation of PTH in a subset of parathyroid adenomas, providing new insights into the pathophysiology of this condition and adding PTH to the list of amyloid protein derived from hormones.

Key contribution of eIF4H-mediated translational control in tumor promotion.

Dysregulated expression of translation initiation factors has been associated with carcinogenesis, but underlying mechanisms remains to be fully understood. Here we show that eIF4H (eukaryotic translation initiation factor 4H), an activator of the RNA helicase eIF4A, is overexpressed in lung carcinomas and predictive of response to chemotherapy. In lung cancer cells, depletion of eIF4H enhances sensitization to chemotherapy, decreases cell migration and inhibits tumor growth in vivo, in association with reduced translation of mRNA encoding cell-proliferation (c-Myc, cyclin D1) angiogenic (FGF-2) and anti-apoptotic factors (CIAP-1, BCL-xL). Conversely, each isoform of eIF4H acts as an oncogene in NIH3T3 cells by stimulating transformation, invasion, tumor growth and resistance to drug-induced apoptosis together with increased translation of IRES-containing or structured 5'UTR mRNAs. These results demonstrate that eIF4H plays a crucial role in translational control and can promote cellular transformation by preferentially regulating the translation of potent growth and survival factor mRNAs, indicating that eIF4H is a promising new molecular target for cancer therapy.

Prevalence of the Leptospira serovars bratislava, grippotyphosa, mozdok and pomona in French dogs.

Although most French dogs are correctly vaccinated against leptospirosis with inactivated strains of canicola and icterohaemorrhagiae, the disease is still very prevalent in France raising the question of whether the vaccines used require updating. The aim of the present study was to provide serological data regarding circulation of the Leptospira serovars: grippotyphosa, bratislava, pomona and mozdok, which are contained in vaccines available in other parts of the world and which could be rapidly adapted for France. Results indicated that the epidemiology was consistent with the circulation of Leptospira belonging to the serogroups Australis and Grippotyphosa and that the case to support the inclusion of either pomona or mozdok in a dog vaccine for France was weak.

High third generation/second generation PTH ratio in a patient with parathyroid carcinoma: clinical utility of third generation/second generation PTH ratio in patients with primary hyperparathyroidism.

BACKGROUND: Primary hyperparathyroidism (PHP) is caused by parathyroid adenomas or hyperplasia, and occasionally by parathyroid carcinoma. Recently a high third generation/second generation PTH ratio has been observed in some patients with parathyroid carcinoma. PATIENTS AND METHODS: We report the case of a 60-year old woman who was presented a fourth episode of PTH-related hypercalcaemia due to a parathyroid carcinoma. Serum PTH levels were measured using a second generation assay and a third generation assay before, 4 and 7 months after the fourth surgery. Then, PTH levels were measured in 294 osteoporotic normocalcaemic patients as well as in 30 consecutive PHP patients. RESULTS: Before surgery of the patient with parathyroid carcinoma, second generation PTH was 229 pg/ml, third generation PTH was 675 pg/ml and third generation/second generation PTH ratio was 2.95. Four and 7 months after surgery the third generation/second generation PTH ratio was 0.70 and 0.66, respectively. All osteoporotic patients had a normal third generation/second generation PTH ratio (0.585 +/- 0.118) whereas only one patient (3.3%) with PHP had a third generation/second generation PTH ratio > 1 (1.54). CONCLUSION: A high third generation/second generation PTH ratio could be observed in patients with parathyroid carcinoma, is uncommon in benign PHP and is absent in osteoporotic patients without PHP. Therefore, PTH level can be measured using second and third generation assays in some PHP patients, and a specific surgical protocol for possible parathyroid carcinoma could be discussed in patients with a high third generation/second generation PTH ratio.

Impact of induction treatment on postoperative complications in the treatment of non-small cell lung cancer.

INTRODUCTION: A main drawback of neoadjuvant chemotherapy is that it may increase operative morbidity and mortality. The aim of this study was to determine the impact of chemotherapy on these complications. METHODS: Patient data were collected from the Epithor database. From June 2002 to June 2004, 3888 successive observations of surgery for lung cancer have been reported from 51 thoracic surgery departments throughout France. Logistic regression analysis was performed to identify preoperative clinical characteristics of patients with significant postoperative complications. RESULTS: Of 3888 patients, 555 (14.3%) received induction chemotherapy. The groups were similar with respect to sex and the number of comorbidities. The in-hospital mortality rate was 3.01%. The multivariate analysis allows us to identify age (older than 65 years), sex (male), preoperative clinical score (moderate and severe), surgical procedure (right pneumonectomy and bilobectomy) as significantly associated with in-hospital mortality. No statistical difference was observed according to the delivery or preoperative chemotherapy. In total, 1219 patients (31.4%) had at least one postoperative complication. Using a multivariate analysis, we observed a significant correlation between morbidity and age (older than 65 years), sex (male), presence of comorbidities (two or more), clinical score (moderate), and type of operation (bilobectomy). Preoperative administration of chemotherapy did not significantly influenced postoperative morbidity. CONCLUSIONS: Preoperative chemotherapy is not associated with an increase in either the mortality rate or major surgical complications. Future randomized trials are warranted to confirm the survival benefit of this strategy.

Videothoracoscopic silver nitrate pleurodesis for primary spontaneous pneumothorax: an alternative to pleurectomy and pleural abrasion?

BACKGROUND: The optimal surgical management of primary spontaneous pneumothorax (PSP) is still controversial, especially in terms of the technique to be used. The aim of this paper was to report our experience of videothoracoscopic silver nitrate pleurodesis (VATSNP). METHODS: Between 1995 and 2004, all the medical records of the patients who had undergone silver nitrate videothoracoscopic pleurodesis (SNVTP) were reviewed. All the patients had systematic prospective clinical and radiological follow-up at 1 month. The last 250 patients were retrospectively recontacted for long-term follow-up. RESULTS: Six hundred and three patients underwent SNVP. No intra-operative death or major complication occurred during or after the procedures. Mean operating time was 40.2+/-10.7 min. The conversion to thoracotomy rate was 2.5%. Main postoperative complications were prolonged air leak (15.6%), partial residual pneumothorax (5.1%), pleural effusion (2.5%) and postoperative bleeding (2.0%). The follow-up was 100% complete 1 month after discharge; at 1 month, the recurrence rate was 0.5%. The last 250 patients were retrospectively recontacted with a mean follow-up of 2.9+/-2.3 years (184 patients). The long-term recurrence rate was 1.1%. CONCLUSIONS: It is one of the first reports on the use of video-assisted thoracoscopic silver nitrate pleurodesis for PSP. We demonstrate safety and effectiveness of the procedure with long-term results comparable with standard open pleural abrasion or pleurectomy.

Pulmonary angiomyolipoma.

Extrarenal angiomyolipoma are benign lesions that have rarely been described in the thorax. We present the clinical, radiographic, and pathologic findings of a pulmonary angiomyolipoma in a 63-year-old woman who had no diagnosis of tuberous sclerosis or lymphangioleiomyomatosis. We believe that this report is one of the first descriptions of angiomyolipoma of the lung.

Classification for predicting mediastinal lymph node metastases in patients with T1 or T2 lung cancer.

The aim of this study is to classify patients into risk groups for mediastinal lymph node metastases. Three hundred and thirty-seven patients underwent lung resection for lung cancer. The nodal status was pN0 in 181 patients, pN1 in 62 and pN2 in 94. The presence of the involvement of one mediastinal compartment (superior or inferior) or two mediastinal compartments (superior and inferior) was considered to be the main end point. One mediastinal compartment was involved in 65 patients and two mediastinal compartments in 29 patients. Two variables (visceral pleural invasion and the primary tumor location) were retained in the model. The regression tree analysis categorized patients into 3 risk groups for the involvement of two mediastinal compartments. The low-risk group included 118 patients with a tumor located in the left side and no visceral pleural invasion. The intermediate-risk group included 160 patients with a tumor located in the right side and no visceral pleural invasion. The high-risk group included 59 patients with visceral pleural invasion and a tumor located in the right side or left lower lobe. A practical, easy-to-use risk grouping system is proposed to aid the decision making and to simplify mediastinal lymphadenectomy procedure.

Complete tracheal rupture after a failed suicide attempt.

Tracheal rupture is life-threatening and its management poses a considerable challenge to both anesthesiologists and surgeons. We report the case of a 44-year-old patient with a complete tracheal rupture after a failed suicide attempt by hanging. A rare bilateral injury of the laryngeal nerves was associated. An original tracheal intubation was performed using the video unit for thoracoscopy. The severity of the lesions required the placement of a tracheostomy cannula after the tracheal repair. The postoperative course was uneventful. The patient was discharged on the 12th day, with a remaining moderate dysphonia.

Clinical experience and Doppler echocardiographic assessment of the first one hundred ATS AP (advanced performance) prosthetic valve in the aortic position.

BACKGROUND AND AIM OF THE STUDY: The ATS Medical mechanical bileaflet valve is composed of pyrolitic carbon and is available in two forms: Standard and Advanced Performance. The study aim was to evaluate the clinical results and define, in blinded manner, the Doppler echocardiographic characteristics of normally functioning ATS AP prostheses with respect to their size. METHODS: One hundred patients (63 men, 37 women; mean age 63.6 +/- 10.6 years) were studied between January 1996 and February 1999. Doppler echocardiography was performed at least three months after valve replacement (mean 1.68 +/- 0.86 months; range: 3 months to 3 years). RESULTS: The in-hospital mortality was 3%, and there were four late deaths. None of the deaths was valve-related. Thromboembolic and anticoagulant-related hemorrhagic rates were 0.55% per patient-year (pt-yr) and 1.1% per pt-yr, respectively. Maximum and mean gradients were calculated using the simplified Bernoulli equation. Functional valve surface area was assessed using the continuity equation and time-velocity integrals using echographic measurements to calculate the subaortic surface. The Doppler velocity index was obtained from the ratio of subaortic and transaortic velocities. For the most frequently used aortic valve (22 mm), the maximum pressure gradient was 18.67 +/- 8.31 mmHg, the mean gradient 9.97 +/- 3.84 mmHg, functional surface area 1.50 +/- 0.35 cm2, and Doppler velocity index 0.41 +/- 0.08. CONCLUSION: Based on Doppler echocardiographic characteristics, the new ATS Medical AP prosthesis, when implanted in the aortic position, has an excellent hemodynamic profile which compares favorably with that of similarly designed prostheses. The clinical results show a very low rate of thromboembolic and anticoagulant-related hemorrhagic events, perhaps due to the new design of the pivoting area.