Indeterminate Nodules Research Articles

Pathomic Features Reveal Immune and Molecular Evolution From Lung Preneoplasia to Invasive Adenocarcinoma

Recent statistics on lung cancer, including the steady decline of advanced diseases and the dramatically increasing detection of early-stage diseases and indeterminate pulmonary nodules, mark the significance of a comprehensive understanding of early lung carcinogenesis. Lung adenocarcinoma (ADC) is the most common histologic subtype of lung cancer, and atypical adenomatous hyperplasia is the only recognized preneoplasia to ADC, which may progress to adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) and eventually to invasive ADC. Although molecular evolution during early lung carcinogenesis has been explored in recent years, the progress has been significantly hindered, largely due to insufficient materials from ADC precursors. Here, we employed state-of-the-art deep learning and artificial intelligence techniques to robustly segment and recognize cells on routinely used hematoxylin and eosin histopathology images and extracted 9 biology-relevant pathomic features to decode lung preneoplasia evolution. We analyzed 3 distinct cohorts (Japan, China, and United States) covering 98 patients, 162 slides, and 669 regions of interest, including 143 normal, 129 atypical adenomatous hyperplasia, 94 AIS, 98 MIA, and 205 ADC. Extracted pathomic features revealed progressive increase of atypical epithelial cells and progressive decrease of lymphocytic cells from normal to AAH, AIS, MIA, and ADC, consistent with the results from tissue-consuming and expensive molecular/immune profiling. Furthermore, pathomics analysis manifested progressively increasing cellular intratumor heterogeneity along with the evolution from normal lung to invasive ADC. These findings demonstrated the feasibility and substantial potential of pathomics in studying lung cancer carcinogenesis directly from the low-cost routine hematoxylin and eosin staining.

Artificial intelligence in the diagnosis of thyroid cancer: Recent advances and future directions

The diagnosis and management of thyroid cancer is fraught with challenges despite the advent of innovative diagnostic, surgical, and chemotherapeutic modalities. Challenges like inaccuracy in prognostication, uncertainty in cytopathological diagnosis, trouble in differentiating follicular neoplasms, intra-observer and inter-observer variability on ultrasound imaging preclude personalised treatment in thyroid cancer. Artificial intelligence (AI) is bringing a paradigm shift to the healthcare, powered by quick advancement of the analytic techniques. Several recent studies have shown remarkable progress in thyroid cancer diagnostics based on AI-assisted algorithms. Application of AI techniques in thyroid ultrasonography and cytopathology have shown remarkable impro-vement in sensitivity and specificity over the traditional diagnostic modalities. AI has also been explored in the development of treatment algorithms for indeterminate nodules and for prognostication in the patients with thyroid cancer. The benefits of high repeatability and straightforward implementation of AI in the management of thyroid cancer suggest that it holds promise for clinical application. Limited clinical experience and lack of prospective validation studies remain the biggest drawbacks. Developing verified and trustworthy algorithms after extensive testing and validation using prospective, multi-centre trials is crucial for the future use of AI in the pipeline of precision medicine in the management of thyroid cancer.

The histologic outcomes of indeterminate thyroid nodules with rat sarcoma mutations: A case series.

Molecular testing is an adjunct test for thyroid fine needle aspirations with indeterminate diagnoses, with certain mutations showing a greater risk of malignancy (ROM). Rat sarcoma (RAS) point mutations are the most common alterations in indeterminate thyroid nodules. While they can have a high ROM, they are also found in benign disease. This study describes the histologic outcomes of indeterminate nodules with RAS mutations. Bethesda III and IV thyroid nodules with ThyroSeq results showing RAS mutations (NRAS, KRAS, and HRAS) were identified between November 1, 2018 and February 28, 2023. Baseline patient characteristics, ThyroSeq results, and surgical diagnoses were collected. We identified 18 nodules with RAS mutations from 17 patients. Fourteen were NRAS (isolated NRAS in 6; NRAS with other abnormalities [NRAS+] in 8); one was isolated KRAS; and three were HRAS with other abnormalities (HRAS+). NRAS Q16R was the most common amino acid change. Twelve cases had follow-up. Two were malignant, a minimally invasive follicular carcinoma (NRAS+) and a papillary thyroid carcinoma, follicular variant (HRAS+). Three were noninvasive follicular thyroid neoplasms with papillary-like nuclear features (NIFTP), 2 HRAS+ and 1 NRAS+. Four were follicular adenomas, one being atypical (3 NRAS+ and one isolated NRAS). One was an oncocytic adenoma (isolated NRAS). Two were nodular hyperplasias (isolated NRAS and NRAS+, respectively). Twenty-eight percent of our RAS-mutated nodules were malignant or NIFTP. All three HRAS-mutated nodules were malignant or NIFTP. The three isolated RAS mutations with follow up were benign (adenomas or nodular hyperplasia). These findings were in line with the literature.

Diagnostic values of nuclear score combined with cyclin D1 immunocytochemistry in indeterminate thyroid follicular nodules in preoperative fine needle aspiration

Objective: To assess the feasibility of nuclear score combined with cyclin D1 immunocytochemistry in classifying indeterminate thyroid nodules with fine-needle aspiration (FNA) cytological diagnosis of Bethesda category Ⅲ-Ⅴ. Methods: A consecutive cohort of 118 thyroid FNA specimens with indeterminate diagnosis (TBSRTC category Ⅲ-Ⅴ) and available histopathologic follow-up data were collected between December 2018 and April 2022 at the Department of Pathology, Beijing Hospital, China. These cases were subjected to cytological evaluation and cyclin D1 immunocytochemistry. The optimal cut-off points of a simplified nuclear score and the percentage of cyclin D1-positive cells for the diagnosis of malignancy or low-risk neoplasm were determined using the receiver operating characteristic (ROC) curves and area under the ROC curve (AUC). The specificity, sensitivity, positive predictive value (PPV) and negative predictive value (NPV) of nuclear score and cyclin D1 immunostaining were evaluated from the crosstabs based on cut-off points. The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining was estimated using ROC curve analysis. Results: Nuclear grooves, intra-nuclear inclusions and chromatin clearing were more commonly found in malignancy/low-risk neoplasms than benign lesions (P=0.001, P=0.012 and P=0.001 respectively). A cut-off point of≥2 for the simplified nuclear score was sensitive for defining malignancy/low-risk neoplasm, and its PPV, NPV, sensitivity and specificity were 93.6%, 87.5%, 99.0% and 50.0% respectively. A positive cut-off point of 10% positive thyroid cells in cyclin D1 immunostaining demonstrated sensitivity of 88.5%, specificity of 100%, PPV of 100% and NPV of 53.8% for correctly detecting thyroid malignancy or low-risk neoplasm. The sensitivity and PPV of simplified nuclear score combined with cyclin D1 immunostaining were 93.3% and 100%, respectively. Both specificity and NPV were maintained at high levels (100% and 66.7%, respectively). The diagnostic accuracy of simplified nuclear score combined with cyclin D1 immunostaining in detecting thyroid malignancy/low-risk neoplasm was increased to 94.1% compared to using either of them alone. Conclusions: Combing simplified nuclear score and cyclin D1 immunostaining on FNA cytology specimens can increase the diagnostic accuracy in classifying thyroid nodules of indeterminate cytological categories. Thus, this supplementary approach provides a simple, accurate, and convenient diagnostic method for cytopathologists so that may reduce unnecessary thyroidectomies.

Multi-Omic Biomarkers Improve Indeterminate Pulmonary Nodule Malignancy Risk Assessment.

The clinical management of patients with indeterminate pulmonary nodules is associated with unintended harm to patients and better methods are required to more precisely quantify lung cancer risk in this group. Here, we combine multiple noninvasive approaches to more accurately identify lung cancer in indeterminate pulmonary nodules. We analyzed 94 quantitative radiomic imaging features and 41 qualitative semantic imaging variables with molecular biomarkers from blood derived from an antibody-based microarray platform that determines protein, cancer-specific glycan, and autoantibody-antigen complex content with high sensitivity. From these datasets, we created a PSR (plasma, semantic, radiomic) risk prediction model comprising nine blood-based and imaging biomarkers with an area under the receiver operating curve (AUROC) of 0.964 that when tested in a second, independent cohort yielded an AUROC of 0.846. Incorporating known clinical risk factors (age, gender, and smoking pack years) for lung cancer into the PSR model improved the AUROC to 0.897 in the second cohort and was more accurate than a well-characterized clinical risk prediction model (AUROC = 0.802). Our findings support the use of a multi-omics approach to guide the clinical management of indeterminate pulmonary nodules.

Circulating proteome for pulmonary nodule malignancy.

Although lung cancer screening with low-dose computed tomography is rolling out in many areas of the world, differentiating indeterminate pulmonary nodules remains a major challenge. We conducted one of the first systematic investigations of circulating protein markers to differentiate malignant from benign screen-detected pulmonary nodules. Based on 4 international low-dose computed tomography screening studies, we assayed 1078 protein markers using prediagnostic blood samples from 1253 participants based on a nested case-control design. Protein markers were measured using proximity extension assays, and data were analyzed using multivariable logistic regression, random forest, and penalized regressions. Protein burden scores (PBSs) for overall nodule malignancy and imminent tumors were estimated. We identified 36 potentially informative circulating protein markers differentiating malignant from benign nodules, representing a tightly connected biological network. Ten markers were found to be particularly relevant for imminent lung cancer diagnoses within 1 year. Increases in PBSs for overall nodule malignancy and imminent tumors by 1 standard deviation were associated with odds ratios of 2.29 (95% confidence interval: 1.95 to 2.72) and 2.81 (95% confidence interval: 2.27 to 3.54) for nodule malignancy overall and within 1 year of diagnosis, respectively. Both PBSs for overall nodule malignancy and for imminent tumors were substantially higher for those with malignant nodules than for those with benign nodules, even when limited toLung Computed Tomography Screening Reporting and Data System (LungRADS) category 4 (P < .001). Circulating protein markers can help differentiate malignant from benign pulmonary nodules. Validation with an independent computed tomographic screening study will be required before clinical implementation.

Diagnostic performance of ultrasound risk stratification systems on thyroid nodules cytologically classified as indeterminate: a systematic review and meta-analysis.

Ultrasound (US) risk stratification systems (RSSs) are increasingly being utilized for the optimal management of thyroid nodules, including those with indeterminate cytology. The goal of this study was to evaluate the category-based diagnostic performance of US RSSs in identifying malignancy in indeterminate nodules. This systematic review and meta-analysis was registered on PROSPERO (CRD42021266195). PubMed, EMBASE, and Web of Science were searched through December 1, 2022. Original articles reporting data on the performance of US RSSs for indeterminate nodules were included. The numbers of nodules classified as true negative, true positive, false negative, and false positive were extracted. Thirty-three studies evaluating 7,225 indeterminate thyroid nodules were included. The diagnostic accuracy was quantitatively synthesized using a Bayesian bivariate model based on the integrated nested Laplace approximation in R. For the intermediate- to high-risk category, the sensitivity levels of the American College of Radiology, the American Thyroid Association, the European Thyroid Association, the Korean Thyroid Association/Korean Society of Thyroid Radiology, and Kwak et al. were found to be 0.80, 0.72, 0.76, 0.96, and 0.97, respectively. The corresponding specificity measurements were 0.36, 0.50, 0.49, 0.28, and 0.17. Furthermore, for the high-risk category, the sensitivity values were 0.40, 0.46, 0.55, 0.47, and 0.10, while the specificity levels were 0.91, 0.90, 0.71, 0.91, and 0.99, respectively. The overall diagnostic performance of the US RSSs was moderate in the differentiation of indeterminate nodules.

The Thoracic Research Evaluation and Treatment 2.0 Model: A Lung Cancer Prediction Model for Indeterminate Nodules Referred for Specialist Evaluation

Appropriate risk stratification of indeterminate pulmonary nodules (IPNs) is necessary to direct diagnostic evaluation. Currently available models were developed in populations with lower cancer prevalence than that seen in thoracic surgery and pulmonology clinics and usually do not allow for missing data. We updated and expanded the Thoracic Research Evaluation and Treatment (TREAT) model into a more generalized, robust approach for lung cancer prediction in patients referred for specialty evaluation. Can clinic-level differences in nodule evaluation be incorporated to improve lung cancer prediction accuracy in patients seeking immediate specialty evaluation compared with currently available models? Clinical and radiographic data on patients with IPNs from six sites (N= 1,401) were collected retrospectively and divided into groups by clinical setting: pulmonary nodule clinic (n= 374; cancer prevalence, 42%), outpatient thoracic surgery clinic (n= 553; cancer prevalence, 73%), or inpatient surgical resection (n= 474; cancer prevalence, 90%). A new prediction model was developed using a missing data-driven pattern submodel approach. Discrimination and calibration were estimated with cross-validation and were compared with the original TREAT, Mayo Clinic, Herder, and Brock models. Reclassification was assessed with bias-corrected clinical net reclassification index and reclassification plots. Two-thirds of patients had missing data; nodule growth and fluorodeoxyglucose-PET scan avidity were missing most frequently. The TREAT version 2.0 mean area under the receiver operating characteristic curve across missingness patterns was 0.85 compared with that of the original TREAT (0.80), Herder (0.73), Mayo Clinic (0.72), and Brock (0.68) models with improved calibration. The bias-corrected clinical net reclassification index was 0.23. The TREAT 2.0 model is more accurate and better calibrated for predicting lung cancer in high-risk IPNs than the Mayo, Herder, or Brock models. Nodule calculators such as TREAT 2.0 that account for varied lung cancer prevalence and that consider missing data may provide more accurate risk stratification for patients seeking evaluation at specialty nodule evaluation clinics.

The presence of circulating genetically abnormal cells in blood predicts risk of lung cancer in individuals with indeterminate pulmonary nodules

PurposeComputed tomography is the standard method by which pulmonary nodules are detected. Greater than 40% of pulmonary biopsies are not lung cancer and therefore not necessary, suggesting that improved diagnostic tools are needed. The LungLB™ blood test was developed to aid the clinical assessment of indeterminate nodules suspicious for lung cancer. LungLB™ identifies circulating genetically abnormal cells (CGACs) that are present early in lung cancer pathogenesis.MethodsLungLB™ is a 4-color fluorescence in-situ hybridization assay for detecting CGACs from peripheral blood. A prospective correlational study was performed on 151 participants scheduled for a pulmonary nodule biopsy. Mann-Whitney, Fisher’s Exact and Chi-Square tests were used to assess participant demographics and correlation of LungLB™ with biopsy results, and sensitivity and specificity were also evaluated.ResultsParticipants from Mount Sinai Hospital (n = 83) and MD Anderson (n = 68), scheduled for a pulmonary biopsy were enrolled to have a LungLB™ test. Additional clinical variables including smoking history, previous cancer, lesion size, and nodule appearance were also collected. LungLB™ achieved 77% sensitivity and 72% specificity with an AUC of 0.78 for predicting lung cancer in the associated needle biopsy. Multivariate analysis found that clinical and radiological factors commonly used in malignancy prediction models did not impact the test performance. High test performance was observed across all participant characteristics, including clinical categories where other tests perform poorly (Mayo Clinic Model, AUC = 0.52).ConclusionEarly clinical performance of the LungLB™ test supports a role in the discrimination of benign from malignant pulmonary nodules. Extended studies are underway.

Molecular Testing for Indeterminate Nodules: Is It Necessary? Counterpoint: It Is Not Necessary

Molecular Testing for Indeterminate Nodules: Is It Necessary? Counterpoint: It Is Not Necessary

Evaluation of the Appropriateness of Thyroid Fine-Needle Aspiration

This study aims to perform an integrative literature review on FNAB of the thyroid and its current contributions facing thyroid nodules, as an important diagnostic tool to eliminate early thyroid cancer, a recurrent pathology in offices. Regarding the methods, because this is an integrative review of literature, through a descriptive study, we used databases such as Medical Literature Analysis and Retrieval System Online (Medline/PubMed), Scientific Electronic Library Online (SciELO) and Virtual Health Library (VHL). The query was performed using the controlled descriptors from DeCS/MeSH: "thyroid nodule", "fine needle biopsy", "thyroid", "liquid-based cytology", "molecular test". Moreover, as a result we obtained a general review about the appropriateness of FNAB of the thyroid, an efficient and reliable diagnostic method in the decision and selection of patients who will need surgery. However, this method presents some limitations, such as the need for improvement in the quality of the sample collection or in its interpretation, limitations that can be reduced, decreasing the cases of false positives and negatives, when collected by experienced professionals, guided by ultrasound, and can be combined with color Doppler, as well as, seek opinions from other specialists. The present study also addressed the new diagnostic methods for thyroid nodules, such as liquid-based cytology, used as a technique in conjunction with conventional smears when ancillary techniques are applied, and molecular tests, which have given professionals the opportunity to provide a more accurate evaluation in cases of indeterminate nodules. With this, we reiterate the importance of identifying the best individualized strategy for the patient, preventing unnecessary procedures and offering improved quality of life.

A high-resolution transcriptomic atlas depicting nitrogen fixation and nodule development in soybean.

Although root nodules are essential for biological nitrogen fixation in legumes, the cell types and molecular regulatory mechanisms contributing to nodule development and nitrogen fixation in determinate nodule legumes, such as soybean (Glycine max), remain incompletely understood. Here, we generated a single-nucleus resolution transcriptomic atlas of soybean roots and nodules at 14 days post inoculation (dpi) and annotated 17 major cell types, including six that are specific to nodules. We identified the specific cell types responsible for each step in the ureides synthesis pathway, which enables spatial compartmentalization of biochemical reactions during soybean nitrogen fixation. By utilizing RNA velocity analysis, we reconstructed the differentiation dynamics of soybean nodules, which differs from those of indeterminate nodules in Medicago truncatula. Moreover, we identified several putative regulators of soybean nodulation and two of these genes, GmbHLH93 and GmSCL1, were as-yet uncharacterized in soybean. Overexpression of each gene in soybean hairy root systems validated their respective roles in nodulation. Notably, enrichment for cytokinin-related genes in soybean nodules led to identification of the cytokinin receptor, GmCRE1, as a prominent component of the nodulation pathway. GmCRE1 knockout in soybean resulted in a striking nodule phenotype with decreased nitrogen fixation zone and depletion of leghemoglobins, accompanied by downregulation of nodule-specific gene expression, as well as almost complete abrogation of biological nitrogen fixation. In summary, this study provides a comprehensive perspective of the cellular landscape during soybean nodulation, shedding light on the underlying metabolic and developmental mechanisms of soybean nodule formation.

Diagnostic follow-up of indeterminate pulmonary nodules in the Medicare population.

Management of indeterminate pulmonary nodules (IPNs) is associated with redistribution of lung cancer to earlier stages, but most subjects with IPNs do not have lung cancer. The burden of IPN management in Medicare recipients was assessed. Surveillance, Epidemiology, and End Results-Medicare data were analyzed for IPNs, diagnostic procedures, and lung cancer status. IPNs were defined as chest computed tomography (CT) scans with accompanying International Classification of Diseases (ICD) codes of 793.11 (ICD-9) or R91.1 (ICD-10). Two cohorts were defined: persons with IPNs during 2014-2017 comprised the IPN cohort, whereas those with chest CT scans without IPNs during 2014-2017 comprised the control cohort. Excess rates of various procedures due to reported IPNs over 2 years of follow-up (chest CT, positron emission tomography [PET]/PET-CT, bronchoscopy, needle biopsy, and surgical procedures) were estimated using multivariable Poisson regression models comparing the cohorts adjusted for covariates. Prior data on stage redistribution associated with IPN management were then used to define a metric of excess procedures per late-stage case avoided. Totals of 19,009 and 60,985 subjects were included in the IPN and control cohorts, respectively; 3.6% and 0.8% had lung cancer during follow-up. Excess procedures per 100 persons with IPNs over a 2-year follow-up were 63, 8.2, 1.4, 1.9, and 0.9 for chest CT, PET/PET-CT, bronchoscopy, needle biopsy, and surgery, respectively. Corresponding excess procedures per late-stage case avoided were 48, 6.3, 1.1, 1.5, and 0.7 based on an estimated 1.3 late-stage cases avoided per 100 IPN cohort subjects. The metric of excess procedures per late-stage case avoided can be used to measure the benefits-to-harms tradeoff of IPN management.

Comparison of surgical completeness in patients operated on conventional open total thyroidectomy (OT) or trans-axillary robot-assisted total thyroidectomy (RATT) by a single axillary approach.

Trans-axillary robot-assisted total thyroidectomy (RATT) is nowadays worldwide accepted but the completeness obtained by RATT is still debated. The Aim of this study was to compare the completeness and safety of RATT with conventional open thyroidectomy (OT). We enrolled patients with nontoxic multinodular goiter, cytologically indeterminate nodules and well differentiated thyroid cancer without local and/or distant metastasis. In all cases the biggest nodule should be < 6cm. The surgical completeness was evaluated by means of serum thyroglobulin (hs-Tg) and neck ultrasound (nUS) performed three months postoperatively. 100 patients underwent either RATT or OT. The type of surgical procedure was chosen by patients. They were then divided in two subgroups based on benign or malignant histology. There were no significant differences in the postoperatively values of hs-Tg in patients operated with RATT or OT, both in benign and malignant subgroups. The post-operative thyroid remnant volume estimated by nUS was not significantly different between the two groups, both in benign and malignant subgroups. We also analyzed the difference of the volume of the thyroid remnant ipsilateral to the axillary access vs that of the remnant on the contralateral side and there was not significantly difference in both subgroups. RATT was demonstrated to determine a comparable surgical completeness as OT, both in benign and malignant thyroid diseases, with no differences in the prevalence of surgical complications. In our hands the surgical completeness of RATT by a single trans-axillary was satisfying.

Ultrasound Parameters Can Accurately Predict the Risk of Malignancy in Patients with "Indeterminate TIR3b" Cytology Nodules: A Prospective Study.

The increase in the incidence of thyroid nodules with cytological findings of TIR3b requires the identification of predictive factors of malignancy. We prospectively evaluated 2160 patients from January 2018 to June 2022 and enrolled 103 patients with indeterminate cytology TIR3b nodules who underwent total (73 patients) and hemi-thyroidectomy (30 patients). Among them, 61 had a histological diagnosis of malignancy (30 classic papillary thyroid carcinoma, 19 had follicular papillary thyroid carcinoma variant, 3 had Hurtle cell carcinoma and 9 had follicular thyroid carcinoma), while 42 had a benign histology. Clinical, ultrasonographic and cytological characteristics were recorded. In addition, BRAF mutation was analysed. Patients with a histological diagnosis of malignancy had a higher frequency of nodule diameter ≤11 mm (p = 0.002), hypoechogenicity (p < 0.001), irregular borders (p < 0.001), peri- and intralesional vascular flows (p = 0.004) and microcalcifications (p = 0.001) compared to patients with benign histology. In contrast, patients with benign histology had more frequent nodules with a halo sign (p = 0.012) compared to patients with histological diagnosis of malignancy. No significant differences were found in BRAF mutation between the two groups. Our study suggests that the combination of ultrasonographic and cytological data could be more accurate and reliable than cytology alone in identifying those patients with TIR3b cytology and a histology of malignancy to be referred for thyroidectomy, thus reducing the number of patients undergoing thyroidectomy for benign thyroid disease.

Improving the surgical indication of the Indeterminate TIR3B nodules: a prediction model based on clinical, ultrasound and cytological features

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Abstract #1412022: A Rare Case of Multiple Endocrine Neoplasia Type 1 (MEN1) Presenting with Recurrent Abdominal Pain

MEN1 is a rare genetic disorder characterized by combined occurrence of two or more tumors involving parathyroid, anterior pituitary and the neuroendocrine tissue of gastro-entero-pancreatic organ system. We present a case of a young male with recurrent abdominal pain who was later diagnosed with MEN1 syndrome. 27-year-old male with past medical history of chronic abdominal pain presented for an episode of acute upper abdominal pain which was constant and worsened with any movement or palpation. His family history was significant for father having parathyroid disorder and skin lesions. On examination, he was ill appearing with tachycardia, multiple skin lesions and tenderness in upper abdomen. Labs were significant for leukocytosis and hypercalcemia (corrected level 10.5 mg/dl). Rest of the electrolytes, kidney function, liver enzymes and lipase were normal. Computed tomography (CT) abdomen showed inflammatory changes and thickening along the distal stomach/proximal duodenum with scattered free air, concerning for a perforated ulcer. Indeterminate bilateral adrenal nodules were also noted. Patient underwent emergent exploratory laparotomy and was noted to have small perforation in the anterior proximal portion of the duodenum which was repaired. Post-operatively, work up for persistent hypercalcemia revealed parathyroid hormone levels of 152 pg/ml and 25-hydroxy vitamin D of 13.7 ng/ml. He was diagnosed with primary hyperparathyroidism and upon stabilization, discharged with plan for outpatient follow-up. After few months, he had another admission due to worsening epigastric pain. Repeat CT abdomen showed multiple pancreatic lesions involving head, tail and uncinate process and stable adrenal nodules. Presence of pancreatic lesions, gastric ulcers, hyperparathyroidism, adrenal nodules, and multiple skin lesions raised concern of MEN1. Further evaluation showed elevated gastrin level (633 pg/ml), chromogranin level (2464 ng/mL) and mildly elevated prolactin. Rest of pituitary and adrenal axis hormone levels were normal. MEN1 gene testing was positive. No pituitary lesion was identified on magnetic resonance imaging brain. He underwent subtotal parathyroidectomy and cervical thymectomy. He was continued on twice daily pantoprazole and was discharged home in stable condition. MEN1 tumor types and age of tumor onset can differ significantly, and tumors become evident either by hormonal overproduction or by tumor growth. There are no genotype phenotype correlations, even within the same family. Pharmacological therapies to suppress hypersecretion are often first line and can be successful in up to 50% patients. Surgery is an option for patients with hypersecretion unresponsive to medical therapy, compression of the optic nerves and/or chiasma endangering vision or when there is uncertainty of diagnosis requiring biopsy. MEN1 is linked with higher mortality. Approximately 70% of the MEN1 deaths are due to thymic neuroendocrine tumors (NETs) and duodenopancreatic-NETs. Early diagnosis of tumors with appropriate interventions can significantly improve patient survival.

Management And Assessment Of Indeterminate (U3) Thyroid Nodules: A 5-Year Multisite Retrospective Study.

The U grading of Ultrasound scan (USS) is used to assess the likelihood of malignancy in a thyroid nodule and help determine those that warrant an FNAC confirmation. All those of a U3-5 warrant an FNAC for confirmation and typing. This study aims to review the follow-up practice and the likelihood of picking up a malignancy on subsequent USS and FNAC, for those determined as an indeterminate U3 nodule. We retrospective reviewed the trust database (Portal) for patients who had a U3 nodule reported on USS identified, and clinical, operative and outcomes data were analysed. 258 scans were identified over a 5-year period. The average age was 59 (range 15- 95) years old at first USS with a female to the male sex ratio of 4:1. The average number of USS that each patient prior to final diagnosis had averaged at 2.8 (range 1-12). Of those with an initial Thy status, 64 (33%) were benign (Thy2) and a further 49 (25%) were non diagnostics (Thy1). Over time, only 7 nodules were upgraded to a potential malignancy. Of those who underwent surgery, a final histological diagnosis was obtained in 41 cases. Only Thy1, 2 and 3f produced benign final histology results. For those indeterminate (U3) nodules of Th1-3f, electing for a watch and wait management strategy is reasonable for up to 2.5 years and 4 follow-up scans at an interval of 6-12 months should be implemented. A Thy2 result on a U3 nodule should not be taken as completely reassuring, a high index of suspicion of malignancy must be maintained.

Longitudinal lung cancer prediction convolutional neural network model improves the classification of indeterminate pulmonary nodules

A deep learning model (LCP CNN) for the stratification of indeterminate pulmonary nodules (IPNs) demonstrated better discrimination than commonly used clinical prediction models. However, the LCP CNN score is based on a single timepoint that ignores longitudinal information when prior imaging studies are available. Clinically, IPNs are often followed over time and temporal trends in nodule size or morphology inform management. In this study we investigated whether the change in LCP CNN scores over time was different between benign and malignant nodules. This study used a prospective-specimen collection, retrospective-blinded-evaluation (PRoBE) design. Subjects with incidentally or screening detected IPNs 6–30 mm in diameter with at least 3 consecutive CT scans prior to diagnosis (slice thickness ≤ 1.5 mm) with the same nodule present were included. Disease outcome was adjudicated by biopsy-proven malignancy, biopsy-proven benign disease and absence of growth on at least 2-year imaging follow-up. Lung nodules were analyzed using the Optellum LCP CNN model. Investigators performing image analysis were blinded to all clinical data. The LCP CNN score was determined for 48 benign and 32 malignant nodules. There was no significant difference in the initial LCP CNN score between benign and malignant nodules. Overall, the LCP CNN scores of benign nodules remained relatively stable over time while that of malignant nodules continued to increase over time. The difference in these two trends was statistically significant. We also developed a joint model that incorporates longitudinal LCP CNN scores to predict future probability of cancer. Malignant and benign nodules appear to have distinctive trends in LCP CNN score over time. This suggests that longitudinal modeling may improve radiomic prediction of lung cancer over current models. Additional studies are needed to validate these early findings.

Lung Cancer resection in the absence of pre-operative histology: The Accuracy of Multidisciplinary Team Consensus

BackgroundLung resection remains the gold-standard of treatment for non-small cell lung cancer (NSCLC). British Thoracic Society (BTS) guidelines recommends the pursuit of pre-operative histological diagnosis and staging where possible. In the absence of pre-operative histology, surgical treatment can be offered in conjunction with multidisciplinary team (MDT) and patient consensus. We undertook a single-centre analysis of the accuracy of the lung cancer MDT in recommending surgical resection for those with suspected lung malignancy in the absence of pre-operative histological diagnosis over a six-year period. MethodsA retrospective review was performed of patients undergoing any pulmonary oncological resection with therapeutic intent without pre-operative histological diagnosis at the recommendation of the lung cancer MDT in our unit between May 2016 and July 2022. Results270 consecutive patients underwent lung resection for a lung nodule of indeterminate significance. This accounted for 45% of the oncological resections performed over this period. The mean age of the cohort was 67.9 years, and 47.4% were male. Overall, 10% of resected specimens (n = 27) were benign on final histopathology. 93% of those undergoing a lobectomy received a malignant diagnosis. Across the study cohort, surgical resection was well tolerated with a low complication rate. ConclusionsLung cancer resection in the absence of pre-operative histological diagnosis is feasible in a select patient cohort. This approach requires an experienced multi-disciplinary team and careful patient counselling. Our study demonstrates this adapted approach to be a pragmatic solution to the management of indeterminate pulmonary nodules in centres where biopsy is not routinely available due to existing constraints on the health system.