Endocrinology and Metabolism

Original Articles

Thyroid Thyroid Cancer Screening
A Comprehensive Assessment of the Harms of Fine-Needle Aspiration Biopsy for Thyroid Nodules: A Systematic Review: Ji Yong Park, Wonsuk Choi, A Ram Hong, Jee Hee Yoon, Hee Kyung Kim, Ho-Cheol Kang; Endocrinol Metab. 2023;38(1):104-116. Published online February 27, 2023; DOI: https://doi.org/10.3803/EnM.2023.1669

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Background
There have concerns related with the potential harms of fine-needle aspiration biopsy (FNAB). We aimed to summarize the clinical complications and evaluate the safety of FNAB.
Methods
Studies related with the harms of FNAB were searched on MEDLINE, Embase, Cochrane library, and KoreaMed from 2012 to 2022. Also, studies reviewed in the previous systematic reviews were evaluated. Included clinical complications were postprocedural pain, bleeding events, neurological symptoms, tracheal puncture, infections, post-FNAB thyrotoxicosis, and needle tract implantation of thyroid cancers.
Results
Twenty-three cohort studies were included in this review. Nine studies which were related with FNAB-related pain showed that most of the subjects had no or mild discomfort. The 0% to 6.4% of the patients had hematoma or hemorrhage after FNAB, according to 15 studies. Vasovagal reaction, vocal cord palsy, and tracheal puncture have rarely described in the included studies. Needle tract implantation of thyroid malignancies was described in three studies reporting 0.02% to 0.19% of the incidence rate.
Conclusion
FNAB is considered to be a safe diagnostic procedure with rare complications, which are mainly minor events. Thorough assessement of the patients’ medical condition when deciding to perform FNABs would be advisable to lower potential complications.

Citations

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Thyroid
Diagnostic Performance of Thyroid Core Needle Biopsy Using the Revised Reporting System: Comparison with Fine Needle Aspiration Cytology: Kwangsoon Kim, Ja Seong Bae, Jeong Soo Kim, So Lyung Jung, Chan Kwon Jung; Endocrinol Metab. 2022;37(1):159-169. Published online February 28, 2022; DOI: https://doi.org/10.3803/EnM.2021.1299

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Background
We aim to validate the diagnostic performance of thyroid core needle biopsy (CNB) for diagnosing malignancy in clinical settings to align with the changes made in recently updated thyroid CNB guidelines.
Methods
We retrospectively analyzed 1,381 thyroid CNB and 2,223 fine needle aspiration (FNA) samples. The FNA and CNB slides were interpreted according to the Bethesda System for Reporting Thyroid Cytopathology and updated practice guidelines for thyroid CNB, respectively.
Results
Compared to FNA, CNB showed lower rates of inconclusive results: categories I (2.8% vs. 11.2%) and III (1.2% vs. 6.2%), and higher rates of categories II (60.9% vs. 50.4%) and IV (17.5% vs. 2.0%). The upper and lower bounds of the risk of malignancy (ROM) for category IV of CNB were 43.2% and 26.6%, respectively. The CNB subcategory IVb with nuclear atypia had a higher ROM than the subcategory without nuclear atypia (40%–62% vs. 23%–36%). In histologically confirmed cases, there was no significant difference in the diagnostic performance between CNB and FNA for malignancy. However, neoplastic diseases were more frequently detected by CNB than by FNA (88.8% vs. 77.6%, P=0.046). In category IV, there was no difference in unnecessary surgery rate between CNB and FNA (4.7% vs. 6.9%, P=0.6361).
Conclusion
Thyroid CNB decreased the rate of inconclusive results and showed a higher category IV diagnostic rate than FNA. The revised guidelines for thyroid CNB proved to be an excellent reporting system for assessing thyroid nodules.

Citations

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Clinical Study
Comparison of Natural Course between Thyroid Cancer Nodules and Thyroid Benign Nodules: Kyun-Jin Yun, Jeonghoon Ha, Min-Hee Kim, Ye Young Seo, Mee Kyoung Kim, Hyuk-Sang Kwon, Ki-Ho Song, Moo Il Kang, Ki-Hyun Baek; Endocrinol Metab. 2019;34(2):195-202. Published online June 24, 2019; DOI: https://doi.org/10.3803/EnM.2019.34.2.195

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Background

The natural course of thyroid cancer nodules and benign nodules is different. This study was to compare the changes in size between thyroid cancer nodules and thyroid benign nodules. The risk factors associated with the changes of thyroid cancer nodules were assessed.

Methods

This study contains retrospective observational and prospective analysis. A total of 113 patients with 120 nodules were recruited in the cancer group, and 116 patients with 119 nodules were enrolled in the benign group. Thyroid ultrasonography was performed at least two times at more than 1-year interval.

Results

The mean follow-up durations were 29.5±18.8 months (cancer group) and 31.9±15.8 months (benign group) (P=0.32). The maximum diameter change in length was 0.36±0.97 mm/year in the cancer group and –0.04±0.77 mm/year in the benign group (P<0.01). The volume was significantly increased in the cancer group compared with the benign group (0.06±0.18 mL/year vs. 0.004±0.05 mL/year, respectively, P<0.01; 26.9%±57.9%/year vs. 1.7%±26.0%/year, P<0.01). Initial maximum diameter (β=0.02, P<0.01) and initial volume (β=0.13, P<0.01) were significantly associated with volume change (mL)/year. Initial maximum standardized uptake value did not predict the nodule growth.

Conclusion

It is suggested that thyroid cancer nodules progress rapidly compared with benign nodules. Initial size and volume of nodule were independent risk factors for cancer nodule growth.

Citations

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Thyroid
A Comparison of Ultrasound-Guided Fine Needle Aspiration versus Core Needle Biopsy for Thyroid Nodules: Pain, Tolerability, and Complications: Eun Ji Jeong, Sae Rom Chung, Jung Hwan Baek, Young Jun Choi, Jae Kyun Kim, Jeong Hyun Lee; Endocrinol Metab. 2018;33(1):114-120. Published online March 21, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.1.114

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Background

To compare pain, tolerability, and complications associated with fine needle aspiration (FNA) versus core needle biopsy (CNB).

Methods

FNAs were performed using 23-gauge needles and CNBs were performed using 18-gauge double-action spring-activated needles in 100 patients for each procedure. Patients were asked to record a pain score using a 10-cm visual analog scale and procedure tolerability. Complications and number of biopsies were recorded.

Results

The median pain scores were similar for the FNA and CNB approaches during and 20 minutes after the biopsy procedures (3.7 vs. 3.6, P=0.454; 0.9 vs. 1.1, P=0.296, respectively). The procedure was tolerable in all 100 FNA patients and in 97 CNB patients (P=0.246). The mean number of biopsies was fewer in the CNB group (1.4 vs. 1.2, P=0.002). By subgroup analysis (staff vs. non-staff), no significant difference was detected in any parameter. There were no major complications in either group, but three patients who underwent CNB had minor complications (P=0.246).

Conclusion

FNA and CNB show no significant differences for diagnosing thyroid nodules in terms of pain, tolerability, or complications.

Citations

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Risk of Malignancy in Thyroid Nodules 4 cm or Larger: Uchechukwu C. Megwalu; Endocrinol Metab. 2017;32(1):77-82. Published online February 6, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.1.77

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Background

Several authors have questioned the accuracy of fine-needle aspiration cytology (FNAC) in large nodules. Some surgeons recommend thyroidectomy for nodules ≥4 cm even in the setting of benign FNAC, due to increased risk of malignancy and increased false negative rates in large thyroid nodules. The goal of our study was to evaluate if thyroid nodule size is associated with risk of malignancy, and to evaluate the false negative rate of FNAC for thyroid nodules ≥4 cm in our patient population.

Methods

This is a retrospective study of 85 patients with 101 thyroid nodules, who underwent thyroidectomy for thyroid nodules measuring ≥4 cm.

Results

The overall risk of malignancy in nodules ≥4 cm was 9.9%. Nodule size was not associated with risk of malignancy (odds ratio, 1.02) after adjusting for nodule consistency, age, and sex (P=0.6). The false negative rate for FNAC was 0%.

Conclusion

Nodule size was not associated with risk of malignancy in nodules ≥4 cm in our patient population. FNAC had a false negative rate of 0. Patients with thyroid nodules ≥4 cm and benign cytology should not automatically undergo thyroidectomy.

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Clinical Study
Molecular Diagnosis Using Residual Liquid-Based Cytology Materials for Patients with Nondiagnostic or Indeterminate Thyroid Nodules: Hyemi Kwon, Won Gu Kim, Markus Eszlinger, Ralf Paschke, Dong Eun Song, Mijin Kim, Suyeon Park, Min Ji Jeon, Tae Yong Kim, Young Kee Shong, Won Bae Kim; Endocrinol Metab. 2016;31(4):586-591. Published online November 4, 2016; DOI: https://doi.org/10.3803/EnM.2016.31.4.586

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Background

Molecular analysis for common somatic mutations in thyroid cancer can improve diagnostic accuracy of fine-needle aspiration cytology (FNAC) in the nondiagnostic or indeterminate category of thyroid nodules. In this study, we evaluated the feasibility of molecular diagnosis from residual liquid-based cytology (LBC) material after cytological diagnosis.

Methods

This prospective study enrolled 53 patients with thyroid nodules diagnosed as nondiagnostic, atypia of undetermined significance (AUS), or follicular lesion of undetermined significance (FLUS) after FNAC. DNAs and RNAs were isolated from residual LBC materials. BRAF^V600E and RAS point mutations, PAX8/peroxisome proliferator-activated receptor γ (PPARγ), RET/PTC1, and RET/PTC3 rearrangements were evaluated by real-time polymerase chain reaction and pyrosequencing.

Results

All DNAs from 53 residual LBC samples could be analysed and point mutations were detected in 10 samples (19%). In 17 AUS nodules, seven samples (41%) had point mutations including BRAF (n=4), NRAS (n=2), and KRAS (n=1). In 20 FLUS nodules, three samples (15%) had NRAS point mutations. RNA from only one FLUS nodule could be analysed for rearrangements and there was no abnormality.

Conclusion

Molecular analysis for BRAF and RAS mutations was feasible in residual LBC materials and might be useful for diagnosis of indeterminate thyroid nodules.

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Kras Gene Analysis Using Liquid-Based Cytology Specimens Predicts Therapeutic Responses and Prognosis in Patients with Pancreatic Cancer
Masahiro Itonaga, Reiko Ashida, Shin-Ichi Murata, Yasunobu Yamashita, Keiichi Hatamaru, Takashi Tamura, Yuki Kawaji, Yuudai Kayama, Tomoya Emori, Manabu Kawai, Hiroki Yamaue, Ibu Matsuzaki, Hirokazu Nagai, Yuichi Kinoshita, Ke Wan, Toshio Shimokawa, Masay
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From Traditional Histology to Next-Generation Pathology: A Review of The Workflow for the Characterisation and Molecular Profiling of Non-Small Cell Lung Cancer Samples

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Preanalytic variables in quality and quantity of nucleic acids extracted from FNA specimens of thyroid gland nodules collected in CytoLyt: Cellularity and storage time
Jonas J. Heymann, Lorene M. Yoxtheimer, Hyeon Jin Park, Evan M. Fernandez, Kirk E. Facey, Susan A. Alperstein, Hung V. Tran, Inji Baek, Theresa Scognamiglio, Hanna Rennert, Momin T. Siddiqui, Wei Song
Cancer Cytopathology.2020; 128(9): 656. CrossRef
Diagnostic accuracy of molecular testing with three molecular markers on thyroid fine‐needle aspiration cytology with abnormal category
Hatice Seneldir, Gozde Kir, Tuce Soylemez, Rabia B. Girgin, Nurver Ozbay, Filiz Ozen, Handan Ankarali, Gurhan Bas, Orhan Alimoglu
Diagnostic Cytopathology.2020; 48(6): 507. CrossRef
Small but powerful: the promising role of small specimens for biomarker testing
Qiong Gan, Sinchita Roy-Chowdhuri
Journal of the American Society of Cytopathology.2020; 9(5): 450. CrossRef
Centrifuged supernatants from FNA provide a liquid biopsy option for clinical next‐generation sequencing of thyroid nodules
Wenrui Ye, Brette Hannigan, Stephanie Zalles, Meenakshi Mehrotra, Bedia A. Barkoh, Michelle D. Williams, Maria E. Cabanillas, Beth Edeiken‐Monroe, Peter Hu, Dzifa Duose, Ignacio I. Wistuba, L. Jeffrey Medeiros, John Stewart, Rajyalakshmi Luthra, Sinchita
Cancer Cytopathology.2019; 127(3): 146. CrossRef
Molecular testing of residual cytology samples: Rethink, reclaim, repurpose
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K-ras mutation analysis of residual liquid-based cytology specimens from endoscopic ultrasound-guided fine needle aspiration improves cell block diagnosis of pancreatic ductal adenocarcinoma
Yoko Sekita-Hatakeyama, Takeshi Nishikawa, Mao Takeuchi, Kouhei Morita, Maiko Takeda, Kinta Hatakeyama, Tokiko Nakai, Tomoko Uchiyama, Hiroe Itami, Tomomi Fujii, Akira Mitoro, Masayuki Sho, Chiho Ohbayashi, Giancarlo Troncone
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Comparison of Immunohistochemistry and Direct Sanger Sequencing for Detection of theBRAFV600EMutation in Thyroid Neoplasm
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Next-Generation Sequencing Identifies Gene Mutations That Are Predictive of Malignancy in Residual Needle Rinses Collected From Fine-Needle Aspirations of Thyroid Nodules
Maren Y. Fuller, Dina Mody, April Hull, Kristi Pepper, Heather Hendrickson, Randall Olsen
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Loss of c-KIT expression in thyroid cancer cells
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Thyroid
The Validity of Ultrasonography-Guided Fine Needle Aspiration Biopsy in Thyroid Nodules 4 cm or Larger Depends on Ultrasonography Characteristics: Jin Hwa Kim, Na Kyung Kim, Young Lyun Oh, Hye Jeong Kim, Sang Yong Kim, Jae Hoon Chung, Sun Wook Kim; Endocrinol Metab. 2014;29(4):545-552. Published online December 29, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.4.545

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Background

The objective of this study was to evaluate the validity of fine needle aspiration biopsy (FNAB) according to ultrasonography (US) characteristics in thyroid nodules 4 cm and larger.

Methods

We retrospectively reviewed the cases of 263 patients who underwent thyroid surgery for thyroid nodules larger than 4 cm between January 2001 and December 2010.

Results

The sensitivity of US-FNAB was significantly higher in nodules with calcifications (micro- or macro-) than those without (97.9% vs. 87.% P<0.05). The accuracy of US-FNAB was higher in large thyroid nodules with US features suspicious of malignancy, such as a solid component, ill-defined margin, hypoechogenicity or marked hypoechogenicity, or any calcifications (micro- or macro-) compared to thyroid nodules with none of these features. Furthermore, the accuracy improved as the number of these features increased. The overall false negative rate (FNR) was 11.9%. The FNR of thyroid nodules that appeared benign on US, such as mixed nodules (7.7%) or nodules without calcification (9.8%), trended toward being lower than that of solid nodules (17.9%) or nodules with any microcalcification or macrocalcification (33.3%). In nodules without suspicious features of malignancy, the FNR of US-FNAB was 0% (0/15).

Conclusion

We suggest individualized strategies for large thyroid nodules according to US features. Patients with benign FNAB can be followed in the absence of any malignant features in US. However, if patients exhibit any suspicious features, potential false negative results of FNAB should be kept in mind and surgery may be considered.

Citations

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The Effect of Thyroid Nodule Size and Characteristics on the Accuracy of Fine-Needle Aspiration Biopsy and the Risk of Malignancy
Mehmet Alperen Avcı, Can Akgün, Mustafa Gün, Selim Tamam, Meltem Türk
Hitit Medical Journal.2024; 6(3): 321. CrossRef
Risk of malignancy and diagnostic accuracy of fine-needle aspiration biopsy in thyroid nodules with diameters greater than 4 centimeters
Rafaela N. Barcelos, Cléber P. Camacho, Maria da Conceição de O. C. Mamone, Elza S. Ikejiri, Felipe A. B. Vanderlei, Ji H. Yang, Rosália P. Padovani, Leandro A. L. Martins, Rosa Paula M. Biscolla, Danielle Macellaro, Susan C. Lindsey, Rui M. B. Maciel, Jo
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The comparison of accuracy of ultrasonographic features versus ultrasound-guided fine-needle aspiration cytology in diagnosis of malignant thyroid nodules
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Journal of Ultrasound.2019; 22(3): 315. CrossRef
False negative rate of fine‐needle aspiration in thyroid nodules: impact of nodule size and ultrasound pattern
Hye Shin Ahn, Dong Gyu Na, Jung Hwan Baek, Jin Yong Sung, Ji‐Hoon Kim
Head & Neck.2019; 41(4): 967. CrossRef
Thyroid nodules over 4 cm do not have higher malignancy or benign cytology false-negative rates
Muhammed Kizilgul, Rupendra Shrestha, Angela Radulescu, Maria R. Evasovich, Lynn A. Burmeister
Endocrine.2019; 66(2): 249. CrossRef
Large Cytologically Benign Thyroid Nodules Do Not Have High Rates of Malignancy or False-Negative Rates and Clinical Observation Should be Considered: A Meta-Analysis
Nicole A. Cipriani, Michael G. White, Peter Angelos, Raymon H. Grogan
Thyroid®.2018; 28(12): 1595. CrossRef
Risk of Malignancy in Thyroid Nodules 4 cm or Larger
Uchechukwu C. Megwalu
Endocrinology and Metabolism.2017; 32(1): 77. CrossRef
Usefulness of NRAS codon 61 mutation analysis and core needle biopsy for the diagnosis of thyroid nodules previously diagnosed as atypia of undetermined significance
Eun Kyung Jang, Won Gu Kim, Eui Young Kim, Hyemi Kwon, Yun Mi Choi, Min Ji Jeon, Jung Hwan Baek, Jeong Hyun Lee, Tae Yong Kim, Young Kee Shong, Jene Choi, Dong Eun Song, Won Bae Kim
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Thyroid
Insufficient Experience in Thyroid Fine-Needle Aspiration Leads to Misdiagnosis of Thyroid Cancer: Jung Il Son, Sang Youl Rhee, Jeong-taek Woo, Won Seo Park, Jong Kyu Byun, Yu-Jin Kim, Ja Min Byun, Sang Ouk Chin, Suk Chon, Seungjoon Oh, Sung Woon Kim, Young Seol Kim; Endocrinol Metab. 2014;29(3):293-299. Published online September 25, 2014; DOI: https://doi.org/10.3803/EnM.2014.29.3.293

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Background

Fine-needle aspiration (FNA) of the thyroid is a widely accepted confirmatory test for thyroid cancer with high sensitivity and specificity. FNA is a simple procedure that is learned by many clinicians to enable accurate diagnosis of thyroid cancer. However, it is assumed that because the FNA test is a relatively simple procedure, its cytologic results are reliable regardless of the operator's experience. The aim of this study was to evaluate the differences in the diagnostic indices of FNA between operators with different levels of experience.

Methods

A total of 694 thyroid FNA specimens from 469 patients were reviewed, and were separated based on the experience of the clinicians who performed the procedure. One hundred and ninety were categorized in the experienced group, and 504 in the inexperienced group. All FNA results were then compared with histological data from surgically resected specimens, and the sample adequacy and diagnostic accuracy of the groups were compared.

Results

The age, gender, and nodule size and characteristics were similar in both groups. The sample adequacy rate was not significantly different between the experienced and nonexperienced groups (96.3% vs. 95.4%, P=0.682). However, the non-experienced group had a higher false-negative rate than the experienced group (6.4% vs. 17.2%, P=0.038), and the sensitivity of the FNA test also tended to be lower in the nonexperienced group (95.6% vs. 88.9%, P=0.065).

Conclusion

These results suggest that FNA operators who have less experience may miss cases of thyroid cancer by performing the procedure incorrectly. As such, the experience of the FNA operator should be considered when diagnosing thyroid cancer. When clinicians are being trained in FNA, more effort should be made to increase the accuracy of the procedure; therefore, enhanced teaching programs and/or a more detailed feedback system are recommended.

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Review Article

Thyroid
Indications for Fine Needle Aspiration in Thyroid Nodules: Jin Young Kwak; Endocrinol Metab. 2013;28(2):81-85. Published online June 18, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.2.81

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88 Download
24 Web of Science
24 Crossref

Abstract PDF PubReader

Thyroid nodules are a common clinical problem with the widespread use of ultrasonography. Fine needle aspiration (FNA) is the mainstay for diagnosing a thyroid malignancy. There have been several guidelines on when to perform FNA in thyroid nodules. This review is based on several published recommendations and helps physicians easily understand the factors favoring FNA.

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Case Report

Thyroid
A Case of Acute Suppurative Thyroiditis with Thyrotoxicosis in an Elderly Patient: Bo Sang Kim, Kil Woo Nam, Jeong Eun Kim, Ji Hoon Park, Jun Sik Yoon, Jung Hwan Park, Sang Mo Hong, Chang Bum Lee, Yong Soo Park, Woong Hwan Choi, You Hern Ahn, Dong Sun Kim; Endocrinol Metab. 2013;28(1):50-54. Published online March 25, 2013; DOI: https://doi.org/10.3803/EnM.2013.28.1.50

10,188 View
62 Download
6 Crossref

Abstract PDF PubReader

Acute suppurative thyroiditis (AST) is a rare condition, as the thyroid gland is relatively resistant to infection. Thyroid function tests are usually normal in AST. A few cases of AST associated with thyrotoxicosis have been reported in adults. We report a case of AST that was associated with thyrotoxicosis in a 70-year-old woman. We diagnosed AST with thyroid ultrasonography and fine needle aspiration of pus. The patient improved after surgical intervention and had no anatomical abnormality. Fine needle aspiration is the best method for the difficult task of differentiating malignancy and subacute thyroiditis from AST with thyrotoxicosis. Earlier diagnosis and proper treatment for AST might improve the outcome.

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