Primary Neuroendocrine Carcinoma of the Ileum With Markedly Elevated Carcinoembryonic Antigen (CEA) Levels: A Case Report.

Neuroendocrine carcinomas (NECs) are rare and highly malignant tumors with a generally poor prognosis. Carcinoembryonic antigen (CEA) is often associated with adenocarcinoma, but its significant elevation in NEC cases is unusual. A 69-year-old man was admitted to our hospital in January 2016 due to syncope induced by anemia. The patient had a hemoglobin level of 8.0 g/dL and an ileocecal mass causing small bowel obstruction on computed tomography. His CEA level was markedly elevated at 3625.4 ng/mL. A colonoscopy revealed a neoplastic lesion in the terminal ileum, leading to an emergency ileocecal resection. Pathology confirmed a NEC, positive for synaptophysin and CEA, with a Ki-67 index of 30%. The patient was diagnosed with stage IIIb NEC (pT3N2M0). A postoperative increase in CEA to 4124.6 ng/mL and metastases in the right lung and multiple lymph nodes were detected. Initial chemotherapy with irinotecan, cisplatin (IP), and octreotide acetate proved ineffective. Subsequent octreoscans showed disease progression. Switching to everolimus as second-line therapy temporarily decreased CEA levels and tumor size, but the disease progressed with cervical lymph node involvement. The patient underwent palliative radiotherapy but succumbed to disease progression in May 2018, with a final CEA level of 36,643 ng/mL. Necropsy of the cervical lymph nodes was consistent with the original surgical findings. This case highlights the aggressive nature and challenging management of NEC with significantly elevated CEA levels.

An Increase in Aspartate Aminotransferase Can Predict Worsening Disease Severity in Japanese Patients with COVID-19.

BACKGROUND: The prognostic significance of liver dysfunction in COVID-19 patients remains unclear. In this study, we investigated the association between liver function test results and severe disease progression in COVID-19 patients. METHODS: This retrospective study included consecutive Japanese COVID-19 patients admitted between February 2020 and July 2021. Predictive variables for severe disease progression were identified by multivariate logistic regression analysis. Severe disease-free survival was estimated with the Kaplan-Meier method and Cox regression analysis. Aspartate aminotransferase (AST) was divided into three grades: grade 1, AST < 30 U/L; grade 2, 30 U/L ≤ AST < 60 U/L; and grade 3, AST > 60 U/L. RESULTS: Among 604 symptomatic patients, 141 (23.3%) developed severe disease at a median of 2 days postadmission. The median hospital stay was 10 days, and 43 patients (7.1%) died during hospitalization. Multivariate regression analysis revealed that hypertension, decreased lymphocyte count, and elevated LDH, CRP, and AST levels (grade 2 and grade 3 relative to grade 1) were the significant predictive variables. Severe disease-free survival time was significantly different between the different AST grades (hazard ratio (HR): grade 2 vs. grade 1, 4.07 (95% confidential interval (CI): 2.06-8.03); grade 3 vs. grade 1, 7.66 (95% CI: 3.89-15.1)). CONCLUSIONS: The AST level at admission was an independent risk factor for severe disease in hospitalized Japanese patients with COVID-19.

Hemorrhagic shock from gastric pseudoaneurysm post-percutaneous endoscopic gastrostomy: a case report.

Percutaneous endoscopic gastrostomy (PEG) is widely used for long-term enteral nutrition in patients unable to maintain adequate oral intake. Despite advancements in PEG techniques, complications remain a concern. We report a case of a 94-year-old bedridden man who developed significant complications after PEG placement using the pull method. Initially, minor bleeding at the puncture site was managed using traction compression. However, the patient later experienced hemorrhagic shock owing to pulsatile bleeding around the gastrostomy site. Despite attempts to control the bleeding through traction and transfusions, a pseudoaneurysm adjacent to the PEG button was identified. The patient underwent successful transcatheter arterial embolization (TAE). Post-TAE, no further bleeding or hematoma was observed, and imaging confirmed the resolution of the pseudoaneurysm and hematoma. Methicillin-resistant Staphylococcus aureus (MRSA) infection was detected at the gastrostomy site, which contributed to complications. Despite successful management of the bleeding, the patient's overall condition deteriorated, and he died on postoperative day 66. This case underscores the importance of vigilant monitoring and management of PEG-related complications, particularly infections that may precipitate severe vascular events.

Ruptured pseudoaneurysm in a biliary metallic stent in a patient with pancreatic cancer: a case report.

We report a case of an 87 year-old woman who was admitted with jaundice, but had no pain or fever. Contrast-enhanced computed tomography revealed a tumor in the head of the pancreas, which caused distal malignant biliary obstruction. Initial transpupillary drainage by endoscopic retrograde cholangiopancreatography (ERCP) was difficult due to severe biliary stricture caused by the tumor, but cannulation of the pancreatic duct was successful. Pancreatic ductal adenocarcinoma was revealed through cytologic examination of pancreatic juice and the patient underwent percutaneous transhepatic biliary drainage (PTBD). 16 days after the jaundice was resolved, an uncovered Zilver® metallic stent was successfully deployed using a guidewire from the PTBD route, and the patient was discharged with palliative care due to advanced age. However, 54 days after discharge, the patient presented with black vomiting and recurrent jaundice. ERCP revealed an obstructed stent with black debris, and further evaluation revealed a ruptured pseudoaneurysm that branched off the gastroduodenal artery within the metallic biliary stent. Angiography revealed that embolization was successful. The patient recovered and was discharged without further episodes.

A novel artificial intelligence-based endoscopic ultrasonography diagnostic system for diagnosing the invasion depth of early gastric cancer.

BACKGROUND: We developed an artificial intelligence (AI)-based endoscopic ultrasonography (EUS) system for diagnosing the invasion depth of early gastric cancer (EGC), and we evaluated the performance of this system. METHODS: A total of 8280 EUS images from 559 EGC cases were collected from 11 institutions. Within this dataset, 3451 images (285 cases) from one institution were used as a development dataset. The AI model consisted of segmentation and classification steps, followed by the CycleGAN method to bridge differences in EUS images captured by different equipment. AI model performance was evaluated using an internal validation dataset collected from the same institution as the development dataset (1726 images, 135 cases). External validation was conducted using images collected from the other 10 institutions (3103 images, 139 cases). RESULTS: The area under the curve (AUC) of the AI model in the internal validation dataset was 0.870 (95% CI: 0.796-0.944). Regarding diagnostic performance, the accuracy/sensitivity/specificity values of the AI model, experts (n = 6), and nonexperts (n = 8) were 82.2/63.4/90.4%, 81.9/66.3/88.7%, and 68.3/60.9/71.5%, respectively. The AUC of the AI model in the external validation dataset was 0.815 (95% CI: 0.743-0.886). The accuracy/sensitivity/specificity values of the AI model (74.1/73.1/75.0%) and the real-time diagnoses of experts (75.5/79.1/72.2%) in the external validation dataset were comparable. CONCLUSIONS: Our AI model demonstrated a diagnostic performance equivalent to that of experts.

Colonic diverticular bleeding due to a rupture of an ileocolic artery pseudoaneurysm secondary to colonic diverticulitis.

A 53-year-old woman with a history of recurrent right lower quadrant pain presented with slightly bloody stools in April 2023. She was initially diagnosed with acute diverticulitis using an abdominal computed tomography (CT) scan and was treated conservatively. On the second day, however, she reported significant hematochezia. A subsequent contrast-enhanced CT scan revealed an extravasation in the ascending colon, which was promptly managed with colonoscopy. Despite initial hemostasis, she experienced recurrent bleeding. Another contrast-enhanced CT scan revealed a pseudoaneurysm with ongoing extravasation in the same area. Angiography confirmed a pseudoaneurysm in a branch of the ileocolic artery, which was successfully treated by embolization. She was discharged after an 18 day hospital stay. This case highlights a pseudoaneurysm caused by diverticulitis.

A machine learning model for predicting the lymph node metastasis of early gastric cancer not meeting the endoscopic curability criteria.

BACKGROUND: We developed a machine learning (ML) model to predict the risk of lymph node metastasis (LNM) in patients with early gastric cancer (EGC) who did not meet the existing Japanese endoscopic curability criteria and compared its performance with that of the most common clinical risk scoring system, the eCura system. METHODS: We used data from 4,042 consecutive patients with EGC from 21 institutions who underwent endoscopic submucosal dissection (ESD) and/or surgery between 2010 and 2021. All resected EGCs were histologically confirmed not to satisfy the current Japanese endoscopic curability criteria. Of all patients, 3,506 constituted the training cohort to develop the neural network-based ML model, and 536 constituted the validation cohort. The performance of our ML model, as measured by the area under the receiver operating characteristic curve (AUC), was compared with that of the eCura system in the validation cohort. RESULTS: LNM rates were 14% (503/3,506) and 7% (39/536) in the training and validation cohorts, respectively. The ML model identified patients with LNM with an AUC of 0.83 (95% confidence interval, 0.76-0.89) in the validation cohort, while the eCura system identified patients with LNM with an AUC of 0.77 (95% confidence interval, 0.70-0.85) (P = 0.006, DeLong's test). CONCLUSIONS: Our ML model performed better than the eCura system for predicting LNM risk in patients with EGC who did not meet the existing Japanese endoscopic curability criteria. We developed a neural network-based machine learning model that predicts the risk of lymph node metastasis in patients with early gastric cancer who did not meet the endoscopic curability criteria.

Endoscopic Removal and Conservative Treatment of a Small Bowel Perforation Caused by a Toothpick: A Case Report.

This case report describes a unique instance of small bowel perforation in a 49-year-old woman caused by an ingested toothpick. Initially suspected of colonic diverticulitis, a final diagnosis of small bowel perforation was made later, and the toothpick was successfully removed via endoscopy. This case emphasizes the need to consider foreign body ingestion in the differential diagnosis of abdominal pain and demonstrates the feasibility of conservative endoscopic approaches in similar cases.

Prognosis of anemic patients with atrial fibrillation undergoing percutaneous coronary intervention.

BACKGROUND: There are limited data regarding whether anemia is associated with adverse clinical outcomes in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). METHODS: Patients with AF undergoing PCI at 15 institutions between January 2015 and March 2021 were included in this analysis. Based on the baseline hemoglobin levels, moderate to severe anemia was defined as hemoglobin levels <11 g/dL, and mild anemia was defined as hemoglobin levels 11-12.9 g/dL for men and 11-11.9 g/dL for women. Clinical outcomes within 1 year, including major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, stent thrombosis, and stroke) and major bleeding events (BARC 3 or 5), were compared among patients with moderate/severe anemia, mild anemia, and no anemia. RESULTS: In a total of 746 enrolled patients, 119 (16.0%) and 168 (22.5%) patients presented with moderate/severe and mild anemia. The incidence of MACE (22.5%, 11.0%, and 9.1%, log-rank p < 0.001), all-cause death (20.0%, 7.2%, and 4.8%, log-rank p < 0.001), and major bleeding events (10.7%, 6.5%, and 2.7%, log-rank p < 0.001) were the highest in the moderate/severe anemia group compared with the mild and no anemia groups. Multivariable Cox regression analyses determined moderate/severe anemia as an independent predictor for MACE (p = 0.008), all-cause death (p = 0.005), and major bleeding events (p = 0.031) at 1 year after PCI. CONCLUSION: Moderate/severe anemia was significantly associated with the higher incidence of MACE and all-cause death as well as major bleeding events compared with mild and no anemia in AF patients undergoing PCI.

Ansa Cervicalis External Branch Anastomosis to Restore High Tone Voice in Thyroid Surgery.

OBJECTIVES: Injury to the external branch of the superior laryngeal nerve (EBSLN) causes low-pitch voice and voice fatigue, particularly in female subjects, and available treatments are limited. Here, we assess a novel surgical procedure to restore a high-tone voice: ansa cervicalis to EBSLN anastomosis (A-E anastomosis). METHODS: Between November 2012 and April 2022, 13 patients (12 female) underwent unilateral EBSLN resection and A-E anastomosis, while 20 (16 female) underwent EBSLN resection during thyroid surgery. Patients (4494 women and 1025 men) with normal laryngoscopy scheduled for thyroid surgery served as normal controls. Phonatory function was examined using a Phonation Analyzer PA-1000 preoperatively and intermittently postoperatively. RESULTS: In patients who underwent A-E anastomosis, high-tone voice pitch decreased significantly postoperatively (673.9-471.5 Hz, p = 0.047), with restoration achieved within 5 months. The mean voice pitch in female patients who underwent A-E anastomosis, EBSLN resection, and controls were 580.4, 522.8, and 682.0 Hz, respectively, indicating a significant decrease in EBSLN resection patients than controls (p = 0.002). The (mean - 1SD) of high-tone voice pitch in female controls was 497 Hz; exceeding this may indicate recovery to a high-tone voice. Overall, 73% (8/11) of A-E anastomosis patients exceeded this value, which was marginally larger than the 43% (6/14) who underwent EBSLN resection. Data on male subjects are limited. There were no cases of adverse functional or cosmetic events. CONCLUSIONS: A-E anastomosis, a novel simple procedure, restored high-tone voice to some extent without any adverse events and thus warrants further investigation. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3868-3873, 2024.

Efficacy of prophylactic clip closure in reducing the risk of delayed bleeding after colorectal endoscopic submucosal dissection in patients on anticoagulant therapy: Multicenter prospective study.

OBJECTIVES: The high rate of delayed bleeding after colorectal endoscopic submucosal dissection (ESD) in patients undergoing anticoagulant therapy remains a problem. Whether prophylactic clip closure reduces the rate of delayed bleeding in these patients is unclear. This study aimed to evaluate the efficacy of prophylactic clip closure in patients receiving anticoagulants. METHODS: This multicenter prospective interventional trial was conducted at nine referral centers in Japan. Patients regularly taking anticoagulants, including warfarin potassium or direct oral anticoagulants, and undergoing ESD for colorectal neoplasms were enrolled. The discontinuation of anticoagulants was minimized according to recent guidelines. After the ESD, post-ESD ulcers were prophylactically closed using endoclips. The primary end-point was the incidence of delayed bleeding. The sample size was 45 lesions, and prophylactic clip closure was considered effective when the upper limit of the 90% confidence interval (CI) for delayed bleeding did not exceed 20%. RESULTS: Forty-five lesions were used, and three were excluded. Complete closure was achieved in 41/42 lesions (97.6%). The overall delayed bleeding rate was low, at 4.9% (2/41; 90% [CI] 0.8-14.5), which was significantly lower than that at the prespecified threshold of 20% (P = 0.007). The median closure procedure time was 17 min, and the median number of clips was nine. No massive delayed bleeding requiring transfusion, interventional radiology, or surgery was observed, and no thromboembolic events were observed. CONCLUSION: Prophylactic clip closure may reduce the risk of delayed bleeding following colorectal ESD in patients receiving anticoagulants. TRIAL REGISTRATION: UMIN Clinical Trial Registry (UMIN000036734).

Impact of time from diagnosis to chemotherapy on prognosis in advanced pancreatic cancer.

BACKGROUND: Due to the aggressive nature and poor prognosis of advanced pancreatic cancer, prompt initiation of treatment is critical. We investigated the effect of the interval between cancer diagnosis and initiation of chemotherapy on survival in patients with advanced pancreatic cancer. METHODS: In this retrospective, single-centre study, consecutive patients with advanced pancreatic cancer between April 2013 and March 2022 were analyzed. Data were extracted from the electronic medical records of patients who received chemotherapy for metastatic, locally advanced or resectable pancreatic cancer or who received chemotherapy due to either being intolerant of or declining surgery. We compared overall survival between two groups: the early waiting time group (waiting time ≤30 days from diagnosis to chemotherapy initiation) and the elective waiting time group (waiting time ≥31 days). Prognostic factors, including biliary drainage, were considered. The impact of waiting time on survival was assessed by univariate and multivariate analyses with Cox proportional hazard models. A 1:1 propensity score matching approach was used to balance bias, accounting for significant poor prognosis factors, age and sex. RESULTS: The study involved 137 patients. Overall survival exhibited no statistically significant difference between the early and elective waiting time groups (207 and 261 days, P = 0.2518). Univariate and multivariate analyses identified poor performance status and metastasis presence as predictors of worse prognosis. This finding persisted post propensity score matching (275 and 222 days, P = 0.8223). CONCLUSIONS: Our study revealed that initiating chemotherapy ˃30 days later does not significantly affect treatment efficacy compared to within 30 days of diagnosis.

Utility and advantage of the unroofing technique for gastrointestinal subepithelial tumors: A multicenter retrospective cohort study.

Background and aim: Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term "unroofing technique". We conducted a multicenter retrospective study to assess its efficacy and identify potential complications. Methods: This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis. Results: The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation. Conclusion: The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.

5-Aminosalicylic Acid-Induced Liver Injury in a Patient with Ulcerative Colitis: A Case Report.

Introduction: Drug-induced liver injury (DILI) associated with 5-aminosalicylic acid (5-ASA) is a rare but potentially life-threatening adverse event. Case Presentation: We report the case of a 58-year-old woman with ulcerative colitis who developed DILI after initiating maintenance therapy with the multimatrix system 5-ASA. The patient presented with grade 4 liver enzyme elevation on day 98 after initiating 5-ASA and was admitted to the hospital. Blood tests revealed the mixed liver injury, and imaging studies showed no abnormalities except for mild lymph node enlargement. Liver biopsy revealed acute lobular hepatitis with interfacial activity. The patient's score on the International Autoimmune Hepatitis Group 1999 revised scoring system was a total score of 10, causing a suspicion for the diagnosis of autoimmune hepatitis. The DDW-J 2004 scale calculated a total score of six, indicating a high probability of DILI. We suspected DILI due to 5-ASA, and the 5-ASA formulations were discontinued. The patient was treated with ursodeoxycholic acid and neominophagen C, and her liver function gradually improved without steroid treatment. Finally, we definitively diagnosed DILI based on the pathological findings and clinical course after discontinuation of 5-ASA. Conclusion: This case highlights the importance of monitoring liver function in patients receiving 5-ASA therapy.

Drug-induced Interstitial Nephritis in a Patient with Ulcerative Colitis Treated with 5-Aminosalicylic Acid.

This report describes the case of a 76-year-old man with ulcerative colitis who developed interstitial nephritis after starting 5-Aminosalicylic acid (5-ASA) therapy. The patient experienced an initial improvement in symptoms, but developed fatigue, anorexia, and severe renal dysfunction 2.5 months later. Renal biopsy confirmed drug-induced interstitial nephritis, and conservative treatment with fluid replacement and the discontinuation of 5-ASA improved the patient's condition. Clinicians should monitor patients receiving 5-ASA therapy for potential adverse effects, particularly renal injury, and promptly investigate symptoms of renal dysfunction. Early recognition and discontinuation of the offending agent may prevent further damage and improve patient outcomes.

Comparison of the effect of ethanol infusion into the vein of Marshall between with and without collateral veins.

BACKGROUND: Despite the potential benefits of ethanol infusion into the vein of Marshall (EIVOM) for atrial fibrillation (AF) ablation, concerns about its reversible and unpredictable effects persist. OBJECTIVE: To assess the effectiveness of EIVOM in the vein of Marshall (VOM) with collateral veins (CVs) during mitral isthmus and AF ablation. METHODS: We included 142 AF patients. EIVOM was performed before radiofrequency ablation, and low-voltage areas (<0.5 mV) were measured before, immediately after, and 1 h after EIVOM. RESULTS: Among the 142 patients, 93 (65%) underwent EIVOM, and among these, 35 (37%) were found to have CVs. In the VOM with CVs group, areas with low voltage measured 0 (0-1.85) cm2 before EIVOM, 6.9 (4.1-11.2) cm2 immediately after EIVOM, and 5.7 (3.5-10.6) cm2 1 h after EIVOM. Conversely, in the group designated as VOM without CVs-from which the nine leakage cases were excluded-the areas measured 0 (0-1.35) cm2 , 5.5 (2.6-11.8) cm2 , and 4.7 (1.8-13.5) cm2 at the respective time points. MI line block was fully achieved in 89% (31/35) of cases in the VOM with CVs group and 88% (44/49) in the VOM without CVs groups (p = .94). There was no significant difference in the outcome of AF ablation between these groups (log-rank p = .73). Additionally, no significant difference was observed between EIVOM (+) and EIVOM (-) groups (log-rank p = .59). CONCLUSION: EIVOM effectively creates MI line block, and its beneficial effects are sustained for at least 1 h after the procedure despite the low-voltage areas showing a slight reduction in size.

Active surveillance for adult low-risk papillary thyroid microcarcinoma-a review focused on the 30-year experience of Kuma Hospital.

Active surveillance (AS) for low-risk papillary thyroid microcarcinoma (PTMC), which was initiated at Kuma Hospital (Kobe, Japan) in 1993 and Cancer Institute Hospital (Tokyo) in 1995, is now gradually being adopted worldwide, and several prospective studies have described the favorable outcomes of PTMC patients who underwent AS. The most important factor predicting PTMC growth is young age, and PTMC enlargement in young patients may be affected by high serum levels of thyroid-stimulating hormone. This review notes that one patient showed lung metastasis after conversion surgery (CS) following AS, but there are no reports of patients dying of thyroid carcinoma during or after AS. Some PTMCs enlarge or show newly appeared metastatic nodes requiring CS, and findings on the postoperative prognosis and incidence of significant surgical complications (e.g., permanent vocal cord paralysis, hypoparathyroidism) do not differ significantly between patients who underwent CS after AS and those who underwent immediate surgery (IS). IS has been associated with significantly higher incidences of these complications compared to AS as the initial management. Several studies have examined the quality of life (QoL) of patients who underwent AS versus IS, and reported discrepant findings regarding various psychological conditions (including anxiety). Medical costs for AS and IS vary regionally, and in Japan, the 10-year total cost of IS was 4.1 times greater than that of AS in 2017. Taken together, the existing findings demonstrate that AS can be appropriate for the initial management of patients with PTMC.

Non-Pure Intestinal Phenotype as an Indicator of Progression in Sporadic Nonampullary Duodenal Adenomas: A Multicenter Retrospective Cohort Study.

INTRODUCTION: We aimed to evaluate the natural course of sporadic nonampullary duodenal adenomas (SNDAs) and determine the risk factors of progression. METHODS: We retrospectively analyzed the follow-up outcomes of patients with biopsy-diagnosed SNDA between April 2010 and March 2016 at 13 institutions. All initial biopsy specimens were centrally evaluated. Only those diagnosed with adenomas were included. Mucinous phenotypes were classified into pure intestinal and non-pure intestinal phenotypes. Cumulative incidence rates of carcinoma and tumor enlargement were evaluated. Tumor enlargement was defined as a ≥25% or 5-mm increase in tumor size. RESULTS: Overall, 121 lesions were analyzed. Within a median observation period of 32.7 months, 5 lesions were diagnosed as carcinomas; the cumulative 5-year incidence of carcinoma was 9.5%. Male sex ( P = 0.046), initial lesion size ≥10 mm ( P = 0.044), and non-pure intestinal phenotype ( P = 0.019) were significantly associated with progression to carcinoma. Tumor enlargement was observed in 22 lesions, with a cumulative 5-year incidence of 33.9%. Initial lesion size ≥10 mm ( P < 0.001), erythematous lesion ( P = 0.002), high-grade adenoma ( P = 0.002), Ki67 negative ( P = 0.007), and non-pure intestinal phenotype ( P = 0.001) were risk factors of tumor enlargement. In a multivariate analysis, an initial lesion size ≥10 mm ( P = 0.010) and non-pure intestinal phenotype ( P = 0.046) were independent and significant risk factors of tumor enlargement. DISCUSSION: Lesion size ≥10 mm and non-pure intestinal phenotype on initial biopsy are risk factors of cancer progression and tumor enlargement in cases with SNDA. Thus, management effectiveness may be improved by focusing on lesion size and the mucinous phenotype.

Tumor volume-doubling rate is negatively associated with patient age in papillary thyroid microcarcinomas under active surveillance.

BACKGROUND: Active surveillance of low-risk papillary thyroid microcarcinomas has gained popularity worldwide as a management strategy. We previously reported that young age was associated with tumor enlargement by ≥3 mm. Here, we used the tumor volume-doubling rate to study the age-related tumor volume dynamics of papillary thyroid microcarcinomas under active surveillance. METHODS: Between 2005 and 2019, 2,896 patients diagnosed with low-risk papillary thyroid microcarcinomas underwent active surveillance. We excluded patients who underwent ultrasound examination fewer than 4 times, had coexisting Graves' disease, or were treated with levothyroxine at the time of diagnosis, and we enrolled 2,129 patients for this study. We divided them into 3 subsets based on the age at diagnosis: young (<40 years), middle-aged (40-59 years), and elderly (≥60 years). The tumor volume-doubling rate was calculated based on ultrasound-derived tumor sizes and the respective examination date for each patient. RESULTS: Overall, 140 patients (6.6%) had moderate or rapid growth (tumor volume-doubling rate ≥0.3/year), and the incidence significantly decreased with advanced age (P < .01): 11.3%, 7.1%, and 5.0% in the young, middle-aged, and elderly groups, respectively. Tumor regression (tumor volume-doubling rate <0/year) was detected in 1,200 patients (56.4%), and the incidence significantly increased with age (P < .01): 44.6%, 55.3%, and 60.0% in the young, middle-aged, and elderly groups, respectively. On multivariate analysis, both the ≥60 years and 40 to 59 years age groups were independent negative predictors of papillary thyroid microcarcinoma enlargement and positive predictors of tumor regression. CONCLUSION: Tumor volume-doubling rate analysis demonstrated that the incidence of tumor enlargement decreased and that of tumor regression increased with advancing age in patients with papillary thyroid microcarcinomas.