Plasma circulating tumor DNA (ctDNA) sequencing has demonstrated clinical utility for tumor molecular profiling at initial diagnosis or tumor progression in advanced solid cancers and is being rapidly incorporated into the clinical practice guidelines, including non–small cell lung and breast cancer. Despite relatively low sensitivity, plasma ctDNA sequencing has several advantages over tissue-based assays, including ease of sampling, rapid turnaround time, repeatability, and the ability to overcome spatial heterogeneity, which makes it ideal for investigating acquired resistance and monitoring tumor evolution and dynamics. With technological advancement and declining costs, the clinical application of plasma ctDNA is expanding, and numerous ongoing clinical trials are examining its potential to guide the management of advanced, localized, and even preclinical cancers of various tumor types. The ability of plasma ctDNA analysis to detect minimal residual disease following curative treatment in the absence of clinical disease is among its most promising attributes. Plasma ctDNA sequencing can also facilitate the conduct of clinical trials and drug development, particularly in immunotherapy. In order to incorporate plasma ctDNA sequencing for clinical decision-making, it is important to understand the preanalytical and analytical factors that may affect its sensitivity and reliability.

Historically, small cell carcinoma in the thyroid has been regarded as a kind of lymphoma and small cell carcinoma in the thyroid as a distinct disease entity is still controversial. Here, we present two cases of thyroid small cell carcinoma that were differentiated from lymphoma, based on immunohistochemical staining. One case was misdiagnosed as anaplastic carcinoma that occurred during the treatment of follicular carcinoma. Both cases responded well to chemotherapy. These cases support the hypothesis that thyroid small cell carcinoma is a distinct disease entity. One should consider small cell carcinoma when there is a rapidly growing mass in the thyroid.
Carcinoma ; Carcinoma, Small Cell ; Lymphoma ; Thyroid Gland ; Thyroid Neoplasms

Sunitinib is an oral tyrosine kinase inhibitor with anti-angiogenic activity that is used for the treatment of advanced renal cell carcinoma and advanced gastrointestinal stromal tumors after failure on imatinib. The most common adverse effects of sunitinib are fatigue, diarrhea, nausea, stomatitis, hypertension, hand-foot syndrome, and cytopenia. Sunitinib was recently reported to be associatedwith reversible posterior leukoencephalopathy syndrome (RPLS). Here, we report the case of a 76-year-old woman with sunitinib- induced RPLS that developed after rifampin discontinuation.
Aged ; Benzamides ; Carcinoma, Renal Cell ; Diarrhea ; Fatigue ; Female ; Gastrointestinal Stromal Tumors ; Hand-Foot Syndrome ; Humans ; Hypertension ; Indoles ; Nausea ; Piperazines ; Posterior Leukoencephalopathy Syndrome ; Protein-Tyrosine Kinases ; Pyrimidines ; Pyrroles ; Rifampin ; Stomatitis ; Imatinib Mesylate

Sunitinib is an oral tyrosine kinase inhibitor with anti-angiogenic activity that is used for the treatment of advanced renal cell carcinoma and advanced gastrointestinal stromal tumors after failure on imatinib. The most common adverse effects of sunitinib are fatigue, diarrhea, nausea, stomatitis, hypertension, hand-foot syndrome, and cytopenia. Sunitinib was recently reported to be associatedwith reversible posterior leukoencephalopathy syndrome (RPLS). Here, we report the case of a 76-year-old woman with sunitinib- induced RPLS that developed after rifampin discontinuation.
Aged ; Benzamides ; Carcinoma, Renal Cell ; Diarrhea ; Fatigue ; Female ; Gastrointestinal Stromal Tumors ; Hand-Foot Syndrome ; Humans ; Hypertension ; Indoles ; Nausea ; Piperazines ; Posterior Leukoencephalopathy Syndrome ; Protein-Tyrosine Kinases ; Pyrimidines ; Pyrroles ; Rifampin ; Stomatitis ; Imatinib Mesylate

A primary right atrial (RA) mass is not common; instead, most tumors in the right atrium originate from metastasis through the caval route. Here we describe a patient with a huge RA tumor that showed contiguous spread from the inferior vena cava. This 60-year-old patient, positive for hepatitis B surface antigen, visited the emergency department of our institution due to recently aggravated dyspnea. Transthoracic and transesophageal echocardiography clearly demonstrated a huge RA mass, 6.5x6.0 cm, causing flow disturbance. Cardiac magnetic resonance imaging and dynamic computed tomography of the liver showed multiple large hepatic masses that extended into the right atrium, with tumor thrombi in the inferior vena cava. Given the enhancement pattern in dynamic computed tomography of the liver, the hepatic mass was diagnosed as hepatocellular carcinoma. Due to the risk of spontaneous rupture of the mass, emergency transarterial chemoembolization was performed, without complications. Thereafter, thalidomide, which has been shown to have anti-angiogenic effects, was prescribed to the patient.
Carcinoma, Hepatocellular ; Dyspnea ; Echocardiography ; Echocardiography, Transesophageal ; Emergencies ; Heart Atria ; Hepatitis B Surface Antigens ; Humans ; Liver ; Magnetic Resonance Imaging ; Middle Aged ; Neoplasm Metastasis ; Rupture, Spontaneous ; Thalidomide ; Vena Cava, Inferior

PURPOSE: The aim of this study was to evaluate the performance of a proposed computer-aided detection (CAD) system in automated breast ultrasonography (ABUS). METHODS: Eighty-nine two-dimensional images (20 cysts, 42 benign lesions, and 27 malignant lesions) were obtained from 47 patients who underwent ABUS (ACUSON S2000). After boundary detection and removal, we detected mass candidates by using the proposed adjusted Otsu's threshold; the threshold was adaptive to the variations of pixel intensities in an image. Then, the detected candidates were segmented. Features of the segmented objects were extracted and used for training/testing in the classification. In our study, a support vector machine classifier was adopted. Eighteen features were used to determine whether the candidates were true lesions or not. A five-fold cross validation was repeated 20 times for the performance evaluation. The sensitivity and the false positive rate per image were calculated, and the classification accuracy was evaluated for each feature. RESULTS: In the classification step, the sensitivity of the proposed CAD system was 82.67% (SD, 0.02%). The false positive rate was 0.26 per image. In the detection/segmentation step, the sensitivities for benign and malignant mass detection were 90.47% (38/42) and 92.59% (25/27), respectively. In the five-fold cross-validation, the standard deviation of pixel intensities for the mass candidates was the most frequently selected feature, followed by the vertical position of the centroids. In the univariate analysis, each feature had 50% or higher accuracy. CONCLUSION: The proposed CAD system can be used for lesion detection in ABUS and may be useful in improving the screening efficiency.
Classification ; Humans ; Imaging, Three-Dimensional ; Mass Screening ; Radiographic Image Interpretation, Computer-Assisted ; Support Vector Machine ; Ultrasonography, Mammary*

To conduct the association between vitamin B12 and mental health in children and adolescents. Five databases were searched for observational studies in any language reporting on mental health and vitamin B12 levels or intake in children and adolescents from inception to March 18, 2022. Two authors independently extracted data and assessed study quality. Qualitative and quantitative analysis of data were performed. The review was registered in the PROSPERO database (CRD42022345476). Fifty six studies containing 37,932 participants were identified in the review. Vitamin B12 levels were lower in participants with autism spectrum disorders (ASD) (standardized mean difference [SMD], −1.61;95% confidence interval [95% CI], −2.44 to −0.79; p ＜ 0.001), attention deficit hyperactivity disorders (SMD, −0.39; 95% CI, −0.78 to −0.00; p = 0.049) compared with control group. Vitamin B12 intake were lower in participants with ASDs (SMD, −0.86; 95% CI, −1.48 to −0.24; p = 0.006) compared with control group, but showed no difference between depression group (SMD, −0.06; 95% CI, −0.15 to 0.03; p = 0.17) and the control group. Higher vitamin B12 intake were associated with lower risk of depression (odds ratio [OR], 0.79; 95% CI, 0.63−0.98; p = 0.034) and behavioral problems (OR, 0.83; 95% CI, 0.69−0.99; p = 0.04). The vast majority of included studies supported potential positive influence of vitamin B12 on mental health, and vitamin B12 deficiency may be a reversible cause for some mental health disorders in children and adolescents.

PURPOSE: Splenomegaly is a clinical surrogate of oxaliplatin-induced sinusoidal obstruction syndrome (SOS). We investigated development of splenomegaly and its association with treatment outcome and genetic polymorphisms following adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) in colorectal cancer (CRC) patients. MATERIALS AND METHODS: Splenomegaly was determined by spleen volumetry using computed tomography images obtained before initiation of chemotherapy and after completion of adjuvant FOLFOX in CRC patients. Ten genetic polymorphisms in 4 SOS-related genes (VEGFA, MMP9, NOS3, and GSTP1) were analyzed using DNA from peripheral blood mononuclear cells. RESULTS: Of 124 patients included, increase in spleen size was observed in 109 (87.9%). Median change was 31% (range, -42% to 168%). Patients with splenomegaly had more severe thrombocytopenia compared to patients without splenomegaly during the chemotherapy period (p < 0.0001). The cumulative dose of oxaliplatin and the lowest platelet count during the chemotherapy period were clinical factors associated with splenomegaly. However, no significant associations were found between genetic polymorphisms and development of splenomegaly. Disease-free survival was similar regardless of the development of splenomegaly. CONCLUSION: Splenomegaly was frequently observed in patients receiving adjuvant FOLFOX and resulted in more severe thrombocytopenia but did not influence treatment outcome. Examined genetic polymorphisms did not predict development of splenomegaly.
Colorectal Neoplasms* ; Disease-Free Survival ; DNA ; Drug Therapy ; Fluorouracil ; Hepatic Veno-Occlusive Disease ; Humans ; Leucovorin ; Platelet Count ; Polymorphism, Genetic* ; Spleen ; Splenomegaly* ; Thrombocytopenia ; Treatment Outcome*

PURPOSE: Bevacizumab±irinotecan is effective for treatment of recurrent malignant gliomas. However, the optimal duration of treatment has not been established. MATERIALS AND METHODS: Ninety-four consecutive patients with recurrent malignant glioma who were treated with bevacizumab at our institutions were identified. Patients who continued bevacizumab until tumor progression were enrolled in a late discontinuation (LD) group, while those who stopped bevacizumab before tumor progression were enrolled in an early discontinuation (ED) group. Landmark analyses were performed at weeks 9, 18, and 26 for comparison of patient survival between the two groups. RESULTS: Among 89 assessable patients, 62 (69.7%) and 27 (30.3%) patients were categorized as the LD and ED groups, respectively. According to landmark analysis, survival times from weeks 9, 18, and 26 were not significantly different between the two groups in the overall population. However, the LD group showed a trend toward increased survival compared to the ED group among responders. In the ED group, the median time from discontinuation to disease progression was 11.4 weeks, and none of the patients showed a definite rebound phenomenon. Similar median survival times after disease progression were observed between groups (14.4 weeks vs. 15.7 weeks, p=0.251). Of 83 patients, 38 (45.8%) received further therapy at progression, and those who received further therapy showed longer survival in both the LD and ED groups. CONCLUSION: In recurrent malignant glioma, duration of bevacizumab was not associated with survival time in the overall population. However, ED of bevacizumab in responding patients might be associated with decreased survival.
Bevacizumab* ; Disease Progression ; Glioblastoma ; Glioma* ; Humans

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a). Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study. Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0). Conclusion GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.