Case Report: A Rare Case of Esophagogastric Junctional Squamous Cell Carcinoma After the Successful Treatment of Neuroendocrine Carcinoma: Clonal Tumor Evolution Revealed by Genetic Analysis.

Neuroendocrine carcinoma (NEC) of the esophagogastric junction (EGJ) is a rare disease with no established treatments. Herein, we describe a case of recurrent squamous cell carcinoma (SCC) after achieving complete response to chemotherapy against NEC of the EGJ. A 67-year-old man was referred to our hospital because of epigastric discomfort. Computed tomography imaging and esophagogastroduodenoscopy revealed ulcerated tumors at the EGJ. Endoscopic biopsy revealed small tumor cells with a high nuclear/cytoplasmic ratio, suggesting small-cell NEC. Immunohistochemistry (IHC) analysis showed tumor cells with an MIB-1 index of 80%. The patient achieved complete response after 10 cycles of chemotherapy. Follow-up endoscopic examination revealed small red-colored mucosal lesions in the center of the cicatrized primary lesion. Re-biopsy detected cancer cells harboring large eosinophilic cytoplasm with keratinization and no evidence of NEC components. IHC of the cells were cytokeratin 5/6-positive and p53-negative. The tumor persisted without evidence of metastases after chemoradiotherapy, and total gastrectomy with lymph node dissection was performed. Pathological assessment of the resected specimens revealed SCC, without evidence of NEC. The patient survived without a recurrence for >3 years after the initial presentation. Somatic mutation profiles of the primary NEC and recurrent SCC were analyzed by targeted amplicon sequencing covering common cancer-related mutations. Both tumors possessed TP53 Q192X mutation, whereas SMAD4 S517T was found only in SCC, suggesting that both tumor components originated from a founder clone with a stop-gain mutation in TP53. The somatic mutation profile of the tumors indicated that that loss of heterozygosity (LOH) at the TP53 gene might have occurred during the differentiation of the founder clone into NEC, while a SMAD4 mutation might have contributed to SCC development, indicating branching and subclonal evolution from common founder clone to both NEC and SCC. The mutation assessments provided valuable information to better understand the clonal evolution of metachronous cancers.

Ratios of peripheral-to-central airway lumen area and percentage wall area as predictors of severity of chronic obstructive pulmonary disease.

OBJECTIVE: The purpose of this study was to assess the ability of the ratios of peripheral-to-central airway lumen area (hereafter referred to as LA) and percentage wall area (hereafter referred to as %WA) to predict the severity of chronic obstructive pulmonary disease (COPD) according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. SUBJECTS AND METHODS: We examined 32 patients (27 men and five women; mean age ± SD, 70.0 ± 6.8 years; seven GOLD stage 0 [at risk for COPD], 19 GOLD stage 1-2 [mild to moderate airflow limitation], and six GOLD stage 3-4 [severe to very severe airflow limitation]) using inspiratory CT. Mean LA and %WA were measured for the first (main bronchi), third, and fifth generations of five bronchi in each lobe and the ratios of peripheral to central airways were calculated (third to first, fifth to first, and fifth to third) and statistically compared. RESULTS: The fifth-generation LA, LA fifth to first, and LA fifth to third significantly decreased and fifth %WA, %WA fifth to first, and %WA fifth to third also increased with progression of GOLD stage (p < 0.05), but central measurements, including first and third generations, did not. There were significant differences between GOLD 0 and GOLD 1-2 for %WA fifth to third and LA fifth to third and between GOLD 0 and GOLD 3-4 for all six parameters (p < 0.05); %WA fifth to third had the best cutoff value of 1.02 (sensitivity, 92%; specificity, 86%) for diagnosis of COPD (GOLD 1-4). The %WA fifth to first of 1.51 (sensitivity, 83%; specificity, 89%) was best for diagnosis of GOLD 3-4. CONCLUSION: Ratios of peripheral-to-central airway LA and %WA show improved correlation with COPD severity.

VIBE MRI for evaluating the normal and abnormal gastrointestinal tract in fetuses.

OBJECTIVE: The great potential of MRI for assessing gastrointestinal abnormalities in fetuses has been described. T1-weighted images may add additional information to T2-weighted images in diagnosing fetal gastrointestinal abnormalities. The objective of this study was to assess the performance of a 3D volumetric interpolated breath-hold sequence (VIBE) in evaluating the normal and abnormal fetal gastrointestinal tract. CONCLUSION: VIBE provides high-quality T1-weighted and 3D MR colonography images for the evaluation of the normal and abnormal gastrointestinal tract in fetuses, and 3D MR colonography provides excellent delineation of the meconium.