Esophageal squamous cell carcinoma (ESCC) often recurs after chemoradiotherapy, and the prognosis of ESCC after chemoradiotherapy has not improved over the past few decades. The mutation process in chemoradiotherapy-resistant clones and the functional relevance of genetic alterations remain unclear. To address these problems, we performed whole-exome sequencing of 52 tumor samples from 33 patients with ESCC who received radiotherapy combined with 5-fluorouracil/platinum. In multiregion analyses of pretreatment and locally recurrent lesions from five cases, most driver gene-altered clones remained under chemoradiotherapy selection pressure, while few driver gene alterations were acquired at recurrence. The mutation signatures of recurrent ESCC, including increased deletion frequency and platinum dose-dependent base substitution signatures, were substantially different from those of primary ESCC and reflected the iatrogenic impacts of chemoradiotherapy. Single-region analysis of 28 pretreatment tumors indicated that focal copy-number gain at the MYC locus was significantly associated with poor progression-free survival and overall survival after chemoradiotherapy. MYC gain remained throughout the chemoradiotherapy course and potentially contributes to intrinsic resistance to chemoradiotherapy. Consistent with these findings, MYC copy number and mRNA and protein levels in ESCC cell lines correlated positively with resistance to radiotherapy, and MYC knockdown improved sensitivity to radiotherapy. Overall, these data characterize the clonal evolution process induced by chemoradiotherapy and clinically relevant associations for genetic alterations in ESCC. These findings increase our understanding of therapeutic resistance and support the rationale for precision chemoradiotherapy.
Significance:
Whole-exome sequencing reveals the genetic evolution of ESCC during chemoradiotherapy, highlighting MYC gain in pretreatment tumors as a potential marker of therapy resistance.
• Early gastric cancer with ulceration and advanced gastric cancer have similar endoscopic appearances. • EGC-U shows significantly lower attenuation values in both arterial and portal phases. • Multiphasic dynamic contrast-enhanced MDCT differentiates EGC-U from AGC.
Pelvic schwannoma typically forms a large, well-circumscribed mass in the retroperitoneum or presacral area and frequently undergoes cystic degeneration. It appears as a well-demarcated round or oval mass, often showing prominent cystic degeneration and calcification. Characteristics of these calcifications are punctate, mottled, or curvilinear and are seen along the walls of the mass. Herein, we describe a case of schwannoma presenting a huge pelvic mass with unique eggshell-like calcification.
A 50-year-old man showed massive lower gastrointestinal bleeding without a triggering episode. An emergency colonoscopy revealed a protruding vessel in the lower rectum with no active bleeding. No underlying ulcer was seen within the surrounding mucosa. These findings were consistent with rectal Dieulafoy's lesion. Angiography was requested to identify the source of bleeding and for possible embolization. On the initial angiography, the bleeding point was unclear. Abnormal vessels such as arteriovenous malformation or nidus were not found. He again developed hematochezia, requiring transfusion of red blood cells. However, the second colonoscopy showed no active bleeding from the protruding vessel in the rectum. During the second angiography, sudden bleeding occurred. Angiography showed extravasation of contrast medium from the distal branch of the superior rectal artery. Transcatheter arterial embolization was performed, and was very effective.
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