Cell type–specific gene expression is driven by the interplay between lineage-specific transcription factors and cis-regulatory elements to which they bind. Adaptive immunity relies on RAG-mediated assembly of T cell receptor (TCR) and immunoglobulin (Ig) genes. Although Rag1 and Rag2 expression is largely restricted to adaptive lymphoid lineage cells, it remains unclear how Rag gene expression is regulated in a cell lineage–specific manner. Here, we identified three distinct cis-regulatory elements, a T cell lineage–specific enhancer (R-TEn) and the two B cell–specific elements, R1B and R2B. By generating mice lacking either R-TEn or R1B and R2B, we demonstrate that these distinct sets of regulatory elements drive the expression of Rag genes in developing T and B cells. What these elements have in common is their ability to bind the transcription factor E2A. By generating a mouse strain that carries a mutation within the E2A binding site of R-TEn, we demonstrate that recruitment of E2A to this site is essential for orchestrating changes in chromatin conformation that drive expression of Rag genes in T cells. By mapping cis-regulatory elements and generating multiple mouse strains lacking distinct enhancer elements, we demonstrate expression of Rag genes in developing T and B cells to be driven by distinct sets of E2A-dependent cis-regulatory modules.

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While TAE remains the best method to employ for hemostasis, it still has limitations. Hence, we should be mindful of other possible modalities for hemostasis and their outcomes. Rupture of HCC at an early phase in the development of liver fibrosis is a good indication for elective surgical treatment and should be distinguished from rupture in the terminal phase of liver cirrhosis, which should be treated conservatively. Although elective surgical treatment can be performed in selected patients, tumor size and location of HCC, in addition to liver function, should be taken into consideration.

Intraluminal tumor thrombus in the portal vein (PV) system originating from gastrointestinal (GI) tract cancer is a rare condition. There are two types of such thrombi, one arising indirectly from metastatic liver cancer and the other directly from the primary lesion. We report here three patients with the direct type and two with the indirect type; i.e., a total of five patients with gastric or large intestinal cancer with PV tumor thrombus. In all patients, the primary lesion was surgically resected; in two patients, the tumor thrombus was easily extirpated by direct opening of the PV. It is noteworthy that a patient whose tumor thrombus could not be treated died of cancer with liver failure, caused by expansive growth of the PV tumor thrombus, 4 months after the finding of the PV thrombus. Because PV tumor thrombus may, possibly, determine the patient's length of survival, in addition to causing cancer progression, surgical thrombectomy, combined with resection of the primary cancer and metastatic liver cancer, should be considered for prolongation of survival, if all macroscopic lesions can be controlled and if the tumor thrombus is a synchronous and recent one.

An extremely rare case of a lymphoepithelial cyst associated with persistent elevation of serum carbohydrate antigen (CA) 19-9 levels is described. A 72-year-old man was incidentally found to have a cystic tumor in the uncus of the pancreas and to have a high serum CA 19-9 level. At 2-year follow up, the tumor size had gradually increased and the high CA 19-9 level persisted. Because the malignant potential of the tumor could not be ruled out, a laparotomy was performed. The tumor was excised from the pancreas. On pathological examination, the tumor was proven to be a lymphoepithelial cyst. After the operation, the patient's serum CA 19-9 level decreased to the normal range. Lymphoepithelial cysts of the pancreas are a rare, benign entity. They are true pancreatic cysts, characterized by a mature, keratinizing, squamous lining surrounded by lymphoid tissue. Because the treatment options and the prognosis of these entities are quite different from those of other cystic neoplasms of the pancreas, preoperative differential diagnosis is the main issue. Thus, although they are rare, lymphoepithelial cysts should be considered in the differential diagnosis of cystic tumors of the pancreas.