Low incidence of MYC/BCL2 double‐hit in Burkitt lymphoma

Translocations involving MYC are highly characteristic for Burkitt lymphoma (BL). BCL2 expression has also been found previously in about 10 to 20% of BL cases, and BCL2 translocation is a major mechanism for the deregulation of BCL2 expression in non‐Hodgkin lymphomas. However, we know little about the incidence of MYC/BCL2 double‐hit (DH) in BL. We examined BL cases to determine how frequently they contained BCL2 translocations in combination with MYC translocations using fluorescence in situ hybridization. We also determined the effect of BCL2 expression on clinical outcomes of BL. BCL2 translocations were detected in 3.5% (2/57 cases) of the cases, and BCL2 expression was detected in 33%. Two cases with BCL2 translocation also showed BCL2 expression. The incidence of BCL2 expression was significantly higher in patients 16 years of age and older (46%) than in patients under 16 years of age (6%). Among patients 16 years of age and older, we did not detect significant differences in overall survival with respect to BCL2 expression status. In conclusion, BCL2 translocation is a rare cytogenetic abnormality in BL, and BL probably accounts for only a small fraction of MYC/BCL2 DH lymphomas. BCL2 expression in BL is probably not associated with BCL2 translocations.     

Decreased calcitonin gene-related peptide expression in the dorsal root ganglia of TNF-deficient mice in a monoiodoacetate-induced knee osteoarthritis model

Background: The detailed mechanisms of knee osteoarthritis (OA) pain have not been clarified, but involvement of inflammatory cytokines such as tumor necrosis factor-alpha (TNF) has been suggested. The present study aimed to investigate the more detailed neurological involvement of TNF in joint pain using a TNF-knockout mouse OA model. Methods: The right knees of twelve-week-old C57BL/6J wild and TNF-deficient knockout (TNF-ko) mice (n=15, each group) were given a single intra-articular injection of 10 µg monoiodoacetate in 10 mL sterile saline. The left knees were only punctured as the control. Evaluations were performed immediately after the injection (baseline) and at 7, 14, and 28 days after the injection with a subsequent intra-articular injection of neurotracer into both knees. The animals were evaluated for immunofluorescence of the lumbar dorsal root ganglia (DRG) innervating the knee joints. The injected knees were observed macroscopically and mouse pain-related behaviors were scored. Results: Macroscopic observation showed similar knee OA development in both wild and TNF-ko mice. Calcitonin gene-related peptide (CGRP, a neuropeptide identified as a inflammatory pain-related biomarker) was significantly increased in DRG neurons innervating OA-induced knee joints with significantly less CGRP expression in TNF-ko animals. Pain-related behavior scoring showed a significant increase in pain in OA-induced joints, but there was no significant difference in pain observed between the wild and TNF-ko mice. Conclusions: The result of the present study indicates the possible association of TNF-alpha in OA pain but not OA development.     

Perioperative outcomes of esophagectomy preceded by the laparoscopic transhiatal approach for esophageal cancer

This study was designed to determine the efficacy of esophagectomy preceded by the laparoscopic transhiatal approach (LTHA) with regard to the perioperative outcomes of esophageal cancer. The esophageal hiatus was opened by hand‐assisted laparoscopic surgery, and carbon dioxide was introduced into the mediastinum. Dissection of the distal esophagus was performed up to the level of the tracheal bifurcation. En bloc dissection of the posterior mediastinal lymph nodes was performed using LTHA. Next, cervical lymphadenectomy, reconstruction via a retrosternal route with a gastric tube and anastomosis from a cervical approach were performed. Finally, a small thoracotomy (around 10 cm in size) was made to extract the thoracic esophagus and allow upper mediastinal lymphadenectomy to be performed. The treatment outcomes of 27 esophageal cancer patients who underwent LTHA‐preceding esophagectomy were compared with those of 33 patients who underwent the transthoracic approach preceding esophagectomy without LTHA (thoracotomy; around 20 cm in size). The intrathoracic operative time and operative bleeding were significantly decreased by LTHA. The total operative time did not differ between the two groups, suggesting that the abdominal procedure was longer in the LTHA group. The number of resected lymph nodes did not differ between the two groups. Postoperative respiratory complications occurred in 18.5% of patients treated with LTHA and 30.3% of those treated without it. The increase in the number of peripheral white blood cells and the duration of thoracic drainage were significantly decreased by this method. Our surgical procedure provides a good surgical view of the posterior mediastinum, markedly shortens the intrathoracic operative time, and decreases the operative bleeding without increasing major postoperative complications.     

Emerging Roles for Lysophospholipid Mediators in Pregnancy

Recent progress in lipid research has unveiled new biologic roles for lysophospholipids as mediators of intercellular signaling. Lysophosphatidic acid (LPA) and sphingosine 1‐phosphate (S1P) are representative lysophospholipids. Accumulating evidence suggests that, acting as intercellular mediators, these and other lysophospholipids may play important roles in physiological and pathological situations. This review discusses the possible involvement of LPA and S1P in reproductive processes, with a focus on the regulatory mechanisms of pregnancy maintenance. As LPA promotes prostaglandin synthesis, mediators in the LPA pathway may also play a significant role in implantation and parturition. S1P signaling is thought to be essential in vascular formation within the uteroplacental unit and in fetomaternal immunologic interactions. Derangements in either one of these lysophospholipid signaling pathways could result in pregnancy complications that may include implantation failure, preeclampsia, and preterm labor.