Randomized Trial of Laparoscopic Nissen Versus Anterior 180 Degree Partial Fundoplication - Late Clinical Outcomes at 15 to 20 years.

OBJECTIVE: To determine very late clinical outcomes at up to 20 years follow-up from a randomized controlled trial of Nissen versus anterior 180-degree partial fundoplication. SUMMARY BACKGROUND DATA: Nissen fundoplication for gastroesophageal reflux can be followed by troublesome side effects. To address this, partial fundoplications have been proposed. Previously reports from a randomized controlled trial of Nissen versus anterior 180-degree partial fundoplication at up to 10 years follow-up showed good outcomes for both procedures. METHODS: One hundred seven participants were randomized to Nissen versus anterior 180-degree partial fundoplication. Fifteen to 20 year follow-up data was available for 79 (41 Nissen, 38 anterior). Outcome was assessed using a standardized questionnaire with 0 to 10 analog scores and yes/no questions to determine reflux symptoms, side-effects, and satisfaction with surgery. RESULTS: After anterior fundoplication heartburn (mean score 3.2 vs 1.4, P = .001) and proton pump inhibitor use (41.7% vs 17.1%, P = .023) were higher, offset by less dysphagia for solids (mean score 1.8 vs 3.3, P = .015), and better ability to belch (84.2% vs 65.9%, P = .030). Measures of overall outcome were similar for both groups (mean satisfaction score 8.4 vs 8.0, P = .444; 86.8% vs 90.2% satisfied with outcome). Six participants underwent revision after anterior fundoplication (Nissen conversion for reflux - 6), and 7 underwent revision after Nissen fundoplication (Nissen to partial fundoplication for dysphagia - 5; redo Nissen for reflux - 1; paraesophageal hernia -1). CONCLUSIONS: At 15 to 20 years follow-up Nissen and anterior 180-degree partial fundoplication achieved similar success, but with trade-offs between better reflux control versus more side-effects after Nissen fundoplication.

Mesenchymal lineage cells and their importance in B lymphocyte niches.

Early B lymphopoiesis occurs in the bone marrow and is reliant on interactions with numerous cell types in the bone marrow microenvironment, particularly those of the mesenchymal lineage. Each cellular niche that supports the distinct stages of B lymphopoiesis is unique. Different cell types and signaling molecules are important for the progressive stages of B lymphocyte differentiation. Cells expressing CXCL12 and IL-7 have long been recognized as having essential roles in facilitating progression through stages of B lymphopoiesis. Recently, a number of other factors that extrinsically mediate B lymphopoiesis (positively or negatively) have been identified. In addition, the use of transgenic mouse models to delete specific genes in mesenchymal lineage cells has further contributed to our understanding of how B lymphopoiesis is regulated in the bone marrow. This review will cover the current understanding of B lymphocyte niches in the bone marrow and key extrinsic molecules and signaling pathways involved in these niches, with a focus on how mesenchymal lineage cells regulate B lymphopoiesis.

Retinoic Acid Receptor γ Activity in Mesenchymal Stem Cells Regulates Endochondral Bone, Angiogenesis, and B Lymphopoiesis.

Retinoic acid receptor (RAR) signaling regulates bone structure and hematopoiesis through intrinsic and extrinsic mechanisms. This study aimed to establish how early in the osteoblast lineage loss of RARγ (Rarg) disrupts the bone marrow microenvironment. Bone structure was analyzed by micro-computed tomography (µCT) in Rarg-/- mice and mice with Rarg conditional deletion in Osterix-Cre-targeted osteoblast progenitors or Prrx1-Cre-targeted mesenchymal stem cells. Rarg-/- tibias exhibited less trabecular and cortical bone and impaired longitudinal and radial growth. The trabecular bone and longitudinal, but not radial, growth defects were recapitulated in Prrx1:RargΔ/Δ mice but not Osx1:RargΔ/Δ mice. Although both male and female Prrx1:RargΔ/Δ mice had low trabecular bone mass, males exhibited increased numbers of trabecular osteoclasts and Prrx1:RargΔ/Δ females had impaired mineral deposition. Both male and female Prrx1:RargΔ/Δ growth plates were narrower than controls and their epiphyses contained hypertrophic chondrocyte islands. Flow cytometry revealed that male Prrx1:RargΔ/Δ bone marrow exhibited elevated pro-B and pre-B lymphocyte numbers, accompanied by increased Cxcl12 expression in bone marrow cells. Prrx1:RargΔ/Δ bone marrow also had elevated megakaryocyte-derived Vegfa expression accompanied by smaller sinusoidal vessels. Thus, RARγ expression by Prrx1-Cre-targeted cells directly regulates endochondral bone formation and indirectly regulates tibial vascularization. Furthermore, RARγ expression by Prrx1-Cre-targeted cells extrinsically regulates osteoclastogenesis and B lymphopoiesis in male mice. © 2018 American Society for Bone and Mineral Research.