Zheng Jian, Glezerman Ilya G, Sadot Eran, McNeil Anjuli, Zarama Cristina, Gönen Mithat, Creasy John, Pak Linda M, Balachandran Vinod P, D'Angelica Michael I, Allen Peter J, DeMatteo Ronald P, Kingham Peter T, Jarnagin William R, Jaimes Edgar A
Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY Department of Medicine, Weill Cornell Medical College, New York, NY Department of Surgery, Rabin Medical Center, Petah Tikva, Israel Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
J Am Coll Surg. 2017 Oct;225(4):488-497e2. doi: 10.1016/j.jamcollsurg.2017.06.012. Epub 2017 Jul 6.
Postoperative hypophosphatemia is common and is associated with a lower risk of liver failure after hepatectomy, but higher morbidity after pancreatectomy. Whether different physiologic mechanisms underlie the hypophosphatemia associated with these very different clinical outcomes is unclear. This study aims to evaluate the underlying mechanism in postoperative hypophosphatemia.
We prospectively enrolled 120 patients who underwent major hepatectomy (n = 30), minor hepatectomy (n = 30), pancreatectomy (n = 30), and laparotomy without resection (control group, n = 30). Preoperative and postoperative serum and urinary phosphorus, calcium, and creatinine, as well as phosphaturic factors, including serum nicotinamide phosphoribosyltransferase (NAMPT), fibroblast growth factor-23, and parathyroid hormone were measured. In addition, we evaluated urinary levels of nicotinamide catabolites, N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide.
We found that significant hypophosphatemia occurred from postoperative day (POD) 1 to POD 2 in all 4 groups and was preceded by hyperphosphaturia from preoperative day to POD 1. Phosphate level alterations were associated with a significant increase in NAMPT levels from preoperative day to POD 2 in all 3 resected groups, but not in the control group. The fibroblast growth factor-23 levels were significantly decreased postoperatively in all 4 groups, and parathyroid hormone levels did not change in any of the 4 groups. Urine levels of N-methyl-2-pyridone-5-carboxamide and N-methyl-4-pyridone-3-carboxamide decreased significantly in all 4 groups postoperatively.
This study demonstrates that the mechanism of hypophosphatemia is the same for both liver and pancreas resections. Postoperative hypophosphatemia is associated with increased NAMPT. The mechanism that upregulates NAMPT and its role on disparate clinical outcomes in postoperative patients warrant additional investigation.
术后低磷血症很常见，与肝切除术后肝衰竭风险较低相关，但与胰腺切除术后较高的发病率相关。与这些截然不同的临床结果相关的低磷血症是否存在不同的生理机制尚不清楚。本研究旨在评估术后低磷血症的潜在机制。
我们前瞻性纳入了120例接受大肝切除术（n = 30）、小肝切除术（n = 30）、胰腺切除术（n = 30）以及未行切除的剖腹手术（对照组，n = 30）的患者。测量术前和术后血清及尿磷、钙和肌酐，以及磷排泄因子，包括血清烟酰胺磷酸核糖基转移酶（NAMPT）、成纤维细胞生长因子-23和甲状旁腺激素。此外，我们评估了尿中烟酰胺分解代谢产物N-甲基-2-吡啶酮-5-甲酰胺和N-甲基-4-吡啶酮-3-甲酰胺的水平。
我们发现，所有4组患者术后第1天至第2天均出现显著的低磷血症，且术前至术后第1天出现高磷尿症。在所有3个切除组中，从术前至术后第2天，磷酸盐水平的改变与NAMPT水平的显著升高相关，但对照组未出现这种情况。所有4组患者术后成纤维细胞生长因子-23水平均显著降低，4组中任何一组的甲状旁腺激素水平均未改变。所有4组患者术后尿中N-甲基-2-吡啶酮-5-甲酰胺和N-甲基-4-吡啶酮-3-甲酰胺水平均显著降低。
本研究表明，肝切除和胰腺切除术后低磷血症的机制相同。术后低磷血症与NAMPT升高有关。上调NAMPT的机制及其在术后患者不同临床结果中的作用值得进一步研究。
