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研究生: 呂維勛
Lu, Wei-Hsun
論文名稱: 胰臟部分切除術後,殘餘胰臟組織體積及功能的變化: 胰臟是否能再生?
Volume and functional changes of remnant pancreatic tissue after pancreatectomy: Does pancreas regenerate?
指導教授: 沈延盛
Shan, Yan-Shen
學位類別: 碩士
Master
系所名稱: 醫學院 - 臨床醫學研究所碩士在職專班
Institute of Clinical Medicine(on the job class)
論文出版年: 2019
畢業學年度: 107
語文別: 英文
論文頁數: 50
中文關鍵詞: 胰臟切除術胰十二指腸切除術遠端胰腺切除術胰腺再生胰腺源性糖尿病術後糖尿病C-peptideβ細胞
外文關鍵詞: pancreatectomy, pancreaticoduodenectomy, distal pancreatectomy, pancreas regeneration, pancreatogenic diabetes, post-operative diabetes, C-peptide, β-Cell
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  • 胰臟切除術是幾種適應症的標準治療方法,例如胰腺癌,腺瘤,胰臟囊腫和胰腺炎。胰臟切除術依據胰腺病變的位置和範圍來決定手術的方式,最常見的術式包括胰十二指腸切除術(pancreaticoduodenectomy, PD)和遠端胰臟切除術(distal pancreatectomy, DP)。隨著醫療發展及手術技術的進步,現今的胰臟切除術更加安全。在大規模的醫學中心,胰十二指腸切除術的手術死亡率已降至0%至5%之間。胰臟切除術後存活率的提高,更進一步促使我們對術後血糖變化的重視。與部分肝切除術後的肝臟再生不同,胰臟切除術後的胰腺再生仍充滿爭議。因此,我們的研究目的是為了確定術後殘餘胰腺的體積變化和葡萄糖代謝功能是否相關。本研究納入了2009年1月至2017年12月接受部分胰臟切除術的患者,包括遠端胰臟切除術和胰十二指腸切除術。在追蹤期間,我們會固定在術前、術後3個月、1年及兩年追蹤血清葡萄糖,HbA1C以及C-peptide的數值,並依此評估內分泌功能。此外,我們也會在手術前和術後3個月,1年和2年安排進行腹部電腦斷層掃瞄或核磁共振檢查,並通過影像學檢查來估算術後胰腺改變的體積。在分析的135名患者中,90名患者接受了胰十二指腸切除術,45名患者接受了遠端胰臟切除術。我們的研究結果顯示接受胰十二指腸切除術的殘餘胰腺呈現萎縮性變化。PD術後3個月,1年和2年殘餘胰腺體積與初始殘餘體積相比,平均變化比例分別為80.79%,68.67%和65.34%(p <0.001)。相比之下,大多數DP患者的殘餘胰腺略有增生,術後3個月,1年和2年殘餘胰腺與初始殘餘體積相比,平均變化比例分別為106.25%,106.62%和110.43%(p = 0.019)。 DP患者術後新生糖尿病的發生率高於PD患者,但在統計學上無顯著差異(33.3%vs。22.7%,p = 0.115)。此外,在PD組中,有29.2%術前已診斷有糖尿病的患者,在接受胰十二指腸切除術(PD)後,糖尿病因而改善。然而,殘餘胰腺體積和C-peptide濃度均未與術後新生糖尿病發生與否有顯著相關性。我們的結果也顯示C-peptide濃度變化與殘餘胰腺體積變化之間沒有顯著相關性。兩組胰腺切除術後C-peptide濃度皆隨之下降(p <0.001),而DP組中的C-peptide濃度下降最為嚴重。然而,在術後追蹤的第三個月、第一年及第二年,兩組C-peptide的濃度都會隨著時間而逐漸回升(β±SE = 16.33±5.03,p = 0.001)。而PD組相較於DP組,有較好的恢復分泌C-peptide的能力(β±SE = 13.26±5.50,p = 0.016)。
    由此研究的結果可以得知,殘餘胰腺組織在PD患者中呈現萎縮的變化,但在DP患者中則會增生。部分胰臟切除術後,兩組的β細胞功能皆會隨著時間而改善。而PD組中的殘餘遠端胰腺,與DP組相比,具有較佳的β細胞恢復能力。

    Pancreatectomy is a standard treatment for several indications, such as pancreatic adenocarcinoma, pancreatic adenoma, pancreatic cysts and chronic calcified pancreatitis. There are two major surgical methods of pancreatectomy, including pancreaticoduodenectomy (PD) and distal pancreatectomy (DP), depending on the location and extent of pancreatic lesion. Pancreatectomy is much safer nowadays, the mortality rate of PD has decreased to 0% ~ 5% in large-scale medical centers. The improvement of survival rate after pancreatectomy had promoted the consideration of long-term metabolic consequences. Unlike the well-documented liver regeneration after partial hepatectomy, pancreatic regeneration after pancreatectomy is still controversial. Herein, the aims of this study are to determine the changes of volume in the remnant pancreas and to define whether above volume changes of pancreas correlate with the function of glucose metabolism. This study included the patients from Jan. 2009 to Dec. 2017 undergoing partial pancreatectomy, including PD and DP for a variety of disease. During follow-up, the endocrine functions were assessed according to the level of glucose, HbA1C, C-peptide in serum. The volume of pancreas was determined via abdominal computed tomography (CT) scan before the operation and at 3months, 1 year and 2 years postoperatively. In all enrolled 135 patients, 90 patients underwent PD and 45 patients underwent DP. Our results showed that the remnant pancreas in the PD group had an atrophic change. The mean ratio of the remnant pancreas compared with initial residual pancreas at 3 months, 1 and 2 years after pancreatectomy were 80.79%, 68.67% and 65.34% respectively (p < 0.001). In contrast, the remnant pancreas in most of the DP patients are slightly hypertrophic, the mean ratio of the remnant pancreas at 3 months, 1 and 2 years postoperatively were 106.25%, 106.62% and 110.43% (p = 0.019). Although the DP patients had higher incidence of new-onset diabetes than the PD patients, but the difference was not statistically significant (33.3% vs. 22.7%, p = 0.115). In addition, 29.2% of the PD patients with preoperative diabetes mellitus (DM) had resolved after PD. However, neither the pancreas’ volume nor C-peptide level showed significant correlation with postoperative new-onset DM. Our results also cannot found the relationship between C-peptide level and remnant pancreas’ volume. The C-peptide level dropped significantly after partial pancreatectomy in both groups (p < 0.001) and this phenomenon was more severe in the DP group. Postoperative C-peptide levels were restored partially in both groups (β ± SE= 16.33 ± 5.03, p = 0.001) regardless of the volume change. Compared to DP group, PD group had greater restoration capacity of C-peptide secretion (β ± SE = 13.26 ± 5.50, p = 0.016).In conclusions, the remnant pancreas tissue atrophied in the PD patients but hypertrophied in DP patients. The function of β-Cell would be partially restored after partial pancreatectomy in both groups and the distal portion of remnant pancreas in the PD group had greater restoration capacity of β-Cell

    中文摘要--------------------------------------------------i 英文摘要-------------------------------------------------ii 誌謝----------------------------------------------------iv 目錄-----------------------------------------------------v 表目錄--------------------------------------------------vii 圖目錄-------------------------------------------------viii 符號----------------------------------------------------ix 正文-----------------------------------------------------1 1.Background --------------------------------------------1 1.1 Introduction of pancreatectomy ----------------------1 1.2 β-cell and insulin secretion ------------------------2 1.3 C-peptide ---------------------------------------2 1.4 Pancreatogenic diabetes mellitus --------------------3 1.5 Pancreas regeneration -------------------------------4 2. Specific Aim -----------------------------------------6 3. Research Design --------------------------------------8 4. Methods ---------------------------------------------10 5. Results ---------------------------------------------13 5.1 Clinicopathologic characteristics ----------------13 5.2.1 The residual volume of the pancreas was decreased in the PD group, but increased in the DP group in time-dependent manner----------------------------------------13 5.2.2 DP group had a higher incidence to induces hypertrophic pancreas regeneration ---------------------15 5.3.1 The difference of regenerative volume in head and distal portion of residual pancreas after DP is non-significant --------------------------------------------15 5.3.2 Pancreatic duct obstruction is major factor related to residual pancreas atrophy in the PD group -----------16 5.3.3 Spleen preservation may related to residual pancreas hypertrophy in the DP group ----------------------------16 5.4.1 Higher incidence of new onset DM in the DP group and partial preoperative DM were resolved in the PD group --17 5.4.2 No significant relationship between the perioperative factors and new-onset DM -----------------18 5.4.3 Neither postoperative pancreas volume nor C-peptide level correlated with occurrence of new onset DM -------18 5.5.1 The C-peptide level dropped significantly after partial pancreatectomy in both groups ------------------19 5.5.2 No significant correlation between C-peptide level change (%) and residual volume (%) ---------------------19 5.5.3 The impact on endocrine function after partial pancreatectomy was more severe in the DP group regardless of the change of pancreas volume; the PD group had better restoration in β-cell secretory capacity ---------------19 6. Discussion-------------------------------------------21 參考文獻-------------------------------------------------28 附錄----------------------------------------------------35

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