臺灣博碩士論文加值系統

研究背景:
微創手術，是目前外科界的趨勢。很多過去的研究證實，減少患者不需要的傷害，不但減少術後的不適，更可以加快患者術後的恢復。目前現行的腹腔鏡結腸切除手術雖然已經有很好的術後復原表現，不可避免的，還是需要在腹部額外開一道傷口將標本取出及進行腸道吻合，這樣依舊會造成患者術後的疼痛與併發症。『腹腔鏡結腸切除手術合併自然孔標本取出』是將腹腔鏡大腸切除後的標本直接由肛門或陰道取出，完全不需要額外的腹部傷口，將開刀造成身體的傷害降到最低。這個臨床試驗的主要目標是去比較患者進行『腹腔鏡結腸切除合併自然孔標本取出手術』或『傳統腹腔鏡結腸切除手術』後實際的恢復狀況，次要目標是進一步探討全身的發炎反應是否因傷口的減少而有不同結果。

研究方法：
這是ㄧ個前瞻性的個案統計性研究，自民國100年9月開始第一位患者進行『腹腔鏡結腸切除合併自然孔標本取出手術』，陸續選擇符合條件的患者進行該手術；選擇條件包括 1.腫瘤直徑小於5公分 2.左側結腸病灶3.同意該項手術並簽屬同意書；排除不適合病患條件如下：1.術中發現腸繫膜過度肥厚而影響標本取出 2.男性患者合併肛門狹窄 3.急診手術 4.患者懷孕。全部手術過程都由中國醫藥大學附設醫院結直腸外科團隊完成，並以前瞻性方式收集患者各項資料及術後記錄，這些患者歸入「NOSE」群組。另外我們根據院內的手術紀錄單，選取同一時期 (民國100年9月到102年5月)進行傳統腹腔鏡左側結腸切除手術的患者，並排除掉腹腔鏡轉剖腹手術患者、合併其他手術患者及超過6公分腫瘤的患者，剩餘患者再根據『腫瘤大小』及『BMI體重指標』去和「NOSE」群組的患者以2:1的比例進行配對，隨機選取的患者就是對照組，稱為「ASE」群組。兩組群組患者將進行術後臨床數據的比較，包括手術時間及出血量、Meperidine需求量、排氣時間、住院天數或併發症發生比例等。另外在兩組患者中，選取同一時期開刀的病患 (民國102年3月到102年5月)，進行全身發炎指數的比較；分四個時段：術前、術後、術後24小時、術後72小時，進行抽血，分離出血清後以BDTM CBA Human Inflammatory Cytokines Kit來檢測病患的六項發炎反應： IL-1β, IL-6, IL-8, IL-10, IL-12p70, TNF protein。
研究結果：
在21個月的期間，總共有53位患者接受『腹腔鏡結腸切除合併自然孔標本取出手術』，對照組則選取106位接受『傳統腹腔鏡結腸切除手術』的患者。兩組患者的基本資料無論在年齡、性別、BMI、麻醉評估分數(ASA score)、癌症分期及腫瘤位置方面都沒有任何的差別。NOSE這ㄧ組雖然平均手術時間略高於ASE這ㄧ組(227.9 + 55.8 mins vs 218.1 + 57 mins)，但並沒有統計上的意義 (p=0.304)。至於兩組標本的病理報告，並未因手術方式的不同而有任何差異。有差異的部分還是在術後的臨床表現上，我們發現「NOSE」群組患者有較低的Meperidine需求量(29.3+53.9 mg vs 62.5+90.9g, p=0.007) 及較少的術後住院天數 (4.8+3.4 days vs 5.9+2.4 days, p=0.025)。兩組都沒有患者術後死亡，但都有11.32%的患者發生併發症，兩組各有ㄧ位患者發生接口滲漏。在全身發炎反應的研究方面，「NOSE」群組有10位患者加入，「ASE」群組則有8位患者。結果發現不論在哪個時間檢驗或任ㄧ種發炎指數，幾乎都是「NOSE」群組患者有較嚴重的發炎反應，不過統計學上並無顯著差異。
結論：
『腹腔鏡結腸切除手術合併自然孔標本取出』是ㄧ種安全、可行的新式手術，經過統計比較發現有較少的疼痛及有較佳的術後恢復，而且並未增加術後併發症。本研究中進行發炎反應分析的樣本數甚少，因此這部分的統計未來需要更多的個案加入才可能得到較具代表性的結論。

Background
Minimal invasive surgery had become the trend of current surgical method and many previous randomized trials had proven better surgical short-term outcome in laparoscopic colectomy. However, technique of current laparoscopic colectomy was not a “pure laparoscopic surgery”, because a minilaparotomy for specimen was need. This additional abdominal wound may increase postoperative wound pain and relative complications which may worsen the surgical results.

Aim of this study
In this study, we introduced our surgical methods for natural orifice specimen extraction, instead of adding abdominal wound. The aim of this study is going to compare the surgical outcome and systemic inflammatory response between laparoscopic colectomy with natural orifice specimen extraction and conventional laparoscopic colectomy.

Methods and Materials
Since the 1st case performing laparoscopic anterior resection with natural orifice specimen extraction (NOSE) in September 2011, we prospectively collected data from these patients, who underwent the new surgical technique. The inclusion criteria of eligible patients were left side colon and non-bulky tumor (less than 5cm in diameter). Patients with emergent surgery, visceral obesity, advanced tumor (T4 lesion), peritoneal carcinomatosis or pregnancy were all excluded from our study. All data including patients’ information, surgical outcome, complications and pathologic report were collected until May 2013 and these patients joined into NOSE group. In the same period, we also recorded all data of patients underwent conventional laparoscopic anterior resection by the same laparoscopic colorectal team in our hospital. Patients fitting to the same criteria were randomly selected into group of abdominal specimen extraction (ASE) in ratio of 2:1 to cases underwent NOSE successfully. Tumor size and Body-mass index (BMI) were matched between these two groups.
Since March 2013, we started to evaluate systemic inflammatory response in both groups. Patient’s blood sample was collected before operation and after operation 1 hour 24 hours and 72 hours and then the levels of Interleukin (IL) -1β, IL-6, IL-8, IL-10, IL-12p70, Tumor necrotic factor (TNF) were detected by the commercially available BDTM CBA Human Inflammatory Cytokines Kit. Reported data from both groups were compared statistically.

Results
Between Sep. 2011 and May 2013, there were 53 patient underwent Lap. AR with NOSE and 104 selected patients in ASE group. There was no significant difference in basic patient’s information and pathologic report between two groups. Although we took more operative time in NOSE group than ASE group, it did not show statistical difference (227.9 + 55.8 mins vs 218.1 + 57 mins, p=0.034). The mainly difference was shown in the short-term surgical outcome. The patients with NOSE procedure had less post-operative pain who required less Meperidine dose for pain control (29.3+53.9 mg vs 62.5+90.9g, p=0.007) and the postoperative hospital stay duration was also shorter in NOSE group(4.8+3.4 days vs 5.9+2.4 days, p=0.025). Both groups had no surgical mortality and the morbidity rate was the same (11.32%).
In the study of systemic inflammatory reaction, there were 10 patients included in NOSE group and 8 patients in ASE group. The levels of Interleukin (IL) -1β, IL-6, IL-8, IL-10 were all higher in patients with NOSE procedure than conventional procedure in almost postoperative timing, although there was no significant different.

Conclusion
Laparoscopic anterior resection with natural orifice specimen extraction is a safe and feasible surgical method. This new technique presented better surgical short-term outcome, including less postoperative pain, early return of bowel function and fewer hospital stay. However, we need more cases included to obtain significant results of the systemic inflammatory response after new or conventional laparoscopic methods.

1. 審定合格書 -------------------------------------------------------------------P3
2. 中文摘要------------------------------------------------------------------------P4
3. 英文摘要------------------------------------------------------------------------P8
4. 本文
1) Introduction -----------------------------------------------------------------P11
2) Patient and Method --------------------------------------------------------P13
?? Technique of laparoscopic anterior resection-------------P15
?? Data collection and Analysis --------------------------------------P19
?? Inflammatory cytokine measurement ----------------------------P20
?? Statistical analysis --------------------------------------------------P21
3) Result
?? Clinical surgical outcome ------------------------------------------P22
?? Inflammatory cytokin response ------------------------------------P24
4) Discussion -------------------------------------------------------------------P25
5) Reference --------------------------------------------------------------------P32
6) 附圖及表格
?? Table 1 Patient selection algorithm-------------------------------P36
?? Table 2 Patients demographic data---------------------------------P37
?? Table 3 Operative results--------------------------------------------P38
?? Table 4 Post-operative complications------------------------------P39
?? Figure 1 Abdominal port site---------------------------------------P40
?? Figure 2 Specimen extraction by different methods-------------P40
?? Figure 3 Setting of Aloxis wound retractor-----------------------P41
?? Figure 4 Transanal specimen extraction---------------------------P42
?? Figure 5 Prevent intraperitoneal contamination------------------P43
?? Figure 6 Abdominal appearance after operation-----------------P44
?? Figure 7 Procedure of BDTM Cytometric Bead Array------------P45
?? Figure 8 Flow cytometry--------------------------------------------P45
?? Figure 9 Mean level of inflammatory cytokine-------------------P46
?? Figure 10 Individual level of inflammatory cytokine------------P47
5. Supplement table 1 受試者同意書-----------------------------------------P48
6. 作者簡介-------------------------------------------------------------------------P56
7. 論文感謝函---------------------------------------------------------------------P58

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