- 學位論文
發展微創手術以治療需要多器官切除及重建之局部侵犯性大腸直腸癌
Development of the Minimally Invasive Surgical Techniques for the Treatment of Locally Advanced Colorectal Cancer Requiring Multivisceral Resection and Reconstruction
摘要
背景：大腸直腸癌近年來已經成為高發生率及高盛行率的惡性腫瘤。使用腹腔鏡手術切除原發性腫瘤併淋巴結廓清已經是標準手術方式。然而外科醫學界對於以腹腔鏡手術治療局部侵犯性大腸直腸癌仍未有定論。所顧慮者在於：使用微創手術進行整塊多器官切除需要較高之技術難度，再者亦不清楚使用微創手術能否達到腫瘤學所要求之R0切除率並且得到令人滿意之手術成績，故目前標準治療方式仍以開腹手術為主。隨著近十年來腹腔鏡手術技術的之成熟及設備器材之發展，吾人猜想以微創手術治療局部侵犯性大腸直腸癌應為可行、安全及有效力之手術方式，值得回顧文獻評估並開發微創手術在此議題之適應症。另外機器人手術系統具有高解析度影像和多自由度的機器手腕可以達到細緻的體腔內縫合重建，近年來機器人各領域手術之發展呈現跳躍式進步，吾人亦猜測機器人手術之使用在局部侵犯性大腸直腸癌扮演愈來愈重要的角色。 目的：本研究旨在開發以微創手術治療需要多器官切除和重建之局部侵犯性大腸直腸癌之手術技巧，並且探討和更新微創手術在此議題之適應症，希望能夠提供日後以微創手術治療這類病人的實證以及指引未來研究方向。 方法：由前瞻性建置的資料庫中，吾人回溯性收集於2006年6月至2020年11月之間在臺大醫院、新竹分院及雲林分院三院區，接受腹腔鏡手術和機器人手術之局部侵犯性大腸直腸癌病人的臨床病理、術中後恢復以及腫瘤學資料。吾人將分析cT4局部侵犯性大腸直腸癌病人的術中後以及腫瘤學結果，並比較以微創手術來治療cT4a病人族群和cT4b需要多器官切除之大腸直腸病人癌族群的手術和腫瘤學結果。吾人將團隊成果和文獻結果進行比較分析，試圖釐清何種遭cT4b局部侵犯之器官，能夠藉由微創手術方式進行整塊多器官切除手術中獲得最好治療成果。其次，吾人聚焦於局部侵犯性大腸直腸癌合併膀胱侵犯的族群。由前部分結果得知膀胱為最容易遭到cT4大腸直腸癌侵犯之器官；重建被部分切除之膀胱需要較高之腹腔鏡手術技巧。吾人將探討以腹腔鏡手術和機器人手術兩種微創手術之手術中後和腫瘤學成績，嘗試開發機器人手術在此議題的應用性。最後，吾人希望建立起局部侵犯性大腸直腸癌的手術策略指引，提供臨床實證力基礎。本研究使用敘述統計、推論統計和Cox比例風險模型進行統計學分析。 結果：本研究共收入128位cT4局部侵犯性大腸直腸癌病人；進食時間中位數為6天，術後住院天數中位數為11天，開腹轉換率為7.8%，併發症率為27.3%，三十天死亡率為0.78%；對於90位cT4M0病人的R0切除率為92.2%。這些結果達到與文獻相當之手術成績。進一步比較cT4a和需要多器官切除cT4b大腸直腸癌，發現後者手術時間、失血量、進食時間和住院天數較長，但併發症和R0切除率無統計顯著差異。本研究受侵犯切除之器官包括膀胱、腹壁/腹膜、子宮附件(和卵巢)及小腸等；上述器官以微創手術方式進行整塊多器官切除和重建是安全而且可行的。本研究亦收納41位侵犯到膀胱之局部侵犯性大腸直腸癌病人進行分析，當中32位接受腹腔鏡手術，9位接受機器人手術。兩組病人在手術中後結果及存活率上無統計顯著差異。R1切除率是降低無病存活率的唯一獨立預後因子。 結論：以腹腔鏡手術治療局部侵犯性大腸直腸癌是安全而且可行的方式，包括需要多器官切除及重建之局部侵犯性大腸直腸癌。膀胱是局部侵犯性大腸直腸癌最常侵犯的器官之一，以機器人手術方式來切除侵犯性大腸直腸癌以及受侵犯之膀胱是可行的手術方式，而且能夠達到和腹腔鏡手術相似的手術成績。本研究也指出：為了克服現階段文獻之選擇性偏差，高證據力之臨床隨機分派研究以探討微創手術治療需要多器官切除及重建之局部侵犯性大腸直腸癌是迫切需要的。另外欲探討微創手術在局部侵犯性大腸直腸癌的角色，以受侵犯器官為區分導向之研究將更能釐清微創手術在真實世界的手術和腫瘤學效益。
並列摘要
Background: The incidence and prevalence of colorectal cancer (CRC) have recently increased worldwide. Laparoscopic colectomy combined with radical lymph node dissection has become the standard surgical method for CRC treatment. However, its application for treating of locally advanced CRC (LACRC) remains controversial. The main concerns surround the high technical demands of minimally invasive surgery for en bloc multivisceral resection, which may lead to inadequate R0 resection and increased surgical complications. Therefore, open surgery remains the standard treatment for LACRC. Owing to the maturation of laparoscopic techniques among surgeons and the development of surgical and optical equipment in the last two decades, we hypothesized that laparoscopic surgery is a safe, feasible, and efficacious method for treating LACRC; therefore, the indication for minimally invasive surgery is broadened. On the other hand, a robotic surgical system equipped with high-resolution imaging systems and high-freedom robotic wrists allows intracorporeal reconstruction, which facilitates robotic surgery to a giant leap. We also hypothesized that robotic surgery plays an increasingly important role in the treatment of LACRC. Methods: A prospectively maintained database of patients who underwent laparoscopic or robotic surgery at the National Taiwan University Hospital, Hsinchu Branch, and Yunlin Branch was retrospectively reviewed from June 2006 to November 2020. Clinicopathological, intraoperative, postoperative and oncologic results of these patients were collected. Then, patients with LACRC were classified into the cT4a and cT4b groups requiring multivisceral resection. Surgical and oncologic outcomes were compared between the cT4a and cT4b groups. A literature review will be conducted, and the results will be compared with those of our study. We aimed to identify which organs invaded by cT4b LACRC can achieve the best surgical outcomes using laparoscopic en bloc multivisceral resection. In our previous study, the urinary bladder was the organ most vulnerable to invasion by cT4b LACRC, which requires high surgical skills for reconstruction after partial cystectomy. This study focused on a specific patient group with cT4b LACRC and urinary bladder invasion. Robotic surgery was performed in patients with cT4b LACRC who required multivisceral resection. The surgical and oncologic results of robotic and laparoscopic surgeries were compared between the two surgical methods. Finally, we established guidelines for the surgical planning of LACRC, which may serve as a basis for future studies. Descriptive statistics, inferential statistics, and Cox proportional hazard models were used. Results: We recruited 128 cT4 LACRC patients undergoing MIS. The open conversion was 7.8%. The complication rate, defined as Clavien–Dindo classification ≥ II, was 27.3%, and the postoperative 30-day mortality was 0.78%. R0 resection rate was 92.2% for 90 cT4M0 patients. The median time to soft diet was 6 days, and the median postoperative length of stay was 11 days. These surgical results are comparable with those reported in previous studies. Further subgroup analysis showed cT4b LACRC patients requiring multivisceral resection demonstrated a longer operative time, increased blood loss, prolonged time to resume a soft diet and postoperative length of stay than those of cT4a LACRC patients. However, no significant difference between the two groups was found in terms of complications and R0 rates. The resected organs in this study included the urinary bladder, abdominal wall/peritoneum, adnexa, and small bowel, which can be safely and feasibly performed laparoscopically. Furthermore, we recruited 41 patients with LACRC patients invading the urinary bladder. Among them, laparoscopic surgery was performed in 31 patients, whereas robotic surgery in nine patients. There was no statistical difference in terms of surgical and oncologic outcomes between two groups. R1 resection was detected as the only independent prognostic factors for reduced disease-free survival (hazard ratio 21.386; 95% confidence interval 1.991–229.723; p = 0.0115). Conclusions: The present dissertation indicates that laparoscopic surgery is safe and feasible for treating LACRC, including cT4 LACRC which requires multivisceral resection and reconstruction in selected patients. It has been shown that the urinary bladder is the organ most frequently invaded by LACRC. The robotic surgery can be performed safely for treating LACRC invading the urinary bladder, with similar surgical results to laparoscopic surgery. However, further prospective, randomized controlled trials are mandatory to reach high-level evidence to clarify the role of minimally invasive surgery for cT4b LACRC. Moreover, further organ-oriented studies will provide better convincing functional and oncologic data regarding the role of minimally invasive surgery in multivisceral resection for treating cT4b LACRC in the real world.