





摘要: 目的 分析原發性膽總管結石復發患者的總體情況、膳食因素等臨床特征,為積極預防結石復發提供依據。方法 回顧性收集2013年1月—2023年12月內蒙古自治區人民醫院肝膽胰脾外科因膽石病行膽囊切除治療的23 730例患者臨床資料,其中術后復發334例。按性別分類,對復發患者的復發率、復發周期、復發年齡、復發結石類別,以及一般資料、疾病資料、影像學資料和膳食因素資料進行匯總分析。計量資料2組間比較采用成組t檢驗,計數資料2組間比較采用χ 2 檢驗。結果 膽囊切除術后原發性膽總管結石復發率為1. 41%,復發周期頻數最高集中在術后10年,男、女性復發周期差異有統計學意義(t=5. 238,Plt;0. 001)。首次診斷為單純膽囊結石和膽囊合并膽總管結石者其術后結石復發率分別為1. 23%和2. 76%,差異有統計學意義(χ 2 =42. 104,Plt;0. 001)。復發者中年齡gt;60歲在總計及男、女性中均占比最高,92%為漢族居民;10%的復發者有膽囊結石家族史;合并癥中以伴高血壓者占比最高。復發者中吸煙和飲酒者占比分別為76. 7%和10. 3%。63. 8%的復發者BMI正常、23. 2%為超重,且距第1次膽囊手術時體質量相比,60. 1%的復發者體質量下降,22. 9%體質量增加。不同性別復發者的年齡構成、民族分布、居住地類型、合并癥、吸煙、飲酒、BMI分類、體質量變化差異均有統計學意義(P值均lt;0. 001)。復發結石類型中多發、單發、泥沙樣結石的比例為74∶15∶11;結石大小lt;1 cm、1~2 cm、gt;2 cm的占比分別為40. 5%、48. 8%和10. 6%;手術方式為開腹和腹腔鏡的比例分別為66. 1%和33. 9%;各類型血脂異常的比例均低于30%。不同性別復發者的初次結石種類、結石類型、結石大小、手術方式及高密度脂蛋白異常占比差異均有統計學意義(P值均lt;0. 001)。影像學資料分析發現膽道結構異常者僅4例,表現為膽囊管長而彎曲,術后73. 1%者伴有膽總管擴張。膳食因素隨訪發現55. 8%的復發者平素飲食不規律。平素飲食結構以肉類和主食為主者分別占比43. 8%和37. 8%,且有性別差異,男性以肉類為主、女性以主食為主;64. 1%的復發者平素有高鹽高油的飲食習慣;59. 8%的患者第1次結石術后飲食有改變,其中80%的患者能將飲食調整為規律(即飲食規律者可提高至92%)。結論 本地區原發性膽總管結石復發率較低且無性別差異,復發高峰在術后10年,60歲以上人群是結石復發的集中群體。膳食因素及臨床特征分析有助于醫、患進一步認識原發性膽總管結石復發的特點,為后續采取針對性的預防提供基礎依據。
關鍵詞: 膽囊切除術; 膽總管結石病; 復發; 病理狀態, 體征和癥狀
基金項目: 內蒙古醫學科學院公立醫院科研聯合基金項目(2023GLLH0021); 內蒙古自治區科技計劃項目(2021GG0116);內蒙古自治區自然科學基金項目(2019MS08086)
Clinical features of patients with recurrent primary common bile duct stones after cholecystectomyLU Jianhui 1a ,LI Yongli 2 ,GUO Ruifang 1a ,XUE Rongquan 1b1. a. Clinical Nutrition Center, b. Department of Hepatobiliary, Pancreatic and Spleen Surgery, Inner Mongolia People’s Hospital,Hohhot 010017, China; 2. Inner Mongolia Clinical College, Inner Mongolia Medical University, Hohhot 010059, China
Corresponding authors: GUO Ruifang, 6872_grf@163.com (ORCID: 0000-0002-0756-3549); XUE Rongquan, xrq1212@189.com(ORCID: 0009-0003-9411-8121)
Abstract: Objective To investigate the general situation, dietary factors, and clinical features of patients with recurrent primary common bile duct stones, and to provide a basis for effective prevention of stone recurrence. Methods A retrospective analysiswas performed for 23 730 patients who underwent cholecystectomy due to cholelithiasis in Department of Hepatobiliary, Pancreaticand Spleen Surgery, Inner Mongolia People’s Hospital, from January 2013 to December 2023, and according to the presence orabsence of recurrence of primary common bile duct stones after surgery, 334 patients were divided into recurrence group. Therecurrence group was further analyzed based on sex in terms of recurrence rate, recurrence cycle, recurrence age, recurrence type,and general, disease, imaging, and dietary factors. The independent-samples t test was used for comparison of continuous databetween two groups, the chi-square test was used for comparison of categorical data between two groups. Results There were 334cases of recurrence of primary bile duct stones after cholecystectomy, with a recurrence rate of 1.41%, and the highest frequency ofrecurrence cycle was observed in 10 years after surgery, with a significant difference in recurrence cycle between the male andfemale patients (t=5.238, Plt;0.001). There was a significant difference in the recurrence rate of stones after surgery between thepatients with simple gallstones and those with gallbladder and common bile duct stones at initial diagnosis (1.23% vs 2.76%, χ 2 =42.104, Plt;0.001). The patients with recurrence aged gt;60 years accounted for the highest proportion in the whole population and in bothmale and female populations, and 92% were Han residents; 10% of the patients with recurrence had a family history of gallstones, andas for comorbidities, the patients with hypertension accounted for the highest proportion. Among the patients with recurrence, thepatients with smoking or drinking accounted for 76.7% and 10.3%, respectively. As for body weight, 63.8% of the patients withrecurrence had a normal body mass index (BMI), and 23.2% of the patients were overweight; compared with body weight at the time ofthe first gallbladder surgery, a reduction in body weight was observed in 60.1% of the patients with recurrence, while an increase in bodyweight was observed in 22.9% of the patients with recurrence. There were significant differences between the male and female patientswith recurrence in age composition, ethnicity, the type of place of residence, comorbidities, smoking, drinking, BMI, and the changein body weight (all Plt;0.001). As for the type of stone recurrence, the ratio of multiple stones, solitary stones, and muddy stones was 74∶15∶11, and the stone size of lt;1 cm, 1-2 cm, and gt;2 cm accounted for about 40.5%, 48.8%, and 10.6%, respectively. As for thesurgical procedure, the patients undergoing laparotomy accounted for 66.1%, and those undergoing laparoscopy accounted for 33.9%.The patients with various types of dyslipidemia accounted for a percentage oflt;30%. There were significant differences between the maleand female patients with recurrence in the type of stones at initial onset, the type and size of stones, and surgical procedure (all Plt;0.001). Imaging data showed that 4 patients had an abnormal structure of the bile duct, manifesting as long and curve cystic ducts, and73.1% of the patients had common bile duct dilatation after surgery. The follow-up of dietary factors showed irregular diets in 55.8% of thepatients with recurrence. As for the dietary structure, meat and staple food accounted for 43.8% and 37.8%, respectively, which showed asex difference, with meat in male patients and staple food in female patients; 64.1% of the patients with recurrence had a high-salt andhigh-oil diet; 59.8% of the patients had changes in diet after the first surgery for stones, among whom 80% were able to have a regulardiet, and the patients with a regular diet accounted for 92%. Conclusion There is a relatively low recurrence rate of primary commonbile duct stones in this area, and there is no sex difference. The peak of recurrence is 10 years after surgery, and recurrence of stones ismainly observed in the population aged gt;60 years. The analysis of dietary and clinical features can help doctors and patients to furtherunderstand the characteristics of the recurrence of primary common bile duct stones and provide a basis for subsequent targeted prevention.
Key words: Cholecystectomy; Choledocholithiasis; Recurrence; Pathological Conditions, Signs and SymptomsResearch funding: Inner Mongolia Academy of Medical Sciences Public Hospital Research Joint Fund Project (2023GLLH0021);Science and Technology Project of Inner Mongolia Autonomous Region (2021GG0116); Natural Science Foundation Project of InnerMongolia Autonomous (2019MS08086)
膽石病是消化系統的常見病和多發病,主要包括發生在膽囊和膽管的結石。近年來其發病率呈上升趨勢,膽囊結石在成年人中的發病率為6%~10%,其中5%~15%的膽囊結石患者同時合并有膽總管結石[1-2] 。隨著“保膽”到“切膽”治療理念的轉變,膽囊切除目前是治療膽結石的首選方法[3] 。然而,膽囊切除后并非一勞永逸,術后意外遺留的結石是一種罕見但公認的并發癥,研究者們一般將膽囊切除術后6個月內再發的結石認為是殘余結石[4-5] 。除殘余結石外,原發性膽總管結石復發的問題更是困擾醫生和患者的難題之一。目前已有保膽取石、內鏡逆行胰膽管造影(endoscopic retrogradecholangiopancreatography, ERCP)及 腹 腔 鏡 膽 囊 切 除(laparoscopic cholecystectomy, LC)聯合腹腔鏡下膽總管探查(laparoscopic common bile duct exploration, LCBDE)術后結石復發的文獻報道,但因大多研究樣本量小,隨訪周期短、僅限于臨床資料等,研究結論有待進一步統一和完善。鑒于此,本文收集并分析了近10年因膽石病行膽囊切除治療術后結石復發患者的臨床相關資料,為識別結石復發高風險人群、及早預防提供依據。
1 資料與方法
1. 1 研究對象 回顧性收集內蒙古自治區人民醫院肝膽胰脾外科 2013 年 1 月—2023 年 12 月因膽石病行開腹、LC或 LC+LCBDE 患者的臨床資料。納入標準:(1)術后6個月及以上經腹部超聲、CT或MRI證實結石復發或術后病理提示結石復發者;(2)相關及隨訪資料完整者。排除標準:(1)ERCP或膽囊造瘺術后結石復發者;(2)伴有相關嚴重肝膽疾病者,如原發性硬化性膽管炎、肝膽惡性腫瘤等;(3)有殘余結石者。
1. 2 研究內容
1. 2. 1 一般資料 包括性別、年齡、民族、居住地類型(市區、縣城、村鎮)、膽囊結石家族史、合并癥、吸煙、飲酒、身高、體質量、身體質量指數(body mass index, BMI)、與第1次膽石病手術時相比較體質量變化。
1. 2. 2 疾病資料 初次膽石病相關情況:手術時間、結石類別(單純膽囊結石、膽囊合并膽總管結石)、結石類型(單發、多發、泥沙樣)、結石大小(最大結石直徑)、手術方式(開腹或腹腔鏡)、血脂指標[甘油三酯、總膽固醇、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)];復發情況:復發時間、復發結石類別(Ⅰ:膽囊殘端結石,Ⅱ:膽總管結石,Ⅲ:二者均有)。
1. 2. 3 影像學資料 觀察膽道結構有無異常、術后膽總管有無擴張。
1. 2. 4 膳食資料 平素飲食規律與否(不吃早餐、夜加餐、就餐時間不固定、規律)、飲食結構(主食為主、肉類為主、均衡飲食、素食)、飲食習慣(高油高鹽、適中)、術后飲食有無改變(飲食變規律、調整飲食結構、二者均改變)。
1. 2. 5 相關定義及分類 (1)殘余結石:膽囊切除術后6個月內被再次確診為結石者。 (2)血脂指標:納入患者住院系統中入院時的相關數據。(3)多發結石:結石數量≥3枚。(4)膽總管擴張:術后首次復查時膽總管最大直徑≥8 mm。(5)膳食相關因素調查:采用食物頻率回顧法,記錄被調查者過去至少1個月或平素絕大多數情況下的膳食相關情況。(6)飲食結構:在整個膳食模式中,哪類食物提供能量占總能量的50%左右,即定義為以該類食物為主[6] ;素食指不食畜禽肉、水產品等動物性食物,但食用從動物而來的蛋類和奶類,即蛋奶素。(7)飲食習慣:高鹽指家庭人均每日食鹽攝入量在6 g以上,高油指家庭人均每日食用油攝入量超過30 g。
1. 3 統計學方法 采用SPSS 21. 0統計軟件進行分析。
計量資料用 x ˉ ±s表示,2組間比較采用成組t檢驗;計數資料 2 組間比較采用 χ 2 檢驗。Plt;0. 05 為差異有統計學意義。
2 結果
2. 1 結石復發概況 共收集到23 730例患者臨床資料,其中結石復發者345例,進一步排除殘余結石者11例,最終納入原發性膽總管結石復發患者334例,復發率為1. 41%,復發年齡在30~90歲,平均(63±12)歲。術后復發周期為1~42年,復發高峰在術后10年,不同復發周期的頻數分布見圖1。
334例結石復發者中男性108例(32%)、女性226例(68%),男、女復發率分別為1. 42%和1. 40%,差異無統計學意義(P=0. 953)。男性復發年齡為30~87歲,復發周期為術后1~23年;女性復發年齡為32~90歲,復發周期術后為1~42年;男、女復發周期差異有統計學意義(Plt;0. 001),復發年齡、復發結石類別差異均無統計學意義(P值均gt;0. 05)(表1)。
首次診斷為單純膽囊結石和膽囊合并膽總管結石者其術后結石復發率分別為1. 23%(256/20 890)和2. 76%(78/2 829),差異有統計學意義(χ 2 =42. 104,Plt;0. 001)。復發結石類別:膽囊殘端結石35例(10. 5%),膽總管結石263例(78. 7%),二者均有36例(10. 8%),以膽總管結石復發為主(表1)。
2. 2 臨床特征分析
進一步對結石復發者相關資料進行回顧性收集及電話隨訪,失訪者33例,均為首次診斷為膽囊合并膽總管結石復發者,失訪率9. 8%,最終納入301例資料完整者數據進行統計分析。
2. 2. 1 一般資料分析 年齡gt;60 歲者占總復發者的63. 8%,且男、女性均是該年齡段復發者占比最多。92%的復發者為漢族居民,居住在村鎮(41. 5%)和市區者(36. 5%)復發率較高。10% 的復發者有膽囊結石家族史。合并癥:高血壓57例,糖尿病20例,糖尿病合并高血壓17例,呼吸系統疾病15例。復發者中吸煙和飲酒的比例分別為 76. 7% 和 10. 3%。63. 8% 的復發者 BMI正常、23. 2%為超重,且距第1次膽囊切除手術時體質量相比,約60%的復發者體質量下降、23%有增加、17%保持穩定(表2)。
2. 2. 2 疾病資料分析 301例復發者中初次結石種類為單純膽囊結石者256例(85%)、膽囊合并膽管結石45例(15%),男、女性均以單純膽囊結石為主;結石類型以多發結石為主(約74%);結石lt;1 cm者占比40. 5%,結石1~2 cm者占比48. 8%,結石gt;2 cm者占比10. 6%;手術方式為開腹和腹腔鏡的比例分別66. 1%和33. 9%;伴高膽固醇者16例、高甘油三酯58例,HDL和LDL水平異常者分別為83例和30例(表3)。
2. 2. 3 影像學資料分析 膽道結構異常者僅4例,表現為膽囊管長而彎曲;術后有膽總管擴張者220例(73. 1%)(表4)。
2. 3 膳食因素分析 55. 8%的患者平素存在飲食不規律,且以不吃早餐的形式占比最多(53. 0%),但不同性別分析:男性飲食不規律以夜加餐的比例最高,其次是不吃早餐,而女性以不吃早餐和就餐時間不固定為主要表現。約60%的患者第1次膽囊術后飲食有改變,其中80% 者能將飲食調整為規律(飲食規律者可提高至92%)、改變飲食結構者占16. 1%,二者均能改變者僅占3. 9%。飲食結構調查發現,43. 8%的患者平素以肉類為主、37. 8%以主食為主,且體現出性別差異,男性以肉類為主占比最大(53. 6%),女性以主食為主占比最大(42. 6%),超60%的患者有高鹽高油的飲食習慣(表5)。
3 討論
隨著生活水平改善,膽石癥的發病率呈上升趨勢[7],且隨著腹腔鏡微創技術的發展,LC已成為目前治療膽囊結石的首選方式,LC聯合LCBDE+T管引流術是治療膽囊結石伴膽總管結石的一種常用術式,然而,殘余小膽囊及殘余膽囊結石仍是二者術后常見的并發癥之一[8] 。據報道,國外腹腔鏡膽囊切除術后殘余結石的發病率為0. 5%~2. 3%[9],國內文獻報道的腹腔鏡手術后殘余結石的概率為0. 8%~1. 8%[10],其原因主要與膽管解剖變異、術中膽囊三角解剖困難以及操作者技術不熟練等相關,膽囊切除術后膽總管殘余結石大多是因為術前漏診的繼發性膽總管結石,或術中操作使膽囊內的小結石進入膽總管內所致[8] 。本研究中殘余結石的發病率為0. 05%,明顯低于相關文獻報道,可能與初次膽囊結石時手術方式為開腹手術(66. 1%)的比例高有關。除殘余結石問題外,原發性膽總管結石復發是困擾醫患的另一難題,其不僅會給患者帶來再次手術創傷和經濟負擔,而且還可引起急性膽管炎、膽源性胰腺炎、重度梗阻性黃疸等嚴重疾病,尤其對年老體弱患者,可帶來嚴重不良后果[11] 。調查顯示膽總管取石術后結石復發率為4%~25%[5] 。本研究中原發性膽總管結石復發率低于既往報道[12-14] ,可能與研究同時納入開腹和腹腔鏡兩種手術方式,本地區特殊的地理環境、經濟發展狀況,以及人們長期形成的飲食、生活習慣等有關。膽囊合并膽總管結石者術后結石復發率約為單純膽囊結石者的 2. 3倍。既往研究也報道,與單純膽囊結石或膽管結石相比,膽囊結石合并膽總管結石發病機制、原因及病情更為復雜,且并發癥嚴重,治療難度大,術后更易復發[15-16] 。此外,再次復發的結石類別中膽總管結石約占78%,膽囊殘端結石占10%左右,因殘余小膽囊內黏膜仍具有分泌功能,是膽囊繼發感染及結石復發的基礎,也進一步提示術者術中應精細操作以避免殘余小膽囊及結石復發。此外,本研究還發現村鎮和市區居民的復發率較縣城居民高,可能與不同地域固有的生活節奏不同,進而影響其形成不同的飲食習慣和飲食結構有關。男、女性結石復發率最高的年齡階段均在61~70歲,其次為70歲以上,總體年齡gt;60歲者占總復發者的63. 8%,與既往報道[17-18] 的趨勢一致。
膽結石患者的家族遺傳特征顯著,但目前還未明確家族史是通過相似的生活、飲食習慣,還是通過基因遺傳因素或者兩者共同作用對膽結石的發病產生影響,今后還需進一步探討其明確的作用機制[19] 。盡管有研究 [20] 報道膽總管結石相關的家族史也與結石的復發密切相關,但本研究顯示,伴有膽囊結石家族史的復發者僅占總復發者的10%,期待未來更大規模的調查明確其關聯。本文中92%的復發者為漢族居民,主要與本地雖是內蒙古自治區,但總體居住的漢族居民比例最高,以及蒙古族人群偏好選擇蒙醫醫院就診有關。血脂因素調查發現HDL異常者在男、女性復發者中的比例最高,其次為甘油三酯異常。大多數(63. 8%)復發者的 BMI在正常范圍且第1次膽囊術后60. 1%的患者體質量有下降,與平素的認知可能存在差異。
關于原發性膽總管結石復發危險因素的報道主要集中在保膽取石、ERCP及LC+LCBDE術后。有文獻[1]報道,影響LC+LCBDE術后結石復發的因素包括先天解剖因素、結石相關因素和膽道相關因素等。先天解剖因素包括膽總管成角[21-22] 、膽囊管低位匯入 [23] 、壺腹周圍憩室[24] 。本研究對結石復發者影像學資料進行回顧性分析發現,膽道結構異常的患者僅為4例,主要表現為膽囊管長而彎曲,但未收集復發者膽總管成角、膽囊管低位匯入和壺腹周圍憩室等影像學資料,是本研究的局限性之一。
除了膽道自身的解剖因素外,初發結石的性質、數量、位置、最大結石直徑也與復發息息相關。有文獻[25]報道,結石較大及數量較多時手術取石的時間會延長,從而使膽總管管壁的損傷以及膽總管發生炎癥的風險增加,進而影響結石的復發。分別有以膽總管結石數量≥2枚[26] 和≥10枚 [20] 為界值報道結石數量是影響結石復發重要因素的文獻。結石數量多可能導致術中遺漏,引起繼發性結石的可能性大。本研究中初次結石為多發結石者占比74. 1%,且開腹和腔鏡手術均以多發結石占比最大,與文獻報道一致。在結石大小方面,有以膽總管結石最大直徑gt;9 mm[11] 、結石大小lt;8 mm [20] 等為分類標準,報道其是影響結石復發的重要因素。本研究中結石大小以最大直徑為1~2 cm者占比最多,其次為1 cm以下,關于結石大小的截斷值未來仍需更多、更大規模的研究進一步分析。
大量的研究報道,膽總管直徑是結石復發的危險因素,但預測截斷值仍存在爭論。Park等[11]認為膽總管直徑gt;10 mm是LCBDE術后結石復發的危險因素。另有研究[4,27-32] 則認為,膽總管直徑gt;15 mm是ERCP術后結石復發的潛在預測因素。膽總管直徑gt;15 mm的患者結石復發的風險幾乎是直徑lt;10 mm患者的 4倍[33] ,且 Jeon等[34] 發現,膽總管直徑在ERCP術后2周內恢復的患者結石復發率較低。因此,對于內鏡取石后2周內膽總管直徑尚未恢復的患者,應行B超或MRCP監測膽總管直徑的變化。本調查中第1次膽囊術后伴膽總管擴張者占比73. 1%,提示其可能是影響結石復發的因素之一。
與結石復發相關的膳食因素研究中,王春艷等[35]對老年(≥60歲)膽囊結石患者術后結石復發的研究發現,術后1年內復發組鹽類、油類、奶及奶制品、畜禽肉每日攝入量均明顯高于未復發組,而水產品、蔬菜類、水果類、谷薯類、水每日攝入量明顯低于未復發組。另有研究[36]表明,飲食結構對結石復發有一定影響,高膽固醇、高脂肪酸或高碳水化合物的飲食方式會顯著增加結石復發的發病風險。Wu等[14] 回顧性分析了1 255例膽總管結石患者,指出術后高脂飲食、每周蔬菜攝入頻率lt;4次和飲酒是結石復發的獨立危險因素。本研究因考慮到具體食物種類攝入量可能存在的偏倚較大,故只從宏觀角度調查和分析了復發者的膳食因素特征,便于從總體把握認識膳食因素與結石復發的聯系。臨床上普遍認為飲食不規律,尤其是不吃早餐,以及典型的高熱量、高膽固醇、高脂肪酸或高碳水化合物的飲食會增加患膽結石的風險[5,37-39]。近來也有飲食種類對膽總管結石復發影響的研究,但鮮見其他飲食因素與結石復發的相關研究。本研究通過對復發者膳食因素進行隨訪調查發現,約56%的患者平素飲食不規律,不吃早餐是其主要形式。分性別發現,男性飲食不規律以夜加餐的形式比例最高,其次為不吃早餐,可能與男性晚上社會應酬較多有關。飲食結構方面也體現出性別差異,男性以肉類為主者比例最高,而女性以主食為主者比例最高;有64%的患者有高鹽高油的飲食習慣,男性以肉食類攝入多、女性以食用油攝入多為特點,與內蒙古地區特有的膳食喜好有關。約60%的復發者第1次手術后飲食方面會做出改變,其中 80% 能將飲食調整為規律,而改變飲食結構者為16%。結合上述文獻可以推測,飲食結構不合理可能是影響術后結石復發的重要因素,但本研究未行病例對照分析,尚無法統計飲食規律、飲食結構等與結石復發是否存在統計學關聯,后期將進一步納入對照人群分析。
綜上所述,內蒙古地區原發性膽總管結石復發率較低,需重點關注年齡gt;60歲患者以及膳食因素、臨床特征與結石復發的關聯性,提示臨床醫護人員開展針對性的手術改進及健康宣教,以積極預防結石復發,改善預后。
倫理學聲明: 本研究方案于2024年6月14日經由內蒙古自治區人民醫院倫理委員會審批,批號:202406706L,患者均知情同意。
利益沖突聲明: 本文不存在任何利益沖突。
作者貢獻聲明: 蘆建慧設計課題思路,擬定論文框架,起草、撰寫并修改論文;李勇利負責數據收集,統計學分析、繪制圖表;郭瑞芳、薛榮泉負責課題思路設計,指導文章撰寫并最后定稿。
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收稿日期:2024-06-14;錄用日期:2024-07-31
本文編輯:劉曉紅