132例女性疑难腹水的诊断分析与研究
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摘要
目的：女性疑难性腹水病因多样,而妇科肿瘤出现腹水往往已属于病程晚期,如不及时明确诊断将失去治疗机会,本研究目的是如何使患者获得准确、快速的诊断,寻找理想的肿瘤标志物和微创新技术,探讨最佳诊断流程。
方法：收集与整理浙江大学医学院附属第一医院2005年12月-2010年3月收住内科、外科、妇科的132例女性疑难性腹水病例,其中恶性腹水组53例,结核性腹水组17例,肝源性腹水组22例,其他性质良性腹水组20例,不明原因腹水组20例。分析患者年龄分布、病因构成、临床表现等特点；分别比较腹水性状与病因的关系,血清及腹水肿瘤标志物、腹水蛋白、腹水LDH、腹水ADA与良恶性腹水的关系,恶性腹水中血清及腹水肿瘤标志物的敏感性差异；计算血清及腹水肿瘤标志物的敏感性与特异性、B超和CT的检出率、腹水细胞学检查的阳性率；探讨剖腹和腹腔镜探查的应用。实验室指标界值按检验科试剂说明书选定,统计学处理应用SPSS16.0软件在微机完成,P<0.05(双侧)有统计学意义。
结果：(1)女性疑难性腹水患者平均年龄56±15岁,年龄分布呈现：肝源性腹水组>恶性腹水组>结核性腹水组,有显著性差异；<55岁组结核性腹膜炎占21.5%,≥55岁组肝源性腹水占23.9%,两组恶性腹水分别占30.8%和49.3%。
(2)132例腹水的病因主要为恶性肿瘤(40.3%),肝硬化(16.7%),结核性腹膜炎(12.9%)；恶性肿瘤中消化系统肿瘤和生殖系统肿瘤共占47.17%。
(3)腹水LDH、血清及腹水CA125、CA19-9在良恶性腹水间有显著性差异(分别为P<0.01和P<0.05)；腹水LDH在恶性组是良性组的3倍,血清CA125在恶性组是良性组的4倍,CA199在恶性组是良性组的10倍,腹水CA125在恶性组是良性组的4倍,CA199在恶性组是良性组的100倍。
(4)CA125的敏感性血清显著高于腹水(P<0.05)；CA199和CEA的敏感性腹水显著高于血清(P<0.05)
(5)B超检出率为94.4%,CT检出率为95.6%,但没有特异性。腹水细胞学检查阳性率为39.6%,确诊常需要诊断性腹腔镜或剖腹探查。
结论：
(1)女性疑难性腹水特点：病程复杂,诊断困难,多医院就诊,多科入住；年龄跨度大；恶性肿瘤占首位。
(2)女性疑难性腹水三大首要考虑病因：生殖系统恶性肿瘤、肝硬化、结核性腹膜炎,其中卵巢癌所致腹水是女性生殖系统恶性肿瘤中最常见病因。
(3)腹水LDH、血清及腹水的CA19-9、CA125水平对于鉴别良、恶性腹水有诊断价值；恶性腹水中腹水CA19-9、CEA的检测比血清更有鉴别意义。
(4)对疑诊为卵巢恶性肿瘤可尽早行诊断性腹镜镜探查,以早期明确诊断。
Objective:The causes of ascites in female patients are various, and it is often at the advanced stage when ascites occurs in patients with gynecological tumor, and treatment timing will be missed if the right diagnosis hasn't been made in time. The objective of this study was to search for ideal tumor markers and micro-invasive techniques, and discuss the best diagnostic procedure for ascites in order to make a quick and accurate diagnosis.
Methods:One hundred and thirty-two female patients with ascites of unknown origin who received treatment at the departments of internal medicine, surgery and gynecology, the First Affiliated Hospital of Medical School, Zhejiang University from December 2005 to March 2010 were adopted for the study. All the patients were distributed into five groups:malignant ascites group (n=53), tuberculous ascites group (n=17), hepatic ascites group (n=22), benign ascites group (n=20) and unexplained ascites group (n=20). The age distribution, causes, clinical manifestations of these patients were analyzed. The characteristics of ascitic fluid based on different causes were compared; the tumor markers in serum and ascitic fluid, and the protein, LDH and ADA levels in ascitic fluid IV were compared between the malignant ascites group and the benign ascites group; the sensitivities were also compared between serum tumor markers and ascitic fluid tumor markers in the malignant ascites group. The sensitivity and specificity of tumor markers in serum and ascitic fluid, the detection rates of ascites with ultrasound scan and CT scan, and the positive rate in cytologic examination of ascitic fluid were calculated respectively. The application of exploratory laparotomy and laparoscopic exploration were also evaluated. Critical Values for laboratory test results were adopted from the reagent datasheets. The software SPSS 16.0 was chosen for statistical analysis, and p<0.05 (two-sided test) represents that there is a statistically significant difference.
Results:
(1) The average age of these female patients was 56±15 years. The age distribution: hepatic ascites group> malignant ascites group> tuberculous ascites group, and there was significant differences between them. The patients with tuberculous ascites accounted for 21.5% of the patients with the age<55 years. The patients with hepatic ascites accounted for 23.9% of the patients with the age>55 years. The patients with malignant ascites accounted for 30.8% and 49.3% of the patients with the age<55 years and>55 years respectively.
(2) The most common causes of ascites for these 132 patients were malignant tumors (40.3%), cirrhosis (16.7%) and tuberculous peritonitis (12.9%). Tumors of the digestive system and the reproductive system accounted for 47.17% of all the malignant tumors.
(3) There were significant differences in ascitic LDH, serum and ascitic fluid CA125 levels (p<0.01) and CA199 levels (p<0.05) between the malignant ascites group and the benign ascites group. The ascetic LDH in the malignant ascites group was 3 times the level of the one in the benign ascites group, the serum CA125 in the malignant ascites group was 4 times the level of the one in the benign ascites group and the serum CA199 in the malignant group was 10 times the level of the one in the benign ascites group. The ascitic fluid CA125 in the malignant group was 4 times the level of the one in the benign ascites group and the ascitic fluid CA199 in the malignant group was 100 times the level of the one in the benign ascites group.
(4) The sensitivity of serum CA125 was significantly higher than the sensitivity of ascitic fluid CA125 (p<0.05), while the sensitivities of ascitic fluid CA199 and CEA were significantly higher than the sensitivities of serum CA199 and CEA respectively (P<0.05).
(5) The detection rates of ultrasound scan and CT scan were 94.4% and 95.6% respectively, but without specificity. The positive rate in cytologic examination of ascitic fluid was 39.6%. And exploratory laparotomy or laparoscopic exploration was always needed for confirmative diagnosis.
Conclusions:
(1) The feature of ascites of unknown origin in female patients is the complex course of disease, difficult diagnosis, multi-hospital and multidisciplinary stay, big span in age distribution, and primary location of malignant tumors in the list.
(2) Three main causes for ascites of unknown origin in female patients which need to be first considered are malignant tumors of the reproductive system, cirrhosis and tuberculous peritonitis. Ovarian cancer is the most common cause for ascites among malignant tumors of the female reproductive system.
(3) The levels of LDH in ascitic fluid, CA199 and CA125 in serum and ascitic fluid were of diagnostic value in differentiation between malignant ascites and benign ascites. The detection of ascitic fluid CA199 and CEA was more significant in differential diagnosis than the detection of serum CA199 and CEA for malignant ascities patients.
(4) Diagnostic laparoscopy should be performed as soon as possible when malignant ovarian tumor is suspected in order to make confirmative diagnosis as early as possible.
方法：收集与整理浙江大学医学院附属第一医院2005年12月-2010年3月收住内科、外科、妇科的132例女性疑难性腹水病例,其中恶性腹水组53例,结核性腹水组17例,肝源性腹水组22例,其他性质良性腹水组20例,不明原因腹水组20例。分析患者年龄分布、病因构成、临床表现等特点；分别比较腹水性状与病因的关系,血清及腹水肿瘤标志物、腹水蛋白、腹水LDH、腹水ADA与良恶性腹水的关系,恶性腹水中血清及腹水肿瘤标志物的敏感性差异；计算血清及腹水肿瘤标志物的敏感性与特异性、B超和CT的检出率、腹水细胞学检查的阳性率；探讨剖腹和腹腔镜探查的应用。实验室指标界值按检验科试剂说明书选定,统计学处理应用SPSS16.0软件在微机完成,P<0.05(双侧)有统计学意义。
结果：(1)女性疑难性腹水患者平均年龄56±15岁,年龄分布呈现：肝源性腹水组>恶性腹水组>结核性腹水组,有显著性差异；<55岁组结核性腹膜炎占21.5%,≥55岁组肝源性腹水占23.9%,两组恶性腹水分别占30.8%和49.3%。
(2)132例腹水的病因主要为恶性肿瘤(40.3%),肝硬化(16.7%),结核性腹膜炎(12.9%)；恶性肿瘤中消化系统肿瘤和生殖系统肿瘤共占47.17%。
(3)腹水LDH、血清及腹水CA125、CA19-9在良恶性腹水间有显著性差异(分别为P<0.01和P<0.05)；腹水LDH在恶性组是良性组的3倍,血清CA125在恶性组是良性组的4倍,CA199在恶性组是良性组的10倍,腹水CA125在恶性组是良性组的4倍,CA199在恶性组是良性组的100倍。
(4)CA125的敏感性血清显著高于腹水(P<0.05)；CA199和CEA的敏感性腹水显著高于血清(P<0.05)
(5)B超检出率为94.4%,CT检出率为95.6%,但没有特异性。腹水细胞学检查阳性率为39.6%,确诊常需要诊断性腹腔镜或剖腹探查。
结论：
(1)女性疑难性腹水特点：病程复杂,诊断困难,多医院就诊,多科入住；年龄跨度大；恶性肿瘤占首位。
(2)女性疑难性腹水三大首要考虑病因：生殖系统恶性肿瘤、肝硬化、结核性腹膜炎,其中卵巢癌所致腹水是女性生殖系统恶性肿瘤中最常见病因。
(3)腹水LDH、血清及腹水的CA19-9、CA125水平对于鉴别良、恶性腹水有诊断价值；恶性腹水中腹水CA19-9、CEA的检测比血清更有鉴别意义。
(4)对疑诊为卵巢恶性肿瘤可尽早行诊断性腹镜镜探查,以早期明确诊断。
Objective:The causes of ascites in female patients are various, and it is often at the advanced stage when ascites occurs in patients with gynecological tumor, and treatment timing will be missed if the right diagnosis hasn't been made in time. The objective of this study was to search for ideal tumor markers and micro-invasive techniques, and discuss the best diagnostic procedure for ascites in order to make a quick and accurate diagnosis.
Methods:One hundred and thirty-two female patients with ascites of unknown origin who received treatment at the departments of internal medicine, surgery and gynecology, the First Affiliated Hospital of Medical School, Zhejiang University from December 2005 to March 2010 were adopted for the study. All the patients were distributed into five groups:malignant ascites group (n=53), tuberculous ascites group (n=17), hepatic ascites group (n=22), benign ascites group (n=20) and unexplained ascites group (n=20). The age distribution, causes, clinical manifestations of these patients were analyzed. The characteristics of ascitic fluid based on different causes were compared; the tumor markers in serum and ascitic fluid, and the protein, LDH and ADA levels in ascitic fluid IV were compared between the malignant ascites group and the benign ascites group; the sensitivities were also compared between serum tumor markers and ascitic fluid tumor markers in the malignant ascites group. The sensitivity and specificity of tumor markers in serum and ascitic fluid, the detection rates of ascites with ultrasound scan and CT scan, and the positive rate in cytologic examination of ascitic fluid were calculated respectively. The application of exploratory laparotomy and laparoscopic exploration were also evaluated. Critical Values for laboratory test results were adopted from the reagent datasheets. The software SPSS 16.0 was chosen for statistical analysis, and p<0.05 (two-sided test) represents that there is a statistically significant difference.
Results:
(1) The average age of these female patients was 56±15 years. The age distribution: hepatic ascites group> malignant ascites group> tuberculous ascites group, and there was significant differences between them. The patients with tuberculous ascites accounted for 21.5% of the patients with the age<55 years. The patients with hepatic ascites accounted for 23.9% of the patients with the age>55 years. The patients with malignant ascites accounted for 30.8% and 49.3% of the patients with the age<55 years and>55 years respectively.
(2) The most common causes of ascites for these 132 patients were malignant tumors (40.3%), cirrhosis (16.7%) and tuberculous peritonitis (12.9%). Tumors of the digestive system and the reproductive system accounted for 47.17% of all the malignant tumors.
(3) There were significant differences in ascitic LDH, serum and ascitic fluid CA125 levels (p<0.01) and CA199 levels (p<0.05) between the malignant ascites group and the benign ascites group. The ascetic LDH in the malignant ascites group was 3 times the level of the one in the benign ascites group, the serum CA125 in the malignant ascites group was 4 times the level of the one in the benign ascites group and the serum CA199 in the malignant group was 10 times the level of the one in the benign ascites group. The ascitic fluid CA125 in the malignant group was 4 times the level of the one in the benign ascites group and the ascitic fluid CA199 in the malignant group was 100 times the level of the one in the benign ascites group.
(4) The sensitivity of serum CA125 was significantly higher than the sensitivity of ascitic fluid CA125 (p<0.05), while the sensitivities of ascitic fluid CA199 and CEA were significantly higher than the sensitivities of serum CA199 and CEA respectively (P<0.05).
(5) The detection rates of ultrasound scan and CT scan were 94.4% and 95.6% respectively, but without specificity. The positive rate in cytologic examination of ascitic fluid was 39.6%. And exploratory laparotomy or laparoscopic exploration was always needed for confirmative diagnosis.
Conclusions:
(1) The feature of ascites of unknown origin in female patients is the complex course of disease, difficult diagnosis, multi-hospital and multidisciplinary stay, big span in age distribution, and primary location of malignant tumors in the list.
(2) Three main causes for ascites of unknown origin in female patients which need to be first considered are malignant tumors of the reproductive system, cirrhosis and tuberculous peritonitis. Ovarian cancer is the most common cause for ascites among malignant tumors of the female reproductive system.
(3) The levels of LDH in ascitic fluid, CA199 and CA125 in serum and ascitic fluid were of diagnostic value in differentiation between malignant ascites and benign ascites. The detection of ascitic fluid CA199 and CEA was more significant in differential diagnosis than the detection of serum CA199 and CEA for malignant ascities patients.
(4) Diagnostic laparoscopy should be performed as soon as possible when malignant ovarian tumor is suspected in order to make confirmative diagnosis as early as possible.
引文
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[1]Moore KP, Wong F, Gines P, et al. The management of ascites in cirrhosis:report on the consensus conference of the International Ascites Club [J]. Hepatology, 2003,38:258-266.
[2]Gines P, Cardenas A, Arroyo V, et al. Management of cirrhosis and ascites [J]. N Engl J Med,2004,350:1646-1654.
[3]Chien-Min Han, Chyi-Long Lee, Kuan-Gen Huang, et al. Diagnostic Laparoscopy in Ascites of Unknown Origin:Chang Gung Memorial Hospital 20-year Experience [J]. Chang Gung Med J,2008,4(31):378-383.
[4]Kashani A, Landaverde C, Medici V, et al. Fluid retention in cirrhosis: pathophysiology and management [J]. QJM,2008,101:71-85.
[5]ROS Karoo, TDR Lloyd, G Garcea, et al. How valuable is ascitic cytology in the detection and management of malignancy [J]. Postgrad Med J,2003,79: 292-294.
[6]Porcel AG, Alcain G, Moreno M, et al. Value of laparoscopy in ascites of undetermined origin [J]. Rev Esp Enferm Dig,1996,88:485-489.
[7]Milingos S, Protopapas A, Papadimitriou C, et al. Laparoscopy in the evaluation of women with unexplained ascites:an invaluable diagnostic tool [J]. J Minim Invasive Gynecol,2007,14:43-48.
[8]Bedioui H, Ksantini R, Nouira K, et al. Role of laparoscopic surgery in the etiologic diagnosis of exsudative ascites:a prospective study of 90 cases [J]. Gastroenterol Clin Biol,2007,31(12):1146-1149.
[9]Agesta F, Ciardo LF, Mazzarolo G, et al. Peritonitis:laparoscopic approach [J]. World J Emerg surg,2006,24(3):1-9.
[10]Leppaniemi AK, Elliott DC. The role of laparoscopy in blunt abdominal trauma [J]. Ann Med,1996,28:483-489.
[11]Garofalo A, Valle M. Laparoscopy in the management of peritoneal carcinomatosis [J]. Cancer J,2009,15(3):190-5.
[12]YUAN Jing, LI Xiang-hong. Evaluation of pathological diagnosis using ultrasonography-guided lymph node core-needle biopsy [J]. Chin Med J, 2010,123(6):690-694.
[13]Casaccia M, Torelli P, Cavaliere D, et al. Laparoscopic lymph node biopsy in intra-abdominal lymphoma:high diagnostic accuracy achieved with a minimally invasive procedure. [J]. Surg Laparosc Endosc Percutan Tech.2007,17(3): 175-178.
[14]MP Sharma, Vikram Bhatia. Abdominal tuberculosis [J]. Indian J Med Res, 2004,305-315.
[15]Bhargava DK, Shriniwas, Chopra P, et al. Peritoneal tuberculosis:laparoscopic patterns and its diagnostic accuracy. [J]. Am J Gastroenterol 1992,87:109-112.
[16]曾定元,沈铿.卵巢正常大小癌综合征的研究进展.[J].中华医学杂志,2005,85(16)：1149-1151.
[17]Gottwald L, Korczynski J, Gora E. Abdominal Burkitt lymphoma mimicking the ovarian cancer. Case report and review of the literature. [J]. Ginekol Pol.2008 Feb;79(2):141-5.
[18]Bedioui H, Ksantini R, Nouira K, et al. Role of laparoscopic surgery in the etiologic diagnosis of exudative ascites:a prospective study of 90 cases [J]. Gastroenterologie Clinique et Biologique,2007,31(12):1146-1149.
[19]Vergote I, Marquette S, Amant F, et al. Port-site metastases after open laparoscopy:a study in 173 patients with advanced ovarian carcinoma [J]. Int J Gynecol Cancer,2005,15(5):776-779.
[20]Karnam US, Reddy KR. Diagnostic laparoscopy:an update [J]. Endoscopy,2003, 34(2):146.
[21]Angioli R, Muzii L, Battista C, et al. The role of laparoscopy in ovarian carcinoma [J]. Minerva Ginecol,2009,61(1):35-43.
[22]Schneider AR, Benz C, Adamek HK, et al. Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic disease [J]. Gastrointest Endosc,2001, 53(7):771.
[23]Zorron R, Soldan M, Filgueiras M, et al. NOTES:transvaginal for cancer diagnostic staging:preliminary clinical application. [J]. Surg Innov.2008, 15(3):161-5.
[24]Velaseo JM, Rossi H, Hieken TJ, et al. Laparoscopic ultrasound enhances diagnostic laparoscopy in the staging of intra-abdominal neoplasms [J]. Am Surg,2000,66:407-411.
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[1]Moore KP, Wong F, Gines P, et al. The management of ascites in cirrhosis:report on the consensus conference of the International Ascites Club [J]. Hepatology, 2003,38:258-266.
[2]Gines P, Cardenas A, Arroyo V, et al. Management of cirrhosis and ascites [J]. N Engl J Med,2004,350:1646-1654.
[3]Chien-Min Han, Chyi-Long Lee, Kuan-Gen Huang, et al. Diagnostic Laparoscopy in Ascites of Unknown Origin:Chang Gung Memorial Hospital 20-year Experience [J]. Chang Gung Med J,2008,4(31):378-383.
[4]Kashani A, Landaverde C, Medici V, et al. Fluid retention in cirrhosis: pathophysiology and management [J]. QJM,2008,101:71-85.
[5]ROS Karoo, TDR Lloyd, G Garcea, et al. How valuable is ascitic cytology in the detection and management of malignancy [J]. Postgrad Med J,2003,79: 292-294.
[6]Porcel AG, Alcain G, Moreno M, et al. Value of laparoscopy in ascites of undetermined origin [J]. Rev Esp Enferm Dig,1996,88:485-489.
[7]Milingos S, Protopapas A, Papadimitriou C, et al. Laparoscopy in the evaluation of women with unexplained ascites:an invaluable diagnostic tool [J]. J Minim Invasive Gynecol,2007,14:43-48.
[8]Bedioui H, Ksantini R, Nouira K, et al. Role of laparoscopic surgery in the etiologic diagnosis of exsudative ascites:a prospective study of 90 cases [J]. Gastroenterol Clin Biol,2007,31(12):1146-1149.
[9]Agesta F, Ciardo LF, Mazzarolo G, et al. Peritonitis:laparoscopic approach [J]. World J Emerg surg,2006,24(3):1-9.
[10]Leppaniemi AK, Elliott DC. The role of laparoscopy in blunt abdominal trauma [J]. Ann Med,1996,28:483-489.
[11]Garofalo A, Valle M. Laparoscopy in the management of peritoneal carcinomatosis [J]. Cancer J,2009,15(3):190-5.
[12]YUAN Jing, LI Xiang-hong. Evaluation of pathological diagnosis using ultrasonography-guided lymph node core-needle biopsy [J]. Chin Med J, 2010,123(6):690-694.
[13]Casaccia M, Torelli P, Cavaliere D, et al. Laparoscopic lymph node biopsy in intra-abdominal lymphoma:high diagnostic accuracy achieved with a minimally invasive procedure. [J]. Surg Laparosc Endosc Percutan Tech.2007,17(3): 175-178.
[14]MP Sharma, Vikram Bhatia. Abdominal tuberculosis [J]. Indian J Med Res, 2004,305-315.
[15]Bhargava DK, Shriniwas, Chopra P, et al. Peritoneal tuberculosis:laparoscopic patterns and its diagnostic accuracy. [J]. Am J Gastroenterol 1992,87:109-112.
[16]曾定元,沈铿.卵巢正常大小癌综合征的研究进展.[J].中华医学杂志,2005,85(16)：1149-1151.
[17]Gottwald L, Korczynski J, Gora E. Abdominal Burkitt lymphoma mimicking the ovarian cancer. Case report and review of the literature. [J]. Ginekol Pol.2008 Feb;79(2):141-5.
[18]Bedioui H, Ksantini R, Nouira K, et al. Role of laparoscopic surgery in the etiologic diagnosis of exudative ascites:a prospective study of 90 cases [J]. Gastroenterologie Clinique et Biologique,2007,31(12):1146-1149.
[19]Vergote I, Marquette S, Amant F, et al. Port-site metastases after open laparoscopy:a study in 173 patients with advanced ovarian carcinoma [J]. Int J Gynecol Cancer,2005,15(5):776-779.
[20]Karnam US, Reddy KR. Diagnostic laparoscopy:an update [J]. Endoscopy,2003, 34(2):146.
[21]Angioli R, Muzii L, Battista C, et al. The role of laparoscopy in ovarian carcinoma [J]. Minerva Ginecol,2009,61(1):35-43.
[22]Schneider AR, Benz C, Adamek HK, et al. Minilaparoscopy versus conventional laparoscopy in the diagnosis of hepatic disease [J]. Gastrointest Endosc,2001, 53(7):771.
[23]Zorron R, Soldan M, Filgueiras M, et al. NOTES:transvaginal for cancer diagnostic staging:preliminary clinical application. [J]. Surg Innov.2008, 15(3):161-5.
[24]Velaseo JM, Rossi H, Hieken TJ, et al. Laparoscopic ultrasound enhances diagnostic laparoscopy in the staging of intra-abdominal neoplasms [J]. Am Surg,2000,66:407-411.