摘要
研究背景和目的
研究背景：胃肠道间质瘤是消化道最常见的间叶源性肿瘤,由胃肠道间叶组织发生,且具有多向分化及恶变潜能的一种肿瘤。由于其起源于粘膜下层,普通内镜诊断较为困难,且难以与其它消化道粘膜下病变相鉴别。超声内镜的运用为间质瘤的诊断开辟了新的途径。超声内镜下不但可以依据超声影像判断间质瘤的起源层次、大小、浸润的深度、有无邻近脏器及淋巴结转移,有助于判断间质瘤内镜下治疗的可行性及风险,而且还可以在超声内镜引导下行细针穿刺抽取细胞学检查以明确诊断。手术切除是间质瘤的主要治疗手段,但传统的开腹手术和腹腔镜手术创伤大,病人痛苦大,花费较高。近年来随着内镜器械的发展和内镜技术的成熟,内镜下粘膜切除术(EMR)、内镜粘膜下剥离术(ESD)等微创治疗在临床获得越来越广泛的应用。不仅可以完整切除粘膜下病变,同时还可提供完整的病理诊断资料,病人创伤小、恢复快,具有与外科手术相同的治疗效果。本研究通过对胃间质瘤的超声内镜检查及EMR、ESD等治疗,探讨胃间质瘤的超声内镜诊断价值及内镜微创治疗的可行性、疗效和安全性。
研究方法：
1、收集2004年5月至2010年5月间山东大学齐鲁医院胃镜检查提示上消化道粘膜下隆起性病变者1163例行超声内镜检查,共检出胃间质瘤160例,其中男性89例,女71例；年龄(35-78)岁,平均年龄56岁；101例异位胰腺,其中男57例,女44例；年龄(15—72)岁,平均43岁；12例脂肪瘤,其中男8例,女4例,年龄(27-65)岁,平均年龄47岁。2、应用超声内镜观察间质瘤的起源层次、大小、形态、内部回声及浸润深度,并与异位胰腺、脂肪瘤等粘膜下病变相鉴别。3.选择26例来源于粘膜肌层和/或固有肌层、直径<2cm的胃间质瘤行内镜下微创治疗(ESD、EMR等)。术后随诊。
结果：
1.胃间质瘤多位于胃体(46.8%)和胃底(26.2%),大小为28.7±14.8mm,明显大于异位胰腺和脂肪瘤,P<0.05.胃间质瘤多起源于胃壁第四层(固有肌层)(53.1%)；边缘光滑(64%)；内部回声均质(74,7%),主要表现为低回声和中等回声(55.3%,42.5%)。异位胰腺和脂肪瘤多起源于第三层(粘膜下层)(69.3%,75%)。异位胰腺边缘不规则(75.2%)、内部回声不均质,以中等回声为主(63.4%)。脂肪瘤主要表现为高回声(83.3%),内部回声均质(83.3%)。
2.26例胃间质瘤根据不同超声内镜下特点分别给予高频电切3例(11.5%),套扎+电切10例(38.5%),ESD13例(50%)。所有病例均完整切除。只有1例发生穿孔转外科手术；1例发生出血,给予止铗血止血。所有患者术后随访3到12个月,创面愈合,均无复发。
结论：
1.超声内镜下胃间质瘤主要位于胃体胃底部,多来源于固有肌层,边缘光滑,内部回声均质,为中等偏低回声。在起源、部位、大小、内部回声方面与脂肪瘤、异位胰腺有明显区别。因而超声内镜检查对于胃间质瘤的诊断具有重要意义。
2、对于起源于肌层、直径小于2cm的胃部间质瘤,内镜下微创治疗安全、疗效高,病人花费低。超声内镜检查对间质瘤内镜微创治疗方式的选择具有重要的指导价值。
Backgrounds and aims:
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. They are submucosal lesion covered by the normal mucosa. The histological diagnosis is usually difficult when tissue speciemens are obtained using a standard forcep biopsy through the conventional endoscopy. The ability of endoscopic ultrasonography (EUS) to clearly demonstrate the gastric wall and its layers makes it a great tool for the clinician to make the differential diagnosis of "real" submucosal lesions. Moreover, it can also assist in their exact pathologic diagnosis by EUS-guided fine needle aspiration (EUS-FNA). Because of the potential malignant features of GISTs, surgical resection was the main treatment in the past time. With the progression of the endoscopy instruments and endoscpic operation, importantly, under the guidance of the EUS, GISTs can be removed by appropriate endoscopic treatment such as endoscopic mucosa resection (EMR), endoscopic sunmucosal dissection (ESD) without severe complications. In this study, we evaluate the role of EUS in the diagnosis and differentiation of gastric gastrointestinal stromal tumor. And also evaluate the feasibility, curative effect and safety of endoscopic treatment.
Methods:
1. A total of 1163 consecutive patients with submucosal lesions in upper gastrointestinal tract found by conventional endoscope were included in EUS examination during the period from May 2004 to May 2010 in Qilu Hospital of Shandong University, China. There were 160 (13.7%) gastric stromal tumor composed of 89 males and 71 females, and aged from35 to 78 years, with a mean of 56 years.101 ectopic pancreases (8.6%) including 57 males and 44 females aged from 15 years to 72 years (mean 43 years).12 lipoma(1.0%),8 males and 4 females, aged from 27 years to 65 years, their mean age was 47 years.
2. EUS examination was used to observe the location, size, layers of origin and the internal echo pattern of the stromal tumors. And furthermore differentiate from lipoma and ectopic pancrease.
3.26 gastric stromal tumors with the diameter smaller than 2cm and muscularis layer origin underwent different kinds of endoscopic treanment according to the EUS findings.
Results:
1. Gastric stromal tumors were predominantly located in the body (46.8%) which usually originated from the fourth layer (53.1%). Gastric stromal tumors were larger than ectopic pancreas or lipomas (28.7±14.8mm vs 11.5±5.6mm or 1.34±0.38mm, p<0.05) with smooth margin (64%) and homogeneous hypoechoic (55.3%) or intermediate internal echo (42.5%). While the ectopic pancreas and lipoma mainly originated from the third layer (69.3%,75%). Lipoma shows hyperechoic (83.3%). Ectopic pancreas predominately shows intermediate inner echo (63.4%) with irregular maigin (75.2%).
2. Based on EUS images, we treated 26 GISTs by different endoscopic therapies, including snare electrosection, endoloop and ESD. Complete resection of the lesions was achieved in all cases. Only two patients suffered from bleeding or resection-related perforation. All wounds were closed up nicely and no recurrence was found in the follow-up after 12 months.
Conclusions:
1. Gastric stromal tumors mainly located in the body or fundus with smooth margin and homogeneous hypoechoic or intermediate inner echo. It predominately originated from the musculrus propria. Gastric stromal tumors are quite different from ectopic pancreas and lipoma on the respect of location, size, origin and inner echo pattern. So the EUS is of great value in diagnosing stromal tumors.
2. Preoperative EUS examination is important for choosing the type of endoscopic therapy for stromal tumors. By which the lesions can be treated safely and effectively.
引文
1. Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs):Definition, occurrence, pathology, differential diagnosis and molecular genetics.Pol J Pathol, 2003,54(1):3-24
2. Mazur MT, Clark HB.Gastric stromal tumours.Reappraisal of histogenesis.Am J Surg Pathol.1983(7):507-509
3. Rosai J. Ackerman's surgical pathology [M], ed 8. St Louis:MO Mosby,1995,645-647
4. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. Jan 23 1998; 279(5350):577-80
5. Heinrich M C, Rubin B P, Longley B J. et al. Biology and genetic aspects of gastrointestinal stromal tumors:KIT activation and cytogenetic alterations. Hum Pathol.2002,33:484-495.
6. Duensing A, Heinrich M C, Fletcher C D. et al. Biology of gastrointestinal stromal tumors:KIT mutations and beyond. Cancer Invest,2004,22:106-116
7. Ashman L K. The biology of stem cell factor and its receptor C-kit. Int J Biochem Cell Biol,1999.31:1037-1051
8. Duensing A, Medeiros F, McConarty B, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene,2004, 23:3999-4006
9. Miettinen M, Lasota J. Gastrointestinal stromal tumors:review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med.2006 Oct; 130(10):1466-1478
10. Thomas RM, Sobin LH.Gastrointestinal cancer [J].Cancer,1995,7 (suppl):154-170。
11. Fletcher CD, Berman JJ, Corless C, et al.Diagnosis of gastroin-testinal stromal tumors:A consensus approach [J].Hum Pathol,2002,33 (15):459-465
12. Miettinen M. Diagnostic soft tissue pathology [M].New York:Churchill Livingstone,2003.259-270.
13. Hillemanns M, Pasold S, Bottcher k, et al. Prognostic factors of gastrointestinal stromal tumors of the stomach. Verh Dtsch Ges Pathol.1998; 82:261-266
14. Jaap V, Paolo G, John I, et al. Progression-free survival in gastrointestinal stromal tumors with high-dose imatinib:randomized trial. The Lancet; Sep 25-Oct 1,2004; 364,1127-1134
15. Reith JD, Goldblum JR, Lyles RH, et al.Extragastrointestinal (soft tissue)stromal tumors:an analysis of48cases with emphasis on histologic predictors of outcome [J].Mod Pathol,2000,13 (5):577-585
16. Miettinen M, El-Rifai W, Lasota J, Sobin LH:Evaluation of malignancy and prognosis of gastrointestinal stromal tumors:a review. Hum Pathol 2002,33, 478-483.
17. Seidal T, Edvardsson H. Diagnosis of gastrointestinal stromal tumor by fine needle aspiration biopsy:a cytological and immunocytochemical study. Diagn Cytopathol.2000,23(6):397-401
18. Gu M, Ghafari S, Nquyen PT, et al. Cytologic diagnosis of gastrointestinal stromal tumors of the stomach by endoscopic ultrasound-guided fine-needle aspiration biopsy:cytomorphologic and immunohistochemical study of 12 cases. Diagn Cytopathol.2001,25(6); 343-350
19. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O'Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW. Diagnosis of gastrointestinal stromal tumors:A consensus approach. Hum Pathol.2002 May; 33 (5):459-65. Review
20. Miettinen M, Sobin L H, Lasota J. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol.2005,2952-2968
21. Burkill GJC, Badran M, Al-Muderis O, et al. Malignant gastrointestinal stromal tumors:distribution, imaging features, and pattern of metastatic spread. Radiology 2003; 226:527-532
22. Lewis RJ, Kunderman PJ, Sislcr GE, et al. Direct diagnostic thoracoscopy Ann Thorae Surg,1996,21(6):536-539
23. Aibe T, Fuji T, Okita K et al. A fundamental study of normal layer structure of the gastrointestinal wall visualized by endoscopic ultrasonography[J]. Scand J Gastroenterol,1986,21(suppl 123):615-618.
24. Kawamoto K, Yamada Y, Utsunomiya T et al. Gastrointestinal submucosal tumors:evaluation with endoscopic us. Radiology,1997; 205:733-740.
25. Caletti G, Bolondi L, Zani L, Labo G. Technique of endoscopic ultrasonography investigation:esophagus, stomach and duodenum. Scand J Gastroenterol 1986; 123(suppl):Sl-S
26. Penman ID, Williams DB. Endoscopic ultrasonography(EUS):glllTent applications andfuture potential. Proe R Coil Physicians Edinb 1999; 29:54-63
27. Van Stolk IL Subepithelial lesions. In:vall Dam J, Sivak M, eds. Gastrointestinal Endosonography. Philadelphia,Pennsylvania:WB Saunders,1999:153-165
28. Nickl N. Endosonography at a crossroads:the outcomes obligation. GastrointestEndosc 1999; 50:875-882.
29. Kawamoto kYamada Y, Utsunomiya T, Okamma H, Mizuguchi M, Motooka M, et al. Gastrointestinal submucosal tumors:evaluation with endoscopic US. Radiology 1997; 205:733-740.
30. Kindblom L G, Remotti H E, Aldenborg F, et al. Gastrointestinal pacemaker cell tumor (GIPACT):gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol.1998,152:1259-1269.
31. Huizinga J D, Thuneberg L, Kluppel M, et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature.1995,373:347-349
32. Sircar K, Hewlett B R, Huizinga J D, et al. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. Am J Surg Pathol.1999,23:377-389
33. Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science.1998,279:577-580
34. Cassier PA, Blay JY Gastrointestinal stromal tumors of the stomach and duodenum. Curr Opin Gastroenterol.2011, Sep 20 [Epub ahead of Print]
35. Chak A, Canto MI, Rosch T, et al. Endosonographic differentiation of benign and malignant stromal cell tumors. Gastrointest Endosc.1997,45(6):468-473
36. Lack EE. Congenital and developmental abnormalities of the pancreas. In: Pathology of the pancreas, gallbladder, extrahepatic biliary, and ampullary region.1st ed. New York[J]. Oxford University Press Inc,2003.44-62
37. Changchien CS,Hsiaw CM,Hu TH.Endoscopic ultrasonographic classification of gastric aberrant pancreas.Chang Gung Med J 2000;23;600-607.
38. Heer C, Pfortner M, Hamberqer U, et al. Heterotopic pancreatic tissue in the bifurcation of the bile duct:Rare diagnosis mimicking a klatskin tumour [J]. Chirurq, 2009:22. [Epub ahead of print].
39. Mulholland KC, Wallace WD, Epanomeritakis E, Hall SR. Pseudocyst formation in gastric ectopic pancreas. J Pancreas (Online) 2004; 5(6):498-501
40. Vilmann P, Hancke S, Henriksen FW, Jacobsen GK. Endoscopic ultrasonography-guided fine-needle aspiration biopsy of lesions in the upper gastrointestinal tract. Gastrointest Endosc 1995;41:230-235.
41. Yang AM, Lu XH, Lu CM, et al. Use of endoscopic ultrasonography to diagnose submucosal tumors of upper gastrointestinal tract [J]. Chin J Dig Endosc,2000,17 (3): 163-165
42. Alberti D, Grazioli L, Ofizio P, et al. Asymptomatic giant gastric lipoma: what to do? Am J Gastroenterol,1999,94:3634-3637
43. Taylor AJ, Stewart ET, Dodds WJ. Gastrointestinal lipomas:a radiologic and pathologic review. AJR Am J Roentgenol 1990; 155:1205-1210
44. Thompson WM, Kende AI, Levy AD. Imaging characteristics of gastric lipomas in 16 adult and pediatric patients. AJR Am J Roentgenol 2003; 181:981-985
45. Polkowski M, Butruk E,Submucosal lesions.Gastrointest Endosc Clin.N Am,2005;15:33-54,viii
46. Lee EY,Kim TD,Oh HA.Is the invasive approach for all the upper gastrointestinal mesenchymal tumors necessary? Korean J
47. Nishida T,Hirota s.Biological and clinical review of stromal tumors in the gastrointestinal tract.Histol,Histopathol.2000; 15:1293-301
48. Matsushita M, Hajiro K, Okazaki K, Takakuwa H. Gastric aberrant pancreas:EUS analysis in comparison with the histology. Gastrointest Endosc.1999; 49:493-497
49. Miettinen M, Kopczynski J, Makhlouf H R, et al. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum:a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol, 2003,27:625-641
50. Dematteo RP, Gold JS, Saran L, et al. Tumor mitotic rate, size, and location, independently predict recurrence after resection of primary gastrointestinal stromal tumor (GIST). Cancer,2008,112(3):608-615
51. Ronald P, Dematteo MD, Jonathan J, et al. Two hundred gastrointestinal stromal tumors:recurrence patterns and prognostic factors for survival. Ann Surg.2000, 231(1):51-58
52. Mudan SS, Conlon KC, Woodruff JM, et al. Salvage surgery for patients with recurrent gastrointestinal sarcoma:prognostic factors to guide patient selection. Cancer,2000,88(1):66-74
53. Igwilo OC, Byrne MP, Nguyen KD, et al. Malignant gastric stromal tumor: unusual metastatic patterns. South Med J,2003,96:512-515
54. Rosenberg N. Submucosal saline wheal as safety factor in fulguration or rectal and sigmoidal polypi. AM A Arch Surg,1955,70:120-122.
55. Deyhle P, Largiader F, Jenny S, et al. A method for endoscopic electroresection of sessile colonic polyps. Endoscopy,1973,5:38-40.
56. Tada M, Shimada M, Murakami F, et al. Development of the strip-off biopsy. Gastroenterol Endosc,1984,26(83):34-39.
57. Hirao M, Masuda K, Asanuma T, et al. Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic saline-epinephrine. Gastrointest Endosc,1988,34:264-269.
58. Monma K, Sakaki N, YoshidaM, et al. Endoscopic mucosectomy for precise evaluation and treatment of esophageal intraepithelial cancer. Endoscopic Digestive, 1990,2:501-506.
59. Inoue H, Endo M. Endoscopic esophageal mucosal resection using a transparent tube. Surg Endosc,1990,4(4):198-201.
60. Inoue M, Shiozaki H, Tamura S, et al. Endoscopic mucosal resection for early esophageal cancer, Nihon Rinsho,1996,54(5):1286-1291. Review, Japanese.
61. Inoue H, Noquchi O, Saito N, et al. Endoscopic mucosectomy for early cancer using a pre-looped plastic cap. Gastrointest Endosc,1994,4o:263-264.
62. Fleischer DE, Wang GQ, Dawsey S, et al. Tissue band ligation followed by snare resection (band and snare):a new technique for tissue acquisition in the esophagus. Gsatrointest Endosc,1996,44:68-72.
63. Soehendra N, Binmoeller KF, Bohnacker S, et al. Endoscopic snare mucosectomy in the esophagus without any additional equipment:a simple technique for resection of flat early cancer. Endoscopy,1997,29:380-383.
64. Takekoshi T, BabaY, Ota H, et al. Endoscopic resection of early gastric carcinoma: results of a retrospective analysis of 308 cases. Endoscopy,1994,26:352-358
65. Sun S, Ge N, Wang C, et al. Endoscopic band ligation of small gastric stromal tumors and follow_up by endoscopic ultrasonography. Surg Endosc,2007,21: 574-578
66.马丽黎,陈世耀,周平红等.内镜下粘膜剥离术治疗上消化道病灶的初步评价.中华消化内镜杂志,2008(10),25：529-534.
67. Matthews BD, Walsh RM, Kercher KW, et al. Laparoscopic vs open resection of gastric stromal tumors. Surg Endosc,2002,16:803-807
68. J F Graadt van Roggen, M L F van Velthuysen, P C W Hogendoorn. The histopathological differential diagnosis of gastrointestinal stromal tumors. J Clin Pathol,2001,54:96-102