胃肠道间质瘤的诊断及外科治疗体会

目的分析胃肠道间质瘤（GIST）的临床特征及手术方式。方法回顾性分析2001年1月至2005年12月经手术病理证实的GIST47例资料。结果肿瘤发生于胃部18例，十二指肠8例，小肠19例，直肠2例。4例因肿瘤广泛转移行姑息性切除，1例直肠GIST经肛门切除，其余42例均达到外科根治性切除，其中行受累脏器局部切除4例，大部切除26例，多脏器切除12例。术后平均随访20个月，术后复发和转移9例，复发问期平均为13个月。其中8例行再次手术治疗，1例再复发后行3次手术治疗。本组无手术死亡病例，术后并发细菌性腹膜炎1例，切口裂开1例，均治愈。结论外科手术是GIST治疗的首选，对复发病例仍应争取再手术治疗。     

影响胃肠道间质瘤患者预后的因素分析

目的探讨影响胃肠道间质瘤预后的临床病理因素。方法 收集临床病理资料,单因素及多因素分析各变量与患者预后的关系。结果患者1、3、5 a生存率分别是89.7%、79.3%和70.7%。单因素分析和多因素分析均显示肿瘤大小、核分裂像数目、肿瘤原发部位是影响预后的重要因素（P〈0.05）。结论肿瘤直径〉10 cm、核分裂数〉10个/50 HPF常提示胃肠道间质瘤恶性度较高,预后不良。     

Multiple sporadic gastrointestinal stromal tumors (GISTs) of the proximal stomach are caused by different somatic KIT mutations suggesting a field effect

Multifocal gastrointestinal stromal tumors (GISTs) are observed in patients with germline KIT or PDGFRA mutations, and in those with neurofibromatosis 1. However, the pathogenesis of apparently sporadic multifocal gastric GISTs in adults is poorly understood. We analyzed 27 GISTs from 11 patients (mean age, 75 y) with 2 to 4 tumors each. All tumors represented incidental findings in surgical (n=8) and autopsy (n=3) specimens and were located in the gastric body or fundus within < or =4 cm distance from each other. The 8 surgical cases represented 10% of GISTs involving the proximal stomach in our case material. Tumor size ranged from 1.5 mm to 45 mm (mean, 9 mm). Histology revealed a uniform spindle cell morphology with a variable sclerosis/calcification and a low mitotic activity (<5 mitoses/50 high-power fields). All tumors were KIT+/CD34+. Nineteen of 22 tumors (79%) revealed mutations in KIT exon 11 (13 deletions and 6 point mutations). Individual lesions from the same patient displayed different mutations in all, but 1 case, thus ruling out germline mutations and neurofibromatosis 1. Our findings indicate that multifocal gastric GISTs in elderly patients are unrelated to hereditary GIST syndromes. Clustering of these lesions in the proximal stomach, their close proximity, and the demonstration of different KIT mutations in individual lesions from the same patient point to the existence of distinct subsets of interstitial cells of Cajal with a higher propensity for different somatic KIT exon 11 mutations, possibly as a result of a field effect involving premutational epigenetic alterations or yet unidentified etiologic factors.     

Gastrointestinal stromal tumors (GIST) of the stomach as a cause of upper gastrointestinal bleeding

Gastrointestinal stromal tumors (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. GIST is currently defined as a gastrointestinal tract mesenchymal tumor containing spindle cells (less commonly epitheloid cells or rarely both) and showing CD 117 (c-kit protein) positivity in more than 95% of cases. Although they may arise throughout the gut, the commonest site are stomach (60-70%), small intestine (20-30%), colorectum (5%) and esophagus (up to 5%). Rarely, GISTs develop in the retroperitoneum, omentum or mesentery. GIST originates from the intestinal cell of Cajal (ICC). ICCs are located in and around the myenteric plexus and are thought to function as intestinal pacemaker cells. Historicaly, GIST were often misclassified as leiomyomas or leiomyosarcomas. Subsequently, it has been determined that GISTs have distinct ultrastructural features and immunophenotypical markers compared with smooth muscle and smooth muscle tumors. GIST predominantly occur in middle aged and older patients, with no significant difference in the sex incidence. Data from the recent population study suggest an incidence of about 10-22 cases per million persons per year. Clinical presentation of GIST varies widely, and depends on tumor size and location. GISTs that caused symptoms tended to be larger with an average size of 6cm versus 2cm for asymptomatic GISTs. Symptoms are most commonly related to mass effect or bleeding. GISTs can grow very large before producing symptoms. Commonest symptom of gastric GIST is manifest or occult bleeding. Abudant, life-threateting bleeding that require urgent surgery is rare. For patient with primary, localized, nonmetastatic GIST, complete surgical resection represents the only chance for cure. Lymhadenectomy is not necessary, because lymph node metastasis is very rare. The 5 year survival rate in patients with resected primary GISTs ranges from 48-65%. Conventional chemotherapy and radiation therapy is ineffective in the treatment of GIST. Imatinib mesilate (a tyrosine kinase inhibitor) was confirmed to be effective against metastatic or unresectable GISTs.     

Laparoscopic approach for the management of gastrointestinal stromal tumours (GIST) of the stomach

Aim-Background

The present review of the literature evaluates whether laparoscopic resection of gastric GISTs can become the new “gold standard” treatment, analyzing perioperative characteristics and long-term oncological outcome. Surgery remains the standard treatment for non-metastatic gastrointestinal stromal tumours (GISTs). Laparoscopic surgery is considered a suitable option, since the biological behaviour of these tumours allows for curative resection without the necessity for large margins or extensive lymphadenectomies.

Methods

A systematic review of gastrointestinal stromal tumours of the stomach treated by laparoscopy was conducted.

Results

Up to 2008, laparoscopic surgery was attempted in 442 patients, of whom 254 were male and 188 female. Their average age was 61 years. The mean tumour size was 4.3 cm (1.0–7.5 cm); operative time ranged from 49–194.3 min, blood loss from 15–196ml, and hospital stay from 2.3 up to 12.2 days. All lesions had negative resection margins. The follow-up period for all patients ranged from 19 up to 61 months while the overall survival was 82%.

Conclusions

The review of the literature concurred that laparoscopic resection is safe and effective in treating gastric GISTs. Taking into consideration the associated benefits of this minimally invasive approach, laparoscopic surgery should be considered in the surgical treatment of small- and medium-sized gastrointestinal stromal tumours of the stomach.     

Two von Recklinghausen''s disease cases with pheochromocytomas and gastrointestinal stromal tumors (GIST) in combination

We here document two cases of von Recklinghausen's disease with both pheochromocytomas and gastrointestinal stromal tumors (GIST). It is very rare that these three disorders are found to occur simultaneously, although the fact that preoperative detection of GIST is difficult except with large tumors may be important in this respect. In the present cases, GIST were not evident on preoperative computed tomography and magnetic resonance imaging, and were identified unexpectedly during surgery. Our findings indicate that investigation of the intraperitoneal space should be performed during adrenalectomy for pheochromocytomas with von Recklinghausen's disease.     

Laparoscopic resection of locally advanced gastrointestinal stromal tumour (GIST) of the stomach following neoadjuvant imatinib chemoreduction

IntroductionLaparoscopic resection of locally advanced gastrointestinal stromal tumours (GISTs) is rarely offered to patients as a first line of treatment.Presentation of casesWe present two cases of locally advanced gastric GISTs successfully treated with neoadjuvant imatinib and followed up by complete laparoscopic excision of the residual tumour mass. There was no evidence of local recurrence or distant metastases after a mean follow up of more than 40 months.DiscussionOver the last decade, the development of imatinib has totally revolutionized management of metastatic GISTs and it is now possible to achieve primary tumour downstaging of more than 80%. Unfortunately, current literature on laparoscopic excision of locally advanced gastric GISTs following neoadjuvant treatment of imatinib remains scarce. The present cases strongly suggest that this new therapeutic approach might become the preferred medical option in such clinical situation.ConclusionPatients with locally advanced non-metastatic gastric GISTs should be offered first-line neoadjuvant. Imatinib-based cytoreductive chemotherapy as an alternative to radical debulking surgery, as a substantial proportion of them will experience significant tumour shrinkage and therefore benefit from a much less invasive laparoscopic approach.     

Cox-2和VEGF在胃肠道间质瘤中的表达及其相关性研究

目的：探讨环氧合酶-2（Cox-2）和血管内皮生长因子（VEGF）在胃肠道间质瘤（GIST）中的表达及其与临床病理特征的关系,分析两者在GIST中的作用及相关性。方法：用免疫组织化学染色检测104例GIST中Cox-2和VEGF的表达．分析Cox-2和VEGF的表达与GIST临床病理特征的关系及其相关性。结果：①104例GIST中Cox-2和VEGF的阳性表达率分别为76．0％、68.3％。②Cox-2和VEGF的表达与病人的性别、年龄、肿瘤部位、大小等临床病理特征无关．而与组织学分级有关。③Cox-2和VEGF的表达呈正相关。结论：Cox-2和VEGF的表达与组织学分级相关,提示Cox-2和VEGF在GIST的发生、发展中发挥重要作用,可作为GIST组织学良恶性评价的潜在指标.     

Gastrointestinal stromal tumors: insights from a new familial GIST kindred with unusual genetic and pathologic features

Familial gastrointestinal stromal tumor (GIST) is a rare autosomal dominant genetic disorder. We report the second family to date with a germline point mutation in exon 17 of the KIT gene that leads to substitution of aspartic acid at position 820 with tyrosine (D820Y). One or more GISTs was documented in three generations of this kindred, and there was associated hyperplasia of the interstitial cells of Cajal (ICC). One affected family member complained of dysphagia and another suffered small intestinal diverticulosis with perforation, which may represent additional consequences of ICC hyperplasia. Diffuse and nodular ICC hyperplasia associated with the latter family member's small intestinal diverticulosis is illustrated, providing supportive functional and morphologic evidence for the ICC being the cell of origin of GISTs. Skin hyperpigmentation was not observed. Analysis of a 17-cm malignant GIST in the index patient revealed that it was hemi/homozygous for the germline D820Y mutation, indicating loss of the remaining wild-type KIT allele with tumor progression. Two smaller lesions from this patient were heterozygous for the mutation. This phenomenon has been observed in up to 8% of sporadic malignant GISTs but has not been documented in familial disease.     

Laparoscopic resection of gastric gastrointestinal stromal tumors (GIST) is safe and effective, irrespective of tumor size

Background

Feasibility and long-term safety of laparoscopic removal of gastric gastrointestinal stromal tumors (GISTs) of the stomach is well established for lesions smaller than 2 cm. Our specific aim was to explore whether laparoscopic treatment is equally applicable for gastric GISTs larger than 2 cm.

Methods

Between 1997 and 2010, 31 consecutive patients presenting with a primary gastric GIST were scheduled for laparoscopic resection, irrespective of tumor size. Prerequisites for laparoscopic approach were the absence of metastases and the presence of a well-defined tumor on CT scanning without involvement of adjacent organs, the esophagogastric junction, or the pylorus of the stomach. Data were retrieved retrospectively from a prospectively collected database, including information on patient demographics, surgical procedure, complications, hospital stay, and recurrence. Diagnosis of GIST was based on microscopic analysis, including immunohistochemistry with a panel of antibodies: CD117, CD34, DOG1, S100, desmin, and smooth muscle actin.

Results

All 31 laparoscopic resections were carried out successfully. The most common symptoms were melena, anemia, and abdominal pain. In one case we performed a laparoscopic approach for a GIST with acute bleeding. Tumor size was smaller than 2 cm in 5 patients and larger than 2 cm in 26 patients. The median tumor size was 4.4 cm (range = 0.4–11.0 cm). Median blood loss was identical in both groups (20 ml), but duration of operation (60 vs. 103 min) and duration of hospital stay (6 vs. 8 days) were lower when tumor size was less than 2 cm. Only one patient (with tumor size <2 cm) experienced a postoperative hemorrhage. After a median follow-up of 52 months, there were no recurrences or metastases.

Conclusion

The low morbidity rates and the long-term disease-free interval of 100% observed in our cohort indicate that laparoscopic resection is safe and effective in treating gastric GISTs, even for tumors larger than 2 cm.     

Gastrointestinal stromal tumors/smooth muscle tumors (GISTs) primary in the omentum and mesentery: clinicopathologic and immunohistochemical study of 26 cases.

Gastrointestinal stromal tumor or smooth muscle tumor (GIST) is the designation for a major subset of gastrointestinal mesenchymal tumors that histologically, immunohistochemically, and genetically differ from typical leiomyomas, leiomyosarcomas, and schwannomas. Because GISTs, like the interstitial cells of Cajal, the gastrointestinal pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the interstitial cells of Cajal has been recently proposed. Comparison of GISTs primary in the omentum and mesentery to GISTs primary in the tubular gastrointestinal tract is of particular diagnostic and histogenetic interest in view of the possible similarity of these tumors with the GIST group. In this study, we analyzed 14 omental and 12 mesenteric primary mesenchymal tumors representing smooth muscle tumors or GISTs. These tumors were phenotypically compared with gastric and small intestinal GISTs, leiomyomas of the esophagus, and leiomyosarcomas of the retroperitoneum. Most (13 of 14) omental and mesenteric (10 of 12) tumors showed histologic features similar to GISTs with elongated spindle cells or epithelioid cells with high cellularity; most of these tumors showed low mitotic activity. Omental and mesenteric GISTs were typically positive for CD117 and less consistently for CD34. They often showed alpha-smooth muscle actin reactivity but were virtually negative for desmin and S-100 protein. One omental and two mesenteric tumors showed features of leiomyosarcoma with ovoid, less elongated nuclei, cytoplasmic eosinophilia; all these tumors had significant mitotic activity. These tumors were positive for alpha-smooth muscle actin and two of them for desmin, but all were negative for CD34 and CD117, similar to retroperitoneal leiomyosarcomas. Tumor-related mortality occurred in the group of mesenteric GISTs, but not in the group of omental GISTs. In contrast, all three patients with a true leiomyosarcoma of the omentum or mesentery had documented liver metastases or died of tumor. In summary, we show that tumors phenotypically identical with GISTs occur as primary tumors in the omentum and mesentery. The occurrence of CD117-positive tumors outside the gastrointestinal tract militates against an origin of these tumors exclusively from the interstitial cells of Cajal.     

Rectal gastrointestinal stromal tumor with metastasis to the penis: Case report and review of literature

We report the case of a 51-year-old gentleman with previously diagnosed gastrointestinal stromal tumor (GIST) of the rectum with metastasis to the penis. The patient underwent abdominoperineal resection of the primary tumor with negative margins and completed a three-year course of imatinib mesylate (Gleevec). Forty months after resection of his rectal tumor, the patient presented to his urologist with worsening testicular pain, mild lower urinary tract obstructive symptoms, and nocturia. A pelvic MRI revealed the presence of an ill-defined mass in the right perineum extending from the base of the penis to the penoscrotal junction. Biopsy of this mass was consistent with metastatic GIST. To our knowledge, this is the first report of metastatic GIST to the penis.     

New orientations in the management of advanced, metastatic gastrointestinal stromal tumors (GIST): combination of surgery and systemic therapy with imatinib in a case of primary gastric location

Gastrointestinal stromal tumours (GIST) are rare neoplasms originating from connective tissue in the digestive tract with an incidence of less than 1% and account for most non-epithelial primitive digestive tumours. Metastasis diagnosed at the time of disease discovery confirms GIST malignancy. Kit protein, a trans-membrane tyrosine kinase receptor of staminal cells, is characteristically expressed by GIST. Most GIST have a mutation in the kit proto-oncogene. Resistance to conventional chemotherapy is commonly shown by malignant GIST. Most patients with advanced malignant GIST achieve clinical benefit with imatinib mesilate, an orally administered selective inhibitor of the tyrosine kinase receptor. We treated a 43-year-old male patient suffering from a gastric GIST diagnosed during a surgical emergency operation for peritonitis caused by gastric perforation. At the time of the first operation the patient had lost 10 kg body weight over the previous months and was seriously cachectic. During the emergency operation the perforation was sutured. The biopsy results showed the presence of CD1 17 (c-kit) and CD34 markers. A total body CT scan documented the substantial size of the gastric wall lesion, an increased volume of abdominal lymph nodes and compression of the splenic vein with alternative collateral circulation. The liver presented no less than 5 large metastases distributed in both the left and right lobes. There was also a pulmonary metastasis. Because of frequent spontaneous bleeding and starvation the patient was seriously anaemic. Considering the action mechanism of imatinib and the extent of the lesion we decided to perform a total gastrectomy procedure. At the time of the operation the stomach seemed to have a modified volume and shape: it appeared to be divided into two sacs, the larger and deeper of which was the original gastric cavity, while the superficial, smaller one seemed to be a protrusion of the organ. The stomach was indistinguishable from the spleen, the transverse colon and the distal pancreatic tract. The neoplasm was directly linked to the left liver and to the inferior diaphragmatic surface. We performed total gastrectomy and resection of the tail of the pancreas, the spleen, and the transverse colon all in one and the same session. The patient was discharged on postoperative day 8 and commenced imatinib therapy 30 days after the operation with 4 tablets per day. In the following months the patient repeated the CT scan to monitor the progressive volume reduction of the liver and lung lesions and a PET scan confirmed that the lesions were not active; the patient experienced a 13 kg body weight increase. One year after the operation the outcome appears to be lasting and the patient has tolerated the drug treatment well.