Surgical Resection of Gastrointestinal Stromal Tumors After Treatment with Imatinib

Background Surgical resection of gastrointestinal stromal tumors (GISTs) has been the most effective therapy for these rare tumors. Imatinib has been introduced as systemic therapy for locally advanced and metastatic GIST. In this study, the surgical resection rates and long-term outcomes of patients treated with preoperative imatinib for locally advanced primary, recurrent, or metastatic GISTs were evaluated. Methods Patients were retrospectively assessed for completeness of surgical resection and for disease-free and overall survival after resection. Results Forty-six patients underwent surgery after treatment with imatinib. Eleven were treated for locally advanced primary GISTs for a median of 11.9 months, followed by complete surgical resection. All eleven were alive at a median of 19.5 months, and ten were free of disease. Thirty-five patients were treated for recurrent or metastatic GIST. Of these, eleven underwent complete resection. Six of the eleven patients had recurrent disease at a median of 15.1 months. All eleven patients were alive at a median of 30.7 months. Patients with a partial radiographic tumor response to imatinib had significantly higher complete resection rates than patients with progressive disease (91% vs. 4%; P < .001). Of the 24 patients with incomplete resection, 18 initially responded to imatinib but were unable to undergo complete resection after they progressed before surgery. Conclusions Preoperative imatinib can decrease tumor volume and is associated with complete surgical resection in locally advanced primary GISTs. Early surgical intervention should be considered for imatinib-responsive recurrent or metastatic GIST, since complete resection is rarely achieved once tumor progression occurs. Presented in part at the Annual Meeting of the Society of Surgical Oncology, Atlanta, GA, March 2005.     

Staged surgical approach for metastatic GIST,how far should we go? Case report

IntroductionGastrointestinal stromal tumor (GIST) is an uncommon mesenchymal neoplasm that commonly arises from the stomach and proximal small intestine but can develop in any part of the gastrointestinal tract. The disease can range from primary localized to an advanced metastatic unresectable disease in up to 30% of patients. Usually, metastasis involves the liver, peritoneum, and occasionally the lungs. The current standard treatment of localized resectable tumors is complete oncological resection, while advanced metastatic GISTs treatment remains contentious.Case presentationWe report a case of a 34 years old pregnant female presenting with a 3 days history of multiple episodes of hematemesis and melena. Laboratory investigations were unremarkable except for severe anemia (Hgb 4.4 g/dL). After further investigations a diagnosis of duodenal GIST (DGIST) with liver metastasis was made. She received and showed good response to neoadjuvant Imatinib therapy, which was followed by a successful 2-stage surgery in the form of extended right hepatectomy and Whipple procedure with a good survival.Clinical dissectionThe evolution of Imatinib had a tremendous impact on surgery in metastatic GIST even in initially unresectable cases, thereby providing a better survival. However, the duration of neoadjuvant Imatinib course and the matter of resistance are still unclear those necessitating the use of different agents or the surgical approach.ConclusionAlthough with the advancements in surgical approaches and perioperative care, liver resection might be a curative option. The role of surgery in advanced GIST remains a controversial matter that needs critical selection of cases based on further future research.     

Resection for pulmonary metastasis of gastrointestinal stromal tumor of the stomach at 10 years after gastrectomy; report of a case

A 70-years-old male, who had received gastrectomy for leiomyosarcoma of the stomach 10 years ago, was found to have a left lung tumor on chest X-ray and computed tomography (CT). The tumor was diagnosed to be a pulmonary metastasis of gastric leiomyosarcoma. On admission, another tumor was detected at left occipital region by brain CT and was thought to be meningioma. Left lower lobectomy and brain tumor resection were performed serially. The histologic and immunohistochemical findings showed that both tumors were metastases of gastrointestinal stromal tumor (GIST) of the stomach after long disease-free interval. Compared with the primary tumor, cellular density, mitotic figures, bizarre nuclei, and necrotic foci were prominent in the metastatic tumors. This case suggest that GIST may recurrent as pulmonary metastasis after long disease-free interval and should be follow up longer after resection. Patient prognosis with pulmonary metastases is considered to be reflected more exactly in biological malignant potential of metastatic tumor rather than that of primary tumor.     

Surgery and Imatinib in the Management of GIST: Emerging Approaches to Adjuvant and Neoadjuvant Therapy

Gastrointestinal stromal tumor (GIST) is a neoplasm of the gastrointestinal tract, mesentery, or omentum that expresses the protein-tyrosine kinase KIT (CD117) and is the most common mesenchymal tumor arising at these sites. Surgical resection is the first-line intervention for operable GISTs, particularly localized primary tumors, and it was historically the only effective treatment. However, more than half of all GIST patients present with locally advanced, recurrent, or metastatic disease. The 5-year survival rate ranges from 50% to 65% after complete resection of a localized primary GIST and decreases to approximately 35% for patients with advanced disease who undergo complete surgical resection. A total of 40% to 90% of all GIST surgical patients subsequently have postoperative recurrence or metastasis. Imatinib is a potent, specific inhibitor of KIT that has demonstrated significant activity and tolerability in the treatment of malignant unresectable or metastatic GIST, inducing tumor shrinkage of 50% or more or stabilizing disease in most patients. A key strategy for prolonging the survival of patients with GIST is to improve the outcome of surgery. It is possible that the adjuvant and neoadjuvant use of imatinib (e.g., rendering initially inoperable tumors resectable) in the overall management approach to advanced GIST may contribute to surgeons success in attaining this objective.     

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.     

Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival

OBJECTIVE: To analyze the outcome of 200 patients with gastrointestinal stromal tumor (GIST) who were treated at a single institution and followed up prospectively. SUMMARY BACKGROUND DATA: A GIST is a visceral sarcoma that arises from the gastrointestinal tract. Surgical resection is the mainstay of treatment because adjuvant therapy is unproven. METHODS: Two hundred patients with malignant GIST were admitted and treated at Memorial Hospital during the past 16 years. Patient, tumor, and treatment variables were analyzed to identify patterns of tumor recurrence and factors that predict survival. RESULTS: Of the 200 patients, 46% had primary disease without metastasis, 47% had metastasis, and 7% had isolated local recurrence. In patients with primary disease who underwent complete resection of gross disease (n = 80), the 5-year actuarial survival rate was 54%, and survival was predicted by tumor size but not microscopic margins of resection. Recurrence of disease after resection was predominantly intraabdominal and involved the original tumor site, peritoneum, and liver. CONCLUSIONS: GISTs are uncommon sarcomas. Tumor size predicts disease-specific survival in patients with primary disease who undergo complete gross resection. Tumor recurrence tends to be intraabdominal. Investigational protocols are indicated to reduce the rate of recurrence after resection and to improve the outcome for patients with GIST.     

Metastatic renal cell carcinoma mimicking a meningioma

We report a patient with renal cell carcinoma metastatic to the left trigone, which mimicked an intraventricular meningioma. The metastasis was recognized 1.3 years after removal of the primary tumor, a longer disease-free interval than any previously reported cases with brain metastases of renal cell carcinoma. The patient is now free of disease of years after resection and 17 years after the discovery of the primary tumor. Metastatic disease should be considered in all patients with prior resection of renal cell carcinoma who experience the onset of neurological disease, even after a prolonged disease-free interval. Long term survival is observed after the resection of solitary metastases, particularly if these appear after a prolonged disease-free interval.     

Giant GIST of the mesocolon: report of a case

Gastrointestinal stromal tumors are rare neoplasms arising from mesenchymal cells of the gastrointestinal tract, that strongly express a class III receptor tyrosine kinase, called KIT, due to some mutations in the KIT proto-oncogene. Two thirds of GISTs are found in the stomach, 20% to 50% in the small bowel (one third in the duodenum), and 5% to 15% in colon and rectum; GISTs, however, may rarely be found also in the oesophagus, omentum, mesentery or the retroperitoneum. Their treatment is strictly surgical, and only R0 resection can achieve good RESULTS: Treatment with Imatinib seems to be promising in case of unresectable or metastatic GIST, even if some trials are studying its effects after curative resection. GIST of the mesocolon are rare, and as in the other locations, require extensive surgery. The Autohrs report a case of giant malignant GIST arising from transverse mesocolon, treated by en-bloc resection of the tumor with a segment of transverse colon and great omentum.     

Liver transplantation for metastatic wild‐type gastrointestinal stromal tumor in the era of molecular targeted therapies: Report of a first case

The gastrointestinal stromal tumor (GIST) is a digestive neoplasm of mesenchymal lineage. The treatment strategy for receptor tyrosine kinase‐mutated GISTs is well defined. Wild‐type GISTs (WT‐GISTs) respond unsatisfactorily to specific kinase inhibitors. Moreover, evidence shows that repeat surgery has limited benefit. We report the case of a young female patient who was diagnosed with liver metastatic WT‐GIST, after initial radical resection and adjuvant therapy with molecular targeted drugs. Due to the disease progression, a two‐stage surgery was performed, with the removal of extrahepatic lesions followed by a total hepatectomy. The patient is disease‐free after 4 years from liver transplantation (LT), performed under everolimus‐based immunosuppression. The treatment of WT‐GISTs remains a significant challenge due to the frequent resistance to tyrosine kinase inhibitors (TKIs). Liver transplantation might represent an effective treatment option for such disease.     

Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome.

OBJECTIVE: To update the analysis of technical and biologic factors related to hepatic resection for colorectal metastasis in a large single-institution series to identify important prognostic indicators and patterns of failure. SUMMARY BACKGROUND DATA: Surgical therapy for colorectal carcinoma metastatic to the liver is the only potentially curable treatment. Careful patient selection of those with resectable liver-only metastatic disease is crucial to the success of surgical therapy. METHODS: Two hundred forty-four consecutive patients undergoing curative hepatic resection for metastatic colorectal carcinoma were analyzed retrospectively. Variables examined included sex, stage of primary lesion, size of liver lesion(s), number of lesions, disease-free interval, ploidy, differentiation, preoperative carcinoembryonic antigen level, and operative factors such as resection margin, use of cryotherapy, intraoperative ultrasound, and blood loss. RESULTS: Surgical margin, number of lesions, and carcinoembryonic antigen (CEA) levels significantly control prognosis. Patients with only one or two liver lesions, a 1-cm surgical margin, and low CEA levels have a 5-year disease-free survival rate of more than 30%. Disease-free interval, original stage, bilobar involvement, size of metastasis, differentiation, and ploidy were not significant predictors of recurrence. The pattern of failure correlates with surgical margin. Routine use of intraoperative ultrasound resulted in an increased incidence of negative surgical margin during the period examined. CONCLUSIONS: Surgical resection or cryotherapy of hepatic metastasis from colorectal cancer is safe and curable in appropriately selected patients. Biologic factors, such as number of lesions and carcinoembryonic antigen levels, determine potential curability, and surgical margin governs the patterns of failure and outcome in potentially curable patients. Optimization of selection criteria and surgical resection margins will improve outcome.     

Complete remission of disease for 5 years following initial and repeat resection of the liver for the removal of 22 metastases of colorectal origin

Although liver resection is accepted as the only available treatment that regularly produces long-term survival with possible cure in patients with colorectal carcinoma metastatic to the liver, controversy appears to exist regarding the surgical indication for patients with more than four nodules. Similarly, it may be arguable to perform a repeated hepatic resection for a patient who developed multiple recurrent liver metastases with a short disease-free period after the initial liver resection. During the last 7 years, we have adopted constantly the aggressive surgical approach to patients with colorectal carcinoma metastatic to the liver if the number of tumor nodules identified preoperatively were less than ten and irrespective of the length of disease-free period after the previous resection. Here we report on a patient who underwent hepatic resection twice at an interval of 3 months and in whom a total of 22 metastatic nodules (6 in the initial hepatic resection and 22 in the repeated resection) were removed. The patient is now alive and remains disease-free, 5 years after the first liver resection.     

胃肠间质瘤135例临床诊治分析

目的探讨胃肠道平滑肌肿瘤与胃肠间质瘤(GIST)的关系及外科治疗的效果。方法重新调出1993-2003年间收治的资料完整的86例胃肠道平滑肌瘤或平滑肌肉瘤患者的病理组织重新病理复检,结合2000年1月至2005年7月确诊GIST的71例病例资料进行分析。并完成随访。结果86例原诊断胃肠道平滑肌瘤或平滑肌肉瘤的患者共有78例完成免疫组化检测,有64例(82.1%)被纠正诊断为GIST。共计135例GIST患者中,男性65例,女性70例;平均发病年龄53岁。均接受手术治疗,130例(96.3%)为完全切除;术后总体5年生存率为79.7%。完全切除者术后总体生存率与首诊转移、肿瘤大小、核分裂和术后复发转移有关(P<0.01);无病生存率的多因素回归分析中发现,完全切除术后无病生存率与首诊已有转移和核分裂数有关(P<0.01)。结论既往胃肠道平滑肌肿瘤大部分应纠正诊断为GIST。GIST以外科治疗为主。完全切除很重要。首诊肿瘤转移和核分裂数是独立的预后因素。     

Long-term survival after surgical resection of liver metastasis from lung cancer

Lung cancer metastasis to the liver indicates a poor prognosis, and the majority of patients with metastatic disease to the liver are not indicated for surgery because of the number or distribution of metastases or the presence of extrahepatic disease. We herein describe a case of long-term survival after a surgical resection of liver metastases from lung cancer. Six months after surgery for Stage IB primary lung adenocarcinoma, a 71-year-old male was found to have a metastatic tumor in his liver. A hepatic resection for the metastatic tumor and another small metastatic foci found intraoperatively was carried out, and the tumors were pathologically diagnosed as liver metastases from lung cancer. The patient is presently alive and well without recurrence, as of 5 years and 2 months after the liver resection. This is the first report of the successful surgical treatment of liver metastasis from lung cancer.     

Surgical management of GIST in the era of Gleevec

The diagnostic and treatment options for patients with GIST have evolved rapidly with the discovery of uncontrolled KIT tyrosine kinase and Gleevec that selectively inhibits Kit. Gleevec has already revolutionized the treatment of patients with metastatic disease and is also currently being tested as an adjuvant therapy after the resection of primary GIST. But the majority of responses are limited to partial responses and secondary resistances are emerging. These observations suggest that initial surgical resection remains a vital component of the treatment for patients with primary resectable cKIT+ GISTs and raises the question of secondary surgery after Gleevec. The objective of secondary surgery is to obtain a complete remission when the response to Gleevec is maximum. Surgery should be discussed between 6 and 12 months treatment when no additional improvement is observed on 2 consecutive CT scan. Three subgroups may benefit from secondary surgery: primary unresectable tumors amenable to surgery with Gleevec even in case of complete response, huge necrotic masses before expected complication, local re-progressions. Gleevec should also be discussed when a functionnal benefit can be expected by a tumor size decrease. Surgery is being evaluated in the other responding patients. The majority of responses being limited to partial responses, best indications of surgery are when complete resection may be expected (< 10%).     

Rhabdomyosarcomatous differentiation in gastrointestinal stromal tumors after tyrosine kinase inhibitor therapy: a novel form of tumor progression

Approximately 80% of advanced metastatic gastrointestinal stromal tumors (GISTs) respond to treatment with the tyrosine kinase inhibitor (TKI) imatinib mesylate. However, the majority of patients suffer disease progression at a median of 2 years due to drug resistance. In general, progressing GISTs retain their typical morphology. Herein, we report 5 cases of progressing metastatic GIST with heterologous rhabdomyoblastic differentiation after TKI treatment. Histologic, immunohistochemical, and mutational analyses were performed on histologically classic GISTs and components with rhabdomyoblastic differentiation. There were 3 men and 2 women (ranging from 35 to 66 y of age). Three tumors were localized at presentation (2 stomach and 1 small bowel) and 2 presented with metastases. All localized primary tumors were high risk. Two tumors showed spindle cell morphology and 3 were epithelioid, including 1 with marked pleomorphism. After resection of the 3 localized primary tumors, intra-abdominal (2 patients) and liver (1 patient) metastases developed. All patients were treated with imatinib and showed partial clinical responses (4 patient) or stable disease (1 patient). Four patients subsequently progressed; 2 patients were treated with sunitinib after progression with minor responses. Four patients underwent surgical debulking. At last follow-up (range: 20 to 87 mo), 2 patients died of disease, 2 were alive with metastatic disease resistant to TKIs, and 1 was alive without evidence of disease. In all cases, rhabdomyoblastic differentiation was identified adjacent to areas with classic GIST morphology in at least 1 metastatic site; in 1 case, the primary tumor (after treatment with TKIs) showed heterologous differentiation. The rhabdomyoblastic components showed strong and diffuse positivity for desmin and expressed myogenin, whereas KIT was negative in the rhabdomyoblastic component in all cases. Primary KIT mutations were detected in both the conventional GIST and rhabdomyoblastic components from all patients: KIT exon 11 mutations in 4 cases and a platelet-derived growth factor receptor alpha gene exon 18 deletion in 1 case. No secondary mutations of the type associated with TKI resistance were identified in the rhabdomyoblastic areas. This is the first report of rhabdomyoblastic differentiation occurring in GISTs that progressed on TKI therapy. It is associated with loss of KIT expression, but retention of the receptor tyrosine kinase mutation of the precursor GIST. The rhabdomyoblastic differentiation can represent a diagnostic pitfall. The molecular mechanisms for this form of TKI-resistant clonal evolution remain to be determined.     

Sunitinib Treatment for Multiple Brain Metastases from Jejunal Gastrointestinal Stromal Tumor: Case Report

Gastrointestinal stromal tumors (GISTs) are rare malignant tumors and only a few reported cases of brain metastases can be found. Introduction of a new molecular targeted agent, imatinib mesylate in the last decade has dramatically changed the treatment strategy and prognosis. However, imatinib is usually ineffective for brain metastasis from GISTs. The authors present the case of multiple brain metastases from jejunal GIST. The brain metastasis in the right prefrontal gyrus was detected 20 months after resection of the primary lesion when left hemiparesis began although the patient was on imatinib. Then the patient began taking sunitinib instead of imatinib, and the lesion shrunk and the symptom improved. However, after the dose reduction due to side effects, a new brain metastasis was found and this time, stereotactic radiation was effectively done. Sunitinib is one of the promising receptor tyrosine kinase inhibitors used for metastatic renal cell carcinomas or imatinib-refractory GISTs. Sunitinib is thought to penetrate blood-brain barrier, and recent reports indicate effectiveness to brain metastasis. To the authors'' knowledge, this is the first report of brain metastases from jejunal GIST responding to sunitinib therapy.     

Surgical treatment of solitary adrenal metastasis from non-small cell lung cancer

BACKGROUND: Management of solitary adrenal metastasis from non-small cell lung cancer is still debated. Although classically considered incurable, various reports with small numbers of patients have shown that surgical treatment might improve long-term survival. The aim of this study was to review our experience and to identify factors that could affect survival. METHODS: From January 1989 through April 2003, 23 patients underwent complete resection of an isolated adrenal metastasis after surgical treatment of non-small cell lung cancer. There were 19 men and 4 women, with a mean age of 54 +/- 10 years. The diagnosis of adrenal metastasis was synchronous with the diagnosis of non-small cell lung cancer in 6 patients and metachronous in 17 patients. The median disease-free interval for patients with metachronous metastasis was 12.5 months (range, 4.5-60.1 months). RESULTS: The overall 5-year survival was 23.3%. Univariate and multivariate analysis demonstrated that a disease-free interval of greater than 6 months was an independent and significant predictor of increased survival in patients after adrenalectomy. All patients with a disease-free interval of less than 6 months died within 2 years of the operation. The 5-year survival was 38% after resection of an isolated adrenal metastasis that occurred more than 6 months after lung resection. Adjuvant therapy and pathologic staging of non-small cell lung cancer did not affect survival. CONCLUSIONS: Surgical resection of metachronous isolated adrenal metastasis with a disease-free interval of greater than 6 months can provide long-term survival in patients previously undergoing complete resection of the primary non-small cell lung cancer.     

Our experience in the surgical treatment of gastrointestinal stromal tumors

The authors carry out a retrospective review of 30 patients with gastrointestinal stromal tumours (GISTs) who underwent surgical treatment over the period from 1974 to 2001. Sixteen were male and 14 female, with an average age of 60.9 years. Histologically, 19 tumours showed evidence of differentiation towards smooth muscle elements (10 benign and 9 malignant), 9 towards neural elements (3 benign and 6 malignant) and 2 iacked differentiation towards either cell type. Twenty-one tumours were located in the stomach, 1 in the duodenum, 3 in the jejunum and 5 in the ileum. The main symptoms were abdominal pain and abdominal masses, and the most sensitive diagnostic techniques were abdominal CT scan and endoscopy in gastroduodenal locations. In 21 gastric GISTs, the surgical procedures were local resection (15 cases), partial gastric resection (3 cases), subtotal gastrectomy (2 cases) and total gastrectomy (1 case). In 8 small bowel GISTs, we performed a typical intestinal resection while duodenal undifferentiated GIST was managed by pancreatico-duodenectomy. There was no operative mortality or morbidity. Among the 13 patients with benign GISTs, 1 died of causes unrelated to the disease, while 12 patients are still alive and in good health after a mean follow-up of 148.5 months (range: 6-262). Among patients with malignant muscular GISTs (6 gastric and 3 ileal), 3 with gastric tumours were lost to follow-up, 3 with gastric and 1 with ileal neoplasms are alive and free from disease after a median follow-up of 58 months (range 3-108), while 2 patients with ileal neoplasms died of metastatic disease 39 and 29 months after the surgical procedure. Among 6 patients with malignant neural GISTs (2 gastric, 2 jejunal and 2 ileal) 1 with a gastric tumour and 1 with a jejunal tumour were lost to follow-up, while 3 are still alive and in good health after a median follow-up of 67.6 months (range 19 to 94); another with jejunal disease developed liver metastases 14 months after small bowel resection and died 12 months later. The two patients with undifferentiated GIST both died of liver metastasis 38 months after pancreatico-duodenectomy and 43 months after total gastrectomy. The most frequent symptoms were abdominal pain and a palpable mass, but no specific signs were detected. In gastroduodenal lesions endoscopy plays a very important diagnostic role and CT scan is the most sensitive diagnostic technique in the evaluation of location, size, invasion of adjacent organs and metastases. Prognostic prediction on the basis of histological findings is difficult and in our experience undifferentiated tumours are always malignant.     

复发转移胃肠间质瘤的治疗对策

靶向药物是治疗复发转移胃肠间质瘤（GIST）的首选。酪氨酸激酶抑制剂（TKI）伊马替尼耐药后,特别是外显子9突变者接受舒尼替尼治疗可以获得满意的疾病控制率。TKI联合手术切除可能延长GIST肝转移患者的生存期。在严格掌握适应证的前提下,TKI联合手术可能是目前治疗复发转移GIST的最佳模式。多激酶抑制剂regorafenib和帕唑帕尼（pazopanib）对标准治疗失败的GIST患者仍可获得显著疗效。     

Recurrent metastatic renal cell carcinoma presenting as a bleeding gastric ulcer after a complete response to high-dose interleukin-2 treatment

Immunotherapy with high-dose recombinant interleukin-2 is an effective therapy for selected patients with metastatic renal cell carcinoma (RCC). Objective responses (complete or partial) are observed in about 15% of treated patients. The overall and disease-free survival of patients with a complete response are significantly prolonged. Although RCC is known to spread hematogenously, isolated RCC metastasis to the stomach is a rare event. Recurrent RCC, after a complete response to interleukin-2, presenting clinically as an isolated gastric metastasis, has not been reported to date. In this report, we describe the clinical course of a patient with metastatic RCC who had a complete response to high-dose interleukin-2 and was disease free for 4 years before presenting with massive upper gastrointestinal hemorrhage due to an isolated gastric metastasis. The patient remained disease free for 3 years after resection of the metastasis. Metastatic RCC to the stomach, although rare, should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms. In the absence of diffuse disease, aggressive therapy, including surgical resection, is appropriate for isolated gastric metastasis, because prolonged survival is possible.