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.     

Complete Remission of Recurrent Gastrointestinal Stromal Tumors After Treatment with Imatinib: Report of a Case

A 49-year-old man underwent partial resection of the jejunum for an abdominal tumor, which was histologically confirmed to be a gastrointestinal stromal tumor (GIST). Immunohistochemistry revealed that the tumor cells were positive for c-kit, p52, and MIB-1. He underwent resection of a total of 83 recurrent tumors over the next 36 months. A computed tomography (CT) scan done a few months later showed multiple tumor recurrences. The patient was started on imatinib mesylate 400 mg/day, and 3 months later, a CT image showed an increase in tumor size but a decrease in tumor density. Subsequent CT scans showed a marked decrease in tumor size 3 months later and no evidence of tumor recurrence 9 and 12 months after the commencement of imatinib treatment. The patient remains in complete remission 31 months after the start of treatment.     

Surgical treatment of gastrointestinal stromal tumors in the imatinib (STI-571) era

BACKGROUND: Gastrointestinal stromal tumors (GIST) are rare mesenchymal tumors that are characterized by constitutive overexpression of the tyrosine kinase receptor KIT (CD117). Imatinib mesylate is a selective inhibitor of tyrosine kinase-mediated activity. This study reports a single-institution experience of surgical resection and the use of imatinib in the treatment of GIST. METHODS: A retrospective review from 1995 to 2002 identified 57 patients (M:F, 29:28; median age, 61 years) with GIST who were treated at the University of Chicago. Twenty-eight patients underwent exploratory surgery with curative intent; 29 patients were referred for treatment of metastatic disease after surgery at outside institutions. Twenty-nine patients were treated with oral imatinib for either metastatic disease (n=26 patients) or in the adjuvant setting after complete resection (n=3 patients). RESULTS: Resections were performed in 53 patients, and metastatic disease was identified in 17 patients at the time of exploratory surgery. Immunohistochemical staining for CD117 was positive in 96% of patients. A size larger than 5 cm, a mitotic rate larger than 1/10 high-power field, and tumor necrosis predicted recurrence in patients after resection. The median follow-up period was 18 months (range, 4-81 months). Twenty-three patients (40%) are alive without disease; 22 patients (39%) are alive with disease; 7 patients died, and 5 patients are lost to follow-up. Among the 26 patients with metastatic disease who were treated with imatinib, 5 deaths have occurred, and disease stabilization or tumor regression was observed initially in 22 patients, with a median duration of response of 19 months. CONCLUSIONS: Complete surgical extirpation remains the only curative treatment of GIST. Imatinib-targeted therapy of metastatic disease yields encouraging clinical responses. The true efficacy of imatinib in this setting, as induction therapy or as an adjuvant treatment in patients with GIST, is unknown pending the completion of ongoing prospective trials.     

Outcome of Metastatic GIST in the Era before Tyrosine Kinase Inhibitors

Background Treatment of metastatic GIST with imatinib mesylate results in a 2-year survival of approximately 72%. The outcome of patients with metastatic GIST not treated with tyrosine kinase inhibitors is not well defined. Methods One hundred nineteen patients with metastatic GIST diagnosed prior to July 1, 1998 (approximately 2 years prior to the use of imatinib for GIST) were identified from an institutional database of patients with pathologically confirmed GIST. Mutational analysis was performed in cases with available tissue. The log rank test and Cox regression models were used to assess prognostic factors. Results Median survival was 19 months with a 41% 2-year survival and a 25% 5-year survival. Resection of metastatic GIST was performed in 81 patients (68%), while 50 (42%) received conventional chemotherapy. Twelve patients (10%) were eventually started on imatinib. Primary tumor size <10 cm, <5 mitoses/50 HPF in the primary tumor, epithelioid morphology, longer disease-free interval, and surgical resection were independent predictors of improved survival on multivariate analysis. Mutational status did not predict outcome. In patients who underwent resection, the 2 year survival was 53%, and negative microscopic margins also independently predicted improved survival. Conclusions Treatment with imatinib appears to improve 2-year survival of metastatic GIST by approximately 20% when compared to surgery alone. The combination of imatinib and surgery for the treatment of metastatic GIST therefore warrants investigation. An erratum to this article can be found at     

A Randomized, Phase II Study of Preoperative plus Postoperative Imatinib in GIST: Evidence of Rapid Radiographic Response and Temporal Induction of Tumor Cell Apoptosis

Gastrointestinal stromal tumor (GIST) is the most common sarcoma arising in the gastrointestinal (GI) tract. Imatinib mesylate (imatinib) is efficacious in treating advanced and metastatic GIST. Patients undergoing resection of GIST realize a highly variable median disease-free survival (DFS). In the absence of prospective data, we conducted a randomized, phase II study to assess the safety and efficacy of preoperative and postoperative imatinib for the treatment of GIST. Nineteen GIST patients undergoing surgical resection were randomized to receive 3, 5, or 7 days of preoperative imatinib (600 mg daily). Patients received postoperative imatinib for 2 years. Perioperative adverse events were compared with those in an imatinib-naïve historical control. The efficacy of imatinib was assessed by ¹⁸fluorodeoxyglucose positron emission tomography (¹⁸FDG-PET), dynamic computed tomography (dCT), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, and DFS. Imatinib did not affect surgical morbidity as compared with an imatinib-naïve cohort (p ≥ 0.1). Most patients responded to preoperative imatinib by ¹⁸FDG-PET and dCT (69% and 71%, respectively). Tumor cell apoptosis increased by an average of 12% (range 0–33%) and correlated with the duration of preoperative imatinib (p = 0.04). Median DFS of patients treated with surgery and imatinib was 46 months (range 10–46 months). Tumor size was a predictor of recurrence after postoperative imatinib (p = 0.02). Imatinib appears to be safe and may be considered for patients undergoing surgical resection of their GIST. Radiographic response and tumor cell apoptosis occur within the first week of imatinib therapy.     

Transanal approach after preoperative imatinib treatment of a rectal gastrointestinal stromal tumors with external anal sphincter invasion: A case report

Introduction and importanceRectal gastrointestinal stromal tumors (GISTs) are rare, and preserving anorectal function can be challenging. We report the case of a patient with rectal GIST with external anal sphincter invasion, treated via the laparoscopic and transanal approaches.Case presentationA 61-year-old man with locally advanced GIST in the right anterolateral wall of the lower rectum was examined. Lower endoscopy revealed a 50-mm submucosal tumor located 4 cm from the anal verge. On immunohistochemistry, the biopsy specimen tested positive for CD34 and C-KIT, and the patient was diagnosed with GIST. Abdominal magnetic resonance imaging (MRI) revealed external anal sphincter infiltration. Because of the large tumor size and proximity to the anal verge, preserving the anus was challenging, and colorectal resection was avoided. Instead, neoadjuvant therapy with imatinib was administered to facilitate local resection of the tumor. Post-treatment MRI showed a reduction in tumor size (30 × 20 × 30 mm), and surgery was performed. We identified an appropriate resection line for diplomatic sphincter resection of the infiltrated area by laparoscopy alone. Thus, we performed a hybrid surgery using the laparoscopic and transanal approaches. The patient had an unremarkable postoperative course and was discharged on postoperative day 23.Clinical discussionNo study has reported cases of rectal GIST with external anal sphincter invasion wherein anal function was preserved. Here, imatinib was administered preoperatively, and hybrid surgery was performed using the transanal and laparoscopic approaches.ConclusionPreoperative treatment and surgery preserved anorectal function in a patient with a massive rectal GIST.     

Perisacral gastrointestinal stromal tumor with intracranial metastasis. Case report

A 68-year-old woman presented with an extremely rare intracranial metastasis from a gastrointestinal stromal tumor (GIST) manifesting as left hemiparesis 2 years after resection of a sacral tumor adjacent to the coccygeal bone. Magnetic resonance imaging revealed an intracranial tumor in the right parietal lobe. Craniotomy was performed to completely remove the tumor. Although the tumor was located extra-axially, only internal carotid angiography showed mass staining. Seven months after surgery, the tumor recurred. Repeat craniotomy was performed to remove the recurrent tumor. Immunohistochemical analysis showed that the tumor cells were positive for c-kit and CD34, and the tumors were identified as intracranial metastasis of GIST. Following the second intracranial surgery, the patient developed severe lower back pain caused by metastatic tumor invading the lumbar spine and ureter. To avoid surgical complications and to reduce tumor volume, imatinib mesylate (Gleevec) was administered. The severe pain was relieved, although the tumor was not reduced. In this case, the extra-axial tumor was fed only by the internal carotid artery.     

Laparoscopic resection for a large gastrointestinal stromal tumor (GIST) with diaphragm invasion following preoperative imatinib treatment: A case report

IntroductionNeoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment.Presentation of caseA 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted.DiscussionNeoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery.ConclusionsThis is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.     

�׻���������������θ��������64����Ч�Ͱ�ȫ�Է���

??Safety and efficacy of imatinib mesylate in gastrointestinal stromal tumours??an analysis of 64 cases WANG Ya-jie ??XUE Chun-yan??WANG Ning. Department of Oncology, Changhai Hospital Attached to the Second Military Medical University,Shanghai 200433,China
Corresponding author: WANG Ya-jie, E-mail:yajiewa0459@163.com
Abstract Objective To investigate the efficacy and adverse effects of imatinib mesylate in gastrointestinal stromal tumors??GIST??. Methods A total of 64 patients with GIST were administered with imatinib mesylate between January 2007 and September 2009 at Department of Oncology, Changhai Hospital Attached to the Second Military Medical University.All the patients were managed at a daily dose of 400mg/d and followed up by CT every 3 months. Results Sixty-four patients were followed up for 20 months. Thirty-eight patients were performed local surgical resection and no recurrence was detected.Twenty-six advanced or metastatic GIST patients survived a median overall survival of more than 19 months and 98.4% survived 12 months. One patient (3.85%) showed complete response (CR).Eighteen patients (69.2%) showed partial response(PR),4 patients (15.4%) stable disease and 3 patients (11.5%) progressive disease. The overall response rate (CR + PR) was 73.1%. One year survival rate was 98.4%. The median survival time was more than 19 months. Conclusion Imatinib mesylate as an extremely effective and safe therapy for majority of GIST is believed to be effective against both local and unresectable GIST and toxicity is minimal.     

Genetic changes in advanced gastrointestinal stromal tumor (GIST) patients during imatinib mesylate treatment

Purpose Imatinib mesylate showed a sustained objective response in patients with advanced gastrointestinal stromal tumors (GISTs) since its introduction in 2001. Here we reported genetic changes during imatinib mesylate treatment especially when the patient had partial response or stationary disease.Materials and methods Between 2001 and June 2005, 44 advanced GIST patients were treated with imatinib mesylate. Among them, five patients (11.9%) (four with partial response and one with stationary disease) received surgical treatment during imatinib mesylate treatment. We compared the genetic status of each tumor in the five patients before and after imatinib mesylate treatment.Results Symptomatic gallbladder stone with or without cholecystitis (two patients), lower GI bleeding (one patient), upper GI bleeding (one patient), and enterocutaneous fistula (one patient) comprised the indications for operation. Before imatinib mesylate treatment, four of the five patients displayed deletion mutation and one patient displayed point mutation in exon 11. After treatment, one patient developed second novel missense mutation in exon 17 with acquired resistance since he was administered with only half dose of imatinib mesylate. The other four patients taking the same dose of imatinib mesylate exhibited identical mutation to the previous lesions.Conclusions Necrosis of large and bulky tumors after imatinib mesylate therapy might be the reason of gastrointestinal hemorrhage and enterocutaneous fistula requiring surgical intervention. Imatinib mesylate could induce acquired resistance during treatment and second novel mutation might be the reason.     

Laparoscopic resection of a gastrointestinal stromal tumor of the rectum after treatment with imatinib mesylate: report of a case

This report describes the laparoscopic resection of a rectal GIST after treatment with imatinib mesylate. A 56-year-old male presented with a submucosal tumor (longest diameter, 8?cm) arising in the lower rectum. A core needle biopsy revealed that the tumor contained bundles of spindle-like cells. Immunostaining revealed that the tumor was positive for c-kit and CD34. Analysis of the c-kit gene revealed a substitution of ACA (threonine) by GCA (alanine) at codon 574 of exon 11. Imatinib mesylate (400?mg/day) was given as preoperative adjuvant therapy for 3?months, and the tumor shrank to 5?cm in diameter. Proctectomy with transanal anastomosis could be performed laparoscopically, while preserving the anus. There was no evidence of recurrence 2?years 6?months after surgery. Preoperative adjuvant chemotherapy with imatinib mesylate may permit the use of less invasive treatment procedures, allowing anal preservation.     

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.     

甲磺酸伊马替尼治疗胃肠间质瘤64例疗效和安全性分析

目的 评价甲磺酸伊马替尼治疗胃肠间质瘤的临床疗效及不良反应。方法 分析第二军医大学长海医院肿瘤科2007年1月至2009年9月间64例经术后病理证实的GIST病人的临床资料。病人均给予甲磺酸伊马替尼400mg/d口服。每3个月复查CT,以明确病人病情变化情况。结果 64例病人平均随访20个月。局限可切除GIST病人38例,无一例发生复发或转移;26例局部晚期/转移性GIST中完全缓解1例（3.85%）,部分缓解18例（69.2%）,稳定4例（15.4%）,进展3例（11.5%）,客观缓解率（完全缓解 +部分缓解）为73.1%。1年存活率为98.4%。中位生存时间超过19个月。结论 甲磺酸伊马替尼用于GIST术后辅助治疗,对预防肿瘤的复发和转移可能具有一定的作用;对于复发/转移性病人具有高的有效率和较好的安全性。     

A ruptured gastrointestinal stromal tumour of the transverse mesocolon: a case report

We discuss the long history of a patient still alive with a primary gastrointestinal stromal tumour (GIST) of the transverse mesocolon: initially it presented as an acute complication, namely a haemorrhagic shock caused by rupture of the tumour and it recurred twice locally in the years following primary resection. Each time, a macroscopically complete resection could be achieved. Six years after the resection of the primary tumour, a liver metastasis was discovered, which was removed by radio frequency ablation (RFA). Eight months later, the patient developed a new liver metastasis and a retropancreatic mass deemed unresectable. He is treated with imatinib mesylate (Glyvec, Novartis, Vilvoorde, Belgium) since and has had a stable disease for 6 months. Gastrointestinal stromal tumours outside the gastrointestinal tract are rare. Until a few years ago the only possible therapy was surgical resection. Nowadays radio frequency ablation can be a solution for irresectable liver metastases, and imatinib mesylate can bring improvement for advanced and metastasized tumours. Whether this could also be useful as an adjuvant therapy has not yet been investigated, but it could be important knowing that 38% of the tumours recur locally and 15% metastasize. The most important prognostic factors for gastrointestinal stromal tumours are grading and complete resection.     

A Ruptured Gastrointestinal Stromal Tumour of the Transverse Mesocolon: a Case Report

We discuss the long history of a patient still alive with a primary gastrointestinal stromal tumour (GIST) of the transverse mesocolon: initially it presented as an acute complication, namely a haemorrhagic shock caused by rupture of the tumour and it recurred twice locally in the years following primary resection. Each time, a macroscopical-ly complete resection could be achieved. Six years after the resection of the primary tumour, a liver metastasis was discovered, which was removed by radio frequency ablation (RFA). Eight months later, the patient developed a new liver metastasis and a retropancreatic mass deemed unresectable. He is treated with imatinib mesylate (Glyvec®, Novartis, Vilvoorde, Belgium) since and has had a stable disease for 6 months.

Gastrointestinal stromal tumours outside the gastrointestinal tract are rare. Until a few years ago the only possible therapy was surgical resection. Nowadays radio frequency ablation can be a solution for irresectable liver metastases, and imatinib mesylate can bring improvement for advanced and metastasized tumours. Whether this could also be useful as an adjuvant therapy has not yet been investigated, but it could be important knowing that 38% of the tumours recur locally and 15% metastasize.

The most important prognostic factors for gastrointestinal stromal tumours are grading and complete resection.     

胃肠间质瘤治疗进展

胃肠间质瘤（GIST）是胃肠道最常见的间叶来源肿瘤。大部分患者存在c-kit或PDGFRa基因突变。手术根治性切除是治疗胃肠间质瘤的基石,但是术后复发率较高。近年来,以伊马替尼为代表的靶向治疗大大提高了GIST治疗效果。对于手术可以切除的患者,手术切除联合新辅助或辅助治疗改善了高危患者的预后：对于手术不可切除的患者,靶向治疗也有效地抑制、延缓了病情的进展。     

胃肠间质瘤临床病理特点及其相关性分析

目的：总结胃肠道间质瘤（GIST）的病理及临床特点及其外科治疗和预后。方法回顾性分析我院术后病理证实的160例GIST患者的临床资料,其中随访145例,对其临床特点、病理特点、免疫标志物多因素进行预后的分析。结果160例行外科根治切除术患者,术中、术后均无死亡病例。生存的单因素分析病理特点显示,肿瘤的核分裂象、有无转移与Fletcher分级在胃肠间质瘤间差异有统计学意义（P＜0．05）;分析免疫组化 KIA、CD133免疫因子的阳性率分别为97．6％和81．3％。对生存预后有统计学意义（P＜0．05）。术后随访145例（91．25％）,其中53例多发肝转移患者,术后均进行甲磺酸伊马替尼（400 mg／d）药物治疗,疗效显著（P＜0．05）,多因素回归分析显示,Fletcher分级、甲磺酸伊马替尼是影响预后的独立危险因素。结论 Fletcher分级是评估GIST预后的有效手段,GIST患者采用外科根治性切除术联合甲磺酸伊马替尼治疗对原病灶、转移病灶治疗,其疗效显著。     

Successful Resection of an Advanced Duodenal Gastrointestinal Stromal Tumor After Down-Staging with Imatinib: Report of a Case

The diagnosis of gastrointestinal stromal tumor (GIST) relies on a combination of the following criteria: anatomic location, typical histopathology, and the presence of CD 117-antigen (the tyrosine kinase receptor, c-kit) or CD 34-antigen. Imatinib mesylate, a specific tyrosine kinase inhibitor, is highly efficient against locally advanced or metastatic GIST. We report a case of unresectable duodenal GIST, which we were able to resect with curative intent after down-staging treatment with a dosage of imatinib 400 mg daily for 8 months. We performed Whipple's procedure combined with en bloc resection of the right kidney and adrenal gland. The patient was recurrence free at his 24-month follow-up examination. Down-staging treatment may be worthwhile in selected patients, but further prospective studies of imatinib in this setting are necessary. We think that imatinib should be continued postoperatively, as the risk of recurrence in these patients may be high.     

晚期胃肠道间质瘤靶向治疗后的外科治疗

目的探讨手术对于伊马替尼治疗后晚期胃肠道间质瘤（GIST）患者的临床疗效。方法回顾性分析13例术前予以伊马替尼治疗,然后接受手术切除的晚期GIST患者的临床资料。结果13例伊马替尼治疗后手术切除的患者中,有3例为局部晚期原发肿瘤,10例为复发或转移患者。治疗有效（RD组）的5例中有4例、疾病进展（PD组）的8例中有1例共计5例（38．5％）患者肿瘤获得完全切除。RD组无疾病进展生存（PFS）为24．8个月,PD组的PFS为2．8个月,两组比较,差异有统计学意义（P〈0．01）。RD组和PD组患者的总生存率比较,差异无统计学意义（P〉0．05）。结论在对伊马替尼治疗有效的晚期GIST患者中,伊马替尼治疗后再行外科手术切除是可行的。     

胃肠道间质瘤肝转移的诊断和治疗

目的 探讨胃肠道间质瘤(gastrointestinal stromal tumor,GIST)肝转移的诊断和治疗.方法 回顾性分析1993年12月至2007年5月收治的16例GIST肝转移患者的临床资料.结果 14例行根治性切除术,2例行姑息性切除术.3例根治性切除术及2例姑息性切除术患者术后服用伊马替尼治疗.术后随访时间3～161个月,14例根治性切除患者中共8例复发、转移.其中7例肝转移,3例采用肝动脉栓塞治疗,1例服用伊马替尼,2例手术切除,1例未治疗;1例腹壁转移,行手术切除.本组16例患者1、3年生存率分别为92%和74%.结论 GIST肝转移术后复发率高,手术治疗GIST肝转移及术后复发、转移效果较好,联合服用伊马替尼可进一步提高患者生存率.