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.     

Palliative Resection of Colorectal Cancer: Does It Prolong Survival?

BACKGROUND: It is still a matter of debate as to whether resective surgery of the primary tumor may prolong the survival of patients affected by incurable colorectal cancer (CRC). The main goal of this retrospective study, carried out on patients not undergoing any therapy other than surgery, was to quantify the benefit of primary tumor removal in patients with differently presenting incurable CRC. METHODS: One hundred and thirty consecutive patients were operated on for incurable CRC (83 undergoing resective and 47 non-resective procedures). With the purpose of comparing homogenous populations and of identifying patients who may benefit from primary tumor resection, the patients were classified according to classes of disease, based on the "metastatic pattern" and the "resectability of primary tumor." RESULTS: In patients with "resectable" primary tumors, resective procedures are associated with longer median survival than after non-resective ones (9 months vs 3). Only patients with distant spread without neoplastic ascites/carcinosis benefit from primary tumor removal (median survival: 9 months vs 3). Morbidity and mortality of resective procedures is not significantly different from that of non-resective surgery, either in the population studied or in any of the groups considered. CONCLUSIONS: Palliative resection of primary CRC should be pursued in patients with unresectable distant metastasis (without carcinomatosis), and, intraoperatively, whenever the primary tumor is technically resectable.     

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.     

Optimizing Surgical and Imatinib Therapy for the Treatment of Gastrointestinal Stromal Tumors

Introduction

The discovery of activating KIT and PDGFRα mutations in gastrointestinal stromal tumors (GISTs) represented a milestone as it allowed clinicians to use tyrosine kinase inhibitors, like imatinib, to treat this sarcoma. Although surgery remains the only potentially curative treatment, patients who undergo complete resection may still experience local recurrence or distant metastases. Therapeutic strategies that combine surgical resection and adjuvant imatinib may represent the best treatment to maximize patient outcomes. In addition to the use of imatinib in the adjuvant and metastatic settings, neoadjuvant imatinib, employed as a cytoreductive therapy, can decrease tumor volume, increase the probability of complete resection, and may reduce surgery-related morbidities. Thus, selected patients with metastatic disease may be treated with a combination of preoperative imatinib and metastasectomy. However, it is critical that patients with GIST be evaluated by a multidisciplinary team to coordinate surgery and targeted therapy in order to maximize clinical outcomes.

Discussion

Following a systematic literature review, we describe the presentation, diagnosis, and treatment of GIST, with a discussion of the risk assessment for imatinib therapy. The application of surgical options, combined with adjuvant/neoadjuvant or perioperative imatinib, and their potential impact on survival for patients with primary, recurrent, or metastatic GIST are discussed.     

A nomogram for predicting disease-specific survival after hepatic resection for metastatic colorectal cancer

PURPOSE: To develop a tool for predicting survival after liver resection for patients with stage IV colorectal cancer. By using a nomogram we are trying to improve on the current practice of using prognostic scores for evaluating risks of therapeutic failure. PATIENTS AND METHODS: All patients admitted to Memorial Sloan-Kettering Cancer Center (MSKCC) for curative intent for treatment of metastatic disease from colorectal cancer between January 1986 and December 1999 were included. A nomogram was developed as a graphical representation of a Cox proportional hazards regression model. The nomogram was verified for discrimination and calibration, both employing bootstrapping to obtain relatively unbiased estimates. RESULTS: Using nodal status of the primary tumor, disease-free interval, size of the largest metastatic tumor, preoperative carcinoembryonic antigen, bilateral resection, extensive resection (lobectomy or more), gender, number of hepatic tumors, primary cancer site (colon vs. rectum), and age, the nomogram achieved a concordance index of 0.61, statistically significantly greater than chance. The nomogram also had very good calibration. CONCLUSION: This nomogram is a predictive tool, upon external validation, that can routinely be used to counsel patients in making treatment decisions. The discriminatory ability of the nomogram indicates that this population should not be considered homogeneous with respect to risk of death.     

Primary and secondary hepatic manifestation of neuroendocrine tumors

BACKGROUND: In comparison with most other malignancies, in the treatment of metastatic neuroendocrine tumors one also has to consider endocrine symptoms and natural progression of disease. Since hepatic metastasis predominates and endocrine symptoms correlate with functional tumor mass, hepatic resection may improve prognosis or even cure patients. PATIENTS AND METHODS: We reviewed 41 consecutive patients with metastatic neuroendocrine tumors and four patients with primary hepatic disease presenting between 1989 and 1999. The neuroendocrine tumors were classified according to their origin, pattern of metastasis, endocrine activity, and histology. Operative therapy including hepatic resections of different extent, liver transplantation, and removal of the primary tumor was analyzed. The median survival after initial diagnosis and after hepatic resection were major parameters of outcome. RESULTS: There were 26 low-grade malignant, 12 high-grade malignant, 2 biphasically differentiated neuroendocrine carcinomas, and 5 pancreatic endocrine tumors. Hepatic resections were performed in 25 patients, resections of the primary tumor in 40 patients. The median survival after initial diagnosis was 49 months; 50.5 months in patients with hepatic resection versus 47 months in those with no liver surgery. CONCLUSION: Hepatic resection improved the outcome of patients with liver metastasis due to neuroendocrine tumors tendentiously but not significantly.     

Laparoscopic Surgery for Malignant Adrenal Tumors

Advances in imaging have improved early detection of primary and metastatic adrenal tumors. The laparoscopic approach, the gold standard for benign adrenal diseases, is controversial for malignant adrenal tumors. A prospective randomized study of the role of laparoscopic surgery in adrenal cancer is not feasible because of the rarity of the disease. A review of the literature demonstrates the safety and efficacy of laparoscopic adrenalectomy for solitary adrenal tumors. In primary adrenal malignancies, the laparoscopic approach should be considered cautiously, only when it can achieve complete tumor resection with an intact adrenal capsule. Conversion to an open procedure should be an early decision, prior to tumor morcellation or fracture of the tumor capsule. Patients who have local invasion, tumors that are too large, or require organ resection require an open procedure.     

Cytoreductive hepatic surgery for neuroendocrine tumors.

We retrospectively reviewed 37 patients who underwent hepatic resection between 1970 and 1989 to evaluate the role of cytoreductive hepatic surgery in patients with metastatic neuroendocrine tumors (carcinoid, 24; islet cell, 13). Seventeen resections were curative (no gross residual tumor); nine patients had symptomatic endocrinopathies and seven patients had symptoms caused by the primary tumor. Eight of nine patients with symptomatic endorcrinopathies obtained complete relief of symptoms; five are alive with no evidence of disease at 2 to 82 months (mean, 26 months). Six of seven patients with symptoms caused by the primary tumor obtained complete relief; five are alive with no evidence of disease at 5 to 28 months (mean, 14 months). One symptom-free patient underwent curative hepatic resection 5 years after abdominoperineal resection for a rectal carcinoid. Twenty resections were palliative (gross residual tumor); 16 patients had symptomatic endocrinopathies and 4 patients had symptoms caused by the primary tumor. Eight of 16 patients with symptomatic endocrinopathies obtained complete relief; five are alive at 2 to 30 months (mean, 11 months), with a mean duration of complete relief of 6 months (3 to 12 months). All four patients who underwent resection for symptoms caused by the primary tumor obtained complete relief; two are alive and symptom free at 10 and 101 months. Our experience suggests that curative surgery should be considered in all patients with completely resectable metastatic disease and that palliative surgery, despite the short duration of complete relief, should be considered in selected patients because it delays and may reduce the subsequent need for medical therapy.     

Metastatic Tumors to the Oral Cavity: A Clinical Study of 18 Cases

The aim of this study was to describe the clinical features of 18 cases of metastatic tumors to the oral cavity. The files of patients seen between 1992 and 2009 with oral (soft tissue and jawbones) metastatic lesions were reviewed. Clinical features, including gender, age, site of the primary tumor, site of metastatic tumor and treatment were evaluated. Patients were 11 males and 7 females, with mean age of 64.6 years. In males, most primary tumors originated in the lungs. In females, the lung and breast were the most common sites of the primary tumors. The mandible was the main site for the development of the metastatic lesions and the most common histologic type was adenocarcinoma. Treatment modalities included radiotherapy, chemotherapy and surgical resection. Metastatic lesions should be considered in the differential diagnosis of oral lesions, particularly when a previous history of cancer is present.     

Role of Surgery Combined with Kinase Inhibition in the Management of Gastrointestinal Stromal Tumor (GIST)

Background  

Surgery is the standard treatment for primary, gastrointestinal stromal tumor (GIST); however, surgical resection often is not curative, particularly in large GIST. Five years after complete removal of their tumor, approximately half of treated patients relapse. Imatinib, an oral tyrosine kinase inhibitor (TKI), is first-line treatment in patients with metastatic or unresectable GIST. It has resulted in durable objective responses or stable disease in 84% of patients and is well tolerated. The efficacy of imatinib in advanced GIST has created interest in a variety of potential multimodal approaches to management that combine surgery with systemic therapy.     

Radiofrequency Ablation of Unresectable Primary and Metastatic Hepatic Malignancies: Results in 123 Patients

OBJECTIVE: To describe the safety and efficacy of radiofrequency ablation (RFA) to treat unresectable malignant hepatic tumors in 123 patients. BACKGROUND: The majority of patients with primary or metastatic malignancies confined to the liver are not candidates for resection because of tumor size, location, or multifocality or inadequate functional hepatic reserve. Local application of heat is tumoricidal; therefore, the authors investigated a novel RFA system to treat patients with unresectable hepatic cancer. PATIENTS AND METHODS: Patients with hepatic malignancies were entered into a prospective, nonrandomized trial. The liver tumors were treated percutaneously or during surgery under ultrasound guidance using a novel LeVeen monopolar array needle electrode and an RF 2000 generator. All patients were followed to assess complications, treatment response, and recurrence of malignant disease. RESULTS: RFA was used to treat 169 tumors (median diameter 3.4 cm, range 0.5 to 12 cm) in 123 patients. Primary liver cancer was treated in 48 patients (39.1%), and metastatic liver tumors were treated in 75 patients (60.9%). Percutaneous and intraoperative RFA was performed in 31 patients (35.2%) and 92 patients (74.8%), respectively. There were no treatment-related deaths, and the complication rate after RFA was 2.4%. All treated tumors were completely necrotic on imaging studies after completion of RFA treatments. With a median follow-up of 15 months, tumor has recurred in 3 of 169 treated lesions (1.8%), but metastatic disease has developed at other sites in 34 patients (27.6%). CONCLUSIONS: RFA is a safe, well-tolerated, and effective treatment to achieve tumor destruction in patients with unresectable hepatic malignancies. Because patients are at risk for the development of new metastatic disease after RFA, multimodality treatment approaches that include RFA should be investigated.     

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。     

Surgical treatment of metastatic lung tumors

Surgical treatments were performed in 88 cases of metastatic lung tumors, where 5 years survival rate in all resected cases was 37.5%. We report our principles on the surgical treatment for metastatic lung tumors. First of all, the biological characteristics of the primary lesion is among the most important factors in considering the indication for the surgical treatment in metastatic lung tumors. For example, chemotherapy must be the first choice in treating lung metastasis of choriocarcinoma, and hormone therapy in lung metastasis of mammary carcinoma. On the other hand, such tumors as osteogenic sarcoma, soft tissue sarcoma, colorectal carcinoma and Grawitz's tumor, should be treated by surgery. Another point in the surgery of the metastatic lung tumor is the choice of the mode of operation for the solitary metastatic tumor according to tumor type. As a principle, partial or segmental resection is preferably chosen for metastatic lung tumor. However, the location of the lung tumor, tumor size, hilar lymph node metastasis and the pattern of invasion to the surrounding lung tissue must be considered to decide the surgical procedure. From these considerations, the segmental or partial resection for metastatic sarcomas and the lobectomy for the metastatic carcinomas are appropriate in general.     

Jejunal GIST masquerading as an ovarian mass: A case report

Introduction and importanceGastrointestinal stromal tumors (GIST) are rare mesenchymal tumors originating in the wall of the gastrointestinal tract. Jejunal GIST is the rarest subtype. Large GIST can present with an abdominopelvic mass which can be preoperatively misdiagnosed as a gynecological tumor.Case historyA 44-year regularly menstruating woman presented with lower abdominal pain which was diagnosed as a malignant ovarian tumor preoperatively with an MRI. However, intraoperatively, a lobulated mass was present in the abdominal cavity arising from a jejunal portion of the small intestine. With an intraoperative diagnosis of jejunal GIST, the mass was excised and jejunum anastomosed. Histopathology examination report showed GIST which was further confirmed by immunohistochemistry.DiscussionGIST presenting as a large abdominopelvic mass can mimic a gynecological tumor. Contrast-enhanced CT scan is the preferred imaging modality for the evaluation of patients with suspected GIST to determine the extent of the tumor, the presence or absence of metastatic disease alongside evaluation of the possibility of complete resection. Adjuvant imatinib therapy following complete excision can decrease the disease recurrence.ConclusionGynecologists should keep in mind that primary gastrointestinal tumors can present as a pelvic mass. A proper histopathological examination helps to confirm the diagnosis. Complete surgical removal of the tumor should be obtained as it determines the prognosis of the disease.     

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.     

Islet cell tumors of the pancreas: the medical oncologist's perspective.

Islet cell tumors of the pancreas are rare, indolent, neuroendocrine tumors. Approximately 50% of the patients diagnosed with these tumors present with symptoms related to various biologically active hormones that are secreted by these neoplasms. Currently, the only curative treatment for islet cell tumors is complete surgical resection. Management of metastatic disease is conservative. Initial treatment of these tumors includes expectant observation and medical management of symptoms with clinical monitoring and serial CT scans to assess tumor growth. Patients with rapidly progressive disease, with local symptoms caused by tumor bulk, or with uncontrolled symptoms related to hormone secretion require more aggressive medical or surgical intervention. The somatostatin analogue octreotide may help control hormone secretion and stabilize tumor growth. Patients refractory to octreotide with tumor predominantly in the liver are potential candidates for mechanical ablative techniques, such as hepatic arterial embolization. Radiofrequency ablation and cryosurgical techniques may also be useful, although specific data are limited. Surgical resection of metastatic disease may offer palliative relief of symptoms related to hormone secretion in carefully selected patients. Chemotherapy may be used for palliation when ablative techniques have failed or when significant extrahepatic disease is present. Streptozicin-based combinations remain the first line standard, but major objective responses are less common than had been previously thought. Because of the overall modest success of current chemotherapeutic regimens, patients with advanced disease in need of treatment should be encouraged to enroll in clinical trials testing newer antineoplastic agents or newer treatment strategies.     

Management der Wirbels?ulenmetastasen, Strategien und operative Indikationen

The number of bone metastases increases with prolonged survival of primary tumors of kidney, breast, prostate and other tumors. The spine is the most frequent site of bone metastases. This leads to high number of patients where the decision has to be made what kind of treatment should be the best. Several scores have been developed to solve this problem. The decision has to include the biology of the metastatic disease according to primary tumor and dissemination of the disease, the general condition of the patient, the residual stability of the spine, the neurologic status and most important the quality of life of the patient. Treatment options range from conservative treatment up to en bloc resection of the metastatic lesion. Therefore, the strategy of treatment always has to be decided on an individual base.     

酪氨酸激酶抑制剂联合手术治疗转移性胃肠间质瘤

目的 探讨酪氨酸激酶抑制剂（TKI）甲磺酸伊马替尼或舒尼替尼联合手术治疗晚期转移性胃肠间质瘤（GIST）的临床疗效.方法 回顾分析中山大学附属第一医院2007年6月至2009年12月接受TKI治疗后进行手术治疗的转移性GIST患者临床病理资料.结果 共计15例转移性GIST患者在TKI治疗后接受肿瘤切除手术.术前TKI治疗反应分别为疾病控制6例（40.0%）,局限性进展4例（26.7%）,全面性进展5例（33.3%）.手术相关并发症发生率20.0%.全组患者中位无进展生存期18.7个月.其中疾病控制和局限性进展组患者术后无进展中位生存期25.0个月,全面性进展组则仅为3.0个月（P＜0.01）;疾病控制和局限性进展组患者至今仍全部存活,而全面性进展组患者中位总生存期为10.5个月（P＜0.01）.结论 靶向治疗后,疾病控制或局限性进展的晚期转移性GIST患者行手术治疗安全有效,而全面性进展患者手术治疗不能改善其预后,应谨慎选择.     

Carcinoid tumors: the relationship between clinical presentation and the extent of disease

In this study the relationship between the initial clinical presentation and the extent of tumor progression was determined in a group of 31 patients with carcinoid tumors. The proportion of patients with symptomatic tumors was similar to those patients with carcinoid tumors that were incidentally found (55% versus 45%; SE = 0.089). Symptoms were caused by metastatic tumor in nine (30%) of the patients and by local effects of the primary tumor in eight (26%) of the patients. The patients with symptoms had a significantly increased frequency of metastatic disease, even when the symptoms were due to the primary tumor, compared to patients with no symptoms (76% versus 7%; p less than 0.001). Tumor size was related to the presence of symptoms and metastases. Symptoms were most common when the size of the primary tumor was greater than 1.0 cm (p less than 0.005), although the rate of metastases increased when primary tumors were 2.0 cm and larger (p less than 0.01). These results indicate that the presence of symptoms or a primary tumor 2.0 cm or larger are associated with an increased risk of metastatic disease in patients with carcinoid tumors. These patients should be treated with wide resection of the primary tumor and its lymphatic drainage.     

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.