Gastrointestinal Stromal Tumor (GIST) has gradually become familiar to the surgical community in recent years, but due to its low incidence (1-2/100,000), the disease is still quite unfamiliar to the general public and some primary hospitals. In order to better popularize and promote this relatively new tumor concept and to update knowledge and standardize treatment in a timely manner, the China Clinical Oncology Collaborative Group (CSCO) established an expert committee in 2010 to write the GIST China Consensus (2011 edition) for the first time. In November 2012, the consensus update was discussed, and in addition to adding new contents, some ambiguous and lengthy parts of the original consensus were also revised. The author would like to discuss the hot issues and controversial areas of surgery in the process of new consensus revision. GIST biopsy principles and indications: GIST is insidious, GI bleeding, abdominal discomfort and abdominal mass are common symptoms of GIST, but they lack specificity, only pathological examination is the only way to confirm the diagnosis of GIST. However, GIST is rich in blood supply, brittle, and some of the tumors are combined with intra-tumoral necrosis and bleeding, which are cystic in nature. Blind biopsy may cause tumor bleeding, rupture, and even serious consequences of tumor dissemination and implantation. For most primary limited GISTs that can be completely resected, biopsy is not recommended before surgery. Preoperative biopsy of primary limited GIST is generally only indicated for patients who are to be treated with preoperative adjuvant Imatinib, and a definitive pathological diagnosis must be obtained before treatment. For suspected GIST with combined metastases at the first diagnosis, biopsy should be performed to clarify the diagnosis before starting targeted drug therapy. As for intraoperative frozen biopsy, the consensus does not recommend it to be routinely performed. Intraoperative frozen biopsy should be considered only when lymph node metastasis around GIST is suspected during surgery or when other malignancies cannot be excluded by visual inspection during surgery. The new consensus is controversial about whether to retain endoscopic ultrasound-guided aspiration biopsy (fine-needle aspiration biopsy, EUS-FNA). Some pathologists believe that fine needle aspiration harvests too little tissue to make a histologic diagnosis at times. However, the US NCCN guidelines continue to consider it the preferred method of biopsy. With this biopsy method, the risk of tumor bleeding from puncture is minimal due to the small diameter of the puncture needle; in addition, the needle is inserted from within the gastrointestinal cavity, effectively avoiding percutaneous puncture that can cause needle tract implantation and tumor rupture leading to abdominal dissemination and metastasis. Although fewer tissues are obtained, the positive biopsy rate is high, with diagnostic accuracy of more than 90% reported abroad. We have performed fine needle biopsy in more than 20 cases of GIST, and it is rare to have 2 consecutive failed biopsies. The obtained tissue is sufficient for HE and immunohistochemical staining, although it is difficult to perform genetic testing. Therefore, the author believes it is necessary to retain and still recommends fine-needle aspiration biopsy as the preferred biopsy method. In addition, some gastric GISTs involve the mucosa and form ulcers; in such cases, the positive rate of taking a conventional clamp biopsy is also higher. Lower and mid-rectal GIST can be biopsied by coarse needle aspiration via rectal wall puncture with a very high positive rate and sufficient harvested tissue for gene mutation detection. Ultrasound-guided percutaneous puncture is only suitable for suspected metastatic GIST due to the risk of needle tract implantation and tumor rupture leading to abdominal dissemination. Surgical treatment of GIST: Undoubtedly, surgery remains the only curative method for GIST. Regarding the surgical treatment, the previous controversial issues such as the indications for surgery of recurrent metastatic GIST, the feasibility of endoscopic GIST resection and the indications for laparoscopic GIST surgery have become more and more consensus after clinical practice and observation in recent years. (A) Indications for surgery: The new version of the consensus enumerates the indications for surgery of GIST as before, and elaborates on primary limited GIST and recurrent metastatic GIST, respectively. For primary limited GIST, this revision only separately lists the recommendations for the management of gastric GIST smaller than 2 cm. Gastric GIST less than 2 cm confirmed by biopsy (fine needle aspiration is recommended) should be considered for surgical resection if there are high-risk signs of endoscopic ultrasound (irregular tumor margins, internal echogenicity, localized cystic or solid echogenicity). Otherwise, ultrasound endoscopy can be reviewed at 6-12 months interval and surgery can be withheld. This also implies that surgical resection is recommended for other sites of GIST, regardless of size, if pathologically confirmed as GIST. More than one retrospective study has confirmed that small GISTs (1-2 cm, milliGIST) or microGISTs (<1 cm, microGIST) are common at autopsy, with a detection rate of 20%-30%. Although KIT or PDGFRA mutations can also be detected in microGISTs, the microscopic morphology is non-invasive and the biological behavior shows self-limiting growth. This type of GIST is commonly found in the stomach, while other sites are less frequently reported. Therefore, citing the NCCN guidelines, it is prudent to suggest that only for small primary GISTs of the stomach, follow-up is possible when high-risk signs on ultrasound endoscopy are excluded. For those with inoperable or critically resectable GIST with high risk; or those with severe impact on organ function, it is advisable to first treat with imatinib (preoperative biopsy is required to confirm the diagnosis) and then resect the tumor after shrinkage. For recurrent or metastatic GIST, the new consensus extends the original formulation, and the indications for emergency surgery include complete intestinal obstruction, gastrointestinal perforation, gastrointestinal hemorrhage if conservative treatment is ineffective, and abdominal hemorrhage due to spontaneous tumor rupture. Elective surgery is limited to patients in whom targeted therapy is effective or in whom only a single or a few lesions have progressed. For GIST with multiple lesions or extensive progression of multiple lesions, surgery does not prolong their survival and is extremely risky. There is significant debate among medical and surgical experts as to whether surgery or targeted therapy should be performed first in patients with recurrence presenting as isolated resectable lesions or a few metastases. To date, there is no clinical evidence to support a preference. In patients with recurrence, whether single lesions or multiple metastases, surgical treatment alone does not improve their prognosis. The postoperative recurrence rate is almost 100%. Targeted drug therapy is the basis for recurrent patients and should be continued without interruption, while surgery combined with targeted therapy should be more beneficial to this group of patients. In the author's opinion, for these patients, especially those with isolated recurrent tumors, as long as they can tolerate surgery and the risk of surgery is not too high, it is appropriate to treat them with surgery first and then receive continuous drug therapy after surgery. (B) Principles of surgical treatment: 1. Surgical treatment of primary, limited GIST: Surgery is still the main treatment for primary, limited GIST. In order to make the consensus more concise and refined, the revision has deleted the principles of surgery for GISTs that are divided into various sites. In fact, it is important to standardize the first surgery for GIST, which should follow the principle of anaplasia and ensure complete tumor resection and negative margins. Preoperative or intraoperative tumor rupture inevitably leads to tumor dissemination and implantation, and postoperative recurrence is almost inevitable. The tumor is rich in blood supply and fragile, so gentle movements should be made during surgery to avoid excessive compression of the tumor. GIST is rarely metastasized by lymph nodes, and unless there is clear evidence of lymph node metastasis, routine debridement is not necessary. Laparoscopy has been widely used in the field of surgery in recent years. Although there are no prospective clinical studies on laparoscopic GIST surgery, there are retrospective studies on successful resection of some gastric and small intestinal GISTs using laparoscopy at home and abroad. However, due to the brittle quality of the tumor, laparoscopic surgery may easily cause tumor rupture and lead to abdominal implantation, so the consensus does not routinely recommend its use. Experienced centers may choose to apply it according to the site and size of the tumor. The principles of minimally invasive surgery are the same as those of open surgery. Throughout the operation, care should always be taken to avoid the forceful grip of the instruments on the tumor to prevent tumor rupture and dissemination. After excision of tumor, it must be removed in specimen bag to avoid tumor rupture and implantation at the poke hole. However, GIST is different from early gastric cancer because its tissue originates from the submucosa or muscle layer. Therefore, endoscopic resection must be chosen with caution. Foreign guidelines do not have statements related to endoscopic GIST resection, and our consensus also believes that this technique should be limited to exploratory treatment and research in experienced endoscopic centers, and is not routinely recommended. 2. Surgical intervention for recurrent metastatic GIST: Although the incidence of gastrointestinal mesenchymal tumor is not high, it is the most successful solid tumor treated with targeted drugs. Before the advent of targeted drugs, the median survival of patients with advanced metastatic GIST was only 18-24 months. With the use of imatinib, about 70-85% of patients with advanced GIST have benefited from it, with a median survival of 36-57 months. The introduction of targeted drugs has greatly prolonged the survival of patients with advanced GIST while also fundamentally improving their quality of life. However, we also found that about 14% of patients exhibited drug resistance to imatinib at the outset, and half of them developed secondary drug resistance at about 2 years of treatment. Patients who progressed to drug resistance had a median progression-free survival of only 21-24 weeks and a median overall survival of no more than 90 weeks, although some patients could regain benefit by increasing the dose and switching to sunitinib. This means that at the present time, second-line therapy has a limited effect and poor prognosis as long as patients show resistance to imatinib. In recent years, the role of surgery in the treatment of advanced GIST has been revisited. A larger retrospective analysis of foreign reports of targeted drug therapy followed by combined surgical resection for advanced GIST showed that patients in partial remission and stable disease had a progression-free survival rate of nearly 65% at 2 years postoperatively and an overall survival rate of nearly 100%; patients with limited progression had a median progression-free survival of 7.7 to 12 months postoperatively and a median overall survival of 19 to 29 months; while patients with extensive progression had a median progression-free survival was only 3 months, and overall survival was only 3-5.6 months. This indicates that patients with well-controlled or limited tumor progression before surgery have a low rate of surgical complications and a better mid- to long-term postoperative outcome, while patients with extensive progression fail to benefit from surgery. Similar results were obtained for the cases counted at our institution. Combined with the surgical treatment of several advanced GIST patients in our institution in recent years, we believe that surgical treatment can indeed benefit patients with recurrent metastases as long as they are appropriately selected. The complexity of surgery and the risks of surgery should be fully considered when selecting patients. First, these patients have usually undergone 1 or more abdominal surgeries, and some of them have severe abdominal adhesions, which increase the difficulty of surgery. Secondly, drug-resistant GIST often shows infiltrative growth with very rich blood supply, which is very likely to lead to intra-tumor bleeding or bleeding on the peeling surface during surgery, and it is more difficult to stop bleeding, so we should be fully prepared to deal with it. Under the premise of ensuring surgical safety, all metastases should be removed as far as possible to complete satisfactory tumor removal surgery or tumor reduction surgery. For advanced GIST targeted drug therapy followed by surgery, it is not only a test for the patient, but also for the consultation and treatment team. Each advanced GIST patient should undergo a multidisciplinary case discussion before surgery, and relevant departments should be invited to consult and develop a perfect treatment plan. As to whether the combination of targeted drugs with surgery is indeed superior to drug therapy alone, the results of a rigorous multicenter controlled trial with a larger sample are still to be known.