• gastrointestinal stromal tumors
• imatinib
• neoadjuvant therapy
• ripretinib
• treatment response

• ENDOSCOPIC PROCEDURES
• GASTRIC NEOPLASIA

• gastrointestinal stromal tumors
• imatinib
• neoadjuvant treatment
• prognosis
• stomach

• Humans
• Gastrointestinal Stromal Tumors/drug therapy
• Gastrointestinal Stromal Tumors/surgery
• Gastrointestinal Stromal Tumors/pathology
• Gastrointestinal Stromal Tumors/mortality
• Male
• Female
• Imatinib Mesylate/therapeutic use
• Imatinib Mesylate/administration & dosage
• Imatinib Mesylate/adverse effects
• Retrospective Studies
• Middle Aged
• Stomach Neoplasms/drug therapy
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Stomach Neoplasms/mortality
• Gastrectomy/adverse effects
• Gastrectomy/methods
• Aged
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• Antineoplastic Agents/adverse effects
• Treatment Outcome
• Adult
• Time Factors

• 81773080 National Natural Science Foundation of China
• National Natural Science Foundation of China

• Duration of admission
• Gastrointestinal stromal tumours
• Minimally invasive surgery
• Rupture
• Textbook outcome

• Humans
• Gastrointestinal Stromal Tumors/surgery
• Gastrointestinal Stromal Tumors/pathology
• Female
• Male
• Aged
• Middle Aged
• Retrospective Studies
• Gastrectomy/methods
• Stomach Neoplasms/surgery
• Stomach Neoplasms/pathology
• Postoperative Complications/epidemiology
• Minimally Invasive Surgical Procedures/methods
• Length of Stay/statistics & numerical data
• Operative Time

• gastrointestinal stromal tumors
• imatinib
• meta‐analysis
• neoadjuvant
• systematic review

• Gastrointestinal Stromal Tumors/drug therapy
• Gastrointestinal Stromal Tumors/mortality
• Gastrointestinal Stromal Tumors/pathology
• Gastrointestinal Stromal Tumors/genetics
• Imatinib Mesylate/therapeutic use
• Humans
• Neoadjuvant Therapy/methods
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Neoplasms/pathology
• Gastrointestinal Neoplasms/mortality
• Gastrointestinal Neoplasms/genetics
• Antineoplastic Agents/therapeutic use
• Treatment Outcome

• c-kit
• gist
• imatinib
• pdgfra
• surgical resection

• bleeding gist
• bowel obstruction
• damage control laparotomy
• gastrointestinal stromal tumor (gist)
• imatinib mesylate
• surgical emergency scenarios

• Humans
• Male
• Middle Aged
• Female
• Imatinib Mesylate/therapeutic use
• Gastrointestinal Stromal Tumors/pathology
• Neoadjuvant Therapy/methods
• Piperazines/therapeutic use
• Pyrimidines/therapeutic use
• Benzamides/therapeutic use
• Antineoplastic Agents/therapeutic use

• Case report
• Gastric volvulus
• Gastrointestinal stromal tumor
• Imatinib
• Neoadjuvant therapy

• LECs
• endoscopy
• gastrointestinal stromal tumors (GISTs)
• risk evaluation (RE)
• surgery

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors that originate from the gastrointestinal tract, mostly from the stomach. GISTs are derived from the myenteric interstitial cells of Cajal and are caused by several mutations in the c-kit and platelet-derived growth factor receptor genes. Clinically, GISTs are detected by endoscopic and imaging findings and are diagnosed by immunostaining. Surgery is the first line of treatment, and if the tumor is relatively small, minimally invasive surgery such as laparoscopy is performed. In recent years, neoadjuvant therapy has been administered to patients with GISTs that are suspected of having a large size or infiltration to other organs. Postoperative adjuvant imatinib is the standard therapy for high-risk GISTs. It is important to assess the risk of recurrence after GIST resection. However, the effect of tyrosine kinase inhibitor use will vary by the mutation of c-kit genes and the site of mutation. Furthermore, information regarding gene mutation is indispensable when considering the treatment policy for recurrent GISTs. This article reviews the clinicopathological characteristics of GISTs along with the minimally invasive and multidisciplinary treatment options available for these tumors. The future perspectives for diagnostic and treatment approaches for these tumors have also been discussed.

• Gastrointestinal stromal tumor
• Minimally invasive surgery
• Laparoscopic surgery
• Imatinib
• Neoadjuvant therapy
• Risk assessment

• gastrointestinal stromal tumour
• low rectum
• para-sacral approach
• sphincter preservation

• Abdominal Cavity/diagnostic imaging
• Aged
• Carcinoma/diagnosis
• Chemotherapy, Adjuvant
• Cysts/diagnosis
• Cysts/pathology
• Cysts/surgery
• Diagnosis, Differential
• Female
• Gastrointestinal Stromal Tumors/diagnosis
• Gastrointestinal Stromal Tumors/secondary
• Gastrointestinal Stromal Tumors/therapy
• Humans
• Ileal Neoplasms/diagnosis
• Ileal Neoplasms/pathology
• Ileal Neoplasms/therapy
• Ileum/diagnostic imaging
• Ileum/pathology
• Ileum/surgery
• Imatinib Mesylate/therapeutic use
• Laparoscopy
• Ovarian Neoplasms/diagnosis
• Pelvis/diagnostic imaging
• Peritoneal Neoplasms/diagnosis
• Peritoneal Neoplasms/secondary
• Peritoneal Neoplasms/therapy
• Tomography, X-Ray Computed
• Treatment Outcome
• Ultrasonography

This study reports a single-center analysis of 55 patients with primary, locally advanced gastric GIST treated with imatinib mesylate (IM) preoperatively for a median of 10 months. The therapy yielded shrinkage of median tumor size from 113 mm to 62 mm. This facilitated 50 patients to undergo significantly less-extensive surgical procedures and resulted in a stomach preservation rate of 96%. The rate of R0 resections was 94% and was followed by a mean recurrence-free-survival time of 132 months with the median not reached. The approach was successful even for patients starting IM during an episode of upper gastrointestinal bleeding. Neoadjuvant IM therapy for locally advanced, non-metastatic gastrointestinal stromal tumors (GIST) of the stomach may play an important role in preserving organ function which might be important for IM plasma levels in an adjuvant or metastatic setting.

Background: Neoadjuvant imatinib mesylate (IM) for advanced, non-metastatic gastrointestinal stromal tumors (GIST) of stomach is recommended to downsize the tumor prompting less-extensive operations and preservation of organ function. Methods: We analyzed the clinical-histopathological profile and oncological outcome of 55 patients (median age 58.2 years; range, 30–86 years) with biopsy-proven, cM0, gastric GIST who underwent IM therapy followed by surgery with a median follow-up of 82 months. Results: Initial median tumor size was 113 mm (range, 65–330 mm) and 10 patients started with acute upper GI bleeding. After a median 10 months (range, 2–21 months) of treatment, tumor size had shrunk to 62 mm (range, 22–200 mm). According to Response Evaluation Criteria In Solid Tumors version 1.0 and version 1.1 (RECIST 1.1), 39 (75%) patients had partial response and 14 patients had stable disease, with no progressive disease. At plateau response, 50 patients underwent surgery with an R0 resection rate of 94% and pathological complete response in 24%. In 12 cases (24%), downstaging allowed laparoscopic resection. The mean recurrence-free survival (RFS) was 123 months (95%CI; 99–147) and the estimated 5-year RFS was 84%. Conclusions: Neoadjuvant IM allowed stomach preservation in 96% of our patients with excellent long-term RFS, even when starting treatment during an episode of upper GI bleeding. Preservation of the stomach provides the physiological basis for the use of oral IM in the adjuvant or metastatic setting.

• GIST
• gastrointestinal stromal tumor
• imatinib
• neoadjuvant therapy
• organ preservation
• stomach

• Gastrointestinal stromal tumor
• Imatinib mesylate
• Preoperative treatment
• Retrospective study

• gists
• preoperative im therapy
• surgical intervention

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• China
• Female
• Gastrointestinal Neoplasms/diagnostic imaging
• Gastrointestinal Neoplasms/mortality
• Gastrointestinal Neoplasms/pathology
• Gastrointestinal Neoplasms/therapy
• Gastrointestinal Stromal Tumors/diagnostic imaging
• Gastrointestinal Stromal Tumors/mortality
• Gastrointestinal Stromal Tumors/pathology
• Gastrointestinal Stromal Tumors/therapy
• Humans
• Imatinib Mesylate/administration & dosage
• Imatinib Mesylate/therapeutic use
• Male
• Medical Records
• Middle Aged
• Neoadjuvant Therapy
• Neoplasm Metastasis
• Neoplasm Recurrence, Local/diagnostic imaging
• Neoplasm Recurrence, Local/mortality
• Neoplasm Recurrence, Local/pathology
• Neoplasm Recurrence, Local/therapy
• Retrospective Studies
• Survival Analysis
• Treatment Outcome

Although the standard treatment for stromal tumours is surgery, in locally advanced forms, it is often necessary to achieve tumour downstaging to improve surgical outcomes. Neoadjuvant treatment in gastrointestinal stromal tumours (GISTs) with tyrosine kinase inhibitors, including imatinib, has been shown to be effective in several studies, but the duration of this treatment is still a subject of debate.

We report a case of a large GIST of the stomach in a 51-year-old patient with atypical presentation that was initially unresectable. Neoadjuvant treatment with imatinib for 16 months resulted in a good response, allowing secondary surgical excision.

Imatinib in neoadjuvant therapy should be continued as long as there is a good response and tolerance to the medication to obtain tumour downsizing compatible with carcinologic excision.

The online version of this article (10.1007/s40487-019-00101-4) contains supplementary material, which is available to authorized users.

• GIST
• Imatinib
• Neoadjuvant therapy
• Surgery

• Duodenal resection
• Gastrointestinal stromal tumors
• Retroperitoneal sarcoma
• Surgical complications

Background: Neoadjuvant imatinib therapy has been proposed for routine practice with favorable long-term results for patients with locally advanced gastrointestinal stromal tumors (GISTs). However, clarification of the optimal duration, safety, and oncological outcomes of neoadjuvant imatinib use before surgical intervention remains necessary. Methods: We prospectively analyzed the treatment outcomes of 51 patients with locally advanced, nonmetastatic GISTs treated with neoadjuvant imatinib followed by surgery. The optimal duration was defined as the timepoint when there was a <10% change in the treatment response or a size decrease of less than 5 mm between two consecutive computed tomography scans. Results: Primary tumors were located in the stomach (23/51; 45%), followed by the rectum (17/51; 33%), ileum/jejunum (9/51; 18%), and esophagus (2/51; 4%). The median maximal shrinkage time was 6.1 months, beyond which further treatment may not be beneficial. However, the maximal shrinkage time was 4.3 months for the stomach, 8.6 months for the small bowel and 6.9 months for the rectum. The R0 tumor resection rate in 27 patients after neoadjuvant imatinib and surgery was 81.5%, and 70.4% of resection procedures succeeded in organ preservation. However, 10 of 51 patients (19.6%) had complications following neoadjuvant imatinib use (six from imatinib and four from surgery). Conclusion: Our analysis supports treating GIST patients with neoadjuvant imatinib, which demonstrated favorable long-term results of combined therapy. However, careful monitoring of complications is necessary. The optimal duration of neoadjuvant imatinib use before surgical intervention is, on average, 6.1 months.

• GIST
• gastrointestinal stromal tumors
• imatinib
• neoadjuvant therapy
• surgery

Tumor rupture is an important risk factor predictive of recurrence after macroscopically complete resection of gastrointestinal stromal tumors (GISTs), and an indication for defined interval or even lifelong adjuvant therapy with imatinib according to guidelines. However, there is no consensus or universally accepted definition of the term ‘tumor rupture’, and, consequently, its incidence varies greatly across reported series. Without predefined criteria, the clinical significance of rupture has also been difficult to assess on multivariate analysis of retrospective data. We reviewed the relevant literature and international guidelines, and, based on the Oslo criteria, proposed the following six definitions for ‘tumor rupture’: (1) tumor fracture or spillage; (2) blood-stained ascites; (3) gastrointestinal perforation at the tumor site; (4) microscopic infiltration of an adjacent organ; (5) intralesional dissection or piecemeal resection; or (6) incisional biopsy. Not all minor defects of tumor integrity should not be classified as rupture, i.e. mucosal defects or spillage contained within the gastrointestinal lumen, microscopic tumor penetration of the peritoneum or iatrogenic damage only to the peritoneal lining, uncomplicated transperitoneal needle biopsy, and R1 resection. This broad definition identifies GIST patients at particularly high risk of recurrence in population-based cohorts; however, its applicability in other sarcomas has not been investigated. As the proposed definition of tumor rupture in GIST has limited evidence based on the small number of patients with rupture in each retrospective study, we recommend validating the proposed definition of tumor rupture in GIST in prospective studies and considering it in clinical practice.

• GIST
• adjuvant
• imatinib
• neoadjuvant

• Gastrointestinal stromal tumors, GIST
• Imatinib
• Preoperative treatment
• Resectability

• Gastrointestinal stromal tumor
• Imatinib
• Margin
• Neodjuvant
• Pathology
• Surgery
• Tumor perforation

The incidence, treatment and outcome of patients with newly diagnosed gastrointestinal stromal tumour (GIST) were studied in an era known for advances in diagnosis and treatment.

Nationwide population‐based data were retrieved from the Netherlands Cancer Registry. All patients with GIST diagnosed between 2001 and 2012 were included. Primary treatment, defined as any treatment within the first 6–9 months after diagnosis, was studied. Age‐standardized incidence was calculated according to the European standard population. Changes in incidence were evaluated by calculating the estimated annual percentage change (EAPC). Relative survival was used for survival calculations with follow‐up available to January 2017.

A total of 1749 patients (54·0 per cent male and median age 66 years) were diagnosed with a GIST. The incidence of non‐metastatic GIST increased from 3·1 per million person‐years in 2001 to 7·0 per million person‐years in 2012; the EAPC was 7·1 (95 per cent c.i. 4·1 to 10·2) per cent (P < 0·001). The incidence of primary metastatic GIST was 1·3 per million person‐years, in both 2001 and 2012. The 5‐year relative survival rate increased from 71·0 per cent in 2001–2004 to 81·4 per cent in 2009–2012. Women had a better outcome than men. Overall, patients with primary metastatic GIST had a 5‐year relative survival rate of 48·2 (95 per cent c.i. 42·0 to 54·2) per cent compared with 88·8 (86·0 to 91·4) per cent in those with non‐metastatic GIST.

This population‐based nationwide study found an incidence of GIST in the Netherlands of approximately 8 per million person‐years. One in five patients presented with metastatic disease, but relative survival improved significantly over time for all patients with GIST in the imatinib era.

Surgery improves survival

• Gastrointestinal stromal tumor (GIST)
• imatinib mesylate
• neoadjuvant therapy

• Duodenum
• Gastrointestinal stromal tumor
• Prognosis
• Surgery

• Adult
• Aged
• Anastomosis, Surgical/adverse effects
• Antineoplastic Agents/therapeutic use
• Chemotherapy, Adjuvant
• Disease-Free Survival
• Duodenal Neoplasms/drug therapy
• Duodenal Neoplasms/pathology
• Duodenal Neoplasms/surgery
• Duodenum/surgery
• Female
• Gastrointestinal Stromal Tumors/drug therapy
• Gastrointestinal Stromal Tumors/secondary
• Gastrointestinal Stromal Tumors/surgery
• Humans
• Imatinib Mesylate/therapeutic use
• Jejunum/surgery
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Mitotic Index
• Neoadjuvant Therapy
• Neoplasm Grading
• Pancreaticoduodenectomy/adverse effects
• Postoperative Complications/etiology
• Retrospective Studies
• Survival Rate
• Tumor Burden
• Young Adult

• Organ-preserving surgery
• duodenal gastrointestinal stromal tumor
• imatinib mesylate
• neoadjuvant therapy
• pancreaticoduodenectomy

To report on a more accurate diagnostic possibility offered by endoscopic ultrasound-guided cutting of holes and deep biopsy (EUS-CHDB) for pathologic diagnosis of gastric infiltrative tumors and gastrointestinal submucosal tumors.

Ten consecutive patients who were suspected of having gastric invasive tumors or gastrointestinal submucosal tumors underwent EUS-CHDB with a novel vertical diathermic loop. We reviewed their medical data and analysed the effectiveness and safety of this new method. The final diagnosis was based on the surgical pathology or clinical/imaging follow-up.

EUS-CHDB was performed successfully in all the ten patients. Neither severe haemorrhage nor perforation occurred in any patient. Among the ten patients, there were three cases of gastric linitis plastica, one case of gastric lymphoma, five cases of gastrointestinal stromal tumors (GISTs), and only one case of chronic non-atrophic gastritis. That is, nine (90%) of the cases treated by EUS-CHDB showed positive findings.

EUS-CHDB may be a technically feasible and safe option for patients with gastric infiltrative tumors or gastrointestinal submucosal tumors. EUS-CHDB may be used as a remedial or even preferred biopsy method for submucosal lesions.

• Endoscopic ultrasound
• Cutting holes
• Deep biopsy
• Vertical diathermic loop
• Gastric linitis plastica
• Gastrointestinal submucosal tumors

• Adult
• Aged
• Biopsy/instrumentation
• Biopsy/methods
• Female
• Humans
• Male
• Middle Aged
• Retrospective Studies
• Stomach/pathology
• Stomach Neoplasms/diagnosis
• Ultrasonography, Interventional/instrumentation
• Ultrasonography, Interventional/methods

• Gist
• KIT mutation analysis
• Locally advanced
• Neoadjuvant imatinib

• Adult
• Aged
• Antineoplastic Agents/administration & dosage
• Antineoplastic Agents/therapeutic use
• Female
• Gastrointestinal Stromal Tumors/drug therapy
• Gastrointestinal Stromal Tumors/pathology
• Humans
• Imatinib Mesylate/administration & dosage
• Imatinib Mesylate/therapeutic use
• Male
• Middle Aged
• Mutation
• Neoadjuvant Therapy/methods
• Young Adult

Background and Goals. In light of current knowledge, it seems that alternations underlying GISTs are well explained, although all that is enhanced by various aspects on a daily basis. More recently, attention has been pointed towards exosomes as important particles able to modify healthy and also diseased tissues including cancer. The goal of the present study was an analysis of CD9, CD63, and GLUT-1 as a marker of hypoxia status within 54 cases of GIST and evaluation of their predictive value. Methods. 54 cases of patients suffering from GIST were enrolled into the study, predominantly in the gastric location. All operated cases had no Imatinib and other chemotherapies up to the day of operation. Expression of targeted proteins was performed by immunohistochemistry and, after that, the results with tabulated clinical data were compared by Kaplan-Meier method and multivariate Cox proportional hazard model of statistical analysis. Results. Our results presented a marked dependence of worsening clinical outcome with high expression CD63 (p = 0.008) as well as with GLUT-1 (p = 0.014). We noted a strict correlation of GLUT-1 expression with CD63 expression (p = 0.03), which could confirm the thesis about the contribution of exosomes in intratumoural hypoxia status. The collected material did not confirm CD9 contribution. Conclusions. As presented here, CD63 and GLUT-1 have a prognostic value in GIST cases. The results confirm the other studies in this scope and can be used in future as an additional prognostic factor.

• Adjuvant therapy
• Gastrointestinal stromal tumor
• Imatinib
• Neoadjuvant therapy
• Surgery

• Gastrointestinal stromal tumor (GIST)
• adjuvant, resectability
• imatinib
• neoadjuvant

• Advanced
• GIST
• Imatinib
• Metastatic
• Sarcoma
• Surgery
• Survival

• gastrointestinal stromal tumor
• multivisceral resection
• surgical oncology
• upper gut

• adjuvant
• gastrointestinal stromal tumor
• imatinib
• molecular target therapy
• risk stratification

• Animals
• Disease Management
• Gastrointestinal Neoplasms/drug therapy
• Gastrointestinal Stromal Tumors/drug therapy
• Humans
• Molecular Targeted Therapy

• Adjuvant treatment
• Complete resection
• Gastrointestinal stromal tumor (GIST)
• Imatinib
• Ki-67
• Surgical treatment

Surgery is the mainstay of treatment for gastrointestinal stromal tumors (GISTs). However, complete resection of rectal GISTs is sometimes difficult because of bulkiness and/or anatomical reasons. Neoadjuvant imatinib therapy has gained attention as an alternative treatment to increase the chance of en bloc resection of rectal GISTs, although it usually takes several months. In this case report, we first demonstrated that neoadjuvant imatinib therapy can be performed safely not only to downsize tumors, but also to allow adequate time for the effective treatment of major comorbid illnesses. A 74-year-old man was diagnosed with a 45 mm GIST of the lower rectum. He also had severe stenosis in the proximal segment of the left anterior descending coronary artery. Following the implantation of a drug-eluting stent, the patient received imatinib together with dual anti-platelet therapy for 12 months without obvious side effects. Follow-up image studies revealed tumor shrinkage as well as stent patency. En bloc resection of the GIST was performed laparoscopically, which preserved the anus. The patient is currently alive without any evidence of relapse for 12 months after surgery.

• Antineoplastic Agents/administration & dosage
• Benzamides/administration & dosage
• Cytoreduction Surgical Procedures/methods
• Disease Progression
• Dissection/adverse effects
• Dissection/methods
• Dose-Response Relationship, Drug
• Gastrointestinal Neoplasms/pathology
• Gastrointestinal Neoplasms/surgery
• Gastrointestinal Stromal Tumors/pathology
• Gastrointestinal Stromal Tumors/surgery
• Hemoperitoneum/etiology
• Hemoperitoneum/surgery
• Humans
• Imatinib Mesylate
• Intestine, Small/pathology
• Male
• Middle Aged
• Neoplasm Recurrence, Local/drug therapy
• Neoplasm Recurrence, Local/surgery
• Piperazines/administration & dosage
• Postoperative Complications/drug therapy
• Postoperative Complications/surgery
• Pyrimidines/administration & dosage
• Risk Assessment
• Rupture, Spontaneous

Although the clinical benefit of imatinib adjuvant therapy for high-risk patients with gastrointestinal stromal tumor (GIST) has been proven, the recurrence rate still remains high. This study aimed to sub-divide high-risk GIST patients with some “very high-risk” factors for more precise prognostic indicator, and possible association with efficiency of imatinib adjuvant therapy.

Clinicopathological data were confirmed by pathological diagnosis and clinical records. Recurrence-free survivals (RFS) were evaluated in 370 GIST patients (212 cases as test cohort and 158 cases as validation cohort) and 48 high-risk GISTs with imatinib adjuvant therapy after R0 resection.

Mitosis count > 10/50 high-power fields (HPF) and serosal invasion are independent prognostic factors for RFS of GIST patients. Mitosis count > 10/50HPF and serosal invasion can sub-divide high-risk GIST patients effectively and significantly improve the area under the curve (AUC) of receiver operating characteristics (ROC) curve for prognostic indicator both in test and validation cohort. Patients with serosal invasion after R0 resection showed a poorer prognosis with imatinib adjuvant therapy.

Sub-division of high-risk GIST patients helps to more precisely predicting the prognosis. Serosal invasion may be an adverse predictive factor in high-risk patients and imatinib treatment outcome.

• Gastrointestinal stromal tumor
• Risk classification
• Surgery
• Treatment standards
• Tyrosine kinase inhibitors