Treatment option of endoscopic stent insertion or gastrojejunostomy for gastric outlet obstruction due to gastric cancer: a propensity score-matched analysis.

BACKGROUND: There are currently two treatment options for gastric outlet obstruction (GOO) due to gastric cancer, endoscopic stenting and surgical gastrojejunostomy. However, their therapeutic effects have not yet been established. Therefore, the present study was undertaken to examine these effects. METHODS: The Japanese Gastric Cancer Association invited its delegates to participate in a retrospective multicenter cohort study on patients with GOO due to gastric cancer who underwent stent therapy or gastrojejunostomy in 2015. RESULTS: We obtained data from 85 patients undergoing stent therapy and 94 undergoing gastrojejunostomy from 42 hospitals. Baseline data revealed that stent patients had lower food intake, poorer performance status, and worse prognostic indices than gastrojejunostomy patients. Postoperative food intake and survival times were worse in stent patients than in gastrojejunostomy patients. We performed propensity score matching to select pairs of patients with similar baseline characteristics in the two treatment groups. After matching, the frequency of postoperative complications was significantly less in stent patients (3%, 1/33) than in gastrojejunostomy patients (21%, 7/34; p = 0.03). A low residue or full diet was achieved by 97% of stent patients (32/33) and 97% of gastrojejunostomy patients (33/34) (p = 0.98). Median survival times were 7.8 months in stent patients and 4.0 months in gastrojejunostomy patients (p = 0.38). CONCLUSIONS: Propensity score matching demonstrated that endoscopic stent placement resulted in less postoperative morbidity than and a similar food intake and equivalent survival times to gastrojejunostomy. These results suggest the utility of stent therapy.

[Outcomes of Staging Laparoscopy in Eight Patients with Positive Peritoneal Washing Cytology after S-1 Administration].

AIM: The aim of this study was to clarify the clinical outcomes of staging laparoscopy(SL)for patients with positive peritonealwashing cytology(CY1P0)after S-1 administration. PATIENTS AND METHODS: Since 2007, eight CY1P0 patients who underwent SL after S-1 administration were enrolled. S-1 was administered according to the ACTS-GC and SL was performed after 8 courses of S-1 treatment. RESULTS: SL was ended with adequate observation of intra-abdominalcavity in allthe patients with a median time of 68 minutes(range: 52-76 minutes). The timing of SL was after 8 courses of S-1 administration in 6 patients, after 11 courses in 1, and 12 courses in 1. Based on the SL results, CY0P0 was attained in 6 patients; CY1P0, in 1 and CY1P1, in 1. For the 6 patients who attained CY0P0, S-1 administration was completed. For the 2 patients who attained CY1P0 and CY1P1, chemotherapy was continued. Only 1 of the patients who attained CY0P0 had peritoneal recurrence 3 months after completion of S-1 administration. CONCLUSION: When CY0P0 is detected by using SL, S-1 administration may be completed. More cases need to be studied to determine the suitable courses or timing of S-1 administration for CY0P0 patients.

[Administration of S-1 Monotherapy as Adjuvant Chemotherapy in a Patient with Advanced Gastric Cancer with HIV Infection].

A 64-year-old man with advanced gastric cancer presented with chief complaints of chest pain. His preoperative blood examination revealed positive results for serum HIV-antibody. His HIV-RNA level was 1.0×10 / 5 copies/mL, and his CD4lymphocyte count was 491 cell/mL; the patient was diagnosed with advanced gastric cancer and HIV infection. Distal gastrectomy with D2 lymphadenectomy and Roux-en-Y reconstruction were performed for treatment of the gastric cancer. Pathological examination revealed T3(SS)N3aM0, Stage III C cancer. After surgery, the patient was administered S-1 monotherapy as adjuvant treatment with antiretroviral therapy including tenofovir/emtricitabine and raltegravir. He completed 8 courses of S- 1 chemotherapy with no adverse events, such as a decrease in the CD4lymphocyte count or an increase in the HIV-RNA level. This patient with gastric cancer and HIV infection was safely treated using both antiretroviral therapy and chemotherapy owing to treatment intervention by chemotherapy and infectious diseases specialists.

[Multidisciplinary Treatment for a Patient with Primary Malignant Melanoma Arising from the Stomach].

A 61-year-old woman was referred to our hospital with the complaint of severe dysphagia. Upper gastrointestinal endoscopy revealed an elevated tumor with an irregular surface located in the upper third of the stomach, and malignant melanoma was confirmed by biopsy specimens. Abdominal CT scan findings revealed that the tumor was invading the lateral segment of the liver and crus of the diaphragm. Total gastrectomy was combined with resection of the lateral segment of the liver and the crus of the diaphragm, and D2 lymphadenectomy and reconstruction by the Roux-en-Y method were carried out. Because of positive peritoneal washing cytology, monotherapy with dacarbazine, and combination therapy, including dacarbazine, nimustine hydrochloride, cisplatin, and tamoxifen citrate, were administered for treating the residual tumor. The patient died from peritoneal relapse 146 days after the initial surgery. Primary malignant melanoma arising from the stomach is reported as an extremely rare disease with a poor prognosis. In our case, multidisciplinary treatment including surgery and chemotherapy was insufficient to achieve long-term survival in a highly advanced malignant melanoma arising from the stomach.

Prognostic significance of initial recurrence site in hematogenous recurrence of esophageal squamous cell carcinoma.

BACKGROUND/AIMS: Hematogenous recurrences of esophageal squamous cell carcinoma (ESCC) have dismal prognoses, but prognostic heterogeneity exists in this disease. The objectives of this study were to clarify the prognosis in this disease with regard to the initial recurrence site and to define the prognostic factors. METHODOLOGY: We retrospectively reviewed the cases of 67 consecutive patients with hematogenous recurrence in major organs after esophagectomy for ESCC of the thoracic esophagus and the esophagogastric junction. We analyzed clinicopathological characteristics, survival probability, and potential prognostic factors. RESULTS: Lung, liver, bone, and multiple-organ metastases occurred in 24, 19, 14, and 10 patients, respectively. Twenty-seven patients simultaneously had locoregional recurrence (combined recurrence). Among all 67 patients, the median disease-free interval (DFI) was 9.7 months, and the median survival time after the initial recurrence was 4.9 months. The patients with initial lung metastasis had most favorable prognosis with the median survival time of 9.8 months. A multivariate analysis identified that initial recurrence site, DFI, combined recurrence, and anti-cancer therapy were independent prognostic factors. CONCLUSIONS: The initial recurrence site contributes to the prognostic heterogeneity of patients with hematogenous recurrence of ESCC. The prognostic factors identified in this study are useful to optimize the management of these patients.

[A case of early gastric cancer with multiple synchronous bone metastases treated complete response with S-1+CDDP].

We report a case of complete response (CR) following induction chemotherapy using S-1 for a patient with early gastric cancer accompanied by multiple synchronous bone metastases. An asymptomatic 70-year-old woman was diagnosed with early gastric cancer by upper gastrointestinal endoscopy during a periodic medical examination. An abdomino-pelvic computed tomography (CT) scan revealed no primary tumor in the stomach and the absence of lymph node or liver metastases. However, osteoplastic changes were detected in the lumbar vertebrae and the ilium. Multiple synchronous bone metastases from early gastric cancer were detected on magnetic resonance imaging, bone scintigraphy, and positron emission tomography- CT. After a regimen consisting of 15 courses of S-1 plus cisplatin (CDDP), and an additional 5 courses of S-1 were administered, clinical CR was confirmed for the bone metastases. Laparoscopic distal gastrectomy with D1 lymphadenectomy was performed for treating the primary gastric cancer 33 months after the initiation of chemotherapy. Pathological CR was also achieved for the primary gastric cancer. Imaging analysis did not show disease progression 48 months after the initiation of chemotherapy. Synchronous bone metastases from early gastric cancer are extremely rare, and a good outcome was achieved in the present case through induction chemotherapy.

[Gastrectomy for a patient with advanced gastric cancer with spleen metastases following induction chemotherapy with S-1 plus cisplatin].

An asymptomatic 56-year-old woman, upon medical examination, was diagnosed with advanced adenocarcinoma of the upper third of the stomach. Computed tomography showed that the primary gastric tumor was directly invading the splenic hilum, and there were multiple metastases in the spleen; incurable gastric cancer was confirmed. S-1 plus cisplatin therapy was introduced as the induction regimen, and the main tumor and splenic metastases reduced significantly. Total gastrectomy with splenectomy and D2 lymphadenectomy was performed after 9 courses of chemotherapy. The surgery was completed with no residual tumor, and intraperitoneal washing cytology was negative. Histologically, the primary tumor was classified as Grade 2, reflecting the effect of chemotherapy, and viable metastatic tumors were confirmed in the spleen. S-1-based treatment was continued as adjuvant chemotherapy, and the patient was alive with no evidence of tumor recurrence 39 months after the initiation of chemotherapy. Although metastasis to the spleen from gastric adenocarcinoma has been reported as a rare metastatic pattern with poor prognosis, our patient had a long survival time after gastrectomy following induction chemotherapy.

[Urgent gastrectomy in a patient who developed perforated gastric cancer during preoperative chemotherapy with S-1 plus cisplatin].

A 66 -year-old man presenting with a chief complaint of upper abdominal pain was diagnosed as having an advanced adenocarcinoma, type 2, of the lower third of the stomach after endoscopy was performed. An abdominal computed tomography( CT)scan revealed 4 lymph node metastases at the infrapyloric nodes(station No. 6)and the nodes around the proximal splenic artery(station No. 11p)and the abdominal aorta(station No. 16a2). The clinical stage was determined to be T3(SS)N2M1(LYM), Stage IV. Gastrectomy with D2 plus para-aortic node dissection was scheduled after 2 courses of S-1 plus cisplatin(CDDP)with curative intent. On day 14 after starting S-1 therapy, the patient complained of severe abdominal pain and peritoneal irritation of acute onset. Because the abdominal CT scan showed a large amount of intra-abdominal free air, we performed an urgent laparotomy with a tentative diagnosis of perforation of the gastric cancer. On laparotomy, we found a perforated malignant ulcer, 5 cm in maximum diameter, in the lesser curvature of the stomach; therefore, distal gastrectomy with D1 plus lymphadenectomy and reconstruction using the Roux-en-Y method were performed. At the end of the surgery, a macroscopic residual tumor remained in the para-aortic lymph node. The postoperative course was uneventful, and the patient was discharged on day 23 after surgery. In the present case, despite the performance of urgent gastrectomy while the patient was receiving strong chemotherapy, perioperative management was successful, with no serious postoperative complication or adverse events as a result of the chemotherapy.

[Effectiveness of chemoradiotherapy for a patient with local recurrence of advanced gastric cancer followed by curable gastrectomy].

We report here the effectiveness of chemoradiotherapy for a patient with local recurrence followed by curable gastrectomy. A 57-year-old man presented with a history of total gastrectomy with distal pancreatectomy and splenectomy, D2 lymphadenectomy, and Roux-en-Y reconstruction for advanced gastric cancer arising from the cardia. Esophageal intramural metastasis and lymph node metastasis around the right recurrent nerve were detected by chest-abdominal computed tomography and gastrointestinal endoscopy 27 months after the initial gastrectomy. Stable disease was achieved following 7 courses of chemotherapy using S-1 plus CDDP. Concurrent chemoradiotherapy including administration of S-1 and radiation of total 50 Gy (2 Gy/25 Fr) was selected for local tumor control. The patient was not able to eat solid food because of esophageal stenosis from regrowth of intramural metastasis of the esophagus 60 months after the chemotherapy. A WallFlex™ Duodenal Stent was placed to improve the dysphagia 67 months after chemotherapy. The patient died from recurrence of gastric cancer 69 months after completion of the initial chemotherapy and 2 months after the stent insertion.

[Current status of adjuvant chemotherapy in patients with p-Stage II and p-Stage III gastric cancer].

The results of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer(ACTS-GC)demonstrated that postoperative chemotherapy using S-1 is a standard treatment in Japan for patients with p-Stage II and p-Stage III gastric cancer. We retrospectively reviewed the effect of adjuvant chemotherapy received by 47 patients with p-Stage II and p-Stage III gastric cancer between January 2007 and June 2012. Our hospital is a local university hospital with a high intensive care unit. S-1 monotherapy was administered to 32 patients(adjuvant S-1 group, 68.1%); 22 patients(68.8%)among them completed one year of therapy without any modification to the administration schedule. A total of 8 patients(25.0%)experienced grade 3 adverse events, and 9 patients required a dose reduction, a modification of the administration schedule, or termination of the therapy. S-1 was not administrated to 15 patients(no adjuvant S-1 group, 31.9%); among these patients, 12(80.0%) were not administered S-1 because of their advanced age and comorbidity. The 3-year overall survival rate was 89.3% in the adjuvant S-1 group and 77.1% in the no adjuvant S-1 group. The completion rate of S-1 and survival rate were high for patients in the adjuvant S-1 group, which was similar to the results of the ACTS-GC. However, 25 of 47 patients(53.2%) with p-Stage II and p-Stage III gastric cancer did not improve after sufficient adjuvant therapy; therefore, it is important to develop new treatment strategies for these patients.

[How does we treat liver metastases from colorectal cancer by cure-intent surgery ?].

Surgery is the most optimal and curative intent strategy for liver recurrence from colorectal cancer. There are scoring systems and grade classification for liver resection. If we carry out preoperative imaging of liver metastases strictly following to liver resection, we can expect to get a cure state satisfactory. Early detection and repeated liver resection improve the outcome of residual liver recurrence after liver resection. The maximum number of liver metastases for cure intent liver resection is unclear. Further examination is necessary.

[Multidisciplinary therapy for 3 patients with lymph node recurrence after curative gastrectomy].

We report multidisciplinary treatment of 3 patients with lymph node recurrence after curative gastrectomy. Case 1: A 71- year-old woman had a history of distal gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Para-aortic lymph node metastasis was observed 36 months after surgery. Complete response( CR) was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 2: A 51-year-old man had a history of total gastrectomy with D2 lymphadenectomy for the treatment of advanced gastric cancer. Right cervical lymph node metastasis was observed 48 months after surgery. CR was achieved after concurrent chemoradiotherapy with S-1 plus radiation. Case 3: A 68-year-old man had a history of distal gastrectomy with D2 lymphadenectomy followed by neoadjuvant chemotherapy for the treatment of advanced gastric cancer. CR was achieved after sequential treatment with irinotecan( CPT-11) plus cisplatin( CDDP), radiation, and 5-fluorouraci(l 5-FU) plus Leucovorin therapy for lymph node recurrence near the head of the pancreas. These cases suggest that the combination of systemic chemotherapy and local radiation therapy might be effective for the treatment of lymph node recurrence in patients with gastric cancer.

Clinicopathological characteristics and prognosis of patients with esophageal carcinoma invading adjacent structures found during esophagectomy.

OBJECTIVES: A treatment strategy for patients with esophageal carcinoma invading adjacent structures found during esophagectomy (surgical T4; sT4) has not been established and the role of esophagectomy remains controversial. The aims of this study were to assess the clinicopathological characteristics and to clarify the prognostic factors of patients who underwent esophagectomy for sT4 tumors. METHODS: A consecutive series of 76 patients who were found to have sT4 tumors was reviewed retrospectively. T4 tumors were divided into two groups according to the invaded structures. Cox's multivariate proportional hazard model was used to identify prognostic factors. RESULTS: Complete tumor clearance with combined resection was performed in 12 patients (16%). Overall 1-, 3-, and 5-year survival rates were 40.8%, 9.2%, and 7.9%, respectively. There was no significant relationship between survival and invaded structure type or residual tumor status. Postoperative therapy was selected as an independent prognostic factor. CONCLUSIONS: The complete resection rate was low and the prognosis of patients with sT4 tumors was poor. Subclassification according to the invaded structures was not a prognostic factor in this study. Postoperative therapy may improve survival in sT4 patients and should be considered irrespective of residual tumor status after esophagectomy.

Gastrectomy as a secondary surgery for stage IV gastric cancer patients who underwent S-1-based chemotherapy: a multi-institute retrospective study.

BACKGROUND: Current advances in chemotherapy provide opportunities for stage IV gastric cancer patients with distant metastasis to undergo potentially curable resection. There are, however, few data on gastrectomy as a secondary surgery aimed at rendering such patients cancer-free. METHODS: We investigated stage IV gastric cancer patients who underwent surgery with curative intent after S-1-based chemotherapy between 2000 and 2008. Twenty-eight patients from 12 hospitals were enrolled in this study. Factors indicating that the tumors were incurable included clinical stage T4 in 9 patients, para-aortic node metastasis in 15, peritoneal metastasis in 7, and liver metastasis in 4. RESULTS: Of the 28 laparotomy patients, 26 underwent complete resection with no residual tumor, obtaining a complete resection rate of 92.9%. There were no in-hospital deaths or reoperations. In four patients, the primary tumor showed pathological complete response. The 1-, 3-, and 5-year overall survival rates after secondary gastrectomy were 82.1, 45.9, and 34.4%, respectively, with a median survival time of 29 months. Univariate analysis revealed histological tumor length, clinical depth of tumor invasion, number of metastatic nodes, pathological depth of tumor invasion, and pathological response to be the factors influencing patient survival after secondary surgery. On multivariate analysis, histological tumor length (5.0 cm or larger) was the only significant prognostic factor (relative risk 3.23, P = 0.028). CONCLUSIONS: Secondary gastrectomy following S-1-based chemotherapy was a safe and effective treatment for stage IV gastric cancer. Primary tumor size is an indicator for the appropriate selection of patients for this treatment.

Prospective observational study of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors: long-term follow-up and second malignancy.

OBJECTIVE: Limited data are available concerning long-term results of imatinib therapy in patients with advanced gastrointestinal stromal tumors. We aimed to clarify the long-term outcomes of imatinib therapy in Japanese patients with advanced gastrointestinal stromal tumors. METHODS: A prospective, observational study of imatinib therapy for unresectable and metastatic gastrointestinal stromal tumors was conducted in our institution. Imatinib was initiated at a dose of 400 mg daily and continued until disease progression. Safety, efficacy and long-term tolerability and survival were evaluated in an intent-to-treat population. The median follow-up period in this study was 68 months. RESULTS: Seventy patients were enrolled between December 2001 and December 2009. Treatment-related Grade 3/4 adverse events occurred in 49 patients (70.0%). Although 14 patients required adverse effect management with hospitalization, only 5 patients (7.1%) withdrew from the treatment owing to imatinib intolerance. The tumor response and clinical benefit rates were 61.4 and 85.7%, respectively. Thirty-seven patients (52.9%) maintained the treatment at 400 mg daily imatinib, whereas 33 patients (47.1%) had their dose reduced to 300 mg daily or less. The overall survival rate at 5 years was 60.9% and the median survival time was 70 months. The median progression-free survival time of all the 70 enrolled patients was 30 months. Seven patients (10.0%) suffered from second malignancies, including three patients with genitourinary carcinomas. CONCLUSIONS: Despite the need for dose reduction, the long-term results of imatinib therapy for advanced gastrointestinal stromal tumors were good in Japanese patients. Physicians should pay attention to the occurrence of second malignancies during imatinib therapy for gastrointestinal stromal tumor patients.

Risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with three-field lymph node dissection.

BACKGROUND: Extended radical esophagectomy with three-field lymph node dissection (3-FLD) has offered significant survival benefit, but some patients still suffer from early recurrence and die within 1 year after surgery. The purpose of this study was to identify the risk factors that influence early death due to cancer recurrence after extended radical esophagectomy with 3-FLD. METHODS: A consecutive series of 276 patients who underwent extended radical esophagectomy with 3-FLD was retrospectively reviewed. Excluding patients who underwent incomplete resection or died of other diseases within 1 year, we compared the clinicopathological characteristics between 203 patients who survived more than 1 year (1-year survival group) and 27 who died of cancer recurrence within 1 year (early-death group) by univariate and multivariate analysis. RESULTS: Sixty-six patients (32.5%) had recurrent disease in the 1-year survival group. Hematogenous recurrences were more frequent in the early-death group than in the 1-year survival group (41% vs. 26%, respectively, p = 0.0481). There was a significant difference in nodal status, number of metastatic nodes, pathological stage, vessel invasion, and intramural metastasis, and there was borderline significance in the difference of depth of invasion and histological type between the two groups by univariate analysis. Multivariate analysis demonstrated that intramural metastasis was an independent risk factor. CONCLUSIONS: Patients with intramural metastasis have a significant risk of early death even after extended radical esophagectomy with 3-FLD; however, it remains unknown whether surgical intervention can play a significant role for these patients.

Community-acquired pneumonia during long-term follow-up of patients after radical esophagectomy for esophageal cancer: analysis of incidence and associated risk factors.

BACKGROUND: There are no data concerning the occurrence of community-acquired pneumonia (CAP) in esophageal cancer patients during long-term follow-up after radical esophagectomy. The aims of the present study were to determine the incidence of CAP in esophageal cancer patients who underwent radical esophagectomy and to identify the risk factors. METHODS: A total of 186 consecutive patients who underwent radical esophagectomy for thoracic esophageal carcinoma in our hospital between 1991 and 2000 were enrolled in this study. Data on the occurrence of CAP were retrospectively collected from medical records, follow-up files, and telephone interviews with patients. The cumulative incidence of CAP was calculated by the Kaplan-Meier method, and the risk factors for CAP were determined by univariate and multivariate analyses. The median follow-up time was 77 months (range 12-216 months). RESULTS: Sixty patients suffered from CAP during the follow-up period. The cumulative incidence was 25.8% at 5 years and 38.4% at 10 years. Multivariate analysis revealed the following as the significant risk factors for CAP: presence of lymph node metastasis (Hazard ratio [HR], 2.64; 95% confidence interval [CI], 1.55-4.50; P < 0.001), colonic interposition (HR, 2.87; 95% CI, 1.41-5.82; P = 0.004), obstructive lung disease (HR, 1.95; 95% CI, 1.11-3.42; P = 0.021), and preoperative hypoalbuminemia (HR, 2.08; 95% CI, 1.20-3.60; P = 0.009). CONCLUSIONS: There is a high incidence of CAP in esophageal cancer patients after esophagectomy. Positive nodal metastasis, colonic interposition, obstructive lung disease, and preoperative hypoalbuminemia are risk factors for this long-term postoperative morbidity.

Phase II study of weekly paclitaxel following fixed three cycles of S-1-based chemotherapy for advanced gastric cancer.

BACKGROUND/AIMS: Awareness of the clinical importance of second-line chemotherapy for incurable gastric cancer has been increasing. To assess the clinical validity of the new concept that second-line chemotherapy following predetermined cycles of first-line chemotherapy would improve survival, we conducted a phase II study. METHODOLOGY: Patients with pathologically proven incurable gastric adenocarcinoma and adequate organ functions were enrolled. S-1 or S-1 plus cisplatin was administered as first-line chemotherapy. The number of cycles of S-1-based chemotherapy was determined to be three as a maximum unless there was disease progression. The treatment was followed by weekly administration of paclitaxel. The primary endpoint was overall survival and the secondary endpoints were progression-free survival and safety. RESULTS: Thirty-seven patients were eligible for enrollment. Twenty-eight patients (76%) underwent the second-line chemotherapy with paclitaxel after completion of S-1-based chemotherapy or disease progression. Treatment-related grade 3 or 4 toxicity was noted in 14 patients during S-1-based chemotherapy, and in 6 patients during paclitaxel treatment. The median survival time was 455 days and the median progression-free survival was 229 days. CONCLUSIONS: Sequential set chemotherapy with three cycles of S-1-based chemotherapy followed by weekly paclitaxel is feasible. The survival results are equivalent to those of other current regimens using S-1.

[An update on surgical treatment for gastrointestinal stromal tumor].

Complete surgical resection is the treatment of choice for primary gastrointestinal stromal tumor (GIST), even with current advances in molecular targeting therapy with imatinib and sunitinib. In recent years, function-preserving and minimally invasive surgeries have also been performed as treatment strategies for submucosal tumors, including GISTs that are clinically diagnosed as low-risk. It is crucial, however, not to compromise radicality when indicating these procedures. On the other hand, a multidisciplinary treatment, including surgical resection, is necessary even for the treatment of advanced or metastatic/ recurrent GISTs in which the treatment of choice is imatinib therapy. Furthermore, surgical treatment is expected to be effective for resectable liver metastases, secondary resistance to imatinib, or residual tumors responding to imatinib. In this regard, surgical resection as a multidisciplinary treatment is considered to have gained recognition as an important option. However, sufficient evidence is lacking, and thus, the results of ongoing clinical trials are highly anticipated. For the surgical treatment of GIST, it is important to select patients carefully based on objective data to obtain maximum therapeutic effects.

[Sunitinib as a second-line therapy for imatinib-resistant gastrointestinal stromal tumors].

Gastrointestinal stromal tumor(GIST)is one ofthe representative diseases for which molecularly targeted therapy is very effective. Imatinib mesylate, a tyrosine kinase inhibitor of KIT and platelet-derived growth factor receptor(PDGFR), has dramatically improved the prognosis ofpatients with advanced, recurrent, and/or metastatic GISTs. Although the rate of response to imatinib therapy is high, the emergence ofimatinib -resistant tumors and the second-line therapy following imatinib therapy have become new clinical problems. Sunitinib malate, a multi-targeted tyrosine kinase inhibitor that shows activity against KIT and other receptor tyrosine kinases, including PDGFR and vascular endothelial growth factor receptor, is the only treatment for imatinib-resistant GISTs that is covered by national health insurance in Japan as ofthis writing. Several clinical trials that evaluated sunitinib as potential second-line therapy in Western countries and Japan found a clinical benefit rate of2 4 to 39% and a median time to progression of7 months. However, it is necessary to adequately manage the adverse events of sunitinib therapy in order to receive the full benefits of the therapy, because various severe adverse events, particularly thrombocytopenia and hand-foot syndrome in Japanese GIST patients, frequently lead to poor tolerability. Further investigation is required to find an appropriate regimen for Japanese GIST patients.