Prognostic factors after imatinib secondary resistance: survival analysis in patients with unresectable and metastatic gastrointestinal stromal tumors.

BACKGROUND: Patients undergoing imatinib therapy for gastrointestinal stromal tumors (GISTs) show drug resistance during treatment in the late stages. The aims of this study were to determine survival after the appearance of imatinib secondary resistance (ISR) and to identify the prognostic factors. METHODS: Eligible were patients with unresectable and metastatic GISTs who were diagnosed with ISR and/or underwent treatment for ISR in our institution between 2001 and 2012. A total of 48 patients were enrolled and overall survival was retrospectively analyzed. The Cox proportional hazards model was used to identify the independent prognostic factors. Median follow-up time was 58 months. RESULTS: As of the cutoff date, 41 of the 48 patients with ISR had died, of which 39 died of GISTs. The overall 1-, 3-, and 5-year survival rates of the 48 patients were 64.6, 32.8, and 20.4 %, respectively, and median survival time was 22 months. The favorable independent prognostic factors identified were long progression-free survival in first-line imatinib therapy (P = 0.04), small diameter of progressive disease (PD) (P = 0.02), and surgical resection of PD (P = 0.01). CONCLUSION: Surgical resection of PD in selected cases could improve prognosis in ISR patients undergoing GIST treatment.

[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.

[A case of advanced gastric cancer treated by TS-1 for 3 years and 7 months].

A 72-year-old man was diagnosed as gastric cancer with pyloric stenosis by an upper gastorintestinal endoscopy for anemia in July 2001. Computed tomography (CT) of the abdomen showed multiple liver metastases. Serum CEA was 6.2 ng/ml. At laparotomy to improve anemia and pyloric stenosis in September 2001, lymphnode metastases invaded the stomach and the pancreatic body. Gastro-jejunostomy was performed without gastrectomy. Oral administration of 100 mg of TS-1 for 28 consecutive days followed by a 14-day rest was given postoperatively. The response assessment of chemotherapy after 1 year was no change (NC) of the primary lesion on endoscopic examination, and liver metastases showed a partial response (PR) on CT. Serum CEA was raised to 86.1 ng/ml in April 2004. The treatment was changed to weekly paclitaxel. The patient died in July 2005. This case with unresectable gastric cancer had been treated by oral administration of TS-1 as an outpatient for 3 years and 7 months.

[Three cases of multiple colorectal liver metastases responding to hepatic arterial infusion chemotherapy undergoing liver resection].

We encountered three cases of multiple liver metastases of colorectal cancer treated with hepatic resection after hepatic arterial infusion. Case 1: A 55-year-old female underwent sigmoidectomy for sigmoid colon cancer and six liver metastases. After responding postoperatively to hepatic arterial infusion chemotherapy (HIA), she underwent resection of liver metastases. Case 2: A 66-year-old man underwent colectomy and hepatic resection for cecal colon cancer and liver metastasis. Multiple liver metastases appeared six months after the operation. HIA resulted in a complete response. Liver metastases recurred twice and liver resection was performed each time. Case 3: A 52-year-old female underwent partial resection of colon and liver for ascending colon cancer and multiple liver metastases. After she responded postoperatively to HIA and systemic chemotherapy, the patient underwent resection of liver metastases. Case 1 has lung metastases at this writing. The other two patients are alive and well, and have been free from recurrence as of 4 years after operation.

Diagnosis of ischemic small bowel disease by measurement of serum intestinal fatty acid-binding protein in patients with acute abdomen: a multicenter, observer-blinded validation study.

BACKGROUND: Intestinal fatty acid-binding protein (I-FABP) is a low-molecular-mass (15 kDa) cytosolic protein found exclusively in the epithelial cells of the small bowel mucosa. We aimed to evaluate the clinical usefulness of serum I-FABP measurement for the diagnosis of ischemic small bowel disease. METHODS: Patients with a clinical diagnosis of acute abdomen were recruited for this multicenter trial at one university hospital and nine city hospitals over a 13-month period. Serum I-FABP levels were measured in 361 eligible patients by an enzyme-linked immunosorbent assay using a specific monoclonal antibody. RESULTS: Of the 361 patients, 242 underwent surgery, and small bowel ischemia was diagnosed in 52 patients. The mean serum I-FABP level in the patients with small bowel ischemia was 40.7 ± 117.9 ng/ml, which was significantly higher than that in patients with non-ischemic small bowel disease (5.8 ± 15.6 ng/ml) and those with non-small bowel disease (1.8 ± 1.7 ng/ml). The serum I-FABP cutoff level for the diagnosis of small bowel ischemia was 3.1 ng/ml. Serum I-FABP was more efficient than conventional biochemical markers, in terms of sensitivity and positive and negative predictive values, in the diagnosis of small bowel ischemia. However, its specificity was slightly lower than that of creatinine phosphokinase or lactate dehydrogenase. The positive and negative likelihood ratios of serum I-FABP were 3.01 and 0.29, respectively. CONCLUSION: Serum I-FABP measurement is a non-invasive method that is potentially useful for the efficient identification of patients with acute abdomen who are at risk of small bowel ischemia.