Impact of preoperative tumor rupture timing on gastrointestinal stromal tumor prognosis: a retrospective multicentric cohort study.

BACKGROUND: A gastrointestinal stromal tumor rupture entails a high risk of recurrence even after curative surgery. However, the definition of rupture is unclear, and the question of whether patients with a minor rupture should be treated with adjuvant imatinib remains controversial. METHODS: The present, retrospective, multicentric study enrolled 57 patients with gastrointestinal stromal tumor with a minor/major tumor rupture, of whom 46 were finally found to be eligible for analysis. Tumor ruptures were subclassified by their degree, timing and cause. Multivariate analysis was performed to identify the risk factors of all types of recurrence as well as of peritoneal recurrence only. RESULTS: The study cohort included minor (n = 24), intraoperative (n = 19) and iatrogenic (n = 20) ruptures besides the typical types (major, preoperative and spontaneous). All intraoperative ruptures were iatrogenic. In total, 27 patients (58.7%) had a recurrence in the peritoneum (n = 17) and/or the liver (n = 13) during a median follow-up period of 5.8 years, but no recurrence was observed in patients with tumor rupture as a single, high-risk factor. Multivariate analysis found the timing of tumor rupture to be an independent risk factor of poor recurrence-free survival (hazard ratio: 2.37; 95% confidence interval: 1.02-5.49; P = 0.045). CONCLUSIONS: Preoperative tumor rupture in patients with a ruptured gastrointestinal stromal tumor was associated with poor recurrence-free survival. Our results suggested that a distinction should be made between preoperative and intraoperative tumor ruptures when considering the indications for adjuvant imatinib therapy for gastrointestinal stromal tumor patients with tumor rupture as a single, high-risk factor of recurrence.

Clinicopathological Features and Prognosis of Primary GISTs with Tumor Rupture in the Real World.

BACKGROUND: Patients with ruptured gastrointestinal stromal tumor (GIST) are recommended for imatinib adjuvant therapy; however, their clinicopathological features and prognosis in the era of imatinib are unknown. PATIENTS AND METHODS: The study cohort included 665 patients with histologically proven primary GISTs who underwent R0 or R1 surgery between 2003 and 2007; the validation cohort included 182 patients between 2000 and 2014. The definitions of tumor rupture in the study included perforation at tumor site, tumor fracture, piecemeal resection including open biopsy, and macroscopic injuries to the pseudocapsule. RESULTS: Tumor rupture occurred in 21 (3.2%) of 665 and 5 (2.9%) of 182 patients in the study and validation cohort, respectively. Ruptured GISTs were more symptomatic, were larger in size, and had higher mitotic count than nonruptured GISTs but were not associated with tumor location or laparoscopic surgery. GISTs with intraoperative rupture had clinicopathological features and prognostic outcomes similar to those with preoperative rupture. Recurrence rates were higher and median recurrence-free survival (RFS) and overall survival (OS) were shorter with ruptured than nonruptured GIST. Tumor rupture was one of the independent prognostic factors for RFS, but not OS, according to multivariate analysis. CONCLUSIONS: Ruptured GISTs were symptomatic larger tumors with high mitotic activity, frequent relapse, and shorter RFS. Tumor rupture was an independent prognostic factor for RFS, but not for OS, in the era of imatinib.

[A case of small intestinal stage IV gastrointestinal stromal tumor in which long-term disease control was maintained for more than 10 Years through a multidisciplinary team approach].

The prognosis of metastatic or recurrent gastrointestinal stromal tumors (GISTs) accompanied by multiple hepatic metastases and peritoneal dissemination is very poor. We encountered a case of stage IV small intestinal GIST with multiple hepatic metastases and peritoneal dissemination that were observed after resection of the primary lesion. Multidisciplinary treatments were performed over time, including hepatic resection, radiotherapy, imatinib therapy, sunitinib therapy, and transcatheter arterial chemoembolization, and the disease had been brought under control following resection of a primary lesion 14 years ago. The patient was a 49-year-old woman diagnosed with hemorrhagic stool in July 1998, when a computed tomography scan revealed an 8-cm-diameter tumor in her small bowel. Partial resection of her small bowel was performed and the pathological diagnosis was a high-risk GIST showing 15 mitoses per 50 high power fields. Several metastases developed in the S4 and S5 segments of the patient's liver 3 years after resection of the primary lesion, and a central two-segmental resection of the liver was performed. Furthermore, 1 year after this procedure, peritoneal dissemination developed near the pancreas, for which radiotherapy was performed. Four months later, the patient again developed multiple liver metastases and was started on treatment with 400 mg imatinib per day, achieving a partial response(PR). Five years and 6 months after imatinib initiation, resistance emerged in one of the liver metastases. The patient was switched to sunitinib(50 mg per day), but was diagnosed with progressive disease at the end of the second course and the procedure was discontinued. Treatment with 400 mg of imatinib per day was resumed, and transcatheter arterial chemoembolization was performed twice over a 17-month period for the resistant hepatic region and a PR was achieved each time. We were able to maintain a PR in this patient; other metastases indicated the effectiveness of imatinib therapy. Therefore, a multidisciplinary team approach can be effective in achieving long-term disease control in patients with metastatic or recurrent GIST.

Early effects of lafutidine or rabeprazole on intragastric acidity: which drug is more suitable for on-demand use?

BACKGROUND: Medication for the relief of heartburn should have the rapid onset of action required for on-demand use. We studied the inhibition of gastric acid secretion by lafutidine and rabeprazole, given in single doses to fasting and postprandial subjects. METHODS: A total of 22 healthy male, Helicobacter pylori-negative volunteers participated in this randomized, two-way crossover study. They were randomly assigned to receive a single oral dose of 10 mg lafutidine or 20 mg rabeprazole after fasting overnight (12 subjects, fasting study) or after eating a test meal (noodles, 364 kcal; protein, 10.1 g; fat, 16 g; carbohydrates, 44.9 g; NaCl, 1.1 g; 10 subjects, postprandial study). Intragastric pH was monitored continuously for 6 h after treatment. The other drug was given after a washout period of at least 7 days, and intragastric pH was similarly monitored. RESULTS: In the fasting study, lafutidine sustained pH at >3 and >4 during the second, third, fourth, fifth, and sixth hours of the study for significantly longer than rabeprazole. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. In the postprandial study, lafutidine sustained pH >3 and >4 for longer periods than rabeprazole during the third, fourth, fifth, and sixth hours of the study. During the first 6 h after treatment, lafutidine sustained pH at more than 2, 3, 3.5, 4, 5, 6, and 7 longer than rabeprazole. CONCLUSIONS: Lafutidine 10 mg produces a prompter rise in intragastric pH than rabeprazole 20 mg in fasting and postprandial Helicobacter pylori-negative male subjects.

The comparative effects of single intravenous doses of omeprazole and famotidine on intragastric pH.

BACKGROUND: The ideal medication for the treatment of acid-related diseases, for example, hemorrhagic ulcers and stress-related gastric bleeding, should have a rapid onset of action to promote hemostasis and alleviate symptoms. The aim of our study was to investigate the inhibitory effects on gastric acid secretion after single intravenous administrations of omeprazole 20mg and famotidine 20 mg. METHODS: Ten healthy Helicobacter pylori-negative male subjects participated in this randomized, double-masked, two-way crossover study. Intragastric pH was monitored continuously for 4 h after a single intravenous administration of omeprazole 20 mg and after a single intravenous administration of famotidine 20 mg. The administration of the two agents was separated by a 7-day washout period. RESULTS: In all ten subjects, the length of time that intragastric pH remained over 3, during the 0- to 3- and 0- to 4-h study periods, was greater after famotidine treatment than after treatment with omeprazole, and famotidine increased the average pH during the 0 to 3- and 0 to 4-h study periods significantly more than omeprazole did. During the 4-h study period, famotidine provided a longer duration of pH of more than 2, 3, 3.5, 4, 5, 6, and 7, compared to omeprazole. CONCLUSIONS: In Helicobacter pylori-negative healthy male subjects, an intravenous dose of 20 mg famotidine increased intragastric pH more rapidly than intravenous omeprazole 20 mg.

Comparison of the effect on intragastric pH of a single dose of omeprazole or rabeprazole: which is suitable for on-demand therapy?

BACKGROUND AND AIMS: An ideal medication for heartburn should have the rapid onset of action needed for on-demand treatment. However, assessment of the onset of action of proton pump inhibitors has been largely subjective. We compared the inhibitory effect on gastric acid secretion of a single oral dose of omeprazole with that of rabeprazole. METHODS: Fourteen Helicobacter pylori-negative men participated in this randomized, double-masked, two-way cross-over study. Intragastric pH was monitored continuously for 6 h after a single, randomly assigned 20 mg oral dose of either omeprazole or rabeprazole. After a 7-day washout period, the other drug was administered. Each patient's S-mephenytoin 4'-hydroxylase (CYP2C19) genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: Intragastric pH and pH holding time did not differ between treatments when the data were analyzed for the whole group without stratifying for CYP2C19 status. In CYP2C19 homozygous and heterozygous extensive metabolizers (10 subjects), rabeprazole maintained the intragastric at pH > 3 and> 4 for longer than omeprazole during both the 5 and 6 h study periods, and the average pH during the 6 h study period was higher with rabeprazole than with omeprazole. In these extensive metabolizers, rabeprazole maintained the pH > 2,> 3,> 3.5 and> 4 for longer during the 6 h study period than did omeprazole. CONCLUSIONS: In H. pylori-negative men who are CYP2C19 homozygous or heterozygous extensive metabolizers, the intragastric pH after a single dose of 20 mg rabeprazole is higher during first 5-6 h than that after a single dose of 20 mg omeprazole.