Kimio Isshi

Predicting 5-FU sensitivity using human colorectal cancer specimens: comparison of tumor dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase activities with in vitro chemosensitivity to 5-FU

Abstract.Background: In tumor cells, the enzyme orotate phosphoribosyl transferase (OPRT) contributes to 5-fluorouracil (5-FU) phosphorylation and another enzyme, dihydropyrimidine dehydrogenase (DPD), is associated with 5-FU catabolic action. We measured OPRT and DPD activities and, to determine whether their levels might serve as indicators of 5-FU sensitivity, simultaneously assayed in vitro chemosensitivity to 5-FU. Methods: Tissue specimens were obtained from colorectal cancer patients and in vitro chemosensitivity was tested using fluorescein diacetate assay (FDA) or histoculture drug response assay (HDRA). DPD and OPRT activities were measured by radioassay. Results: The chemosensitivity assay was performed on 62 colorectal cancer specimens. Results were evaluable in 29 of 30 cases (96.7%) for FDA and 30 of 32 cases (98.3%) for HDRA. The positive sensitivity rate was 37.9% by FDA assay and 30% by HDRA assay. In positive specimens, the mean DPD activity was 44.9 ± 32.6 pmol/min per mg protein, and in negative specimens, it was 53.8 ± 33.7 pmol/min per mg protein (P = 0.875). In contrast, the mean OPRT value was significantly higher in positive specimens (0.418 ± 0.180 nmol/min per mg protein) than in negative specimens (0.325 ± 0.153 nmol/min per mg protein; P < 0.05). The chemosensitivity test proved positive in 60% of the specimens with ORPT activity of 0.413 or above and 50% of those with DPD activity of 30 or below. Of the patient specimens showing OPRT activity of 0.413 or above and DPD activity of 30 or below, 88.9% were positive for 5-FU sensitivity, suggesting the possibility that the combination of these two levels may be predictive of 5-FU positive sensitivity. Conclusion: DPD and OPRT activities within cancer cells may predict positive sensitivity to 5-FU.

Competency assessment for gastric endoscopic submucosal dissection using an endoscopic part-task training box

BackgroundObjective assessment of endoscopist competency is important. Recently, the endoscopic part-task training box (Thompson Endoscopic Skills Trainer [TEST]) was developed to assess endoscopist competency. We aimed to evaluate the ability of the TEST to assess competency during endoscopic procedures, especially endoscopic submucosal dissection (ESD).MethodsTwenty-three physicians were included in this study. Correlations between TEST scores and the following factors were evaluated: years of endoscopic experience, number of esophagogastroduodenoscopies (EGDs) performed, number of colonoscopies (CSs) performed, cecal intubation rate, number of gastric ESDs performed, gastric ESD procedure time/lesion size (min/mm2), and gastric ESD self-completion rate. Also, correlation coefficients between the number of gastric ESDs performed and each of gastric ESD procedure time/lesion size and gastric ESD self-completion rate were calculated.ResultsTEST scores showed strong correlations to different factors: years of experience in endoscopy: 0.957 (p < 0.01); number of EGDs: 0.947 (p < 0.01); number of CSs: 0.947, (p < 0.01); number of gastric ESDs: 0.924 (p < 0.01); gastric ESD procedure time/lesion size: − 0.9 (p < 0.01); self-completion rate of gastric ESDs: 0.857 (p < 0.005). The number of gastric ESDs performed was not more strongly correlated to procedure time of gastric ESDs or self-completion rate of gastric ESDs compared to TEST scores (− 0.824 (p < 0.01) and 0.704 (p < 0.05), respectively). TEST scores of endoscopists with a cecal intubation rate ≥ 90% were > 380, while the scores of physicians with a gastric ESD self-completion rate ≥ 90% were > 700.ConclusionsTEST score correlates with both basic and advanced endoscopic procedures. TEST is therefore a promising option for assessing endoscopist competency, and might be useful for providing threshold scores as competency markers for specific endoscopic procedures such as gastric ESD.

Foveolar gastric metaplasia presenting as a duodenal tumor with an atypical appearance: a case report

BackgroundFoveolar gastric metaplasia of the duodenum is a frequent but not as yet considered correlate of endoscopically detected duodenal polyps. The majority of foveolar gastric metaplasias associated with polyps presented a typical benign endoscopic appearance and they were diagnosed by biopsy. Here we report a case of a surgical-resected foveolar gastric metaplasia manifesting as a duodenal tumor with an atypical appearance.Case presentationAn asymptomatic 56-year-old Asian man who presented with a foveolar gastric metaplasia of atypical appearance and had previously undergone esophagogastroduodenoscopy was referred to our hospital. A biopsy revealed a normal duodenum with an inflamed mucosa. Narrow band imaging with magnifying endoscopy revealed normal microvessels with normal micromucosa, which indicated non-neoplasia. Endoscopic ultrasonography using a miniature probe system (20 MHz) revealed a hypoechoic mass with multiple anechoic lesions (16-mm diameter) located in the mucosal layer. The lesion was excised via laparotomy assisted by endoscopic techniques similar to endoscopic submucosal dissection. The pathology indicated foveolar gastric metaplasia.ConclusionsFoveolar gastric metaplasia can present as a duodenal tumor. We identified two important clinical issues. First, foveolar gastric metaplasia can present as a duodenal tumor with an atypical benign appearance. Second, both endoscopic ultrasonography and narrow band imaging are useful techniques to increase the diagnostic rate of this condition.