Noriko Wada

Detecting Secondary C-KIT Mutations in the Peripheral Blood of Patients with Imatinib-Resistant Gastrointestinal Stromal Tumor

Objective: Imatinib is a standard treatment for metastatic gastrointestinal stromal tumor (GIST). Imatinib resistance is mostly caused by secondary mutations in C-KIT. The antitumor effect of second-line agents is correlated with the type of secondary mutation: indeed, sunitinib is effective against tumors with C-KIT exon 13 or 14 mutations. We investigated whether secondary C-KIT mutations can be detected in circulating tumor DNA (ctDNA) from peripheral blood. Methods: This study included 4 patients who underwent resection of imatinib-resistant GIST. Tumor-specific mutations in each tumor were determined by Sanger sequencing. ctDNA was extracted from peripheral blood obtained before and after the treatment of imatinib-resistant lesions. Each of the secondary target mutations in ctDNA was investigated, using a next-generation sequencer. Results: Imatinib-resistant lesions had single-nucleotide substitutions in C-KIT exon 13 in 3 patients and exon 18 in 1 patient. Identical secondary C-KIT mutations could be detected in ctDNA with a mutant fraction range of 0.010-9.385%. One patient had growth of an imatinib-resistant tumor containing a C-KIT exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. Conclusion: Detection of secondary C-KIT mutations in ctDNA could be useful for the selection of targeted agents and prediction of antitumor effects.

Subgroups of patients with very large gastrointestinal stromal tumors with distinct prognoses: A multicenter study

Any gastrointestinal stromal tumors (GISTs) larger than 10 cm are classified as “high risk” according to the modified National Institutes of Health consensus criteria. We conducted a multicenter study to identify a subgroup with moderate prognosis even within the “high‐risk” group.

Hereditary Gastric Cancer Syndromes

Hereditary gastric cancer syndromes are a rare but distinct cause of gastric cancers. The genetic mutations underlying most affected families are unknown. Mutations of CDH1 occur in some patients affected by hereditary diffuse gastric cancer, and is the only practical marker for guiding management. Carriers of CDH1 mutations are at risk for a highly penetrant, aggressive and early-onset diffuse-type gastric cancer, and these individuals are usually offered prophylactic total gastrectomy. Further research is required to identify other genetic mutations responsible for these syndromes to improve our understanding of the underlying disease mechanisms and optimize the clinical management of affected individuals.

Appropriate Follow-Up Strategies for Gastrointestinal Stromal Tumor Patients Based on the Analysis of Recurrent Interval and Patterns

Background/Aims: Previous studies have proposed risk classifications for patients with gastrointestinal stromal tumor (GIST) after resection and have contributed to the prediction of its prognosis. However, optimal postoperative surveillance has not yet been established. Methods: We retrospectively analyzed data from 115 GIST patients who experienced recurrence after complete resection. The relationships between clinicopathological characteristics and the first recurrence sites, or time to recurrence (TTR), were investigated. We also compared the characteristics between 2 subgroups based on a TTR of ≤5 or >5 years. Results: The first recurrence occurred in the abdomen in 114 of 115 patients (99.1%); one case of esophageal GIST recurred in the lung. Gastric and small intestinal GISTs recurred most frequently in the liver or peritoneum, while the most common recurrences of colorectal GISTs were found to be local. Fourteen patients (12.2%) experienced recurrence after >5 years. Smaller tumors and those categorized as lower risk were significantly more frequent in the TTR >5 years group than in the TTR ≤5 years group. In the TTR >5 years group, local recurrence was the most frequent type of recurrence (42.9%). Conclusion: Based on abdominal examination, postoperative surveillance after complete resection for primary GISTs may be recommended for >5 years.

The examination of appropriate surveillance after resection of GIST from 115 recurrent patients.

12 Background: Previous studies have proposed some risk classifications and contributed to the prediction of the prognosis in gastrointestinal stromal tumor (GIST) patients after resection. However, optimal postoperative surveillance has not been established yet. We investigated the characteristics of GIST patients who developed recurrence after resection to establish optimal postoperative surveillance for recurrence. Methods: Between July 1978 and November 2014, 115 patients developed recurrence after macroscopically complete resection for primary GIST. We investigated the clinicopathological factors, time to recurrence (TTR) and first recurrence sites to determine the optimal duration and methods of surveillance. We also compared the characteristics between the two subgroups with TTR ≤ 5 years or > 5 years. Results: The median age was 60 (15-84) years old and 62% of the patients were men. The most common primary tumor site was the stomach (39%), followed by the small intestine (37%), duodenum (11%), lar...

Laparoscopic Proximal Gastrectomy with Double Tract Anastomosis

Laparoscopic surgery for gastric cancer has increased remarkably, and laparoscopic proximal gastrectomy has also come to be useful as a less invasive surgery for early gastric cancer located in the upper stomach. As laparoscopic proximal gastrectomy is one of the modified surgical approaches, the curability and postoperative quality of life are the critical points of the method. Although there are mainly three reconstruction methods for proximal gastrectomy, the optimal method has not been established. Double tract anastomosis method has advantages as follows: the anastomosis can be performed even if the remnant stomach is small; part of food passes the duodenum; and the remnant stomach can be checked postoperatively using esophagogastroduodenoscopy. The important points of the surgical technique of laparoscopic proximal gastrectomy with double tract anastomosis are described in this section.