<b><i>Objective:</i></b> Imatinib is a standard treatment for metastatic gastrointestinal stromal tumor (GIST). Imatinib resistance is mostly caused by secondary mutations in <i>C-KIT</i>. The antitumor effect of second-line agents is correlated with the type of secondary mutation: indeed, sunitinib is effective against tumors with <i>C-KIT </i>exon 13 or 14 mutations. We investigated whether secondary <i>C-KIT </i>mutations can be detected in circulating tumor DNA (ctDNA) from peripheral blood. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> Imatinib-resistant lesions had single-nucleotide substitutions in <i>C-KIT </i>exon 13 in 3 patients and exon 18 in 1 patient. Identical secondary <i>C-KIT</i> 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 <i>C-KIT</i> exon 13 mutation, and the fraction of ctDNA decreased after initiation of sunitinib. <b><i>Conclusion:</i></b> Detection of secondary <i>C-KIT</i> mutations in ctDNA could be useful for the selection of targeted agents and prediction of antitumor effects.
Case 1: A 67-year-old male had a type 1 tumor in the stomach with a lymph node metastasis 50 mm in size. He was diagnosed with cT4aN(+)M0, cStage Ⅲ and received preoperative docetaxel plus oxaliplatin plus S-1(DOS)therapy. After 3 courses of the regimen, the patient underwent laparoscopic total gastrectomy. The final stage was ypT3N1(1/38) M0, ypStage ⅡB, R0, and the pathological response was Grade 2b. Case 2: A 64-year-old male had a type 3 tumor in the abdominal esophagus and a lymph node metastasis 15 mm in size. He was diagnosed with cT3N(+)M0, cStage Ⅲ and received preoperative DOS therapy. After 3 courses, he underwent laparoscopic esophagectomy. The final stage was ypT0N0M0, ypStage 0, R0, and the pathological response was Grade 3. DOS therapy may be effective as a neoadjuvant chemotherapy.
Abstract Background The aim of this study was to assess the ability of radiologic factors such as mean computed tomography (mCT) value, consolidation/tumor ratio (C/T ratio), solid tumor size, and the maximum standardized uptake (SUVmax) value by F-18 fluorodeoxyglucose positron emission tomography to predict the presence of spread through air spaces (STAS) of lung adenocarcinoma. Methods A retrospective study was conducted on 118 patients those diagnosed with clinically without lymph node metastasis and having a pathological diagnosis of adenocarcinoma after undergoing surgery. Receiver operating characteristics (ROC) analysis was used to assess the ability to use mCT value, C/T ratio, tumor size, and SUVmax value to predict STAS. Univariate and multiple logistic regression analyses were performed to determine the independent variables for the prediction of STAS. Results Forty-one lesions (34.7%) were positive for STAS and 77 lesions were negative for STAS. The STAS positive group was strongly associated with a high mCT value, high C/T ratio, large solid tumor size, large tumor size and high SUVmax value. The mCT values were − 324.9 ± 19.3 HU for STAS negative group and − 173.0 ± 26.3 HU for STAS positive group ( p < 0.0001). The ROC area under the curve of the mCT value was the highest (0.738), followed by SUVmax value (0.720), C/T ratio (0.665), solid tumor size (0.649). Multiple logistic regression analyses using the preoperatively determined variables revealed that mCT value ( p = 0.015) was independent predictive factors of predicting STAS. The maximum sensitivity and specificity were obtained at a cutoff value of − 251.8 HU. Conclusions The evaluation of mCT value has a possibility to predict STAS and may potentially contribute to the selection of suitable treatment strategies.
Beetles of the family Passalidae (Coleoptera: Scarabaeoidea) are termed subsocial. The insects inhabit rotten wood as family groups consisting of the parents and their offspring. The Japanese species Cylindrocaulus patalis has the lowest fecundity among passalids because siblicide occurs among the first-instar larvae; accordingly, parental care toward the survived larva is the highest among Passalidae. To clarify the nutritional relationships between the parents and their offspring, we investigated their ability to digest three types of polysaccharides that are components of wood (cellulose and β-1,4-xylan) and fungal cell walls (β-1,3-glucan). Although carboxymethyl-cellulase activity was barely detectable, β-xylosidase, β-glucosidase, β-1,4-xylanase and β-1,3-glucanase activities were clearly detected in both adults and larvae. Because the activities of enzymes that digest β-1,3-glucan were much higher than those for degrading β-1,4-xylan, in both adults and larvae, it is concluded that they are mainly fungivorous. Furthermore, these digestive enzymatic activities in second- and third-instar larvae were much lower than they were in adults. Although all larval instars grew rapidly when fed chewed wood by their parents, larvae ceased growing and died when fed only artificially ground wood meals. We conclude that the larvae are assumed to be provided with chewed predigested wood in which β-1,3-glucan is degraded by parental enzymes.
The cover image is based on the Case Report Case report: Gastric cancer-associated membranous nephropathy that recurred after complete remission and formation of peritoneal dissemination by Nobuyuki Kajiwara et al., DOI: 10.1002/ccr3.2002.
The characteristics of patients with gastrointestinal stromal tumor(GIST)who need long-term surveillance after resection remain unclear. We investigated the characteristics of 14 patients with GIST who developed recurrence over 5 years after resection. The most common primary tumor site was the stomach, followed by the rectum and small intestine. We found that 58% of patients had low-risk tumors, and 29% of patients developed recurrence over 10 years after resection. The most common first recurrence site was local, followed by the liver and peritoneum. All 4 patients with rectal GIST underwent local resection and developed local recurrence. Late recurrence could be observed even in low-risk tumors. Particularly, patients with rectal GIST frequently developed local recurrence. Thus, postoperative surveillance should be considered depending on operative or pathological findings.
The efficacy of postoperative chemotherapy for patients with ypStageⅠgastric cancer has not been evaluated. We investigated the characteristics and prognosis of7 patients with ypStage Ⅰgastric cancer. cStages were ⅡA, ⅡB, ⅢB, and Ⅳin 1, 1, 1, and 4 patients, respectively. S-1 plus cisplatin and docetaxel plus cisplatin plus S-1 were administered in 5 and 2 patients, respectively, for 2-8 courses before gastrectomy. Microscopic curative resection was performed for all patients. ypStage was 0, ⅠA, and ⅠB in 1, 2, and 4 patients. All patients received postoperative chemotherapy with S-1 or docetaxel plus S-1(DS). The 5-year recurrence-free survival was 71% and the 5-year overall survival was 68%. Two patients developed recurrence. One patient developed recurrence 1 year and 1 month after gastrectomy in spite of S-1 treatment for 4 months. Another patient developed recurrence 11 months after gastrectomy after DS treatment for 4 months followed by S-1. The other 5 patients received S-1 for 1-5 years and have survived without recurrence. Although the prognosis ofypStage Ⅰgastric cancer was comparatively good, the regimen and courses ofpostoperative chemotherapy should be evaluated in a prospective study.
A 70-year-old man visited our hospital because of a body weight loss. Upper gastrointestinal fiberscope revealed a type 3 tumor and an enhanced MRI showed 30 or more liver metastases. He received docetaxel plus cisplatin plus S-1(DCS)therapy. Although main tumor had shrinked only partially, multiple liver metastases could not be detected. Thus, he was performed distal gastrectomy. After gastrectomy, he received S-1 plus oxaliplatin(SOX)therapy followed by S-1 therapy. Two years and 2 months after surgery, chemotherapy was finished because of no signs of tumor progression. He is alive without recurrence for 2 years and 11 months after gastrectomy.
