<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.
Studies have shown that neoadjuvant chemotherapy (NAC) followed by surgical resection improves the survival of patients with esophageal squamous cell carcinoma (ESCC), and that the neutrophil-to-lymphocyte ratio (NLR) nay be a prognostic biomarker in various types of cancer. Despite the noTable changes in the tumor and its microenvironment during NAC, it remains unclear how the NLR changes and which values (before or after NAC) best predict prognosis. The present study aimed to analyze changes in the NLR before and after NAC, and to determine which was a better prognostic factor. This study retrospectively analyzed 338 consecutive patients with ESCC who received NAC followed by curative resection. NLRs before (pre-NLR) and after (post-NLR) NAC were calculated, after which the impact of NAC on NLR, overall survival (OS) and recurrence-free survival (RFS), as well as the relationship between hematological toxicities and NLR, was evaluated. Cutoff values for pre- and post-NLR were 3.7 and 2.5, respectively. Patients with high post-NLR had a worse OS (P=0.0001) and 3-year RFS (P=0.03) than those with low post-NLR. Multivariate analysis identified high post-NLR, pN1 and clinical response as independent prognostic factors. In conclusion, post-NLR was revealed as a better prognostic factor than pre-NLR for patients receiving NAC followed by surgical resection.
Hepatobiliary and pancreatic: A hemodialysis patient with sonographic abnormalitiesThis 56-year-old man has been on hemodialysis for 16 years.At age 27, proteinuria was found, and a diagnosis of chronic glomerulonephritis was made when he was aged 30.He subsequently developed chronic renal failure and was placed on hemodialysis in 1984.In 1986, serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were found elevated to levels between 100 and 200 IU/L, and a diagnosis of chronic hepatitis C (HCV) was made.Serum ALT and AST returned to normal in 1 year and have remained normal thereafter.Although anti-HCV and anti-HBV core antibodies were positive, HCV-RNA was less than 1 K copies/mL.He occasionally had anginal pains since 1994, and a coronary angioplasty was carried out in 1996.Subsequently, he underwent aortic valve replacement and a coronary bypass operation.Plain abdominal film showed marked calcification of the aorta up to the femoral arteries, and an ultrasound examination of the neck demonstrated four enlarged parathyroid glands (the largest being 18.8 ¥ 14.1 ¥ 9.2 mm).Serum calcium was 9.3 mg/dL (normal range: 9.0-10.8mg/dL), phosphate 5.2 mg/dL (normal range: 2.9-4.7 mg/dL) and parathormone 110 ng/mL (normal range: < 0.8).Because of the history of liver disease, an abdominal ultrasound examination was carried out.It demonstrated a number of small hyperechoic dots and lines in the liver parenchyma (arrows in Fig. 1), some of which showed acoustic shadowing (S).
Crohn's disease (CD) is an inflammatory bowel disease. The risk of colorectal cancer (CRC) is increased in patients with CD. In Japan, anorectal cancer accounted for >60% of CRCs associated with CD. These anorectal cancers are typically diagnosed in advanced stages, because a surveillance protocol remains to be established. This study aimed to assess various biopsy methods for detecting CRC.This study included 72 patients (113 examinations) with CD who underwent cancer surveillance between August 2008 and October 2015. Surveillances were performed with a core needle biopsy in perianal regions (54 cases), endoscopic biopsy (90 cases), and excisional biopsy (34 cases). When it was difficult to perform colonoscopy in an outpatient setting, due to perianal pain or stricture, we employed examinations under anesthesia for surveillance.The total CRC detection rate was 6.19% (7 examinations). CRC detection rates were 1.85% (1 case) with core needle biopsy, 5.56% (5 cases) with endoscopic biopsy, and 5.88% (2 cases) with excisional biopsy.We showed that it was important to employ various biopsy methods in cancer surveillance to detect CRC among patients with CD.
<p>This figure shows the association between STAT3 activation and chemotherapy. There were no differences of p-STAT3 and Mcl-1 expression after irradiation.</p>
Abstract: Natural orifice translumenal endoscopic surgery (NOTES) is a new, minimally invasive technique in the field of gastroenterological surgery. Research on NOTES has rapidly progressed all over the world. A joint committee on NOTES organized by the Japan Society for Endoscopic Surgery (JSES) and the Japan Gastroenterological Endoscopy Society (JGES) established Japan NOTES to encourage the responsible development and safe adoption of NOTES into clinical practice. This paper provides an overview of the current activity in regard to NOTES in Japan.
Abstract Background Salvage Lymphadenectomy is regarded as the only curative surgery to residual or recurrence lymph nodes of esophageal cancer after definitive chemoradiotherapy (dCRT). However, salvage lymphadenectomy is not described in the Japanese esophageal cancer treatment guideline because of little evidences for the safety and efficacy. Methods From January 2011 to December 2015, we performed 14 salvage lymphadenectomies to residual or recurrence LN of esophageal squamous cell carcinoma(ESCC) in Osaka University. We assessed postoperative complications and long-term outcome. Results Average age was 64 year-olds (SD: 5.2). Male: Female = 11: 3. cStage I: II-IV = 7: 7. Surgery to cervical LN were 11 patients and abdominal LN were 3 patients. Surgery to residual LN (res-LN) were 9 patients and recurrence LN (rec-LN) were 5 patients. rec-LN patient's median time to recurrence after dCRT was 14.3 months (10.2–29.3). 4 patients were performed lymphadenectomy resecting with adjacent organs, 3 patients were bronchus (trachea? ) and 1 patient was right subclavian artery. 4 patients had postoperative complication, two were pneumonia, one was pulmonary thrombosis and one was lymphorrhea, but there was no serious case (Clavien-Dindo Grade II or less). We didn’t have hospital death. Six of 14 patients had recurrence and died after salvage lymphadenectomy. Recurrence sites were 2 mediastinal lymph nodes and liver, lung, loco-regional and peritoneal. But no patients had recurrence of main tumor. 5-year overall survival rate was 51.1%. Median survival time in 9 patients, surgery to res-LN, was 18.9 months (10.4–132 months) and 5 patients, surgery to rec-LN, was 4.9 months (1.4–26.6 months). Surgery to res-LN patients were longer than rec-LN patients in overall survival after salvage lymphadenectomy (P = 0.395). There was no difference due to the difference in recurrence site of the cancer in overall survival after salvage lymphadenectomy. Conclusion Our data show salvage lymphadenectomy safety and effectiveness after dCRT. Salvage lymphadenectomy may extend the prognosis of patients with esophageal cancer after dCRT. Thus, salvage lymphadenectomy may be one of the treatment options for the patients with residual or recurrent, especially the former, lymph node after definitive CRT, although it is necessary to evaluate in many cases. Disclosure All authors have declared no conflicts of interest.
