Effect of herbal medicine daikenchuto on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: A prospective randomized study

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated

Optimization of prediction methods for risk assessment of pathogenic germline variants in the Japanese population

Predicting pathogenic germline variants (PGVs) in breast cancer patients is important for selecting optimal therapeutics and implementing risk reduction strategies. However, PGV risk factors and the performance of prediction methods in the Japanese population remain unclear. We investigated clinicopathological risk factors using the Tyrer-Cuzick (TC) breast cancer risk evaluation tool to predict BRCA PGVs in unselected Japanese breast cancer patients (n = 1, 995). Eleven breast cancer susceptibility genes were analyzed using target-capture sequencing in a previous study; the PGV prevalence in BRCA1, BRCA2, and PALB2 was 0.75%, 3.1%, and 0.45%, respectively. Significant associations were found between the presence of BRCA PGVs and early disease onset, number of familial cancer cases (up to third-degree relatives), triple-negative breast cancer patients under the age of 60, and ovarian cancer history (all P < .0001). In total, 816 patients (40.9%) satisfied the National Comprehensive Cancer Network (NCCN) guidelines for recommending multigene testing. The sensitivity and specificity of the NCCN criteria for discriminating PGV carriers from noncarriers were 71.3% and 60.7%, respectively. The TC model showed good discrimination for predicting BRCA PGVs (area under the curve, 0.75; 95% confidence interval, 0.69-0.81). Furthermore, use of the TC model with an optimized cutoff of TC score ≥0.16% in addition to the NCCN guidelines improved the predictive efficiency for high-risk groups (sensitivity, 77.2%; specificity, 54.8%; about 11 genes). Given the influence of ethnic differences on prediction, we consider that further studies are warranted to elucidate the role of environmental and genetic factors for realizing precise prediction

大腸癌細胞のSMAD4欠損がCCL15-CCR1 ケモカイン・シグナルを介して骨髄由来免疫抑制細胞(MDSCs)を集簇させ癌浸潤を促進する

京都大学0048新制・課程博士博士(医学)甲第19560号医博第4067号新制||医||1013(附属図書館)32596京都大学大学院医学研究科医学専攻(主査)教授 川口 義弥, 教授 小川 修, 教授 長澤 丘司学位規則第4条第1項該当Doctor of Medical ScienceKyoto UniversityDFA

血清および内溶液中のCA19-9高値を来たした巨大水腎症の1例

68歳男性.患者は全身倦怠感と食欲低下および1年前から徐々に腹部冒満感を来たすようになり, 著者らの泌尿器科へ入院となった.腹部CTの所見では右腎の位置に一致して巨大な内部均一, low densityな腫瘤を認めた.直ちに経皮的腎瘻増設術を施行し6500ml以上の血性内溶液を得た.内容液の細胞診の結果はclass IIIであり, CA19-9値は内容液のみならず血清中においても著明に増加していた.その後, 右腎摘除術を施行した.摘除標本では右腎は著明なUPJ stenosisを呈していた.病理組織学的検査の結果では悪性所見は認めず線維化を主体としたものであったWe report a case of right giant hydronephrosis. A 68-year-old man was admitted to our hospital with chief complaints of general fatigue, loss of appetite and a one-year history of progressive fullness on whole abdomen. Abdominal computed tomography scan exhibited a huge, homogeneous, low density mass originating from the right kidney. We performed right percutaneous nephrostomy and drained over 6, 500 ml bloody fluid. Cytological examination of the drained fluid revealed atypical nuclear appearance defined as class III. Increased values of carbohydrate antigen 19-9 were observed both in the fluid as well as in the serum. We performed right nephrectomy. Macroscopic appearance of the resected kidney showed marked stenosis at the portion of ureteropelvic junction. Histological analysis of the stenotic portion demonstrated marked fibrosis without findings of malignancy

Robot-assisted low anterior resection after aluminum potassium sulfate and tannic acid sclerosing therapy for internal hemorrhoids

Background: Internal hemorrhoids are the most common anal diseases. Aluminum potassium sulfate and tannic acid (ALTA) injection is a new sclerosing therapy for the treatment of internal hemorrhoids. Although ALTA injection has been widely used, there are no previous reports of rectal cancer patients who underwent robot-assisted low anterior resection (Rob-LAR) after ALTA injection to treat internal hemorrhoids. Case presentation: A 70-year-old man with rectal cancer was presented to our hospital. He had an ALTA injection 2 months before presentation at a clinic due to hematochezia with internal hemorrhoids. The rectal tumor was located 7 cm above the anal verge, and Rob-LAR with the da Vinci Xi system was performed. The patient had sclerosis on the stump of the anal side, which made it difficult to transect the rectum with linear staplers. This required multiple repeats of compression through the SmartClamp feedback. After anastomosis with the double-stapling technique, we constructed a diverting ileostomy. Conclusion: Although ALTA injection is a promising strategy for internal hemorrhoids, rectal cancer should be excluded before the sclerosing therapy

Structural basis for recognition of H3K4 methylation status by the DNA methyltransferase 3A ATRX–DNMT3–DNMT3L domain

DNMT3 proteins are de novo DNA methyltransferases that are responsible for the establishment of DNA methylation patterns in mammalian genomes. Here, we have determined the crystal structures of the ATRX–DNMT3–DNMT3L (ADD) domain of DNMT3A in an unliganded form and in a complex with the amino-terminal tail of histone H3. Combined with the results of biochemical analysis, the complex structure indicates that DNMT3A recognizes the unmethylated state of lysine 4 in histone H3. This finding indicates that the recruitment of DNMT3A onto chromatin, and thereby de novo DNA methylation, is mediated by recognition of the histone modification state by its ADD domain. Furthermore, our biochemical and nuclear magnetic resonance data show mutually exclusive binding of the ADD domain of DNMT3A and the chromodomain of heterochromatin protein 1α to the H3 tail. These results indicate that de novo DNA methylation by DNMT3A requires the alteration of chromatin structure

Identification of complications requiring interventions after gastrointestinal cancer surgery from real‐world data: An external validation study

Abstract Background Recently, real‐world data have been recognized to have a significant role for research and quality improvement worldwide. The decision on the existence or nonexistence of postoperative complications is complex in clinical practice. This multicenter validation study aimed to evaluate the accuracy of identification of patients who underwent gastrointestinal (GI) cancer surgery and extraction of postoperative complications from Japanese administrative claims data. Methods We compared data extracted from both the Diagnosis Procedure Combination (DPC) and chart review of patients who underwent GI cancer surgery from April 2016 to March 2019. Using data of 658 patients at Kyoto University Hospital, we developed algorithms for the extraction of patients and postoperative complications requiring interventions, which included an invasive procedure, reoperation, mechanical ventilation, hemodialysis, intensive care unit management, and in‐hospital mortality. The accuracy of the algorithms was externally validated using the data of 1708 patients at two other hospitals. Results In the overall validation set, 1694 of 1708 eligible patients were correctly extracted by DPC (sensitivity 0.992 and positive predictive value 0.992). All postoperative complications requiring interventions had a sensitivity of >0.798 and a specificity of almost 1.000. The overall sensitivity and specificity of Clavien–Dindo ≥grade IIIb complications was 1.000 and 0.995, respectively. Conclusion Patients undergoing GI cancer surgery and postoperative complications requiring interventions can be accurately identified using the real‐world data. This multicenter external validation study may contribute to future research on hospital quality improvement or to a large‐scale comparison study among nationwide hospitals using real‐world data

The Role of Chemokines in Promoting Colorectal Cancer Invasion/Metastasis

Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Although most of the primary CRC can be removed by surgical resection, advanced tumors sometimes show recurrences in distant organs such as the liver, lung, lymph node, bone or peritoneum even after complete resection of the primary tumors. In these advanced and metastatic CRC, it is the tumor-stroma interaction in the tumor microenvironment that often promotes cancer invasion and/or metastasis through chemokine signaling. The tumor microenvironment contains numerous host cells that may suppress or promote cancer aggressiveness. Several types of host-derived myeloid cells reside in the tumor microenvironment, and the recruitment of them is under the control of chemokine signaling. In this review, we focus on the functions of chemokine signaling that may affect tumor immunity by recruiting several types of bone marrow-derived cells (BMDC) to the tumor microenvironment of CRC