Endoscopic Submucosal Dissection for Large Colorectal Tumor in a Japanese General Hospital

Background and Aims. Endoscopic submucosal dissection (ESD) is not widely used in large colorectal lesions because of technical difficulty and possible complications. We aimed to examine the efficacy and safety of ESD for large colorectal neoplasms. Patients and Methods. During the past 5 years, 608 cases of colorectal neoplasm (≧20 mm) were treated by ESD. They were divided into Group A (20–49 mm, 511 cases) and Group B (≧50 mm, 97 cases). Results. The average age, lesion size, and procedure time were 67.4 years, 30.0 mm, and 60.0 min in Group A, and they were 67.1 years, 64.2 mm, and 119.6 min in Group B. En bloc resection rates were 99.2% and 99.0% (), and complication rates were 4.1% and 9.9% (). Complications in Group A consisted of perforation (2.7%), bleeding (1.2%), and ischemic colitis (0.2%). Those in Group B were perforation (8.2%) and bleeding (1.0%). Two cases in Group A and none in Group B required emergency surgery for perforation. Conclusions. There was no difference in efficacy between Groups A and B. Complications were more frequent in Group B, but all perforations in Group B were successfully managed conservatively. ESD can be effective and safe for large colorectal tumors

Feasibility of Endoscopy-Assisted Laparoscopic Full-Thickness Resection for Superficial Duodenal Neoplasms

Background. Superficial duodenal neoplasms (SDNs) are a challenging target in the digestive tract. Surgical resection is invasive, and it is difficult to determine the site and extent of the lesion from outside the intestine and resect it locally. Endoscopic submucosal dissection (ESD) has scarcely been utilized in the treatment of duodenal tumors because of technical difficulties and possible delayed perforation due to the action of digestive juices. Thus, no standard treatments for SDNs have been established. To challenge this issue, we elaborated endoscopy-assisted laparoscopic full-thickness resection (EALFTR) and analyzed its feasibility and safety. Methods. Twenty-four SDNs in 22 consecutive patients treated by EALFTR between January 2011 and July 2012 were analyzed retrospectively. Results. All lesions were removed en bloc. The lateral and vertical margins of the specimens were negative for tumor cells in all cases. The mean sizes of the resected specimens and lesions were 28.9 mm (SD ± 10.5) and 13.3 mm (SD ± 11.6), respectively. The mean operation time and intraoperative estimated blood loss were 133 min (SD ± 45.2) and 16 ml (SD ± 21.1), respectively. Anastomotic leakage occurred in three patients (13.6%) postoperatively, but all were minor leakage and recovered conservatively. Anastomotic stenosis or bleeding did not occur. Conclusions. EALFTR can be a safe and minimally invasive treatment option for SDNs. However, the number of cases in this study was small, and further accumulations of cases and investigation are necessary

キュウシン コウヒショウ オ ケイキ ニ シンダンサレ フククウキョウカ ニ セツジョ サレタ ソウキ チョクチョウガン ノ 1レイ

An 82-year-old man had systemic rash and itching. He was treated with antihistamines and steroids, but did not improve. We continued treatment at our hospital, but there was no improvement.The deck-chair sign was observed during treatment, and we diagnosed papuloerythroderma. We considered the possibility of merged malignant tumors and carried out a detailed examination.The final diagnosis was clinical stage I rectal cancer. The patient underwent laparoscopic low anterior resection. The refractory systemic rash completely improved by the 23th postoperative day. At present, the rectal cancer has not relapsed for 4 years after the operation

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

Background Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Methods Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. Results We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. Conclusions TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery

Glutamine protects small intestinal mucosa

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO[○R]) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model

A circulating subset of iNKT cells mediates antitumor and antiviral immunity

新規の循環型iNKT細胞を発見 --抗腫瘍・抗ウイルス感染効果の高い免疫細胞療法の開発への貢献に期待--. 京都大学プレスリリース. 2022-10-24.Invariant natural killer T (iNKT) cells are a group of innate-like T lymphocytes that recognize lipid antigens. They are supposed to be tissue resident and important for systemic and local immune regulation. To investigate the heterogeneity of iNKT cells, we recharacterized iNKT cells in the thymus and peripheral tissues. iNKT cells in the thymus were divided into three subpopulations by the expression of the natural killer cell receptor CD244 and the chemokine receptor CXCR6 and designated as C0 (CD244⁻CXCR6⁻), C1 (CD244⁻CXCR6⁺), or C2 (CD244⁺CXCR6⁺) iNKT cells. The development and maturation of C2 iNKT cells from C0 iNKT cells strictly depended on IL-15 produced by thymic epithelial cells. C2 iNKT cells expressed high levels of IFN-γ and granzymes and exhibited more NK cell–like features, whereas C1 iNKT cells showed more T cell–like characteristics. C2 iNKT cells were influenced by the microbiome and aging and suppressed the expression of the autoimmune regulator AIRE in the thymus. In peripheral tissues, C2 iNKT cells were circulating that were distinct from conventional tissue-resident C1 iNKT cells. Functionally, C2 iNKT cells protected mice from the tumor metastasis of melanoma cells by enhancing antitumor immunity and promoted antiviral immune responses against influenza virus infection. Furthermore, we identified human CD244⁺CXCR6⁺ iNKT cells with high cytotoxic properties as a counterpart of mouse C2 iNKT cells. Thus, this study reveals a circulating subset of iNKT cells with NK cell–like properties distinct from conventional tissue-resident iNKT cells

Enteroendocrine cells are specifically marked by cell surface expression of claudin-4 in mouse small intestine.

Enteroendocrine cells are solitary epithelial cells scattered throughout the gastrointestinal tract and produce various types of hormones, constituting one of the largest endocrine systems in the body. The study of these rare epithelial cells has been hampered by the difficulty in isolating them because of the lack of specific cell surface markers. Here, we report that enteroendocrine cells selectively express a tight junction membrane protein, claudin-4 (Cld4), and are efficiently isolated with the use of an antibody specific for the Cld4 extracellular domain and flow cytometry. Sorted Cld4+ epithelial cells in the small intestine exclusively expressed a chromogranin A gene (Chga) and other enteroendocrine cell-related genes (Ffar1, Ffar4, Gpr119), and the population was divided into two subpopulations based on the activity of binding to Ulex europaeus agglutinin-1 (UEA-1). A Cld4+UEA-1- cell population almost exclusively expressed glucose-dependent insulinotropic polypeptide gene (Gip), thus representing K cells, whereas a Cld4+UEA-1+ cell population expressed other gut hormone genes, including glucagon-like peptide 1 (Gcg), pancreatic polypeptide-like peptide with N-terminal tyrosine amide (Pyy), cholecystokinin (Cck), secretin (Sct), and tryptophan hydroxylase 1 (Tph1). In addition, we found that orally administered luminal antigens were taken up by the solitary Cld4+ cells in the small intestinal villi, raising the possibility that enteroendocrine cells might also play a role in initiation of mucosal immunity. Our results provide a useful tool for the cellular and functional characterization of enteroendocrine cells

Cld4 expression and UEA<i>-</i>1 reactivity define the distinct enteroendocrine cell populations.

<p>(<i>A</i>) FACS profiles of biotinylated anti-Cld4 antibody (HKH-189) staining and UEA-1 binding in CD45⁻Ter119⁻PI⁻EpCAM⁺ intestinal epithelial cells from <i>Cldn4</i>^+/+ and <i>Cldn4</i>^−/− mice are indicated. (<i>B</i>, <i>C</i>) Each epithelial cell population of four quadrant fractions in (<i>A</i>) of <i>Cldn4</i>^+/+ mice was sorted separately with FACSAria and examined for the expressions of the indicated genes with quantitative RT<b>-</b>PCR. The mean relative transcripts and standard errors are shown. The results are representative of at least three independent experiments. *<i>P</i> < 0.01 and **<i>P</i> < 0.001, ANOVA.</p

Transepithelial passage of luminal dextran (10-kDa) via Cld4⁺ enteroendocrine cells.

<p>Eight-week-old to 10<b>-</b>week<b>-</b>old WT mice were administered oral rhodamine or fluorescein<b>-</b>conjugated 10-kDa dextran and euthanized 30 minutes later. (<i>A</i>) The small intestines were immunostained with rabbit anti-chromogranin A (green) and rat anti-Cld4 (HKH-189) (blue) antibodies. Characteristic rhodamine<b>-</b>labeled cylindrical columns (red) in association with a Cld4⁺ chromogranin A⁺ cells (closed arrowheads) and a Cld4⁻ chromogranin A⁻ cells (arrows) are indicated. Bar, 20 µm. Asterisks (*) indicate luminal space. (B, C) Single cell suspensions of the small intestinal cells from control mice and those orally administered with fluorescein-dextran 30 minutes before were multi-color analyzed with FACS. The expression profiles of fluorescein-dextran in Cld4^– (dark blue boxes) and Cld4⁺ (red boxes) cells (B) and in Cld4^–UEA-1⁺ (orange boxes), Cld4⁺UEA-1⁺ (yellow boxes), Cld4^–UEA-1^– (light blue boxes) and Cld4⁺UEA-1^– (pink boxes) cells (C) of a PI^– CD45^– Ter119^– EpCAM⁺ cell gate are indicated. Black and green lines in the histograms indicate the profiles of control and dextran-administered mice, respectively. Percentages of fluorescence-positive populations are shown. The results are representative of at least three independent experiments.</p