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Background Tissue-resident memory T (Trm) cells are associated with cytotoxicity not only in viral infection and autoimmune disease pathologies but also in many cancers. Tumour-infiltrating CD103+ Trm cells predominantly comprise CD8 T cells that express cytotoxic activation and immune checkpoint molecules called exhausted markers. This study aimed to investigate the role of Trm in colorectal cancer (CRC) and characterise the cancer-specific Trm. Methods Immunochemical staining with anti-CD8 and anti-CD103 antibodies for resected CRC tissues was used to identify the tumour-infiltrating Trm cells. The Kaplan–Meier estimator was used to evaluate the prognostic significance. Cells immune to CRC were targeted for single-cell RNA-seq analysis to characterise cancer-specific Trm cells in CRC. Results The number of CD103+/CD8+ tumour-infiltrating lymphocytes (TILs) was a favourable prognostic and predictive factor of the overall survival and recurrence-free survival in patients with CRC. Single-cell RNA-seq analysis of 17,257 CRC-infiltrating immune cells revealed a more increased zinc finger protein 683 (ZNF683) expression in cancer Trm cells than in noncancer Trm cells and in high-infiltrating Trm cells than low-infiltrating Trm in cancer, with an upregulated T-cell receptor (TCR)- and interferon-γ (IFN-γ) signalling-related gene expression in ZNF683+ Trm cells. Conclusions The number of CD103+/CD8+ TILs is a prognostic predictive factor in CRC. In addition, we identified the ZNF683 expression as one of the candidate markers of cancer-specific Trm cells. IFN-γ and TCR signalling and ZNF683 expression are involved in Trm cell activation in tumours and are promising targets for cancer immunity regulation.

Fibroblast activation protein (FAP) is known to have prognostic significance in colorectal cancer (CRC). However, FAP and tertiary lymphoid structures (TLSs) have not been associated with each other in predicting the prognosis of CRC recurrence.FAP expression was evaluated by real-time reverse transcription polymerase chain reaction in 195 CRC patients at Osaka International Cancer Institute (first data set). Immunohistochemistry (IHC) was then performed to stain FAP at the invasive margin (IM) and in the central tumour (CT) in 159 CRC patients at Osaka University Hospital (second data set). Consecutive slides were used to evaluate the presence of TLSs in 159 CRC patients from Osaka University Hospital.The high FAP mRNA expression group (n=82) was associated with poor recurrence-free survival (RFS) compared with the low FAP expression group (n=83) (p=0.004). In the second data set, patients with high FAP expression in CT and TLS absence (n=49) showed significantly poorer RFS compared with those with low expression of FAP in CT and presence of TLSs (n=101) (p=0.002).FAP in the CT combined with TLSs was shown to have significant prognostic value in predicting CRC recurrence after curative resection.

Background: Defecation status is an important determinant of quality of life. Previous studies showed that postoperative defecation disorders occurred after open surgery for ulcerative colitis (UC)...

Most patients with Crohn disease (CD), a chronic inflammatory gastrointestinal disease, experience recurrence despite treatment, including surgical resection. However, methods for predicting recurrence remain unclear. This study aimed to predict postoperative recurrence of CD by computational analysis of histopathologic images and to extract histologic characteristics associated with recurrence. A total of 68 patients who underwent surgical resection of the intestine were included in this study and were categorized into two groups according to the presence or absence of postoperative disease recurrence within 2 years after surgery. Recurrence was defined using the CD Activity Index and the Rutgeerts score. Whole-slide images of surgical specimens were analyzed using deep learning model EfficientNet-b5, which achieved a highly accurate prediction of recurrence (area under the curve, 0.995). Moreover, subserosal tissue images with adipose cells enabled highly accurate prediction. Adipose cell morphology showed significant between-group differences in adipose cell size, cell-to-cell distance, and cell flattening values. These findings suggest that adipocyte shrinkage is an important histologic characteristic associated with recurrence. Moreover, there was a significant between-group difference in the degree of mast cell infiltration in the subserosa. These findings show the importance of mesenteric adipose tissue in patient prognosis and CD pathophysiology. These findings also suggest that deep learning-based artificial intelligence enables the extraction of meaningful histologic features.

T cells differentiate into highly diverse subsets and display plasticity depending on the environment. Although lymphocytes are key mediators of inflammation, functional specialization of T cells in inflammatory bowel disease (IBD) has not been effectively described. Here, we performed deep profiling of T cells in the intestinal mucosa of IBD and identified a CD4

Previous studies have shown that postoperative adjuvant chemotherapy improves overall survival in patients with stage III colorectal cancer (CRC). However, adjuvant chemotherapy may not be necessary for some patients. This study aimed to develop a new nutritional-inflammation score, which would be useful in identifying a favorable prognosis group among stage III CRC patients.This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and a new prognostic model was developed.Multivariate analyses in TS revealed that lymph node metastasis (N2) (p=0.002), low albumin (p=0.017), high monocyte counts (p=0.008), and low platelet counts (p=0.018) were independent risk factors for disease free survival (DFS). The Kansai prognostic score (KPS) was assessed by 1 point each for3.5 g/dl albumin level,450 monocyte counts, and1.65×10KPS serves as a new model for the prognosis of patients with stage III CRC.

The submucosal invasion depth predicts prognosis in early colorectal cancer. Although colorectal cancer with shallow submucosal invasion can be treated via endoscopic resection, colorectal cancer with deep submucosal invasion requires surgical colectomy. However, accurately diagnosing the depth of submucosal invasion via endoscopy is difficult. We developed a tool to diagnose the depth of submucosal invasion in early colorectal cancer using artificial intelligence. We reviewed data from 196 patients who had undergone a preoperative colonoscopy at the Osaka University Hospital and Osaka International Cancer Institute between 2011 and 2018 and were diagnosed pathologically as having shallow submucosal invasion or deep submucosal invasion colorectal cancer. A convolutional neural network for predicting invasion depth was constructed using 706 images from 91 patients between 2011 and 2015 as the training dataset. The diagnostic accuracy of the constructed convolutional neural network was evaluated using 394 images from 49 patients between 2016 and 2017 as the validation dataset. We also prospectively tested the tool from 56 patients in 2018 with suspected early-stage colorectal cancer. The sensitivity, specificity, accuracy, and area under the curve of the convolutional neural network for diagnosing deep submucosal invasion colorectal cancer were 87.2% (258/296), 35.7% (35/98), 74.4% (293/394), and 0.758, respectively. The positive predictive value was 84.4% (356/422) and the sensitivity was 75.7% (356/470) in the test set. The diagnostic accuracy of the constructed convolutional neural network seemed to be as high as that of a skilled endoscopist. Thus, endoscopic image recognition by deep learning may be able to predict the submucosal invasion depth in early-stage colorectal cancer in clinical practice.

There are few reports on the clinical significance of the geriatric nutritional risk index (GNRI) in patients with locally advanced rectal cancer who undergo preoperative chemotherapy (NAC, neoadjuvant chemotherapy) followed by radical resection; this study examined the relationship between preoperative GNRI, postoperative complications, and prognosis in these patients.Fifty-seven patients with rectal cancer who underwent radical resection after NAC at Osaka University Hospital between November 2011 and May 2018 were included. The GNRI was calculated as follows: GNRI= [1.489×serum albumin level (g/l)]+[41.7×present/ideal body weight (kg)]. Patients were classified into high (GNRI ≥96.74; n=36) and low GNRI (GNRI96.74; n=21) groups, based on the results of the receiver operating characteristic curve analysis.The Kaplan-Meier analysis showed that the low GNRI group had a significantly poorer cancer-specific survival (CSS) and a poorer overall survival tendency than the high GNRI group. In the univariate analysis, venous invasion, lymphatic vessel invasion, and low GNRI were significantly correlated with CSS; depth of tumor invasion, lymph node metastasis, and lymphatic vessel invasion were significantly correlated with disease-free survival (DFS). In the multivariate analysis, there were no significantly poor prognostic factors for CSS and DFS.Preoperative GNRI may be a useful predictor for recurrence and poor prognosis in elderly patients with rectal cancer who undergo radical resection after NAC. Further studies and accumulation of cases should investigate the relationship between preoperative GNRI and prognosis after NAC in elderly patients.

Despite the potential efficacy of hospital-based multidisciplinary child protection team (CPTs), research analyzing Japanese CPT databases is scarce.We aimed to describe the characteristics of children and families reported to a CPT in Japan and investigate factors associated with the substantiation of maltreatment.This retrospective, cross-sectional study took place in a national children's hospital in Japan and included 350 children who were reported to CPTs between April 2014 and March 2018.Univariable and multivariable logistic regression analyses were conducted using the CPT database and medical records.Among 350 cases, 33.4 % were substantiated. Children of6 years of age comprised 73.4 % of the cases. The majority (67.7 %) received an injury-related diagnosis and physical maltreatment was suspected in 68.3 % of cases. In the univariable analysis, older age, a primary diagnosis other than injury, reporting department, psychological maltreatment, witnessing intimate partner violence, maltreatment by relatives other than biological father or mother, developmental disability, emotional/behavioral difficulty or psychological disorder, maternal/paternal psychological difficulty, and maternal history of maltreatment were significantly associated with substantiation. When adjusted for demographic, child and familial factors, a diagnosis other than injury (AOR 2.02, 95 % CI = 1. 11-3.65) and parental psychological difficulties (AOR 2.49, 95 % CI = 1.37-4.55) were independently associated with substantiation.Most cases reported to our CPT were young children with an injury-related diagnosis. Substantiation was associated with a diagnosis other than injury and parental psychological difficulties. Further prospective and comprehensive studies are needed to establish universal guidelines for databases of hospital-based CPTs.

Background Endoscopic and transanal local resection without lymph node dissection are treatment options for patients with a low risk of lymph node metastasis; however, some patients might have undiagnosed lymph node metastases before surgery. This retrospective study aimed to evaluate the efficacy of preoperative PET/CT for diagnosing regional lymph node metastasis. Methods Patients who underwent curative resection with lymph node dissection for colorectal cancer at Osaka University between January 2012 and December 2015 were included. The cut-off values appropriate for diagnosing lymph node metastasis were calculated by way of a receiver operating characteristic (ROC) curves from maximum standard unit value (SUVmax) of main tumour, and lymph node short axis, and SUVmax of lymph node. The cut-off values of primary tumour SUVmax: 7, short-axis diameter of the lymph node at 7 mm, and lymph node SUVmax at 1.5 were set. Result A total of 541 patients were included. Regional lymph node metastases were confirmed in resected specimens from 187 patients (35 per cent). With a primary tumour SUVmax of 7 used as a cut-off value, the sensitivity and specificity of regional lymph node metastasis were 70.1 per cent and 45.5 per cent respectively. With a cut-off short-axis diameter of the regional lymph node of 7 mm, the sensitivity and specificity of regional lymph node metastasis were 75.2 per cent and 82.6 per cent respectively, and with a cut-off regional lymph node SUVmax of 1.5, the sensitivity and specificity of regional lymph node metastasis were 78.6 per cent and 96.8 per cent respectively. When the diagnostic criteria were defined by a lymph node short-axis diameter of 7 mm or SUVmax of 1.5, the sensitivity and specificity were 87.4 per cent and 81.8 per cent respectively. Conclusion Preoperative PET/CT is a useful modality for evaluating regional lymph node metastasis in patients with colorectal cancer.

Crohn’s disease causes chronic inflammation in the gastrointestinal tract and its pathogenesis remains unclear. In the intestine of Crohn’s disease patients, CD14+CD11+CD163low macrophages contribute to inflammation through the induction of Th17 cells and production of inflammatory cytokines; the CD14+CD11c+163high fraction is anti-inflammatory through the production of IL-10 in normal cases. In this report, the 16S rRNA gene amplicon sequencing method was used to identify bacteria that are specifically present in intestinal CD14+CD11c+ macrophages of Crohn’s disease patients. Bacteria present in intestinal CD14+CD11c+ macrophages and mucus of Crohn’s disease patients were separated into different clusters in principal coordinates analysis. There was a statistically significant increase in the relative composition of CD14+CD11c+ macrophages from mucus in two phyla (Proteobacteria [p = 0.01] and Actinobacteria [p = 0.02]) and two families (Moraxellaceae [p Pseudomonadaceae [p = 0.01]). In addition, OTU-1: Acinetobacter and OTU-8: Pseudomonadaceae tended to concentrate in the CD14+CD11c+CD163low subset, whereas OTU-10: Proteus, OTU-15: Collinsella tended to concentrate more in the CD14+CD11c+CD163high subset than the other subset and mucus.

Purpose Inflammation and nutritional status are known to be associated with the prognosis of several malignancies. Herein, we attempted to develop inflammation–nutrition scores and predict the prognosis of stage III colorectal cancer (CRC). Methods This retrospective study included 262 patients with stage III CRC who underwent curative surgery and were divided into two groups: a training set (TS) of 162 patients and a validation set (VS) of 100 patients. In the TS, clinicopathological factors were tested using a Cox regression model, and the Kansai prognostic score (KPS) was assessed by 1 point each for 450 monocyte counts, and 5 platelet counts, which were associated with disease-free survival (DFS). Using KPS, DFS and overall survival (OS) were validated in VS. Results The C-indices of KPS to predict DFS and OS in TS were 0.707 and 0.772. It was validated in VS that the C-indices of KPS to predict DFS and OS were 0.618 and 0.708, respectively. A high KPS was a significant predictor of DFS and OS. Conclusion KPS serves as a new model for the prognosis of patients with stage III CRC.

Postoperative carcinoembryonic antigen (post-CEA) has recently been reported to be a reliable prognostic factor for colon cancer. However, most clinicians decide whether or not to conduct adjuvant chemotherapy (AC) for stage II colon cancer according to major guidelines, which do not include post-CEA in their high-risk criteria. The present study aimed to assess post-CEA in stage II colon cancer for which the significance of AC is unknown. The present study analyzed 199 consecutive patients with stage II colon cancer who underwent curative surgery between January 2007 and December 2016. The CEA value was considered high when it was ≥5.0 ng/ml. The prognostic value of high post-CEA values was assessed. Overall, 19 patients exhibited high post-CEA levels. Kaplan-Meier survival curve analysis demonstrated that patients with high post-CEA levels had significantly worse relapse-free survival (RFS) and overall survival (OS) than those with normal post-CEA [RFS, 63.5 (high post-CEA) vs. 88.0% (normal post-CEA), P=0.003; OS, 76.5 (high post-CEA) vs. 96.8% (normal post-CEA), P0.001]. Multivariate analysis demonstrated that high post-CEA remained a significant independent risk factor for worse RFS [hazard ratio (HR), 3.98; P=0.006]. The same was also demonstrated for patients without AC (HR, 5.43; P=0.008). To the best of our knowledge, the present study was the first to demonstrate that high post-CEA levels may be an indicator of high-risk stage II colon cancer, even for patients without AC. These results highlight the need for a multicenter prospective study.

The histone methyltransferase G9a is expressed in various types of cancer cells, including colorectal cancer (CRC) cells. Interleukin 8 (IL)-8, also known as C-X-C motif chemokine ligand 8 (CXCL8), is a chemokine that plays a pleiotropic function in the regulation of inflammatory responses and cancer development. Here, we examined the relationship between G9a and IL-8 and the clinical relevance of this association. We immunohistochemically analyzed 235 resected CRC samples to correlate clinical features. Samples with high G9a expression had better overall survival and relapse-free survival than those with low G9a expression. Univariate and multivariate analyses demonstrated that low G9a expression remained a significant independent prognostic factor for increased disease recurrence and decreased survival (P < 0.05). G9a was expressed at high levels in commercially available CRC cell lines HCT116 and HT29. Knockdown of G9a by siRNA, shRNA or the G9a-specific inhibitor BIX01294 upregulated IL-8 expression. The number of spheroids was significantly increased in HCT116 cells with stably suppressed G9a expression, and the number of spheroids was significantly decreased in HCT116 cells with stably suppressed IL-8 expression. Thus, the suppression of IL-8 by G9a may result in a better prognosis in CRC cases with high G9a expression. Furthermore, G9a may suppress cancer stemness and increase chemosensitivity by controlling IL-8. Therefore, G9a is a potential novel marker for predicting CRC prognosis, and therapeutic targeting of G9a in CRC should be controversial.

Despite advances in medical treatments, most patients with Crohn's disease (CD) will still require surgery, with 20%-50% needing redo surgery within 10 years after the primary procedure. There is no consensus on the application of laparoscopic redo surgery for recurrent CD.This study included 107 patients with CD who underwent surgery from 2012 to 2020 at Osaka University Hospital. All procedures were laparoscopic. Patients were grouped based on whether the surgery was redo or primary for evaluation of the safety and feasibility of laparoscopic redo surgery.The study included 40 patients undergoing redo surgery and 67 having primary surgery. The median age at the time of the procedure was higher for those undergoing redo surgery (43 years vs 34 years,These results suggest that laparoscopic redo surgery is safe and feasible, with comparable conversion rates and postoperative complications in experienced institutions.

We examined the association between pathological lateral pelvic lymph node (LPLN) metastasis and the LPLN diameter in patients with locally advanced rectal cancer (LARC) who received a neoadjuvant chemotherapy (NAC) regimen based on oxaliplatin as induction chemotherapy. We aimed to determine whether or not the LPLN size predicts LPLN metastasis in NAC cases. We retrospectively examined data from 3 institutes for 60 patients with LARC who received mesorectal excision and LPLN dissection after NAC. We evaluated the LPLN size on magnetic resonance imaging (MRI) scans acquired before and after NAC. We performed multivariate analyses to analyze the relationship between the LPLN size and clinicopathological factors. For patients with visible LPLNs, the median short-axis diameter (SA) was significantly reduced from 5.1 mm (range 2.0–17.4) before NAC to 3.7 mm (range 2.1–19.0) after NAC (p = 0.0479). SA diameters were significantly larger in pathological LPLNs than in healthy LPLNs, both before (p = 0.0002) and after NAC (p

Regarding metastatic potential of cancer cells and the refractory status, regulatory and epigenetic factors underlie the cancer treatment resistance by inducing cellular heterogeneity. Circulating tumor cells (CTCs) and their stemness are critical for metastases formation associated with poor survival rates. In colorectal cancer (CRC), several stem-cell markers, such as CD44v9 and LGR5, the positive cells cause intertumoral heterogeneity and promote refractory potential. However, the mastermind of the cells which is critical for the treatment resistance remains unknown. Here, we aimed to identify the mechanisms of the treatment resistance of the CRC by focusing on typical stem cells. We selected several stem cell-related genes such as pluripotency related genes, based on the expression profile analysis of CRC patients along with drug susceptibility assays using patient-derived organoids. Despite the small number of cancer stem cells, the single cell produced heterogeneous cell populations in vitro and in vivo, expressing various differentiation and stem biomarkers, and confirmed by the knockdown analysis. Single-cell trajectory analysis suggested that heterogeneous populations including cancer stem and some persister cells were derived from the stem cells following administration of anti-cancer drugs. Furthermore, the stem cells formed heterogeneous liver metastases at a high rate, and these unique cells were observed in the bloodstream of CRC patients. This present study unveils a mechanism of CRC treatment resistance and highlights the potential of stem marker-expressing cells as CTCs. Citation Format: Norikatsu Miyoshi, Shiki Fujino, Yuki Sekido, Tsuyoshi Hata, Takayuki Ogino, Hidekazu Takahashi, Mamoru Uemura, HIrofumi Yamamoto, Yuichiro Doki, Hidetoshi Eguchi. Heterogeneity inducible tumor stem cells relate distant metastasis and the treatment resistance [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2630.

In-person models of genetic counseling (GC) have been the common method in Japan for pregnant women to receive GC. However, recent increases in the number of pregnant women considering undergoing prenatal testing have made it challenging to retain individualized in-person care. To explore pregnant women’s opinions toward pretest GC models and the ideal time duration, a self-administered questionnaire survey was conducted for women at their first prenatal visit. A total of 114 valid respondents (93.4%) were included in the analyses. Of these, 80.7% of women preferred in-person GC, followed by classroom (9.6%), group (3.5%), and telegenetic-based GC (2.6%). Women with experience in undergoing prenatal testing significantly did not prefer in-person GC (p = 0.05). Sixty-two women (54.4%) preferred a duration of 15–29 min for pretest GC sessions, followed by 30–59 min (28.9%) and

Objective : Surgical treatment is an important option for inducing remission in Crohn's disease (CD); indeed, the longer the disease duration, the higher the cumulative surgical rate. Previous studies have shown that the pathogenesis of Crohn's disease was associated with sarcopenia, a condition of reduced skeletal muscle mass. Here, we investigated the effect of preoperative sarcopenia on postoperative disease activity. Methods : This retrospective study included 56 patients with CD with medical records that met our inclusion criteria. Sarcopenia was diagnosed, based on the psoas muscle mass index (PMI) derived from computed tomography (CT) images, with predetermined PMI cut-off values of Results : Of the 56 included subjects, nine (16%) had sarcopenia. The rate of preoperative treatment with biological drugs was significantly lower in the sarcopenia group than in the normal group. In addition, the operation time was significantly longer, and hemorrhage occurred more often in the sarcopenia group than in the normal group. Postoperatively, the CD activity index at six months had significantly decreased in the normal group (p = 0.01), but not in the sarcopenia group (p = 0.20). Univariate and multivariate analyses showed that a low total serum protein level was significantly associated with sarcopenia. Conclusion : Our results suggested that, to maximize the effect of surgical treatment for CD, an appropriate nutritional intervention should be performed before surgery, or surgery should be postponed until the patient recovers from sarcopenia.

Crohn’s disease causes chronic inflammation in the gastrointestinal tract and its pathogenesis remains unclear. In the intestine of Crohn’s disease patients, CD14+CD11+CD163low macrophages contribute to inflammation through the induction of Th17 cells and production of inflammatory cytokines; the CD14+CD11c+163high fraction is anti-inflammatory through the production of IL-10 in normal cases. In this report, the 16S rRNA gene amplicon sequencing method was used to identify bacteria that are specifically present in intestinal CD14+CD11c+ macrophages of Crohn’s disease patients. Bacteria present in intestinal CD14+CD11c+ macrophages and mucus of Crohn’s disease patients were separated into different clusters in principal coordinates analysis. There was a statistically significant increase in the relative composition of CD14+CD11c+ macrophages from mucus in two phyla (Proteobacteria [p = 0.01] and Actinobacteria [p = 0.02]) and two families (Moraxellaceae [p

Background: Human intestinal innate myeloid cells can be divided into 3 subsets: HLA-DRCD14 cells, HLA-DRCD103 dendritic cells (DCs), and HLA-DRCD14CD103 cells. CD103 DCs generate Treg cells and Th17 cells in the ileum, but their function in the colon remains largely unknown. This study characterized CD103 DCs in the colon and investigated whether these cells are implicated in the pathogenesis of ulcerative colitis (UC). Methods: Normal intestinal mucosa was obtained from intact sites of patients with colorectal cancer (n = 24). Noninflamed and inflamed colonic tissues were obtained from surgically resected specimens of patients with UC (n = 13). Among LinCD45HLA-DR intestinal lamina propria cells, CD14 cells and CD103 DCs were sorted and analyzed for microRNA expression of cytokines and toll-like receptors by quantitative real-time polymerase chain reaction. In addition, IL-4/IL-5/IL-13/IL-17/IFN-γ production and Foxp3 expression by naive T cells cultured with CD14 cells and CD103 DCs were analyzed. Results: CD103 DCs in the normal colon showed lower expression of toll-like receptors and proinflammatory cytokines than CD14 cells. Coculture with naive T cells revealed that CD103 DCs generated Treg cells. CD103 DCs from patients with UC did not generate Treg cells, but they induced IFN-γ-, IL-13-, and IL-17-producing CD4 T cells and showed higher expression of IL6 (P < 0.0001), IL23A (P < 0.05), IL12p35 (P < 0.05), and TNF (P < 0.05). Conclusions: In patients with UC, CD103 DCs show the impaired ability to generate Treg cells, but exhibit a colitogenic function inducing Th1/Th2/Th17 responses. These findings show how human CD103 DCs could contribute to the pathogenesis of UC.

Background Familial gastrointestinal stromal tumor (GIST) is a rare disease with germline mutations in the c-kit gene (KIT) or platelet-derived growth factor receptor alpha gene (PDGFRA). We had encountered multiple GISTs in the stomach and small intestine during a screening of ovarian cancer for a woman with hereditary breast and ovarian cancer syndrome (HBOC) with breast cancer susceptibility gene II (BRCA2) mutations. The aim of this study was to examine this case in detail. Case report A 65-year-old woman diagnosed with HBOC harboring BRCA2 mutations was found to have multiple tumors in the stomach and small intestine by abdominal screening. All tumors were resected, and KIT gene mutations (p.Trp557Leu and p.Lys558Glu) in exon 11 were detected in all tumors and peripheral blood leukocytes. The patient was diagnosed with familial GIST. Conclusion This was an extremely rare case in which familial GIST with germline KIT gene mutations co-existed with HBOC.

Objectives Inflammation-associated microsatellite alterations (also known as elevated microsatellite alterations at selected tetranucleotide repeats [EMAST]) result from IL-6-induced nuclear-to-cytosolic displacement of the DNA mismatch repair (MMR) protein MSH3, allowing frameshifts of dinucleotide or longer microsatellites within DNA. MSH3 also engages homologous recombination to repair double-strand breaks (DSBs), making MSH3 deficiency contributory to both EMAST and DSBs. EMAST is observed in cancers, but given its genesis by cytokines, it may be present in non-neoplastic inflammatory conditions. We examined ulcerative colitis (UC), a preneoplastic condition from prolonged inflammatory duration. Methods We assessed 70 UC colons without neoplasia, 5 UC specimens with dysplasia, 14 UC-derived colorectal cancers (CRCs), and 19 early-stage sporadic CRCs for microsatellite instability (MSI) via multiplexed polymerase chain reaction capable of simultaneous detection of MSI-H, MSI-L, and EMAST. We evaluated UC specimens for MSH3 expression via immunohistochemistry. Results UC, UC with dysplasia, and UC-derived CRCs demonstrated dinucleotide or longer microsatellite frameshifts, with UC showing coincident reduction of nuclear MSH3 expression. No UC specimen, with or without neoplasia, demonstrated mononucleotide frameshifts. EMAST frequency was higher in UC-derived CRCs than UC (71.4% vs 31.4%, P = 0.0045) and higher than early-stage sporadic CRCs (66.7% vs 26.3%, P = 0.0426). EMAST frequency was higher with UC duration >8 years compared with ≤8 years (40% vs 16%, P = 0.0459). Discussion Inflammation-associated microsatellite alterations/EMAST are prevalent in UC and signify genomic mutations in the absence of neoplasia. Duration of disease and advancement to neoplasia increases frequency of EMAST. MSH3 dysfunction is a potential contributory pathway toward neoplasia in UC that could be targeted by therapeutic intervention.

Introduction The aim of this study was to introduce and examine a modified mechanical end-to-side esophagogastrostomy method (“reverse-Tornado" anastomosis) in laparoscopy-assisted proximal gastrectomy. Methods Five patients with gastric cancer who underwent laparoscopy-assisted proximal gastrectomy were analyzed retrospectively. Esophagogastrostomy in the anterior wall was performed in three patients, and esophagogastrostomy in the posterior wall was performed in two patients. Clinicopathological features, operative outcomes (operative time, operative blood loss), and postoperative outcomes (complications, postoperative hospital stay, reflux esophagitis) were evaluated. Results Operative time was normal (278 min). There was no marked operative blood loss, postoperative complications, prolonged hospital stay, or reflux esophagitis. Conclusion Esophagogastrostomy was completed in a normal time with reverse-Tornado anastomosis. This method can be safe and can enable good postoperative quality of life.

Background/Aims: There is a heterogeneous subset innate myeloid cells, such as macrophages and dendritic cells, in the human intestinal lamina propria. Several studies have demonstrated that these cells contribute to the maintenance of gut homeostasis through the induction of inflammatory responses and tolerance via cell type-specific mechanisms; whereas, disrupted innate immune responses are implicated in the pathogenesis of Crohn’s disease (CD). However, the detailed mechanisms by which each innate myeloid subset regulates gut homeostasis and inflammation largely remain unknown. We aimed to clarify the comprehensive gene expression profiles of innate myeloid cell ­subsets in the lamina propria from normal human colons (NC) and the inflamed colon sites from patients with Crohn’s disease (CDi). Methods: We performed RNA-sequencing analysis and precise bioinformatics analysis on 3 innate myeloid cell subsets, CD14–CD11c–, CD14–CD11c+, and CD14+CD11c+CD163low cells from NC and CDi. Results: Transcriptional analysis of the 3 subsets from the NC showed distinct gene expression patterns and gene ontology (GO) enrichment analysis revealed the associated innate myeloid subset-specific biological process (BP) terms. In addition, changes in gene expression patterns were observed in innate myeloid subsets from CDi. Furthermore, the core GO-BP terms for the genes upregulated in the innate myeloid cells from CDi were distinct from those found in NC. Conclusion: Our data identified the innate myeloid cell subset-specific transcriptomes and the associated enriched GO-BP terms in the NC and found these patterns were altered in CDi.

Familial gastrointestinal stromal tumor (GIST) is a rare disease with germline mutations in the c-kit gene (KIT) or platelet-derived growth factor receptor alpha gene (PDGFRA). We had encountered multiple GISTs in the stomach and small intestine during a screening of ovarian cancer for a woman with hereditary breast and ovarian cancer syndrome (HBOC) with breast cancer susceptibility gene II (BRCA2) mutations. The aim of this study was to examine this case in detail.A 65-year-old woman diagnosed with HBOC harboring BRCA2 mutations was found to have multiple tumors in the stomach and small intestine by abdominal screening. All tumors were resected, and KIT gene mutations (p.Trp557Leu and p.Lys558Glu) in exon 11 were detected in all tumors and peripheral blood leukocytes. The patient was diagnosed with familial GIST.This was an extremely rare case in which familial GIST with germline KIT gene mutations co-existed with HBOC.