Shinobu Ohnuma

Tohoku University | Tohokudai · Department of Gastroenterological Surgery

Background According to several clinical trials for patients with rectal cancer, laparoscopic surgery significantly reduces intraoperative complications and bleeding compared with laparotomy and demonstrated comparable long‐term results. However, obesity is considered one of the risk factors for increased surgical difficulty, including complication...

ABCC3 (also known as MRP3) is an ATP binding cassette transporter for bile acids, whose expression is downregulated in colorectal cancer through the Wnt/β‐catenin signaling pathway. However, it remained unclear how downregulation of ABCC3 expression contributes to colorectal carcinogenesis. We explored the role of ABCC3 in the progression of colore...

Objective To clarify the long-term oncological outcomes and postoperative anal, urinary, and sexual functions after laparoscopic surgery for clinical stage I very low rectal carcinoma located near the anal canal. Summary Background Data Laparoscopic surgery is widely applied for rectal cancer; however, concerns remain, with some studies showing po...

Backgrounds: Reserpine is an agent that is used for the treatment of hypertension. ABCG2 also known as breast cancer resistance protein (BCRP) is a member of the ABC transporters associated with multidrug resistance (MDR). Our high-throughput screening assay has revealed that reserpine analog inhibits transport function of ABCG2. Aim: To investigat...

Background: Drug development is important for cancer therapy to improve patient outcomes. In most cases, drug development starts in discovering candidate compounds from a chemical library in high-throughput screening (HTS). Tohoku University Graduate School of Pharmaceutical Science owns the original chemical library consisting of thousands of orig...

ABCC3 (also known as MRP3) is an ATP binding cassette transporter and it works as a bile acids transporter. We previously elucidated that ABCC3 expression is downregulated in colorectal cancer through the Wnt/β-catenin signaling pathway. However, it remained unclear how downregulation of ABCC3 expression contributes to colorectal carcinogenesis. We...

Introduction Duodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreat...

Background and aims Conversion to laparotomy is among the serious intraoperative complications and carries an increased risk of postoperative complications. In this cohort study, we investigated whether or not the Endoscopic Surgical Skill Qualification System (ESSQS) affects the conversion rate among patients undergoing laparoscopic surgery for re...

Objectives To verify the value of the pathological criteria for additional treatment in locally resected pT1 colorectal carcinoma (CRC) which have been used in the Japanese Society for Cancer of the Colon and Rectum (JSCCR) guidelines since 2009. Methods We enrolled 4719 patients with pT1 CRC treated at 27 institutions between July 2009 and Decemb...

Background The Endoscopic Surgical Skill Qualification System (ESSQS) in Japan evaluates the surgical skills required for laparoscopic surgery as an operator as well as a supervisor. This study aimed to demonstrate the benefits of an ESSQS-certified surgeon's participation in laparoscopic rectal resections as a supervisor (assistant or advisor). M...

Objective: To investigate how omitting additional surgery after local excision (LE) affects patient outcomes in high-risk T1 colorectal cancer (CRC). Summary background data: It is debatable whether additional surgery should be performed for all patients with high-risk T1 CRC regardless of the tolerability of invasive procedures. Methods: Pati...

Background: A molecular budding signature (MBS), which consists of seven tumor budding-related genes, was recently presented as a prominent prognostic indicator in colon cancer (CC) using microarray data acquired from frozen specimens. This study aimed to confirm the predictive power of MBS for recurrence risk based on formalin-fixed, paraffin-emb...

Inflammatory bowel diseases (IBDs), such as Crohn’s disease or ulcerative colitis, can be treated with anti TNF-alpha (TNF-α) antibodies (Abs), but they also put patients with IBDs at risk of cancer. We aimed to determine whether the anti TNF-α Ab induces colon cancer development in vitro and in vivo, and to identify the genes involved in colitis-a...

We report a case of an elderly patient, 82 years-old, with initially-unresectable pancreatic head cancer, who successfully underwent complete resection of the primary lesion after systemic chemotherapy for 6 months. The patient had a history of pancreatic body-tail resection for intraductal papillary mucinous carcinoma in 2005. In 2020, a routine e...

Background and aims: Since 2009, the Japanese Society for Cancer of the Colon and Rectum guidelines have recommended that tumor budding and submucosal invasion depth, in addition to lymphovascular invasion and tumor grade, be included as risk factors for lymph node metastasis (LNM) in patients with T1 colorectal cancer (CRC). In this study, a nove...

A 50s woman with a stomachache was referred to our hospital with diagnosed gastric cancer. Upper endoscopy showed a type 3 tumor in the lower gastric body, and CT demonstrated a pelvic tumor 10 cm in size. Laparoscopic surgery was performed; since the pelvic tumor was found to derive from the left ovary, left oophorectomy and total gastrectomy were...

A 21-year-old woman with bloody stool was referred to our hospital with multiple submucosal tumors at the posterior and anterior wall of the gastric angle under upper gastrointestinal endoscopy. Both of the tumors were diagnosed with gastric gastrointestinal stromal tumor(GIST)by EUS-FNA, then laparoscopic distal gastrectomy with D1 lymph node diss...

A 56-year-old man was referred to our hospital with an awareness of anal tumor. The tumor extended from the anal verge to the back of left testicle. Colonoscopy showed no tumor in the rectum and the anal canal. Biopsy showed mucus- producing adenocarcinoma(sig), and we diagnosed anal canal adenocarcinoma with immunostaining. Laparoscopic abdominope...

Both viable and non-viable orally administered Lacticaseibacillus rhamnosus CRL1505 modulate immunity in local (intestine) and distal (respiratory) mucosal sites. So, intestinal adhesion and colonization are not necessary for this probiotic strain to exert its immunomodulatory effects. In this work, a mucus-binding factor knockout CRL1505 strain (Δ...

Esophageal intramural pseudodiverticulosis (EIPD) is a rare disease. A 78-year-old man with dysphagia presented to our hospital. The presence of diffuse esophageal spasm was suspected by his primary-care doctor. High-resolution manometry (HRM) showed no abnormal findings. The patient was diagnosed with EIPD and Candida esophagitis, by esophagogastr...

We report a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) after total proctocolectomy followed with ileal pouch-anal anastomosis (TPC-IPAA) for ulcerative colitis (UC). The patient was a 46-year-old woman. She was diagnosed with UC of pancolitis in 2000. High grade dysplasia was detected in the transverse colon aft...

Intestinal malrotation (IM) is an abnormality due to a failure of the normal midgut rotation and fixation. We report a case of 46‐year‐old man with ulcerative colitis whose IM was apparent after laparoscopically total proctocolectomy (TPC) followed by ileal‐pouch‐anal anastomosis (IPAA) and ileostomy. There was no abnormal anatomy except for mobile...

Anal canal cancer (ACC) has been reported to be an uncommon cancer in Japan, as in the USA, Europe, and Australia. This retrospective multi‐institutional study was conducted to clarify the characteristics of ACC in Japan. First, the histological ACC type cases treated between 1991 and 2015 were collected. A detailed analysis of the characteristics...

Background Adjuvant chemotherapy reduces the risk of recurrence of stage III colon cancer (CC). However, more effective prognostic and predictive biomarkers are needed for better treatment stratification of affected patients. Here, we constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. M...

A 62-year-old man underwent radical surgery for the treatment of remnant gastric cancer with mesojejunal lymph node metastasis. According to the 15th edition of the Japanese Gastric Cancer Association, a histological diagnosis of B-35-A, type 3, tub2>tub1, pT3(SS), pN3a(10/37), cM0, CY0, pStage ⅢB was made. All lymph node metastases were recognized...

A 70's woman complaining blood stool and lower abdominal pain visited a local doctor and was given the diagnosis of rectal cancer by colonoscopy. CT, MRI, and bone scintigraphy revealed multiple lymph node and bone metastasis and peritoneal dissemination. She had developed disseminated intravascular coagulation(DIC)during hospitalization, and the c...

A 56-year-old man was referred to our hospital for multidisciplinary treatment of advanced sigmoid colon carcinoma with a suspected bladder invasion. The patient received 8 courses of modified Leucovorin, fluorouracil, and oxaliplatin (mFOLFOX6)plus panitumumab as neoadjuvant chemotherapy for reliable and safe radical resection after ileostomy cons...

The ATP-binding cassette subfamily G member 2 (ABCG2) transporter is involved in the development of multidrug resistance in cancer patients. Many inhibitors of ABCG2 have been reported to enhance the chemosensitivity of cancer cells. However, none of these inhibitors are being used clinically. The aim of this study was to identify novel ABCG2 inhib...

The splicing of microexons (very small exons) is frequently dysregulated in the brain of individuals with autism spectrum disorder. However, little is known of the patterns, regulatory mechanisms and roles of microexon splicing in cancer. We here examined the transcriptome‐wide profile of microexon splicing in matched colorectal cancer (CRC) and no...

Background Nonalcoholic fatty liver disease, which is highly associated with obesity, includes nonalcoholic steatohepatitis. Lipopolysaccharides from the intestine would induce inflammation in the liver in nonalcoholic fatty liver disease. This study aimed to examine the role of the bilio-pancreatic limb in the effect of duodenal–jejunal bypass on...

Cancer-associated fibroblasts (CAFs) are a major component of the tumor microenvironment and have been shown to promote cancer aggressiveness. In our previous study, analysis of expression profiles obtained from paired CAFs and normal fibroblasts from colorectal cancer (CRC) tissue revealed that gene sets related to the Wnt signaling pathway were h...

The mitogen-activated protein kinase (MAPK) pathway plays an important role in the colorectal cancer (CRC) progression, being supposed to be activated by the gene mutations, such as BRAF or KRAS. Although the inhibitors of extracellular signal-regulated kinase (ERK) have demonstrated efficacy in the cells with the BRAF or KRAS mutations, a clinical...

Background Adjuvant chemotherapy reduces the recurrence risk in stage III colon cancer (CC). However, better prognostic and predictive biomarkers are required to stratify patients for treatment. We constructed a 55-gene classifier (55GC) and investigated its utility for classifying patients with stage III CC. Methods We retrospectively identified...

Background: Intestinal fibrosis is a major complication of inflammatory bowel disease (IBD), which can be prevented with anti-inflammatory therapies. However, inflammatory biomarkers do not necessarily reflect the progression of fibrosis, and hence, an indicator that reflects the therapeutic effects of available anti-inflammatory drugs on fibrosis...

Introduction: Exosomes are membrane-enclosed nanovesicles, which are increasingly being recognized as important cell communication components for their role in transmitting microRNAs (miRNAs). No previous study has addressed the exosomal miRNA profile in colorectal adenomas (CRAs) because the long-term culture of CRA is challenging. This study aim...

Background Antimesenteric cutback end‐to‐end isoperistaltic anastomosis (Sasaki‐Watanabe anastomosis; Sasaki‐W anastomosis), which was developed in our department, is a novel hand‐sewn anastomotic technique for Crohn's disease intended to prevent anastomotic stenosis and preserve the peripheral circulation. Aim The aim of the present study is to p...

Aim Crohn’s disease (CD) can affect any part of the gastrointestinal tract; however, the frequency of CD lesions differs by location. Resection rates were examined by location to clarify locational characteristics of the small intestine in surgical CD cases. Method Single‐centre retrospective case notes review of patients who had undergone resecti...

Background Left ventricular assist devices (LVADs) currently play an important role in the treatment of patients with end-stage heart failure who require a bridge to heart transplantation or destination therapy. With the development and improvement of the LVADs, the morbidity and mortality rates are declining and life expectancies increasing, and t...

A 50's man was referred to our hospital because of sigmoid colon cancer with multiple liver metastases and para-aortic lymph node metastases. Although blood test showed elevated D-dimer(50 μg/mL), there was no significant thrombus in contrast-enhanced CT scan. Since cancer pain and symptoms of bowel obstruction had continued after endoscopic stent...

A 30's extremely obese patient(body mass index: BMI 45 kg/m2)was referred to our hospital with a chief complaint of bloody urine and stool. Colonoscopy revealed a sigmoid colon tumor. Barium enema examination revealed stenosis of the sigmoid colon. CT scan showed a tumor in the sigmoid colon, with bladder invasion. The para-aortic lymph node was pa...

Urinary incontinence is one of the common complications after radical prostatectomy along with inguinal hernia. Artificial urethral sphincter implantation is widely accepted as a treatment option. We report two surgical cases of inguinal hernia after artificial urethral sphincter implantation for urinary incontinence following radical prostatectomy...

p> Backgrounds : In inflammatory bowel disease (IBD), chronic inflammation results in the development of colon cancer known as colitis-associated cancer (CAC), that is associated with tumor necrosis factor-α (TNF-α) signaling. In addition, intestinal fibrosis in IBD patients is a common clinical complication, which is promoted by transforming growt...

Introduction: DNA microarrays, such as the consensus molecular subtype (CMS) classification using >600 genes, are used to predict cancer patient prognosis. We recently constructed a simple 55-gene classifier (55GC) system to risk stratify colon cancer (CC). Objective: Here, we validate the 55GC specifically for stage II CC and compare it with CM...

Cripto-1 is a plasma membrane protein which is not expressed in adult tissue, but some tumors are accompanied by re-activation. We studied the clinical and biological significance of Cripto-1 in colorectal cancer. Cripto-1 was positive in 68 out of 192 cases (35%) by immunohistochemistry. Cripto-1 expression was correlated with worse prognosis and...

A 65-year-old male was diagnosed with rectal cancer invading the urinary bladder, swollen para-aorticlymph nodes, and multiple liver metastases in abdominal CT. After 8 courses of mFOLFOX6 plus panitumumab, the rectal cancer, para-aortic lymph nodes metastasis, and liver metastases decreased significantly in size. Rectal cancer and liver metastases...

A 45-year-old woman was referred to our hospital complaining of diarrhea. Colonoscopy showed a rectal tumor. Histological examination showed moderately differentiated adenocarcinoma. A CT scan revealed a tumor extending from the lower rectum to the anal canal with a lateral pelvic lymph node(LPLN)swelling. We administered neoadjuvant chemoradiother...

A 69-year-old man was referred to our institute for the surgical resection of focal resistant peritoneal GIST during imatinib administration. He had been diagnosed with GIST of the small intestine with liver and peritoneal metastases, and imatinib treatment was initiated. Shortly after imatinib administration, the primary lesion perforated, and thu...

A 60s man was diagnosed with rectal cancer and underwent low anterior resection of the rectum. The pathological diagnosis was mucinous adenocarcinoma, pT3(SS), pN0, pM0, pStage Ⅱ. Two years after the primary surgery, contrast-enhanced CT showed local recurrence on the oral side of the anastomosis. As the tumor had invaded the left seminal vesicle a...

Background Patients with long-standing Crohn’s disease (CD) are at a high risk of development of anorectal cancer (ARC), however, the clinical features of ARC complicating CD are still uncertain. The aim of the present study was to clarify the clinical features of ARC complicating CD. Methods From 1995 to 2018, 483 patients with CD underwent surge...

In inflammatory bowel disease, chronic inflammation results in the development of colon cancer known as colitis-associated cancer. This disease is associated with tumor necrosis factor-α (TNF-α) signaling. In addition, intestinal fibrosis is a common clinical complication that is promoted by transforming growth factor β1 (TGF-β1). In our previous s...

Aim: To reveal whether anti TNF-α antibody (Ab) induces colon carcinogenesis or not in colitic cancer models. Methods: The effects of TNF-α and anti TNF-α Ab were analyzed with cell-proliferation, migration, and invasion assays in human colon cancer cell lines, in vitro. Then, the effects of anti TNF-α Ab, infliximab (10 mg/kg, i.p.) were investiga...

Background: ABCG2, also known as breast cancer resistance protein (BCRP), is a member of the ATP-binding cassette (ABC)-family of membrane transport proteins associated with multidrug resistance (MDR). No ABCG2 inhibitor has shown clinical significance yet. Aim: To identify novel inhibitors of ABCG2 by high-throughput screening. Material & Methods:...

Aim: To reveal whether anti TNF-α antibody (Ab) induces colon carcinogenesis or not in colitic cancer models. Methods: The effects of TNF-α and anti TNF-α Ab were analyzed with cell-proliferation, migration, and invasion assays in human colon cancer cell lines, in vitro. Then, the effects of anti TNF-α Ab, infliximab (10 mg/kg, i.p.) were investiga...

Background: ABCG2, also known as breast cancer resistance protein (BCRP), is a member of the ATP-binding cassette (ABC)-family of membrane transport proteins associated with multidrug resistance (MDR). No ABCG2 inhibitor has shown clinical significance yet. Aim: To identify novel inhibitors of ABCG2 by high-throughput screening. Material & Methods:...

3597 Background: Patient prognosis can be predicted based on cancer subtypes classified according to DNA microarray results. The most robust classification system involves the consensus molecular subtypes, which uses over 600 genes for classification. To simplify this classification, we recently constructed a 55-gene classifier (55GC) to classify c...

A55 -year-old man was diagnosed with rectal cancer invading the urinary bladder and swollen para-aortic lymph nodes. Since distant metastasis was indicated and total pelvic exenteration was required, 6 courses of chemotherapy with mFOLFOX6 plus panitumumab were performed. After the chemotherapy, the rectal cancer and para-aortic lymph nodes signifi...

A woman in her 40s who presented to a local hospital with bloody stool was referred to our hospital. Colonoscopy showed a rectal tumor, and histological examination showed moderately differentiated adenocarcinoma. CT and MRI revealed that the tumor was 65mm in diameter with no distant metastasis. After the construction of ileostomy, neoadjuvant che...

Case 1: A female patient in her 60s underwent laparoscopic intersphincteric resection for rectal cancer. After 42 months, the serum level of carcinoembryonic antigen(CEA)was elevated, and PET-CT showed a locally recurrent rectal cancer that increased FDG-uptake. Carbon ion radiotherapy(CIRT)(73.6 GyE/16 Fr)was performed. Serum CEA level and FDG-upt...

According to the treatment guideline for rectal neuroendocrine tumor(NET), tumor with a diameter ofC10mm should be resected endoscopically, while tumor with a diameter of>10mm should be resected surgically with lymph node dissection. We experienced a case of a rectal NET with a diameter of 5mm with lymph node metastasis. A 69-year-old man underwent...

Background BRCA-1 associated protein (BAP1) is a de-ubiquitinating enzyme that regulates gene expression. Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers. However, the frequency of BAP1 mutation and down-...

Primer sequences used for 17 exon sequencing of DNA. (PDF)

Sequences of siRNA. (PDF)

Sequences of M primer and UM primer. (PDF)

Expression of BAP1 in the GBC cell lines by RT-PCR. (PDF)

DNA methylation analysis of CpG island of BAP1. (PDF)

BAP1 expression of BAP1-methylated GBC cell line after treatment with 5-azacytidine. (PDF)

Schema of domains and detected mutations of BAP1. (PDF)

Sequences of primer of BAP1 and GAPDH for the RT-PCR. (PDF)

BAP1 down-regulation by siRNA in the GBC cell line. (PDF)

Epithelial mesenchymal transition (EMT) markers in the BAP1 knockdown GBC cell line. (PDF)

Kaplan–Meier survival analysis of BAP1 expression (Stage III, IV). (PDF)

BAP1 expression and detected mutations in clinical GBC (ID 14). (PDF)

Expression of BAP1 in the GBC cell lines by Western blotting. (PDF)

Purpose: The lymphatic flow along the posterior gastric artery (PGA) is considered of possible clinical importance in terms of lymphatic metastasis; however, little is known about the lymph nodes (LNs) around this artery. The purpose of this study was to establish if LNs exist around the PGA and to evaluate their clinical implications. Methods:...