Kazuhito Oka

Bio: Kazuhito Oka is an academic researcher from Yamaguchi University. The author has contributed to research in topics: Laparoscopic surgery & Sigmoid colon. The author has an hindex of 5, co-authored 13 publications receiving 165 citations.

Laparoscopic cecopexy for mobile cecum syndrome manifesting as cecal volvulus: Report of a case

Abstract: A 44-year-old woman was admitted to our hospital for investigation and treatment of sudden abdominal pain and distention. Plain abdominal radiography and abdominal computed tomography (CT) findings were suggestive of sigmoid volvulus. She underwent an emergency colonoscopy, and the scope passed easily through the sigmoid colon and reached the ascending colon quickly. However, stenosis with concentricity of the fold was observed in the cecum, which was shifted upward and to the left. Based on these findings, we diagnosed cecal volvulus caused by mobile cecum syndrome. The patient’s symptoms resolved quickly after colonoscopic reduction and elective laparoscopic surgery was performed 18 days after admission. Perioperative examination revealed a mobile cecum caused by an elongated ascending colon. We sutured the cecum and ascending colon to the lateral peritoneum laparoscopically with interrupted sutures. The patient recovered well and was discharged on postoperative day 7. An unfixed intestine can be detected easily during laparoscopic surgery, which is minimally invasive and cosmetically, physically, and economically beneficial. Thus, we recommend laparoscopic cecopexy for mobile cecum syndrome.

DNA damage signaling is activated during cancer progression in human colorectal carcinoma.

Abstract: Purpose: Recent studies have shown that the DNA damage response (DDR) is activated in precancerous lesions, suggesting that neoplastic cells may avoid apoptosis by impairing the DDR which acts as a barrier against tumor progression. To define the role of the DDR pathway in human colorectal carcinoma, we investigated the level of phosphorylated proteins of the DDR pathway.Experimental Design: Colorectal tissue samples were obtained at the time of surgery, from 55 patients at two hospitals. The tissues were classified into four groups according to pathology: normal mucosa, adenoma, early carcinoma and advanced carcinoma. We evaluated phosphorylated ataxia telangiectasia mutated (pATM), phosphorylated H2AX (γH2AX) and Chk2 (pChk2) protein levels by immunohistochemistry and Western blot analysis. We also evaluated apoptosis by the TUNEL assay.Results: Immunostaining for pATM, γH2AX and pChk2 revealed that all were significantly expressed during tumor progression in advanced carcinoma (vs. normal tissue for pA...

Laparoscopic resection of an ileal lipoma: Report of a case.

Abstract: A 63-year-old woman was admitted to our hospital for investigation of upper abdominal pain and vomiting. Ultrasonography (US) showed a hyperechoic mass in the right lower abdomen, and computed tomography (CT) showed a low-density mass and intestinal invagination. Thus, we made a diagnosis of intestinal lipoma with intussusception and performed laparoscopic partial resection of the ileum, including the tumor. The resected specimen contained a round tumor, 25 × 22 × 20 mm, which was identified as an intestinal lipoma histopathologically. Our experience supports earlier reports that US and CT are effective tools in the diagnosis of bowel lipoma. Laparoscopic surgery is the treatment of choice for benign tumors of the small intestine because it is minimally invasive, with cosmetic, physical, and economic benefits.

Early laparoscopic cholecystectomy for acute gangrenous cholecystitis.

Abstract: Treatment of severe acute cholecystitis by laparoscopic cholecystectomy remains controversial because of technical difficulties and high rates of complications and conversion to open cholecystectomy We investigated whether early laparoscopic cholecystectomy is appropriate for acute gangrenous cholecystitis Pathologic diagnoses and outcomes were analyzed in patients who underwent laparoscopic or open cholecystectomy at our hospital, January 2002 to September 2005 Of 30 patients with acute gangrenous cholecystitis, 16 underwent early laparoscopic cholecystectomy, 10 underwent open cholecystectomy, and 4 were converted to open cholecystectomy (conversion rate, 200%) There was no significant difference in operation time or intraoperative bleeding The requirement for postoperative analgesics was significantly lower (64+/-73 vs 15+/-12 doses, P<005) and hospital stay significantly shorter (86+/-21 vs 156+/-63 d, P<001) after laparoscopic cholecystectomy There were no postoperative complications in either group Thus, early laparoscopic cholecystectomy seems appropriate for acute gangrenous cholecystitis Conversion to open cholecystectomy may be required in difficult cases with complications

Loss of skeletal muscle mass after curative gastrectomy is a poor prognostic factor

Abstract: Sarcopenia has been reported to relate to poor prognosis in various malignant cancer types. The present study aimed to clarify the prognostic impact of skeletal muscle mass (SMM) loss after curative gastrectomy in patients with gastric cancer. A total of 119 patients who underwent curative gastrectomy for gastric cancer between 2009 and 2016 were analyzed. The SMM loss at 6 months postoperatively compared with the SMM prior to surgery was calculated using the hospital records. The median loss of SMM was 3.8%. Multivariate logistic regression analysis demonstrated that total gastrectomy was a significant and independent risk factor for SMM loss of ≥5% (odds ratio=2.58; P=0.02). Results from multivariate analysis using stepwise Cox proportional hazards regression indicated that the following factors were significantly associated with shorter overall survival after curative gastrectomy: Age [>70 years; hazard ratio (HR)=2.46, P=0.04], TNM stage (≥2; HR=2.65, P=0.04) and loss of SMM (≥5%; HR=2.57, P=0.03). The present findings suggested that loss of SMM after curative gastrectomy for gastric cancer is an independent predictive factor for poor prognosis.

Role of oxidative stress and DNA damage in human carcinogenesis.

Abstract: Cells in tissues and organs are continuously subjected to oxidative stress and free radicals on a daily basis. This free radical attack has exogenous or endogenous (intracellular) origin. The cells withstand and counteract this occurrence by the use of several and different defense mechanisms ranging from free radical scavengers like glutathione (GSH), vitamins C and E and antioxidant enzymes like catalase, superoxide dismutase and various peroxidases to sophisticated and elaborate DNA repair mechanisms. The outcome of this dynamic equilibrium is usually the induction of oxidatively induced DNA damage and a variety of lesions of small to high importance and dangerous for the cell i.e. isolated base lesions or single strand breaks (SSBs) to complex lesions like double strand breaks (DSBs) and other non-DSB oxidatively generated clustered DNA lesions (OCDLs). The accumulation of DNA damage through misrepair or incomplete repair may lead to mutagenesis and consequently transformation particularly if combined with a deficient apoptotic pathway. In this review, we present the current status of knowledge and evidence on the mechanisms and involvement of intracellular oxidative stress and DNA damage in human malignancy evolution and possible use of these parameters as cancer biomarkers. At the same time, we discuss controversies related to potential artifacts inherent to specific methodologies used for the measurement of oxidatively induced DNA lesions in human cells or tissues.

Intussusception of the bowel in adults: a review.

Abstract: Intussusception of the bowel is defined as the telescoping of a proximal segment of the gastrointestinal tract within the lumen of the adjacent segment. This condition is frequent in children and presents with the classic triad of cramping abdominal pain, bloody diarrhea and a palpable tender mass. However, bowel intussusception in adults is considered a rare condition, accounting for 5% of all cases of intussusceptions and almost 1%-5% of bowel obstruction. Eight to twenty percent of cases are idiopathic, without a lead point lesion. Secondary intussusception is caused by organic lesions, such as inflammatory bowel disease, postoperative adhesions, Meckel’s diverticulum, benign and malignant lesions, metastatic neoplasms or even iatrogenically, due to the presence of intestinal tubes, jejunostomy feeding tubes or after gastric surgery. Computed tomography is the most sensitive diagnostic modality and can distinguish between intussusceptions with and without a lead point. Surgery is the definitive treatment of adult intussusceptions. Formal bowel resection with oncological principles is followed for every case where a malignancy is suspected. Reduction of the intussuscepted bowel is considered safe for benign lesions in order to limit the extent of resection or to avoid the short bowel syndrome in certain circumstances.

Histone γH2AX and Poly(ADP-Ribose) as Clinical Pharmacodynamic Biomarkers

Abstract: Tumor cells are often deficient in DNA damage response (DDR) pathways, and anticancer therapies are commonly based on genotoxic treatments using radiation and/or drugs that damage DNA directly or interfere with DNA metabolism, leading to the formation of DNA double-strand breaks (DSB), and ultimately to cell death. Because DSBs induce the phosphorylation of histone H2AX (γH2AX) in the chromatin flanking the break site, an antibody directed against γH2AX can be employed to measure DNA damage levels before and after patient treatment. Poly(ADP-ribose) polymerases (PARP1 and PARP2) are also activated by DNA damage, and PARP inhibitors show promising activity in cancers with defective homologous recombination (HR) pathways for DSB repair. Ongoing clinical trials are testing combinations of PARP inhibitors with DNA damaging agents. Poly(ADP-ribosylation), abbreviated as PAR, can be measured in clinical samples and used to determine the efficiency of PARP inhibitors. This review summarizes the roles of γH2AX and PAR in the DDR, and their use as biomarkers to monitor drug response and guide clinical trials, especially phase 0 clinical trials. We also discuss the choices of relevant samples for γH2AX and PAR analyses.

The intestinal microbiota, gastrointestinal environment and colorectal cancer: a putative role for probiotics in prevention of colorectal cancer?

Abstract: Colorectal cancer (CRC) is the third most commonly diagnosed cancer in the United States, and, even though 5–15% of the total CRC cases can be attributed to individual genetic predisposition, environmental factors could be considered major factors in susceptibility to CRC. Lifestyle factors increasing the risks of CRC include elevated body mass index, obesity, and reduced physical activity. Additionally, a number of dietary elements have been associated with higher or lower incidence of CRC. In this context, it has been suggested that diets high in fruit and low in meat might have a protective effect, reducing the incidence of colorectal adenomas by modulating the composition of the normal nonpathogenic commensal microbiota. In addition, it has been demonstrated that changes in abundance of taxonomic groups have a profound impact on the gastrointestinal physiology, and an increasing number of studies are proposing that the microbiota mediates the generation of dietary factors triggering colon cancer. High-throughput sequencing and molecular taxonomic technologies are rapidly filling the knowledge gaps left by conventional microbiology techniques to obtain a comprehensive catalog of the human intestinal microbiota and their associated metabolic repertoire. The information provided by these studies will be essential to identify agents capable of modulating the massive amount of gut bacteria in safe noninvasive manners to prevent CRC. Probiotics, defined as “live microorganisms which, when administered in adequate amounts, confer a health benefit on the host” (219), are capable of transient modulation of the microbiota, and their beneficial effects include reinforcement of the natural defense mechanisms and protection against gastrointestinal disorders. Probiotics have been successfully used to manage infant diarrhea, food allergies, and inflammatory bowel disease; hence, the purpose of this review was to examine probiotic metabolic activities that may have an effect on the prevention of CRC by scavenging toxic compounds or preventing their generation in situ. Additionally, a brief consideration is given to safety evaluation and production methods in the context of probiotics efficacy.

γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies

Abstract: DNA double strand breaks (DSB) are the gravest form of DNA damage in eukaryotic cells. Failure to detect DSB and activate appropriate DNA damage responses can cause genomic instability, leading to tumorigenesis and possibly accelerated aging. Phosphorylated histone H2AX (γH2AX) is used as a biomarker of cellular response to DSB and its potential for monitoring DNA damage and repair in human populations has been explored in this review. A systematic search was conducted in PubMed for articles, in English, on human studies reporting γH2AX as a biomarker of either DNA repair or DNA damage. A total of 68 publications were identified. Thirty-four studies (50.0%) evaluated the effect of medical procedures or treatments on γH2AX levels; 20 (29.4%) monitored γH2AX in specific pathological conditions with a case/control or case/case design; 5 studies (7.4%) evaluated the effect of environmental genotoxic exposures, and 9 (13.2%) were descriptive studies on cancer and aging. Peripheral blood lymphocytes (44.6%) or biopsies/tissue specimens (24.3%) were the most commonly used samples. γH2AX was scored by optical microscopy as immunostained foci (78%), or by flow cytometry (16%). Critical features affecting the reliability of the assay, including protocols heterogeneity, specimen, cell cycle, kinetics, study design, and statistical analysis, are hereby discussed. Because of its sensitivity, efficiency and mechanistic relevance, the γH2AX assay has great potential as a DNA damage biomarker; however, the technical and epidemiological heterogeneity highlighted in this review infer a necessity for experimental standardization of the assay.