Molecular epidemiological study of germline APC variant associated with hereditary gastrointestinal polyposis in dogs: current frequency in Jack Russell Terriers in Japan and breed distribution.

BACKGROUND: Cases of gastrointestinal (GI) neoplastic polyps in Jack Russell Terriers (JRTs) have increased in Japan since the late 2000s. We recently demonstrated that JRTs with GI polyps heterozygously harbor an identical germline variant in the adenomatous polyposis coli (APC) gene, c.[462_463delinsTT]; therefore, this is an autosomal dominant hereditary disease. We conducted a molecular epidemiological study to explore the current frequency of the APC variant in JRTs in Japan and the breed distribution of this disease. RESULTS: Peripheral blood samples from 792 JRTs were collected at 93 veterinary hospitals in Japan in 2020. Using an established polymerase chain reaction-restriction fragment length polymorphism assay, the germline APC variant was detected in 15 JRTs, with an overall frequency of 1.89%. The frequency was not significantly different for sex, age, and coat type criteria. Notably, the variant carriers had a current or previous history of GI neoplastic polyps, providing further evidence of the association of the germline APC variant with GI polyposis. Pedigree analysis of carrier dogs revealed that the germline APC variant was no longer confined to a few specific families but was widely spread among JRTs in Japan. Furthermore, some ancestors of the carriers were from Australia or New Zealand, suggesting the possible presence of carriers in countries other than Japan. Next, we retrospectively investigated the germline APC variant status of dogs with GI epithelial tumors using genomic DNA samples extracted from archived pathological specimens (28 purebred dogs of 14 breeds and four mixed-breed dog), as well as those stored in a canine genome bank (38 dogs of 18 breeds and a mixed-breed dogs). In total, 66 purebred dogs of 25 breeds, including another four JRTs, and five mixed-breed dogs were examined. While three variant carriers were found in JRTs, the germline APC variant was not detected in any of the other breeds. CONCLUSION: The current frequency of the germline APC variant was approximately 2% in JRTs in Japan and the frequency remained roughly flat during the last 15 years. In addition, hereditary GI polyposis associated with the variant was virtually specific to JRTs.

Gestational Age Dependency of Umbilical Cord Serum IL-6 Levels for Detecting Fetal Inflammation.

OBJECTIVE: The fetal inflammatory response syndrome (FIRS) is characterized by elevated concentrations of inflammatory cytokines in fetal blood, with preterm delivery and morbidity. Umbilical cord serum interleukin-6 (UC-s-IL-6) is an ideal marker for detecting FIRS. However, the effect of gestational age (GA) on UC-s-IL-6 levels has not been reported. This study aimed to determine the relationship between GA and UC-s-IL-6 levels, and GA-dependent cutoff values of UC-s-IL-6 levels for detecting fetal inflammation. STUDY DESIGN: UC-s-IL-6 concentrations were measured in 194 newborns (44 extremely preterm newborns (EPNs) at 22-27 weeks' GA, 68 very preterm newborns (VPNs) at 28-31 weeks' GA, and 82 preterm newborns (PNs) at 32-34 weeks' GA). Linear regression analyses were used to correlate GA and UC-s-IL-6 levels. Receiver operating characteristic (ROC) curves analyses were performed for detecting the presence of funisitis, as the histopathological counterpart of FIRS. RESULTS: A significant negative correlation between GA and UC-s-IL-6 levels was found in newborns with severe funisitis (r s = - 0.427, p = 0.004) and those with mild funisitis (r s = - 0.396, p = 0.025). ROC curve analyses revealed the area under the curve for detecting funisitis were 0.856, 0.837, and 0.622 in EPNs, VPNs, and PNs, respectively. The UC-s-IL-6 cutoff value in EPNs (28.1 pg/mL) exceeded those in VPNs and PNs (3.7 and 3.0 pg/mL, respectively). CONCLUSION: UC-s-IL-6 levels were inversely correlated with GA especially in newborns with funisitis. Such GA dependency of UC-s-IL-6 should be considered for detecting fetal inflammation. KEY POINTS: · IL-6 levels inversely correlate with GA.. · Higher IL-6 levels strongly indicate funisitis.. · Detecting cutoff values differ depending on GA..

The potential of organoids in toxicologic pathology: Histopathological and immunohistochemical evaluation of a mouse normal tissue-derived organoid-based carcinogenesis model.

Recently, we introduced an organoid-based chemical carcinogenesis model using mouse normal tissue-derived organoids. In the present review article, the histopathological and immunohistochemical characteristics of mouse normal tissue-derived organoids and tumors derived from these organoids after their in vitro treatment with genotoxic carcinogens and injection into nude mouse are reviewed. In organoids treated in vitro with genotoxic carcinogens, we confirmed macroscopic tumorigenicity and histopathological findings, including neoplastic characteristics, such as multilayered epithelia and/or invasion of epithelia into the surrounding interstitium. In contrast glandular/cystic structures with monolayered epithelia were clearly demarcated from the surrounding Matrigel/interstitium in the untreated control groups. In addition to macroscopic tumorigenicity, these microscopic epithelial changes, which are characteristic of the early stages of carcinogenesis, are included in the requirements for carcinogenicity-positive judgement of the organoid-based carcinogenesis model. Immunohistochemistry of cytokeratins (CKs), used to determine the origin of epithelia and distribution of extraductal invasive lesions, or oncogenic kinases, which reflect molecular activation in epithelia following chemical treatment, is helpful for accurate diagnosis and molecular evaluation in the early stages of carcinogenesis. This information improves our biological understanding of organoid-based chemical carcinogenesis models.

Familial adenomatous polyposis in dogs: hereditary gastrointestinal polyposis in Jack Russell Terriers with germline APC mutations.

Many hereditary disorders in dogs have equivalents in humans and thus attract attention as natural animal models. Breed predisposition to certain diseases often provides promising clues to explore novel hereditary disorders in dogs. Recently, cases of gastrointestinal (GI) polyps in Jack Russell Terriers (JRTs) have increased in Japan. In 21 affected JRTs, polyps were found in either or both the stomach and colorectum, with a predilection for the gastric antrum and rectum. Multiple polyps were found in 13 of 21 examined dogs, including 5 dogs with both gastric and colorectal polyps. Some dogs were found to have GI polyps at an early age, with the youngest case being 2.3 years old. Histopathologically, 43 of 46 GI polyps (93.5%) were diagnosed as adenomas or adenocarcinomas. Immunohistochemical analysis revealed cytoplasmic and nuclear accumulation of ß-catenin in the tumor cells. As in the case of human patients with familial adenomatous polyposis, all examined JRTs with GI polyps (n = 21) harbored the identical heterozygous germline APC mutations, represented by a 2-bp substitution (c.[462A>T; 463A>T]). The latter substitution was a non-sense mutation (p.K155X) resulting in a truncated APC protein, thus suggesting a strong association with this cancer-prone disorder. Somatic mutation and loss of the wild-type APC allele were detected in the GI tumors of JRTs, suggesting that biallelic APC inactivation was involved in tumor development. This study demonstrated that despite differences in the disease conditions between human and dog diseases, germline APC mutation confers a predisposition to GI neoplastic polyps in both dogs and humans.

Specific Deletion of p16INK4a with Retention of p19ARF Enhances the Development of Invasive Oral Squamous Cell Carcinoma.

The cyclin-dependent kinase inhibitor 2A (CDKN2A)/alternate reading frame (ARF) locus consists of two overlapping tumor suppressor genes, p16INK4a and p14ARF (p19ARF in mice), encoding two unrelated proteins in alternative reading frames. Previous reports suggest that p16INK4a and p14ARF alterations independently exhibit differential roles, and p16INK4a is more closely associated with a poor prognosis in oral cancer. However, the role of p16INK4a-specific loss in oral squamous cell carcinogenesis remains unclear. The authors assessed chemical carcinogen 4-nitroquinoline 1-oxide (4NQO)-induced multistep oral squamous cell carcinogenesis in mice carrying p16INK4a-specific loss with retention of the p19ARF gene (p16INK4a-/-). 4NQO-treated p16-/- mice exhibited a higher incidence and multiplicity of oral squamous cell carcinoma (OSCC) development relative to 4NQO-treated wild-type mice. 4NQO-treated p16INK4a-/- OSCC cells exhibited higher proliferation and up-regulation of Arf, transcription factor E2f1, tumor protein p63 (tp63), and oncogenic ΔNp63, an isoform p63, compared with observations in 4NQO-treated wild-type OSCC cells. Furthermore, the overexpression of oncogenic ΔNp63 was associated with human OSCC. In conclusion, these results in mice indicate the biological significance of p16INK4a-specific loss with retention of p19ARF in oral squamous cell carcinogenesis, and ΔNp63 may be a potential target for OSCC.

Rapid changes in serum IL-6 levels in preterm newborns with Gram-negative early-onset sepsis.

Early-onset sepsis (EOS) remains a leading cause of morbidity and mortality for newborns, especially in preterm birth. Serum IL-6 levels are used as an accurate marker for EOS; however, no study has focused on the changes in serum IL-6 levels in newborns with EOS. Here, we investigated 6 preterm newborns (23.4-28.2 wks' gestational age) with birthweights of 570-1080 g who were diagnosed with EOS. All newborns received active treatment, including exchange transfusions and/or polymyxin B-immobilized fiber column direct hemoperfusion for septic shock. In the 3 surviving newborns, serum-IL-6 levels peaked at >500,000, 256,500, and 356,000 pg/mL within 12 h of life, and then decreased to <100 pg/mL by 72 h of life. In the 3 newborns who died at 17, 30, and 61 h of life, serum IL-6 levels increased to >500,000, 198,000, and 1,354,000 pg/mL, respectively, prior to death. Therefore, in preterm newborns suspected of EOS, serial serum IL-6 determinations would be useful for not only detecting EOS, but also for monitoring sepsis severity.

PCR-based genotyping assays to detect germline APC variant associated with hereditary gastrointestinal polyposis in Jack Russell terriers.

BACKGROUND: The prevalence of gastrointestinal (GI) neoplastic polyps in Jack Russell terriers (JRTs) has increased in Japan since the late 2000s. Recently, we demonstrated that JRTs with GI polyps harbor identical germline variant in the APC gene (c.[462_463delinsTT]) in the heterozygous state. Thus, this disease is an autosomal dominant hereditary disorder. Although the affected JRTs have distinct features, such as the development of multiple GI polyps and an early age of disease onset, genetic testing is indispensable for a definitive diagnosis. Here, polymerase chain reaction (PCR)-based assays capable of detecting germline APC variant were designed and validated using synthetic wild-type and mutant DNAs and genomic DNAs from carrier and non-carrier dogs. RESULT: First, the PCR-restriction fragment length polymorphism (PCR-RFLP) assay was developed by taking advantage of the germline APC variant creating a new restriction site for MseI. In the PCR-RFLP assay, the 156-bp region containing the variant site was amplified by PCR and subsequently digested with MseI, yielding diagnostic 51 and 58 bp fragments from the mutant allele and allowing determination of the APC genotypes. It was possible to determine the genotypes using genomic DNA extracted from the peripheral blood, buccal swab, or formalin-fixed paraffin-embedded tissue. Next, a TaqMan duplex real-time PCR assay was developed, where a 78-bp region flanking the variant was amplified in the presence of wild-type allele- and mutant allele-specific fluorescent probes. Using blood-derived DNA, altogether 40 cycles of PCR amplification determined the APC genotypes of all examined samples by measuring the fluorescence intensities. Importantly, false-positive and false-negative errors were never detected in both assays. CONCLUSION: In this study, we developed highly reliable genetic tests for hereditary GI polyposis in JRTs, providing accurate assessment of the presence of the causative germline APC variant. The genotyping assays could contribute to the diagnosis and prevention of hereditary GI polyposis in dogs.

Hepatic neuroendocrine carcinoma in a Japanese macaque (Macaca fuscata).

Primary neuroendocrine neoplasm of the liver is extremely rare in both humans and non-human primates. The present report describes the clinical and pathological findings of an aged Japanese macaque (Macaca fuscata) with hepatic neuroendocrine carcinoma. To our knowledge, this is the first report of hepatic neuroendocrine neoplasm in macaques.

Heterogeneity of Colon Cancer Stem Cells.

Colorectal cancer (CRC) remains the fourth leading cause of cancer death worldwide. Cancer stem cells (CSCs) have attracted a great deal of interest because of their potential clinical implications in a range of cancers, including CRC. CSCs were initially considered to be cell populations with well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent a phenotypically and functionally heterogeneous population. Recent studies also demonstrate colorectal CSCs to be dynamic rather than static populations that are continuously altered by various extrinsic factors in addition to intrinsic cellular factors such as genetic and epigenetic alterations. Thus, CSCs do not represent a fixed target population any longer, and their heterogeneous and dynamic nature present a serious problem in establishing specific therapeutic strategies. This chapter summarizes past and current literature related to CSC population heterogeneity and dynamics in CRC tissues, including evidence of the presence of distinct CSC subpopulations and signaling pathways and intra- and extra-tumoral factors involved in the regulation of CSCs in cancer tissues.

Effects of food restriction on the expression of genes related to acetaminophen-induced liver toxicity in rats.

It is well known that fasting substantially affects the metabolism of drugs and chemicals. Food restriction also affects drug kinetics, such as absorption, metabolism, and excretion, and therefore, it can potentially modulate the onset of chemical toxicity or drug-induced adverse reactions. In the present study, the expression of drug-metabolizing enzyme genes and total glutathione content in the liver, which are related to toxicity induced by overdose of the hepatotoxic drug acetaminophen (N-acetyl-p-aminophenol; APAP), were examined in rats reared under different feeding conditions: ad libitum feeding, 16-h fasting, and food restriction (fed 70% of the average intake of ad libitum feeding for 10 days) conditions. The rats under food restriction conditions as well as fasted rats showed significantly higher expression of Cyp2e1, the gene encoding the enzyme that metabolizes APAP to its toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). They also had lower levels of liver total glutathione, which detoxifies NAPQI. In contrast, the gene expression of UDP-glucuronosyltransferase 1A6 (Ugt1a6), sulfotransferase 1A1 (Sult1a1), and glutathione S-transferase M1 (Gstm1) was not affected by food restriction or fasting. When APAP was administered (800 mg/kg), histopathological changes were not observed in rats fed ad libitum, while hepatocellular necrosis was observed in most of the rats treated with APAP after fasting or food restriction. Taken together, these results suggest that not only fasting but also food restriction exacerbate APAP-induced acute liver injury, probably by the induction of CYP2E1 and the reduction of liver glutathione contents, in rodents.

Brazilian green propolis suppresses acetaminophen-induced hepatocellular necrosis by modulating inflammation-related factors in rats.

Propolis is a resin-like material produced by honey bees from bud exudates and sap of plants and their own secretions. An ethanol extract of Brazilian green propolis (EEBGP) contains prenylated phenylpropanoids and flavonoids and has antioxidative and anti-inflammatory effects. Acetaminophen (N-acetyl-p-aminophenol; APAP) is a typical hepatotoxic drug, and APAP-treated rats are widely used as a model of drug-induced liver injury. Oxidative stress and inflammatory reactions cause APAP-induced hepatocellular necrosis and are also related to expansion of the lesion. In the present study, we investigated the preventive effects of EEBGP on APAP-induced hepatocellular necrosis in rats and the protective mechanism including the expression of antioxidative enzyme genes and inflammation-related genes. A histological analysis revealed that administration 0.3% EEBGP in the diet for seven days reduced centrilobular hepatocellular necrosis with inflammatory cell infiltration induced by oral administration of APAP (800 mg/kg) and significantly reduced the area of necrosis. EEBGP administration did not significantly change the mRNA expression levels of antioxidant enzyme genes in the liver of APAP-treated rats but decreased the mRNA expression of cytokines including Il10 and Il1b, with a significant difference in Il10 expression. In addition, the decrease in the mRNA levels of the Il1b and Il10 genes significantly correlated with the decrease in the percentage of hepatocellular necrosis. These findings suggest that EEBGP could suppress APAP-induced hepatocellular necrosis by modulating cytokine expression.

[A Case of Locally Advanced Sigmoid Colon Cancer Occupying the Pelvis with Successful Total Posterior Pelvic Exenteration after Triplet Chemotherapy].

We report a case of locally advanced colon cancer that directly invaded the rectum wall and uterus resulting in huge mass in the whole pelvis that we could successfully made complete radical resection of the whole tumor without exposing the tumor to the surgical margin after the triplet chemotherapy. The patient was a 57-year-old woman complaining of anus pain, melena, fever, and weight loss. Although swelling of the regional lymph node was observed, no distant metastasis was found resulting in clinical diagnosis of Stage Ⅲb. However, oncologically safe complete resection seemed difficult; thus, chemotherapy( 3 courses of FOLFOX followed by 3 courses of FOLFOXIRI plus bevacizumab)was administered. As a result, significant tumor reduction was observed; therefore, the tumor was completely resected with posterior pelvic exenteration. Final staging was ypT4bypN0M0(ypStage Ⅱ). Eight courses of CapeOX was administered as adjuvant chemotherapy.

Hepatocellular carcinoma with intracranial metastasis in a Japanese macaque (Macaca fuscata).

BACKGROUND: A 23-year-old male Japanese macaque (Macaca fuscata) showed left ptosis, which progressed to exophthalmos. METHODS: The macaque underwent a clinical examination, CT and MRI, and was euthanized. Necropsy and histopathological examination were performed after euthanasia. RESULTS: The CT revealed and MRI confirmed an intracranial mass at the skull base with orbital extension. At necropsy, there were a large hepatic mass and an intracranial mass compressing the left temporal lobe of the brain. Histopathological and immunohistological examinations revealed that the masses were hepatocellular carcinoma (HCC) and a metastatic lesion. In both the primary and metastatic lesions, neoplastic hepatocytes were arranged mainly in a trabecular pattern. Immunohistochemically, the tumor cells were positive for cytokeratin (AE1/AE3 and CAM5.2) and hepatocyte paraffin 1 and negative for cytokeratin 7 and 20 and vimentin. CONCLUSION: To our knowledge, this is the first case report of HCC with intracranial metastasis in a macaque.

Does Braun Anastomosis Have an Impact on the Incidence of Delayed Gastric Emptying and the Extent of Intragastric Bile Reflux Following Pancreatoduodenectomy? - A Randomized Controlled Study.

BACKGROUND/AIMS: This study investigated the impact of Braun anastomosis on the incidence of delayed gastric emptying (DGE) and on the intragastric bile reflux after pancreatoduodenectomy with Child reconstruction. METHODS: Sixty-eight patients who underwent subtotal stomach-preserving pancreatoduodenectomy were included. Patients were randomly assigned to a group with or without Braun anastomosis intraoperatively. Twenty-four-hour intragastric bilirubin monitoring was performed to investigate the extent of intragastric bile reflux after surgery. The incidence of DGE and other complications was also monitored. RESULTS: There were no differences between the non-Braun and Braun groups in terms of patient characteristics. The incidence rate of DGE was 29.4% (n = 10/34) in the non-Braun group and 20.6% (n = 7/34) in the Braun group (p = 0.401). Forty-six of the 68 patients consented to intragastric bilirubin monitoring. The fraction time of intragastric bilirubin reflux was comparable between the 2 groups. Although the fraction time of intragastric bilirubin reflux had no impact on the incidence of DGE, the incidence of pancreatic fistula was significantly higher in patients with DGE than those without DGE (47.1 vs. 21.6%, p = 0.043). CONCLUSION: The addition of Braun anastomosis after pancreatoduodenectomy did not effectively reduce the intragastric bile reflux and had minor impact in reducing the incidence of DGE.

Clinicopathological characteristics of cancer associated with Crohn's disease.

PURPOSE: We examined the clinicopathological characteristics and prognosis of patients with cancer associated with Crohn's disease (CD). METHODS: The subjects of this study were patients with cancer confirmed in a resected specimen of bowel, who were treated at our institution between September, 1974 and December, 2014. RESULTS: We analyzed 34 patients (26 men, 8 women, median age at cancer diagnosis 43.5 years, duration of illness 18 years) and found that the number of those with CD complicated with cancer began to drastically increase after 2005. The site of onset of cancer was in an anorectal lesion in 24 (70.6 %) patients. In 17 (50 %) patients, the cancer was diagnosed before surgery; in 3 patients (8.8 %), it was based on pathological findings during surgery; and in 14 patients (41.2 %), it was based on postoperative pathological findings. Mucinous carcinoma was the dominant histological type, seen in 15 patients (44.1 %), while the special type of signet-ring cell carcinoma was found in 4 patients. The cumulative overall 5 year survival rate was 46.2 %. CONCLUSION: In this group of Japanese CD patients, an anorectal lesion was the most frequent site of origin of cancer. As cancer was diagnosed preoperatively in only 50 % of these patients, the overall prognosis was poor, with a cumulative 5 year survival rate of just 46.2 %.

Rectal-sparing type of ulcerative colitis predicts lack of response to pharmacotherapies.

BACKGROUND: Ulcerative colitis (UC) is known as an immune disorder of the colon that generally involves the rectum, but an atypical distribution of inflamed mucosa has previously been noted in certain subtypes of UC, such as the rectal-sparing type (RST). As noted in a previous report, patients with the RST may be at elevated risk for disease refractoriness, but the clinical significance of RST remains unknown. METHODS: UC patients who underwent surgery between January 2010 and April 2015 were included. Patients were classified as having the RST or a non-RST based on colectomy specimens or a pre-operative endoscopy. Possible risk factors for urgent/emergent surgery were analyzed. We specifically determined whether the RST is a significant predictor for urgent/emergent surgery. RESULTS: In total, 46/482 patients were classified as having the RST. Disease severity was significantly worse in patients with the RST than in other patients (p = 0.02). Urgent/emergent surgery was required for 24/46 patients with the RST, compared with 107/436 non-RST patients (p < 0.01). The overall incidence of urgent/emergent surgery was 131/482. Disease duration < 70.2 months [odds ratio (OR) 2.45], severe disease (OR 87.1), total administered steroid dose < 5000 mg (OR 3.02), daily pre-operative steroid dose ≥ 9 mg (OR 2.59), and the RST (OR 5.59) were identified as independent risk factors for urgent/emergent surgery. CONCLUSION: The RST was an independent risk factor for urgent/emergent surgery in our analysis of surgically treated patients with UC.

Multifaceted Interpretation of Colon Cancer Stem Cells.

Colon cancer is one of the leading causes of cancer-related deaths worldwide, despite recent advances in clinical oncology. Accumulating evidence sheds light on the existence of cancer stem cells and their role in conferring therapeutic resistance. Cancer stem cells are a minor fraction of cancer cells, which enable tumor heterogeneity and initiate tumor formation. In addition, these cells are resistant to various cytotoxic factors. Therefore, elimination of cancer stem cells is difficult but essential to cure the malignant foci completely. Herein, we review the recent evidence for intestinal stem cells and colon cancer stem cells, methods to detect the tumor-initiating cells, and clinical significance of cancer stem cell markers. We also describe the emerging problems of cancer stem cell theory, including bidirectional conversion and intertumoral heterogeneity of stem cell phenotype.

Dose-dependent roles for canonical Wnt signalling in de novo crypt formation and cell cycle properties of the colonic epithelium.

There is a gradient of ß-catenin expression along the colonic crypt axis with the highest levels at the crypt bottom. In addition, colorectal cancers show a heterogeneous subcellular pattern of ß-catenin accumulation. However, it remains unclear whether different levels of Wnt signalling exert distinct roles in the colonic epithelium. Here, we investigated the dose-dependent effect of canonical Wnt activation on colonic epithelial differentiation by controlling the expression levels of stabilised ß-catenin using a doxycycline-inducible transgenic system in mice. We show that elevated levels of Wnt signalling induce the amplification of Lgr5+ cells, which is accompanied by crypt fission and a reduction in cell proliferation among progenitor cells. By contrast, lower levels of ß-catenin induction enhance cell proliferation rates of epithelial progenitors without affecting crypt fission rates. Notably, slow-cycling cells produced by ß-catenin activation exhibit activation of Notch signalling. Consistent with the interpretation that the combination of Notch and Wnt signalling maintains crypt cells in a low proliferative state, the treatment of ß-catenin-expressing mice with a Notch inhibitor turned such slow-cycling cells into actively proliferating cells. Our results indicate that the activation of the canonical Wnt signalling pathway is sufficient for de novo crypt formation, and suggest that different levels of canonical Wnt activations, in cooperation with Notch signalling, establish a hierarchy of slower-cycling stem cells and faster-cycling progenitor cells characteristic for the colonic epithelium.

Retrocolic or Antecolic Roux-en-Y Reconstruction after Distal Gastrectomy: Which Is More Effective in the Prevention of Postoperative Gastroesophageal Reflux Disease.

BACKGROUND: It is unclear which reconstructive route (retrocolic or antecolic) is more effective in preventing postoperative gastroesophageal reflux disease (GERD) in Roux-en-Y reconstruction following distal gastrectomy. METHODS: Eighty-one eligible patients (retrocolic, n = 39; antecolic, n = 42) underwent endoscopies before surgery and 1 year after surgery to evaluate reflux esophagitis according to the Los Angeles classifications. The relative anatomical position of gastrojejunostomy to the cardia was measured by CT imaging. RESULTS: The proportion of patients with reflux esophagitis was also significantly higher in the antecolic group than in the retrocolic group (38.1 vs. 10.3%, p = 0.005). Multivariate analysis revealed that antecolic reconstruction and body mass index (BMI) were independent risk factors for reflux esophagitis. The relative position of gastrojejunostomy to the cardia in the antecolic group was shifted to the left laterally (59.0 vs. 28.8 degree, p < 0.001) and ventrally (65.4 vs. 39.8 degree, p < 0.001) than in the retrocolic group. There was a positive correlation between BMI and left lateral and ventral shifts of gastrojejunostomy in the antecolic group. CONCLUSION: Retrocolic reconstruction may be superior to antecolic reconstruction in preventing postoperative GERD, especially in obese patients. The left lateral and ventral shifts of gastrojejunostomy after antecolic reconstruction may aggravate the occurrence of GERD.

Retinal Cell Degeneration in Animal Models.

The aim of this review is to provide an overview of various retinal cell degeneration models in animal induced by chemicals (N-methyl-D-aspartate- and CoCl2-induced), autoimmune (experimental autoimmune encephalomyelitis), mechanical stress (optic nerve crush-induced, light-induced) and ischemia (transient retinal ischemia-induced). The target regions, pathology and proposed mechanism of each model are described in a comparative fashion. Animal models of retinal cell degeneration provide insight into the underlying mechanisms of the disease, and will facilitate the development of novel effective therapeutic drugs to treat retinal cell damage.