[Ulcerative colitis diagnosed with facial pyoderma gangrenosum: a case report].

Pyoderma gangrenosum (PG) is a sterile inflammatory skin condition that is frequently associated with immune-related diseases, including inflammatory bowel disease (IBD). PG causes noninfectious ulcers. Facial PG is uncommon while PG usually occurs on the trunk and lower limbs. Herein, we report a case of a male teenager with fever, pustules, ulcers, and necrosis on both cheeks. He was initially diagnosed with complicated acne with bacterial infection, but the condition progressed to subcutaneous ulcers despite treatment. Biopsy revealed inflammatory lesions in dermal and subcutaneous tissue with neutrophil infiltration, consistent with PG. Although lacking typical IBD symptoms, blood tests revealed anemia and positive fecal occult blood. Sigmoidoscopy revealed inflammation, ulcers, and pseudopolyps in the colon and rectum, thereby diagnosing ulcerative colitis (UC). After treating PG and UC with prednisolone and skin grafts, golimumab was prescribed. The patient is now in remission. Necrotic tissue buildup can complicate closure in PG cases;this emphasizes the need for effective IBD treatment to facilitate procedures such as skin grafts.

[Ulcerative colitis complicated by multiple aseptic subcutaneous abscesses: a case report].

A woman in her 40s, previously diagnosed with ulcerative colitis (UC), presented with anterior chest pain. A CT scan of her chest and skin examination showed no abnormal findings. She was initially managed with antibacterial agents, but her chest pain worsened, she developed a fever, and there was an overall deterioration of her general condition. A repeat CT scan found abscesses on the anterior surface of her sternum and gluteal region, and colonoscopy found worsening UC lesions. Her multiple subcutaneous abscesses were aseptic, and she was diagnosed with pyoderma gangrenosum (PG), an extraintestinal manifestation of UC. Steroid treatment was initiated and her overall condition as well as her subcutaneous abscesses improved rapidly. There are only a few case reports of PG without skin manifestation but only subcutaneous aseptic abscesses. However, subcutaneous abscesses may progress to PG with skin ulcers if initial treatment is delayed. Even with non-specific clinical features, prompt diagnosis of relapsed UC with potential extraintestinal manifestations must be considered. This is a rare case and aims to highlight the importance of early diagnosis and treatment of PG, which is an extraintestinal manifestation of relapsed UC.

[Inflammatory reactive polyposis caused by dasatinib:a case report].

A 51-year-old man with chronic myeloid leukemia undergoing treatment with dasatinib received colonoscopy for a positive fecal occult blood test. Colonoscopy revealed more than 100 erythematous, multilobulated polyps with mucoid discharge. Endoscopic mucosal resection was performed for diagnosis, and the histological analysis of polyps showed hyperplastic glands and proliferative smooth muscle cells. Our findings suggested that the polyposis was caused by inflammation triggered due to the adverse effects associated with dasatinib. The patient discontinued dasatinib;the follow-up colonoscopy performed four months later revealed significantly improved polypoid lesions in the colon. The erythematous heads of the polyps and mucoid discharge disappeared. The cessation of dasatinib seemed to contribute to the improvement of inflammatory reactive polyposis;therefore, we inferred that the polyposis was caused by dasatinib in the present case.

[A retrospective analysis of cetuximab or panitumumab monotherapy for KRAS wild-type metastatic colorectal cancer in clinical practice].

We performed a retrospective study on the use of cetuximab or panitumumab alone in patients with KRAS wild-type metastatic colorectal cancer between November 2008 and February 2012. Twenty-two patients were analyzed and classified as PS 0/1 (good PS group)and PS 2/3/4 (poor PS group)with 11 patients in each group. The response rate, disease control rate, median progression-free survival, and median overall survival were 9%, 73%, 5.1 months (95%confidence interval[CI]: 1.5-8.7), and 16 months (95% CI: 8.8-24), respectively, in the good PS group, and the corresponding values in the poor PS group were 0%, 18%, 0.7 months (95% CI: 0.3-1.0), and 1.5 months (95% CI: 0.7-2.4). Grade 3 or 4 adverse events were skin toxicities (2 patients with grade 3 toxicities), panitumumab-related interstitial lung disease (1 patient with grade 4 toxicity), and cetuximab infusion-related reaction (1 patient with grade 4 toxicity). No treatment-related deaths were observed. In conclusion, the efficacy and safety of cetuximab or panitumumab monotherapy in patients with a good PS in our study were similar to those reported in previous clinical trials, whereas patients with a poor PS showed poorer outcomes.

Risk factors for submucosal and lymphovascular invasion in gastric cancer looking indicative for endoscopic submucosal dissection.

BACKGROUND: Submucosal and lymphovascular (SM/LV) invasions of early gastric cancer (EGC) are difficult to diagnose accurately prior to endoscopic submucosal dissection (ESD), and are occasionally found in resected specimens, requiring additional gastrectomy and lymph node dissection. We performed a retrospective study to determine the risk factors for SM/LV invasions. METHODS: We analyzed clinicopathological data (age, sex, cancer location, gross morphology, multifocality, tumor size, histological differentiation, depth of invasion, and the presence or absence of lymphovascular invasion) in patients receiving ESD between 2007 and 2012 and presenting with EGC of 2.0 cm or smaller in size, a differentiated-type adenocarcinoma, and without ulceration. RESULTS: Of 208 lesions consecutively resected by ESD, 143 lesions in 132 patients were included in this study. Submucosal and lymphovascular invasions were detected in 16 lesions. Multivariate analysis revealed three independent risk factors for SM/LV invasions: dominant histology of moderately-differentiated or papillary adenocarcinoma, gross type of 0-IIa + IIc or IIc + IIa, and tumor size of ≥1.5 cm. Lesions exhibiting more than two of these three risk factors were associated with having a 47 % increased incidence of SM/LV invasion (odds ratio 15; 95 % confidence interval 4.6-49.0; P < 0.0001). CONCLUSIONS: Moderately-differentiated or papillary adenocarcinoma, 0-IIa + IIc or IIc + IIa, and a tumor size of ≥1.5 cm were identified as independent risk factors for SM/LV invasion among EGCs which appeared to be an endoscopically good indication for ESD. Careful surveillances including endoscopic ultrasonography or enhanced computed tomography might be needed for high risk patients before ESD.

[A case of malignant peritoneal mesothelioma with the epithelioid histological type, successfully treated with pemetrexed plus cisplatin].

A 45-year-old man presented with severe abdominal distention with massive ascites due to a diffusely disseminated peritoneal tumor. A core needle biopsy specimen was obtained from the peritoneal lesion. Histological diagnosis was epithelioid type mesothelioma. He did not choose to receive chemotherapy. For 2.5 years, he went without medical intervention, and his disease gradually progressed, leading to a worsening of his symptoms. The patient then chose to be treated with combination chemotherapy of cisplatin and pemetrexed, followed by pemetrexed alone. There was remarkable tumor shrinkage and his symptoms improved. These effects have been sustained for two years after the initial chemotherapy. Chemotherapy appears to have contributed to survival prolongation for this patient. This case exemplifies the fact that malignant peritoneal mesothelioma may progress slowly when fits with some good prognostic factors, and it is important to consider the prognostic factors.

Effects of Casein-Derived Peptide Met-Lys-Pro on Systolic and Diastolic Blood Pressure: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study.

Hypertension is defined as a systolic blood pressure (SBP) of over 140 mmHg or diastolic blood pressure (DBP) of over 90 mmHg. Hypertension is widely known to be a factor affecting human health, so its prevention is considered important. We investigated the effect of casein-derived tripeptide Met-Lys-Pro (MKP) on blood pressure in a randomized, placebo-controlled, parallel-group study. Participants were healthy adults with SBP between 120 and 139 mmHg, and/or DBP between 80 and 89 mmHg. A total of 121 participants were randomly assigned to the MKP group or placebo group. Participants received either a test powder containing 100 µg of MKP or a placebo powder without MKP for 12 weeks. As a result, SBP and DBP were significantly lower in the MKP group than in the placebo group. No adverse events associated with the MKP intake were observed. This study showed that MKP has a beneficial effect on lowering blood pressure in healthy adults with high-normal and elevated blood pressure and can be safely used for continuous intake.

Inferring the ecology of north-Pacific albacore tuna from catch-and-effort data.

Catch-and-effort data are among the primary sources of information for assessing the status of terrestrial wildlife and fish. In fishery science, elaborate stock-assessment models are fitted to such data in order to estimate fish-population sizes and guide management decisions. Given the importance of catch-and-effort data, we scoured a comprehensive dataset pertaining to albacore tuna (Thunnus alalunga) in the north Pacific Ocean for novel ecological information content about this commercially valuable species. Specifically, we used unsupervised learning based on finite mixture modelling to reveal that the north Pacific albacore-tuna stock can be divided into four pseudo-cohorts. We discovered that smaller body mass pseudo-cohorts inhabit relatively high-subtropical to temperate-latitudes, with hotspots off the coast of Japan. Larger body mass pseudo-cohorts inhabit lower-tropical to subtropical-latitudes, with hotspots in the western and central north Pacific. These results offer evidence that albacore tuna prefer different habitats depending on their body mass, and point to long-term migratory routes for the species that the current tagging technology is unlikely to capture in full. We discuss the implications of the results for data-driven modelling of albacore tuna in the north Pacific, as well as the management of the north Pacific albacore-tuna fishery.

Machine learning approaches to predict gestational age in normal and complicated pregnancies via urinary metabolomics analysis.

The elucidation of dynamic metabolomic changes during gestation is particularly important for the development of methods to evaluate pregnancy status or achieve earlier detection of pregnancy-related complications. Some studies have constructed models to evaluate pregnancy status and predict gestational age using omics data from blood biospecimens; however, less invasive methods are desired. Here we propose a model to predict gestational age, using urinary metabolite information. In our prospective cohort study, we collected 2741 urine samples from 187 healthy pregnant women, 23 patients with hypertensive disorders of pregnancy, and 14 patients with spontaneous preterm birth. Using gas chromatography-tandem mass spectrometry, we identified 184 urinary metabolites that showed dynamic systematic changes in healthy pregnant women according to gestational age. A model to predict gestational age during normal pregnancy progression was constructed; the correlation coefficient between actual and predicted weeks of gestation was 0.86. The predicted gestational ages of cases with hypertensive disorders of pregnancy exhibited significant progression, compared with actual gestational ages. This is the first study to predict gestational age in normal and complicated pregnancies by using urinary metabolite information. Minimally invasive urinary metabolomics might facilitate changes in the prediction of gestational age in various clinical settings.

Maternity Log study: a longitudinal lifelog monitoring and multiomics analysis for the early prediction of complicated pregnancy.

PURPOSE: A prospective cohort study for pregnant women, the Maternity Log study, was designed to construct a time-course high-resolution reference catalogue of bioinformatic data in pregnancy and explore the associations between genomic and environmental factors and the onset of pregnancy complications, such as hypertensive disorders of pregnancy, gestational diabetes mellitus and preterm labour, using continuous lifestyle monitoring combined with multiomics data on the genome, transcriptome, proteome, metabolome and microbiome. PARTICIPANTS: Pregnant women were recruited at the timing of first routine antenatal visits at Tohoku University Hospital, Sendai, Japan, between September 2015 and November 2016. Of the eligible women who were invited, 65.4% agreed to participate, and a total of 302 women were enrolled. The inclusion criteria were age ≥20 years and the ability to access the internet using a smartphone in the Japanese language. FINDINGS TO DATE: Study participants uploaded daily general health information including quality of sleep, condition of bowel movements and the presence of nausea, pain and uterine contractions. Participants also collected physiological data, such as body weight, blood pressure, heart rate and body temperature, using multiple home healthcare devices. The mean upload rate for each lifelog item was ranging from 67.4% (fetal movement) to 85.3% (physical activity), and the total number of data points was over 6 million. Biospecimens, including maternal plasma, serum, urine, saliva, dental plaque and cord blood, were collected for multiomics analysis. FUTURE PLANS: Lifelog and multiomics data will be used to construct a time-course high-resolution reference catalogue of pregnancy. The reference catalogue will allow us to discover relationships among multidimensional phenotypes and novel risk markers in pregnancy for the future personalised early prediction of pregnancy complications.

Successful Treatment with Modified FOLFOX6 and Panitumumab in a Cecal Cancer Patient Undergoing Hemodialysis.

Combination chemotherapy of mFOLFOX6 (5-fluorouracil, leucovorin, and oxaliplatin) plus panitumumab, a fully human monoclonal antibody against epidermal growth factor receptor (EGFR), is one of the standard treatments for metastatic colorectal cancer (mCRC) without KRAS mutation. A few reports suggested no need of dose adjustment of cetuximab, a similar chimeric anti-EGFR antibody, in patients with renal impairment. However, panitumumab combined with cytotoxic drugs for hemodialysis patients has not been reported. We herein report a case of a hemodialysis mCRC patient successfully treated with mFOLFOX6 and panitumumab combination therapy.

Antihypertensive effect of the bovine casein-derived peptide Met-Lys-Pro.

The antihypertensive effect of the bovine casein-derived peptide Met-Lys-Pro (MKP) was examined in vitro and in vivo. MKP showed angiotensin I-converting enzyme (ACE)-inhibitory activity in vitro (IC50 = 0.43 µM). An in vivo kinetics study using radiolabeled Met-[1-(14)C]Lys-Pro ((14)C-MKP) showed that orally administered (14)C-MKP to spontaneously hypertensive rats (SHRs) was absorbed and moved into the plasma. In vitro vasoconstriction of thoracic aorta preparations, which was induced by adding angiotensin I, was reduced by prior exposure of MKP. A single oral dose of MKP lowered systolic blood pressure (SBP) of SHRs, and repeated oral administration of MKP for 28 days significantly lowered SBP of SHRs. The results obtained in the present study suggest that orally administrated MKP can be absorbed into the plasma and its ACE-inhibitory activity may contribute to induce the antihypertensive effect in vivo.

Effectiveness of an endoscopic biopsy procedure using EUS-FNA and EMR-C for diagnosing adenocarcinoma arising from ectopic pancreas: two case reports and a literature review.

Adenocarcinomas arising from the ectopic pancreas in the gastrointestinal wall are rarely described in the literature. In addition, obtaining an accurate preoperative diagnosis is difficult in most cases because these adenocarcinomas occur primarily in the submucosal layer and form submucosal tumors. Endoscopic ultrasonography-guided fine-needle aspiration and endoscopic mucosal resection with a transparent plastic cap-fitted panendoscope followed by a biopsy are useful for histological typing and making the differential diagnosis of adenocarcinoma, gastrointestinal stromal tumor, malignant lymphoma or other. These procedures represent the first step toward diagnosing ectopic pancreatic adenocarcinoma. We herein report two such cases with a review of the pertinent literature.

Novel angiotensin I-converting enzyme inhibitory peptide derived from bovine casein.

Bovine lactic casein was hydrolysed using a combination of three enzymes, namely, subtilisin, bacillolysin, and trypsin, and the resulting preparation was coined CH-3. CH-3 showed angiotensin I-converting enzyme (ACE)-inhibitory activity (IC50: 74 µg/mL). A single oral administration of CH-3 led to a transient but significant decrease in the systolic blood pressure (SBP) of spontaneously hypertensive rats (SHRs), while daily oral administration of CH-3 for 28 consecutive days led to a lower rate of SBP increase. The CH-3 preparation was then fractionated and the αS2-casein-derived tripeptide Met-Lys-Pro (or MKP) was identified as a novel peptide with strong ACE-inhibitory activity (IC50=0.12 µg/mL, 0.3 µM). The MKP peptide constituted only 0.053% of CH-3 but its activity was accounted for 33% of the total ACE-inhibitory activity of CH-3. In addition, a single oral administration of MKP also led to a transient but significant decrease in the SBP of SHRs.

Evaluation of the effectiveness of light streamer tori-lines and characteristics of bait attacks by seabirds in the western North Pacific.

To improve the effectiveness of tori-lines it is necessary to evaluate the ability of tori-lines to mitigate seabird bycatch and determine what kind of seabird species gather during line settings, attack the bait and are incidentally caught. We conducted two experiments in the western North Pacific and examined the effectiveness for seabird mitigation of light streamer tori-lines which have no long streamers but many light (short) streamers and are mainly used in the North Pacific area. Firstly, the effectiveness of two different types of tori-line (light streamer (1 m) and long streamer (up to 7 m) tori-line) and of two different colors (yellow and red) of light streamers for seabird bycatch avoidance was evaluated using 567 sets based on data from 20 offshore surface commercial longliners. No significant difference in the bycatch number between the different tori-line types and streamer colors was found. Secondly, we investigated the characteristics of the seabird bycatch in the North Pacific and the effectiveness of three different types of streamers (light, hybrid and modified light types) by detailed observations of seabird attacks using a chartered longline vessel. Although the appearance rate of albatrosses and shearwaters were 40.9% and 27.7%, Laysan albatross was the main seabird species that followed the vessel but shearwaters seldom followed the vessel and did not aggregate during line setting. In all attacks on bait observed during line settings, 81% and 7% were by albatrosses and shearwaters, respectively. In the number of primary attacks by Laysan albatrosses which attacked most aggressively of all seabirds, there were no significant differences among the tori-line types. No individuals of shearwater were caught. The results of both experiments indicated that light streamer tori-lines were as effective as tori-lines with long streamers for mitigating seabird bycatch in the North Pacific.

Transport and release of chemicals from plastics to the environment and to wildlife.

Plastics debris in the marine environment, including resin pellets, fragments and microscopic plastic fragments, contain organic contaminants, including polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons, petroleum hydrocarbons, organochlorine pesticides (2,2'-bis(p-chlorophenyl)-1,1,1-trichloroethane, hexachlorinated hexanes), polybrominated diphenylethers, alkylphenols and bisphenol A, at concentrations from sub ng g(-1) to microg g(-1). Some of these compounds are added during plastics manufacture, while others adsorb from the surrounding seawater. Concentrations of hydrophobic contaminants adsorbed on plastics showed distinct spatial variations reflecting global pollution patterns. Model calculations and experimental observations consistently show that polyethylene accumulates more organic contaminants than other plastics such as polypropylene and polyvinyl chloride. Both a mathematical model using equilibrium partitioning and experimental data have demonstrated the transfer of contaminants from plastic to organisms. A feeding experiment indicated that PCBs could transfer from contaminated plastics to streaked shearwater chicks. Plasticizers, other plastics additives and constitutional monomers also present potential threats in terrestrial environments because they can leach from waste disposal sites into groundwater and/or surface waters. Leaching and degradation of plasticizers and polymers are complex phenomena dependent on environmental conditions in the landfill and the chemical properties of each additive. Bisphenol A concentrations in leachates from municipal waste disposal sites in tropical Asia ranged from sub microg l(-1) to mg l(-1) and were correlated with the level of economic development.