Glycogenic hepatopathy following attempted suicide by long-acting insulin overdose in patient with type 1 diabetes.

Patients with poorly controlled insulin-dependent type 1 or type 2 diabetes rarely present with glycogenic hepatopathy, which is characterized by hepatomegaly and liver enzyme abnormalities. Glycogenic hepatopathy occurs as a consequence of excessive accumulation of glycogen in hepatocytes caused by insulin. We report a young male patient with type 1 diabetes mellitus who developed glycogenic hepatopathy following a suicide attempt by insulin overdose via subcutaneous injection. The patient's medication/nutrition compliance and adherence to insulin were poorly controlled due to comorbid schizophrenia. Our patient required a large amount of continuous glucose to maintain euglycemia for persistent intractable hypoglycemia induced by overdose of long-acting insulin. On admission day 4, the patient presented elevated transaminases, hepatomegaly, and lactic acidosis. Computed tomography revealed swollen liver parenchyma with a diffusely high absorption. The patient gradually recovered without any medical intervention except for adequate control of blood sugar and was moved to a psychiatric ward on day 8 for schizophrenia management. This report may help emergency physicians be aware of the common symptoms, clinical course, and pathophysiology of glycogenic hepatopathy. Doctors should include glycogenic hepatopathy in the differential diagnosis of abnormal liver enzymes and hepatomegaly for those with poorly controlled insulin-dependent diabetes mellitus or unstable blood sugar levels due to insulin overdose like our patient.

A case of spontaneous mesenteric hematoma successfully diagnosed and treated with aggressive imaging.

INTRODUCTION: Spontaneous mesenteric hematoma is an uncommon syndrome triggered by bleeding localized in the mesenteric vascular tree of a bowel segment for no apparent underlying reason. We herein report a surgical patient with an extremely rapidly growing spontaneous mesenteric hematoma that we successfully diagnosed using careful radiologic examination. PRESENTATION OF CASE: A 56-year-old old male presenting sudden onset lower abdominal pain was referred to our emergency department. At the time of admission, his physical examination revealed stable vital signs without radiological abnormality. On the following day, the patient suddenly presented hypotension, tachycardia, and increased abdominal pain. Contrast-enhanced computed tomography examination showed a mass with both high- and low-density areas with a 130 mm maximum diameter bordering the transverse colon. Since interventional radiologists were not available, we decided to perform emergency exploratory laparotomy. On laparotomy, a 13 × 8 cm hematoma was found in the mesentery of the transverse colon. As bleeding was noted from the branches of the middle colic artery and gastrocolic artery, these responsible vessels were ligated. The patient was finally given the diagnosis of spontaneous mesenteric hematoma. DISCUSSION AND CONCLUSION: The present case, initially diagnosed as enterocolitis, suddenly manifested hypovolemic shock. Close monitoring for any signs of further deterioration, as well as aggressive imaging diagnosis, enabled us to avoid delays in treatment. Early diagnosis and treatment of mesenteric hematomas are essential to prevent them from rupturing and triggering life-threatening adverse events.

Recommended configuration for personal health records by standardized data item sets for diabetes mellitus and associated chronic diseases: a report from a collaborative initiative by six Japanese associations.

It is expected that a large amount of data related to diabetes and other chronic diseases will be generated. However, databases constructed without standardized data item sets can be limited in their usefulness. To address this, the Collaborative Committee of Clinical Informatization in Diabetes Mellitus was established in 2011 by the Japan Diabetes Society and Japan Association for Medical Informatics. The committee has developed core item sets and self-management item sets for diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in collaboration with the Japanese Society of Hypertension, Japan Atherosclerosis Society, Japanese Society of Nephrology, and Japanese Society of Laboratory Medicine, as well as a mapping table that aligns the self-management item sets with the Japanese standardized codes for laboratory testing. The committee also determined detailed specifications for implementing the four self-management item sets in personal health record applications to facilitate risk stratification, the generation of alerts using information and communications technology systems, the avoidance of data input errors, and the generation of reminders to input the self-management item set data. The approach developed by the committee may be useful for combining databases for various purposes (such as for clinical studies, patient education, and electronic medical record systems) and for facilitating collaboration between personal health record administrators.

Recommended configuration for personal health records by standardized data item sets for diabetes mellitus and associated chronic diseases: A report from Collaborative Initiative by six Japanese Associations.

It is expected that a large amount of data related to diabetes and other chronic diseases will be generated. However, databases constructed without standardized data item sets can be limited in their usefulness. To address this, the Collaborative Committee of Clinical Informatization in Diabetes Mellitus was established in 2011 by the Japan Diabetes Society and Japan Association for Medical Informatics. The committee has developed core item sets and self-management item sets for diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease in collaboration with the Japanese Society of Hypertension, Japan Atherosclerosis Society, Japanese Society of Nephrology, and Japanese Society of Laboratory Medicine, as well as a mapping table that aligns the self-management item sets with the Japanese standardized codes for laboratory testing. The committee also determined detailed specifications for implementing the four self-management item sets in personal health record (PHR) applications to facilitate risk stratification, the generation of alerts using information and communications technology systems, the avoidance of data input errors, and the generation of reminders to input the self-management item set data. The approach developed by the committee may be useful for combining databases for various purposes (such as for clinical studies, patient education, and electronic medical record systems) and for facilitating collaboration between PHR administrators.

Ictal Cardiorespiratory Arrest Associated with Status Epilepticus in Panayiotopoulos Syndrome.

A healthy 10-year-old boy vomited during sleep and later complained of abdominal pain; he became drowsy and uncommunicative. At the nearby hospital E.R., he deteriorated rapidly, and his respiratory movements were absent with cardiac arrest. He was immediately resuscitated. Brain MRI showed no abnormalities. EEG revealed an abnormal pattern with recurrent multifocal epileptiform activity over the bilateral occipital and frontal regions during sleep. Based on the clinical/radiological findings we diagnosed Panayiotopoulos syndrome (PS), a benign form of early-onset pediatric epilepsy characterized by autonomic symptoms. Lifethreating cardiopulmonary arrest is rare in PS, but long seizure duration of PS may associate with apnea and bradycardia.

The Inequality of Patient Profile Information in Japanese Hospitals.

A model dataset of patient profile information was created based on the items used at five Japanese university hospitals, the patient information data elements in Health Level 7 (HL7) v2.5, and the standard datasets for medical information exchange used in Japan. In order to check the validity of the model dataset, a cross-sectional survey was performed. A preliminary analysis of 20 Japanese hospitals found that most items were implemented at some hospitals, but the number of items implemented at many hospitals was rather small. This result strongly shows the necessity for a standardized dataset of patient profile information.

Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701).

BACKGROUND: Lentinan (LNT) is a purified ß-1, 3-glucan that augments immune responses. The present study was conducted to assess the efficacy of LNT in combination with S-1 as a first-line treatment for unresectable or recurrent gastric cancer. PATIENTS AND METHODS: Eligible patients were randomly assigned to receive S-1 alone or S-1 plus LNT. The primary end-point was overall survival (OS). Secondary end-points were time-to-treatment failure (TTF), overall response rate (ORR), safety, quality of life (QOL), and biomarker. The percentages of LNT-binding monocytes in peripheral blood prior to treatment were analysed for the biomarker assessment. RESULTS: One hundred and fifty-four and 155 patients were randomly assigned to receive S-1 alone or S-1 plus LNT, respectively. The median OS was 13.8 and 9.9 months (P = 0.208), the median TTF was 4.3 and 2.6 months (P < 0.001), the ORR was 22.3% and 18.7% for the S-1 and S-1 plus LNT groups, respectively. The incidences of haematologic and non-haematologic adverse events were similar, and no significant changes in QOL scores were observed during the treatment in both groups. In a subpopulation of patients with LNT-binding monocytes ≥2%, patients who received more than two cycles of chemotherapy showed a longer survival time in the S-1 plus LNT group. CONCLUSIONS: OS did not improve and TTF was significantly worse in the S-1 plus LNT group as compared with the S-1-only group. This study showed no efficacy of LNT when combined with S-1 treatment in patients with unresectable or recurrent gastric cancer. CLINICAL TRIAL REGISTRATION ID NUMBER: UMIN 000000574.

Multicenter phase II study of S-1 and docetaxel combination chemotherapy for advanced or recurrent gastric cancer patients with peritoneal dissemination.

PURPOSE: Peritoneal dissemination is the most frequent and life-threatening mode of metastasis and recurrence in patients with gastric cancer. A multicenter phase II study was designed to evaluate the efficacy and tolerability of S-1 and docetaxel combination chemotherapy regimen for the treatment of advanced or recurrent gastric cancer patients with peritoneal dissemination. METHODS: Nineteen patients with histologically confirmed unresectable or recurrent gastric cancer with peritoneal dissemination were enrolled. Oral S-1 at 80 mg/m(2)/day was administered twice daily for 2 weeks, followed by 1 drug-free week. Docetaxel infusion at 40 mg/m(2) was performed on day 1, simultaneous with S-1 administration. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary endpoints were the response rates and safety status. RESULTS: Patients received a median of 4 cycles of the S-1 and docetaxel regimen (range 1-43). The disease control rate was 73.7 % (14/19). Median overall survival was 459 days (15.3 months), while median time to progression was 212 days (7.1 months). Neutropenia was the most common type of toxicity (n = 7, 36.8 %). CONCLUSIONS: Combination chemotherapy with S-1 and docetaxel is a tolerable and effective treatment for advanced or recurrent gastric cancer patients with peritoneal dissemination.

Plasma free amino acid profiling of five types of cancer patients and its application for early detection.

BACKGROUND: Recently, rapid advances have been made in metabolomics-based, easy-to-use early cancer detection methods using blood samples. Among metabolites, profiling of plasma free amino acids (PFAAs) is a promising approach because PFAAs link all organ systems and have important roles in metabolism. Furthermore, PFAA profiles are known to be influenced by specific diseases, including cancers. Therefore, the purpose of the present study was to determine the characteristics of the PFAA profiles in cancer patients and the possibility of using this information for early detection. METHODS AND FINDINGS: Plasma samples were collected from approximately 200 patients from multiple institutes, each diagnosed with one of the following five types of cancer: lung, gastric, colorectal, breast, or prostate cancer. Patients were compared to gender- and age- matched controls also used in this study. The PFAA levels were measured using high-performance liquid chromatography (HPLC)-electrospray ionization (ESI)-mass spectrometry (MS). Univariate analysis revealed significant differences in the PFAA profiles between the controls and the patients with any of the five types of cancer listed above, even those with asymptomatic early-stage disease. Furthermore, multivariate analysis clearly discriminated the cancer patients from the controls in terms of the area under the receiver-operator characteristics curve (AUC of ROC >0.75 for each cancer), regardless of cancer stage. Because this study was designed as case-control study, further investigations, including model construction and validation using cohorts with larger sample sizes, are necessary to determine the usefulness of PFAA profiling. CONCLUSIONS: These findings suggest that PFAA profiling has great potential for improving cancer screening and diagnosis and understanding disease pathogenesis. PFAA profiles can also be used to determine various disease diagnoses from a single blood sample, which involves a relatively simple plasma assay and imposes a lower physical burden on subjects when compared to existing screening methods.

Outpatients flow management and ophthalmic electronic medical records system in university hospital using Yahgee Document View.

General electronic medical records systems remain insufficient for ophthalmology outpatient clinics from the viewpoint of dealing with many ophthalmic examinations and images in a large number of patients. Filing systems for documents and images by Yahgee Document View (Yahgee, Inc.) were introduced on the platform of general electronic medical records system (Fujitsu, Inc.). Outpatients flow management system and electronic medical records system for ophthalmology were constructed. All images from ophthalmic appliances were transported to Yahgee Image by the MaxFile gateway system (P4 Medic, Inc.). The flow of outpatients going through examinations such as visual acuity testing were monitored by the list "Ophthalmology Outpatients List" by Yahgee Workflow in addition to the list "Patients Reception List" by Fujitsu. Patients' identification number was scanned with bar code readers attached to ophthalmic appliances. Dual monitors were placed in doctors' rooms to show Fujitsu Medical Records on the left-hand monitor and ophthalmic charts of Yahgee Document on the right-hand monitor. The data of manually-inputted visual acuity, automatically-exported autorefractometry and non-contact tonometry on a new template, MaxFile ED, were again automatically transported to designated boxes on ophthalmic charts of Yahgee Document. Images such as fundus photographs, fluorescein angiograms, optical coherence tomographic and ultrasound scans were viewed by Yahgee Image, and were copy-and-pasted to assigned boxes on the ophthalmic charts. Ordering such as appointments, drug prescription, fees and diagnoses input, central laboratory tests, surgical theater and ward room reservations were placed by functions of the Fujitsu electronic medical records system. The combination of the Fujitsu electronic medical records and Yahgee Document View systems enabled the University Hospital to examine the same number of outpatients as prior to the implementation of the computerized filing system.

Portal/splenic vein thrombosis following splenectomy in gastric cancer surgery.

Although splenectomy is often performed along with en bloc node dissection in gastric cancer surgery, portal/splenic vein thrombosis (PSVT) has been rarely reported. We recently encountered a case of PSVT after a splenectomy was performed during gastric cancer surgery. A 53-year-old woman underwent total gastrectomy, splenectomy, and en bloc regional lymph node dissection for gastric cancer. An uneventful postoperative course ended with abrupt development of a fever and general fatigue. Laboratory tests showed elevated levels of liver transaminases and fibrinogen degenerative products. Contrast-enhanced computed tomography revealed splenic vein thrombosis and partial liver infarction. Immediate anticoagulant treatment resulted in clinical improvement and partial thrombolysis in 2 months. PSVT after splenectomy in haematological disorders has been recognized as a possibly lethal complication. However, it has been underappreciated in cases of splenectomy for gastric cancer. The present case demonstrates the importance of considering PSVT as a possible complication of splenectomy in gastric cancer surgery.

Identification of CCDC62-2 as a novel cancer/testis antigen and its immunogenicity.

Cancer/testis (CT) antigens are expressed in normal germ line tissues and various cancers. They are considered promising target molecules for immunotherapy for patients with various cancers. To identify CT antigens, we performed serological identification of antigens by recombinant expression cloning. The humoral immune response of cancer patients against a newly defined antigen was analyzed. A testicular cDNA library was immunoscreened with serum obtained from a gastric adenocarcinoma patient whose primary cancer had regressed once and most liver metastases had disappeared transiently. We isolated 55 positive cDNA clones comprising 23 different genes. They included 4 genes with testis-specific expression profiles in the Unigene database, including coiled-coil domain containing 62 (CCDC62). RT-PCR analysis showed that the expression of 2 splice variants of CCDC62 was restricted to the testis in normal adult tissues. In malignant tissues, CCDC62 variant 2 (CCDC62-2) was aberrantly expressed in a variety of cancers, including stomach cancer. A serological survey of 191 cancer patients with a range of different cancers by ELISA revealed antibodies to CCDC62-2 in 13 patients, including stomach cancer. None of the 41 healthy donor serum samples were reactive in the same test. The serum reaction against CCDC62-2 was confirmed by western blot. CCDC62-2 is a CT antigen that is immunogenic in cancer patients.

[Stenting and radiotherapy for malignant tracheal stenosis due to mediastinal lymph node recurrence from gastric cancer--a case report].

The case is a 74-year-old woman,who underwent curative resection six years earlier for stomach cancer in the cardia extending to the esophagus (Stage IIIA). She noticed hoarseness and cough in September 2004, and CT revealed lymph node metastasis of the cancer in the upper mediastinum. The tumor pressured the SVC, the esophagus,and especially the trachea that narrowed up to a diameter of 5 mm. To secure the air way, first, a self-expandable metallic stent was placed in the narrowed trachea under general anesthesia. Irradiation to the upper mediastinal tumor was further applied for a total of 46 Gy from October to November, 2004. Symptom relief was obtained over the course by a marked reduction in the size of the metastatic tumor, and the disease remained stable for 5 months. In general,a stomach cancer that is mostly adenocarcinoma has been recognized to have low receptivity for radiotherapy. Nevertheless,this case suggests that radiotherapy can play an important role in local control and symptom relief for symptomatic stomach cancer patients.

A case report--The marked response to gemcitabine combined with irinotecan and low-dose cisplatin chemotherapy for advanced gastric cancer with multiple liver metastases.

A 69-year-old man with no sign of symptoms was admitted to our hospital for further examination and treatment of gastric cancer. Endoscopy revealed a Borrmann 3-type tumor in the cardia of the stomach. CT of the abdomen demonstrated a marked thickening of the stomach wall near the esophago-gastric junction, multiple liver metastases in bilateral liver lobes, and regional lymph node swelling around the cardia of the stomach. He consented and received systemic chemotherapy consisting of 0.5 h infusion of cisplatin (25 mg/body) followed by 0.5 h infusion of gemcitabine (800 mg/body) and 2.5 h infusion of irinotecan (60 mg/body) every 14 days as described below. Only the initial 1 course was administered with 5-FU (500 mg/body) as an inpatient, and further courses were performed as an outpatient with no severe adverse events. His tumors responded immediately to the chemotherapy, and restaging abdominal CT after 4-cycles of chemotherapy showed almost complete regression of liver metastases, and partial response to lymphadenopathy. The patient currently undergoes regular chemotherapy and remains in remission more than 6 months after the diagnosis of unresectable gastric cancer with liver metastases. It may be possible that the current chemotherapy will be neoadjuvant chemotherapy, and curative surgical resection can be performed.

Stable long-term induction of perforin-positive CD8+ T cells in gut by oral administration of streptococcal preparation OK-432.

Perforin is known as a pore-forming cytotoxic granule released from cytotoxic T cells. Previous experiments in vitro revealed the presence of precursor cells that are capable of producing perforin in the immune system cells. The present study was undertaken to examine whether perforin-positive cells could be induced in the digestive tract and to characterize their precursor cells. Expression of perforin-positive cells in the intestine of Balb/c mice induced by OK-432 was analyzed by immunohistochemical staining and RT-PCR. Oral treatment of Balb/c mice with OK-432 resulted in the occurrence of perforin-positive cells in the inferior segment of small intestine, the superior segment of large intestine, mesenteric lymph nodes and spleen. In the small intestine, perforin-positive cells were found in the lamina propria mucosa. The presence of perforin-positive cells was also noted following long-term OK-432 treatment. Similar results were obtained following treatment with biological response modifiers such as lipopolysaccharide. In mice with GVHD (graft-versus-host disease), the presence of perforin-positive cells was noted in the small intestine and spleen. When the serial sections of the small intestinal mucosa from OK-432-treated mice were immunostained with anti-perforin, anti-CD8 and anti-asialo-GM1 antibodies, the perforin-positive cells were found to be CD8-positive. The results suggest that CD8(+) cells in lamina propria mucosa play a significant role as effectors in the mucosal immune system which is activated by various stimuli.

ICAM-1 expression and the soluble ICAM-1 level for evaluating the metastatic potential of gastric cancer.

ICAM-1 plays an important role in cell-cell and cell-extracellular matrix interactions, especially tumor invasion and cytotoxicity of lymphocytes. In the present study, the relationship between metastasis of gastric cancer and ICAM-1 expression by cancer cells or the serum level of s-ICAM-1 was (s-ICAM-1) was examined. ICAM-1 was detected by immunohistochemic staining in 49.0% of 108 patients with gastric cancer. The ICAM-1 expression rate was higher at a more advanced stage, based on lymph node metastasis, being 46.9% in node-negative and 56.1% in node-positive cases. In patients with liver metastasis, the rate was 90.9%, while it was 43.3% in patients without liver metastasis (p < 0.05). The serum s-ICAM-1 level was 262.1 ng/ml (median 205.5, range 176.0-271.0) in healthy subjects and 391.5 ng/ml (median 317.5, range 148.7-1,768.0) in gastric cancer patients (p < 0.001). The serum s-ICAM-1 level was significantly higher in patients with liver metastasis than in patients without liver metastasis (p < 0.0001). In addition, positive ICAM-1 expression cases had significantly higher s-ICAM-1 levels than negative ones, 408.9 +/- 188.4 and 308.1 +/- 88.1 ng/ml, respectively. These results suggested that ICAM-1 was overexpressed in cancer cells and released as s-ICAM-1, which would promote hematogenous metastasis by suppressing local anticancer immunity.

[Interim report of JFMC study no. 23--phase III randomized clinical trial on the effectiveness of low-dose cisplatin plus 5-FU as a postoperative adjuvant chemotherapy for advanced gastric cancer].

The interim analysis of the JFMC study as of May, 2001 covers 190 gastrectomized patients with advanced gastric cancer from 82 institutions between May, 1996 and March, 2000. Patients were randomly assigned to the following two regimens. Group-CD: cisplatin (CDDP) 5 mg/body/day (i.v.) plus 5-FU 300 mg/body/day (cvi) day 1-5, given for 6 weeks, followed by UFT 200 mg (as tegafur) x 2/day for as long as possible. Group-UF: UFT only was administered after surgery as long as possible. The primary endpoint was survival and the secondary endpoint was disease-free survival. The 4-year survival rates were 47.6% in CD and 41.3% in UF, and the hazard ratio of CD versus UF was 0.74 (95% CL: 0.47-1.16, p = 0.189) according to a stratified (with stage) logrank analysis. The 4-year disease-free survival rates were 50.1% in CD and 39.3% in UF, and the hazard ratio of CD versus UF was 0.65 (95% CL: 0.42-1.00, p = 0.049). Cox's regression analysis using time-dependent dummy variables, revealed that the effect on the survival was accentuated within 9 months, that on disease-free survival within 6 months. The quality of life (QOL) of patients for one year after surgery in CD was significantly lower than that of patient in UF, as assessed using a QOL questionnaire. Although the present interim analysis does not statistically confirm the efficacy of the "low-dose CDDP plus 5-FU" regimen, an expectation for better results is suggested if this regimen is administered for a longer period of time. The JFMC Clinical Trial Committee permitted the release of this report on the condition that further study to verify the present study will be conducted.