Adsorptive Granulocyte and Monocyte Apheresis Is Effective in Ulcerative Colitis Patients Both with and without Concomitant Prednisolone.

BACKGROUND: The number of ulcerative colitis (UC) patients is increasing in Japan and other countries. Selective depletion of myeloid lineage leucocytes by adsorptive granulocyte and monocyte apheresis (GMA) with an Adacolumn (JIMRO, Takasaki, Japan) was introduced as a nonpharmacologic treatment strategy in UC patients in 2000. GMA has been reported to be effective in clinical trials; however, the effect of concomitant prednisolone (PSL) on GMA needs to be clarified. METHODS: Thirty-nine patients with active UC were treated with GMA at our institute between June 2009 and September 2018. All patients received GMA therapy once or twice a week with the Adacolumn. Conventional medication was to be continued during the whole GMA treatment course. The clinical response was retrospectively evaluated. RESULTS: According to the partial Mayo score, remission was 33.3%, significant efficacy 25.6%, effective 25.6%, and no response 15.4%. The average partial Mayo score was 6.2 ± 1.4 at entry and significantly declined to 1.8 ± 1.8 after GMA sessions (p < 0.0001). The average number of bowel movements was 9.5 ± 5.6 at entry and significantly declined to 3.0 ± 2.8 after GMA sessions (p < 0.0001). In a comparison between the group treated with concomitant PSL and the group without PSL, the change in partial Mayo score or the number of bowel movements from entry to after GMA sessions was not significantly different. Among 24 patients treated by GMA with concomitant PSL, 75% (18/24) became steroid free. CONCLUSIONS: The effect of GMA with concomitant PSL and that of GMA without PSL were not different, and GMA was effective irrespective of PSL administration. The present study showed that GMA had efficacy and led many UC patients treated by PSL to be steroid free with no safety concern in the real world, although there is the possibility of recruitment bias due to the retrospective nature of the study.

Successful surgical management of mesenteric inflammatory veno-occlusive disease.

BACKGROUND: The term "mesenteric inflammatory veno-occlusive disease (MIVOD)" is used to describe an ischemic injury resulting from phlebitis or venulitis that affects the bowel or mesentery in the absence of arteritis. MIVOD is difficult to diagnose because of its rarity and frequent confusion with other diseases. The incidence and etiology of MIVOD remain unclear; only a few cases have been reported. We describe a case of the successful surgical management of a patient with MIVOD with characteristic images. CASE PRESENTATION: A 65-year-old Japanese man visited a hospital with the chief complaint of abdominal pain in January 2018. CT showed edema and thickening of the intestinal wall from the descending colon to the rectum. The patient was admitted to the hospital. Suspected diagnoses were enteritis, ulcerative colitis, amyloidosis, vasculitis, malignant lymphoma, and venous thrombus, but no definitive diagnosis was obtained. The patient was transferred to our hospital for the treatment of stenosis (located from the descending colon to the rectum) and bowel obstruction. An emergency transverse colostomy was performed. The sigmoid colon and mesentery were too rigid and edematous to resect. Colonic hemorrhage occurred 2 weeks after the surgery. With radiology intervention, coiling for the arteriovenous fistula in the descending colon was performed, and hemostasis was obtained. A colonoscopy at 6 months post-surgery showed neither ulceration nor stenosis in the rectum, indicating that the rectum could be preserved in the next surgery. However, severe stenosis in the descending and sigmoid colon remained unchanged. Ten months after the transverse colostomy, we performed a subtotal colectomy and ileorectal anastomosis, and an ileostomy was created. The sigmoid colon and mesentery were not so rigid compared to the first surgery's findings, and we were able to resect intestine and mesentery. Histopathology revealed phlebitis and venulitis, fibrinoid necrosis, and normal arteries, meeting the diagnostic criteria for MIVOD. Postoperatively, the patient showed no recurrence for 8 months. CONCLUSION: Clinicians should consider MIVOD when examining a patient with intestinal ischemia. When MIVOD is suspected, the patient is indicated for surgery based on an accurate diagnosis and good prognosis.

Plasma exosomal microRNA-125b as a monitoring biomarker of resistance to mFOLFOX6-based chemotherapy in advanced and recurrent colorectal cancer patients.

Liquid biomarkers for the early detection of resistance to chemotherapy are important for improving prognosis. This study investigated the usefulness of plasma exosomal microRNA-125b (ex-miRNA-125b) for the early detection of resistance to modified fluorouracil, leucovorin and oxaliplatin (mFOLFOX6)-based first-line chemotherapy in patients with advanced or recurrent (advanced/recurrent) colorectal cancer (CRC). First, ex-miRNAs associated with resistance to mFOLFOX6-based chemotherapy were profiled via miRNA microarray analysis. In this analysis, ex-miR-125b exhibited the greatest upregulation in patients with progressive disease (PD) compared with the findings for patients with stable disease (SD) and healthy controls. Next, another 55 patients with advanced/recurrent CRC who received mFOLFOX6-based first-line chemotherapy underwent a validation study of ex-miR-125b. Blood samples were collected before and during treatment until tumor progression. Ex-miRNA levels were measured via TaqMan microRNA assays. Patients with CRC had significantly higher ex-miR-125b levels than healthy controls. In patients with partial responses, ex-miR-125b levels at the Response Evaluation Criteria in Solid Tumors (RECIST) judgment point were significantly lower than those measured before treatment. In patients with SD, ex-miR-125b levels did not differ before and during treatment. In patients with PD, ex-miR-125b levels at the RECIST judgment point were significantly higher than those measured before treatment. These changes in ex-miR-125b levels were significantly different between groups even 1 month after the initiation of chemotherapy. Progression-free survival (PFS) was significantly worse in patients with high baseline ex-miR-125b levels than in those with low levels. In the Cox analysis, baseline ex-miR-125b levels and KRAS mutation were indicated to be independent prognostic factors for PFS. The present results suggest that plasma ex-miR-125b levels may be useful for the early detection of resistance to mFOLFOX6-based first-line chemotherapy. Furthermore, ex-miR-125b before chemotherapy is a predictive biomarker for PFS in patients with advanced/recurrent CRC.

Angiotensin I-converting enzyme inhibitors/angiotensin II receptor blockers may reduce tumor recurrence in left-sided and early colorectal cancers.

BACKGROUND: Angiotensin signaling is suggested to be involved in tumorigenesis, tumor proliferation, and metastases. In colorectal cancer (CRC), it was demonstrated that angiotensin I-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) may reduce the risk of CRC; however, their impact on tumor recurrence remains unknown. Therefore, in this study, we evaluated the impact of ACEIs/ARBs on tumor recurrence in CRC patients. PATIENTS AND METHODS: We retrospectively investigated the clinicopathological data of 461 stage I-III CRC patients. We divided the patients into those who took an ACEI and/or ARB (the ACEI/ARB+ group) and those who did not (the ACEI/ARB- group), and we compared the two groups' recurrence-free survival (RFS) using a Kaplan-Meier curve analysis and log rank test. We also examined the impact of AGTR1 expression on tumor recurrence, using two public CRC datasets. RESULTS: The Kaplan-Meier curves showed a trend toward improved RFS in the ACEI/ARB+ group versus the ACEI/ARB- group (p = 0.063). Subgroup analyses demonstrated that the RFS was significantly better in the ACEI/ARB+ group versus the ACEI/ARB- group in the patients with left-sided CRC (p = 0.030) and those with stage I CRC (p = 0.009). Consistent with these findings, the AGTR1 expression was higher in the left-sided versus right-sided colon (p = 0.048). High AGTR1 expression levels were associated with poor RFS in the GSE39582 dataset's stage I-III CRC patients (p < 0.001), and this finding was also validated in the GSE17536 dataset (p = 0.023). CONCLUSION: ACEI/ARB treatment may reduce tumor recurrence in left-sided CRC and early-stage CRC.

A case of intussusception developed at the site of ileocolic anastomosis after laparoscopic right hemicolectomy.

BACKGROUND: Intussusception is a relatively common condition seen in children. In comparison, adult intussusception is rare and usually occurs as a complication in patients with organic diseases. It is responsible for 1% of all bowel obstructions, in most of intussusceptions a malignant tumor is involved. Herein, we present an extremely unusual case of intussusception that occurred as a complication at the site of a functional end-to-end anastomosis. CASE PRESENTATION: A 57-year-old female patient was diagnosed with tumors in the ascending and descending colon and was referred to our department. Laparoscopic hemicolectomy and laparoscopic descending colectomy were performed. The mechanical intestinal obstruction occurred on the 9th day postoperatively, and computed tomography scan revealed intussusception at the site of the ileocolic anastomosis. Endoscopic reduction was attempted, but the procedure was challenging. Surgery was then performed and revealed that the site of ileocolic anastomosis firmly adhered to the side wall and right retroperitoneum. However, the intestine in the oral side of the anastomosis was not fixed. Examination of the anastomotic site revealed that the ileum had passed through the anastomosis and prolapsed into the transverse colon. The ileocolic anastomosis was resected. End-to-end anastomosis was performed, and surgery was then completed. No neoplastic lesions were observed in the resected tissue of the lead point of intussusception. The postoperative clinical course was favorable, and the patient was discharged on the 11th day after the second round of surgery. CONCLUSIONS: There are no reports the anastomosis is involved as part of the intussception, as observed in the present case. Intussusception should thus be considered as one of the causes of postoperative mechanical intestinal obstruction.

Laparoscopic subtotal colectomy for a patient with chronic idiopathic colonic pseudo-obstruction: Report of a case.

A 47-year-old male patient without a documented past medical history was referred to Sanno Hospital because of constipation and abdominal pain, which he had had for more than 5 years. Abdominal X-ray and CT scan showed an enlarged ascending colon from the cecum to the transverse colon, without apparent mechanical obstruction. The patient was diagnosed with chronic idiopathic colonic pseudo-obstruction, and because his symptoms were resistant to medication, surgical treatment was required. Laparoscopic subtotal colectomy was performed without any complications. Constipation was relieved, and the patient began defecating 2-3 times a day without medication. Pathological specimens showed that Meissner's plexus and Auerbach's plexus had decreased and that there were fewer ganglion cells-findings consistent with chronic idiopathic intestinal pseudo-obstruction.

A rare case of perivascular epithelioid cell tumor (PEComa) of the greater omentum.

BACKGROUND: A tumor composed exclusively or predominantly of human melanin black 45 (HMB45)-positive epithelioid cells is called a perivascular epithelioid cell tumor (PEComa). We report a very rare case of a PEComa of the greater omentum. CASE PRESENTATION: MRI conducted to examine the orthopedic disease of the patients, a 49-year-old Japanese woman, also identified a tumor in her pelvis. A CT scan revealed a tumor mass on the right side of the pelvic floor and clear nutrient vessels originating from the splenic and celiac arteries. An omental primary tumor or accessory spleen was thus suspected, and tumor resection was performed. The tumor was a light brown solid tumor with a smooth margin, measuring 5.2 × 3.8 × 3.5 cm. Histopathologically, the tumor was composed mainly of spindle and epithelioid cells, and large and small blood vessel formation was observed. In the immunohistochemical staining, tumor cells were positive for human melanin black 45 (HMB-45) and Melan-A and partially positive for alpha-smooth muscle actin. The final diagnosis was PEComa of the greater omentum. CONCLUSIONS: Although omental PEComa is very rare, it should be considered as a differential disease of an omental primary tumor.

Circulating Exosomal MicroRNA-21 as a Biomarker in Each Tumor Stage of Colorectal Cancer.

OBJECTIVE: We clarified the predictive and prognostic value of circulating plasma exosomal microRNA-21 (miR-21) in each TNM stage of colorectal cancer (CRC) patients. METHODS: The microRNA (miRNA) profiles of the plasma exosomes, primary tumor tissues, and liver metastasis tissues from the same CRC patients were examined using a microarray. For validation analysis, the plasma exosome samples from 326 CRC patients were measured by TaqMan miRNA assays. RESULTS: In the miRNA microarray analyses, miR-21 showed the highest upregulation in exosomes, primary tumor tissues, and liver metastasis tissues. Significant correlations were demonstrated between exosomal miR-21 and tissue miR-21 levels. As for the relationship to the pathological condition, exosomal miR-21 showed a significant association with liver metastasis and TNM stage. The overall survival (OS) rates and disease-free survival (DFS) rates in high-exosomal-miR-21 patients were significantly worse than those in low-miR-21 patients. Exosomal miR-21 levels were an independent prognostic factor for OS and DFS in CRC patients with TNM stage II or III, and for OS in patients with TNM stage IV. CONCLUSION: Plasma exosomal miR-21 levels are a useful biomarker for the prediction of recurrence and poor prognosis in CRC patients with TNM stage II, III, or IV.

Interlaboratory Study of ELISA Kits for the Detection of Egg and Milk Protein in Processed Foods.

The labeling of seven specific allergenic ingredients (egg, milk, wheat, buckwheat, peanut, shrimp, and crab) is mandatory in Japan. To ensure proper labeling, two kinds of ELISA kits using polyclonal antibodies have been developed. However, we developed two novel ELISA kits using monoclonal antibodies with improved specificity, the Allergeneye ELISA Egg (AE-Egg) and Allergeneye ELISA Milk (AE-Milk) Kits, to detect egg and milk proteins in processed foods, respectively. Five types of processed food containing 10 mg/kg of egg or milk soluble protein were prepared for an interlaboratory study of the performance of these kits. The kits showed a relatively high reproducibility level of interlaboratory precision (AE-Egg RSDR, 3.7-5.7%; AE-Milk RSDR, 6.8-10.5%) and satisfied the recovery rate stipulated by Japanese guidelines (AE-Egg, 61.6-89.3%; AE-Milk, 52.1-67%) for all processed foods. Our results suggest that the AE-Egg and AE-Milk Kits are precise and reliable tools for detecting egg or milk proteins in processed foods.

A case of IgG4-related disease coexisted with rectal cancer.

A 67-year-old man was referred to our hospital with suspicion of rectal tumor, hilar tumor, and urinary tumor. Colonoscopic findings were intermittent nodular lesions with redness which were atypical to primary rectal cancer. Endoscopic retrograde cholangiopancreatography showed narrowing of the bilateral intrahepatic bile duct. However, the findings were improved 1 month later. Blood biochemistry showed high level of serum IgG4 up to 1140 mg/dl. The patient matched to comprehensive diagnostic criteria for IgG4-related disease as a possible diagnostic case. Laparoscopic low anterior resection with creation of ileostomy was performed for rectal cancer. Histological findings revealed cancer cells spread horizontally at submucosal layer and subserosal layer. There was marked infiltration of the plasma cells and lymphocytes at tumor stroma, and more than half of the plasma cells were positive for IgG4. After surgery, the level of serum IgG4 was decreased to 597 mg/dl. Although the association with IgG4-related disease and colorectal disease is unclear, the tumor progression was atypical for rectal cancer. Some report that the disease may rise up the risk of a malignant disease. It is necessary to perform systemic examination keeping in mind for concurrence of malignancy.

Feasibility of fiber-optic radiation sensor using Cerenkov effect for detecting thermal neutrons.

In this research, we propose a novel method for detecting thermal neutrons with a fiber-optic radiation sensor using the Cerenkov effect. We fabricate a fiber-optic radiation sensor that detects thermal neutrons with a Gd-foil, a rutile crystal, and a plastic optical fiber. The relationship between the fluxes of electrons inducing Cerenkov radiation in the sensor probe of the fiber-optic radiation sensor and thermal neutron fluxes is determined using the Monte Carlo N-particle transport code simulations. To evaluate the fiber-optic radiation sensor, the Cerenkov radiation generated in the fiber-optic radiation sensor by irradiation of pure thermal neutron beams is measured according to the depths of polyethylene.

Development of an educational program for the helicopter emergency medical services in Japan.

INTRODUCTION: The Japanese helicopter emergency medical service (HEMS) system provides advanced prehospital treatment at the scene. The education of the dispatched HEMS physicians is important for guaranteeing the quality of medical and safety management, but there is no nationally established training program. This study aimed to determine the validity of the HEMS educational program developed by our team. METHODS: A 3-step educational program was designed for HEMS trainees: step 1, 20 HEMS missions as an observer; step 2, 80 missions of on-the-job training; and step 3, certifying examination conducted by a supervisor. As an evaluation standard, scene time, defined as time from landing at the scene to taking off for a hospital, was determined retrospectively. RESULTS: For trainees, scene time was significantly longer (16.3 ± 5.4 min, 95% CI 15.5-17.1) than for experts (doctors who completed >200 HEMS missions; 15.2 ± 6.7 min, 95% CI 14.7-15.8; P = 0.040) but was significantly shorter than for doctors trained before establishment of the HEMS program (17.5 ± 7.0 min, 95% CI 16.9-18.2; P = 0.030). In cases of trauma or intrinsic disease, there was no significant difference in scene time between trainees (17.4 ± 5.6 min and 14.9 ± 4.8 min, respectively) and experts (16.4 ± 7.8 min and 14.2 ± 5.5 min, respectively). CONCLUSION: The finding that scene time was shortened for program trainees demonstrates the validity of our HEMS educational program. The quality of HEMS missions will be better ensured through this educational system.

Application of Cerenkov radiation generated in plastic optical fibers for therapeutic photon beam dosimetry.

A Cerenkov fiber-optic dosimeter (CFOD) is fabricated using plastic optical fibers to measure Cerenkov radiation induced by a therapeutic photon beam. We measured the Cerenkov radiation generated in optical fibers in various irradiation conditions to evaluate the usability of Cerenkov radiation for a photon beam therapy dosimetry. As a results, the spectral peak of Cerenkov radiation was measured at a wavelength of 515 nm, and the intensity of Cerenkov radiation increased linearly with increasing irradiated length of the optical fiber. Also, the intensity peak of Cerenkov radiation was measured in the irradiation angle range of 30 to 40 deg. In the results of Monte Carlo N-particle transport code simulations, the relationship between fluxes of electrons over Cerenkov threshold energy and energy deposition of a 6 MV photon beam had a nearly linear trend. Finally, percentage depth doses for the 6 MV photon beam could be obtained using the CFOD and the results were compared with those of an ionization chamber. Here, the mean dose difference was about 0.6%. It is anticipated that the novel and simple CFOD can be effectively used for measuring depth doses in radiotherapy dosimetry.

Development of landmine detection system based on the measurement of radiation from landmines.

For the detection of landmines, a new gamma-ray detector system, a neutron source, and control and measurement devices were developed. A prototype system has newly been developed by combining these devices. The usefulness of capture gamma-ray and backscattering neutron methods is examined with real explosives in several conditions and the performance of the prototype landmine detection system is demonstrated experimentally in this study. The combination of the methods is confirmed to be sufficiently effective for application to actual landmine detection.