Negative Effects of Diffuse Idiopathic Skeletal Hyperostosis on Bone Fusion after Transforaminal Lumbar Interbody Fusion.

STUDY DESIGN: This study adopted a retrospective cohort study design. PURPOSE: This study aimed to clarify the influence of diffuse idiopathic skeletal hyperostosis (DISH) on bone fusion after transforaminal lumbar interbody fusion (TLIF). OVERVIEW OF LITERATURE: The negative effects of DISH on lumbar degenerative diseases have been reported, and DISH may be involved in the onset and severity of lumbar spinal canal stenosis. Patients with DISH have significantly more reoperations after posterior lumbar fusion, including TLIF. However, the effects of DISH on bone fusion after TLIF have not been reported. METHODS: The medical records of patients with intervertebral TLIF from 2012 to 2018 were retrospectively examined. The patients were divided into those with fusion and those with pseudoarthrosis, and the following data were compared: age, sex, DISH, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation. Statistical analyses were performed using regression models. RESULTS: In this study, 180 patients (78.6%) had fusion and 49 patients (21.4%) had pseudoarthrosis. The number of patients with DISH was significantly higher in the pseudoarthrosis group than in the fusion group (36.7% and 21.7%, respectively; univariate p=0.031, multivariate p =0.019). No significant differences in age, sex, diabetes mellitus, smoking, drinking, albumin levels, body mass index ≥30 kg/m2, and L5/S fixation were observed between the two groups. The risk factors for bone fusion were statistically analyzed in 57 patients with DISH. DISH with a caudal end below Th11 was an independent risk factor for pseudoarthrosis (univariate p=0.011, multivariate p=0.033). CONCLUSIONS: DISH is an independent risk factor for pseudoarthrosis after one intervertebral TLIF, and DISH with a caudal end below Th11 is associated with a higher risk of pseudoarthrosis than DISH without a caudal end below Th11.

Improvement of Constipation Symptoms in an Older Adult Patient by Defecation Care Based on Using a Handheld Ultrasound Device in Home Care Settings: A Case Report.

BACKGROUND: Although previous studies have demonstrated the ability of ultrasound to detect stool in the colon and rectum, the clinical utility of evaluating constipation via ultrasonic imaging by nurses has not been determined. In this case report, we observed fecal retention, assessed the presence of constipation, and performed defecation care in an older adult patient in a home care setting in a city near the metropolitan area in Japan. CASE: An 85-year-old male with advanced stage prostate cancer and multiple metastases was diagnosed with fecal impaction via digital rectal examination and evaluation of stool consistency. He was managed by regular digital evacuation of stool, but ultrasonic imaging indicated constipation with fecal retention in both the rectum and the colon despite this bowel evacuation program. When faced with this situation, we advocate a bowel management program that considers both intestinal elimination dysfunction and fecal transport dysfunction. Based on ultrasonic imaging, stool consistency was altered by promoting water intake, and we promoted self-defecation by asking the patient to attempt to move his bowels (regardless of cues to defecation) by sitting on the toilet every morning. As a result, the number of weekly enemas and digital dis-impaction episodes decreased while the number of spontaneous defecations increased. CONCLUSION: This case report demonstrated that ultrasonography improved bowel management in this patient with clinically severe chronic constipation.

Surgery-related predictable risk factors influencing postoperative clinical outcomes for thoracic myelopathy caused by ossification of the posterior longitudinal ligament: a multicenter retrospective study.

OBJECTIVE: Compression of the spinal cord by thoracic ossification of the posterior longitudinal ligament (T-OPLL) often causes severe thoracic myelopathy. Although surgery is the most effective treatment for T-OPLL, problems associated with surgical intervention require resolution because surgical outcomes are not always favorable, and a small number of patients experience deterioration of their neurological status after surgery. The aim of the present study was to examine the surgery-related risk factors contributing to poor clinical outcomes for myelopathy caused by T-OPLL. METHODS: Data were extracted from the records of 55 patients with thoracic myelopathy due to T-OPLL at institutions in the Fukuoka Spine Group. The mean follow-up period was 5.3 years. Surgical outcomes were assessed using the Japanese Orthopaedic Association (JOA) scale. To investigate the definitive factors associated with surgical outcomes, univariate and multivariate regression analyses were performed with several patient-related and surgery-related factors, including preoperative comorbidities, radiological findings, JOA score, surgical methods, surgical outcomes, and complications. RESULTS: Neurological status improved in 33 patients (60.0%) and deteriorated in 10 patients (18.2%) after surgery. The use of instrumentation was significantly associated with an improved outcome. In the comparison of surgical approaches, posterior decompression and fusion resulted in a significantly higher neurological recovery rate than did anterior decompression via a posterior approach and fusion or decompression alone. It was also found that postoperative neurological status was significantly poorer when there were fewer instrumented spinal levels than decompression levels. CSF leakage was a predictable risk factor for deterioration following surgery. CONCLUSIONS: It is important to identify preventable risk factors for poor surgical outcomes for T-OPLL. The findings of the present study suggest that intraoperative CSF leakage and a lower number of instrumented spinal fusion levels than decompression levels were exacerbating factors for the neurological improvement in T-OPLL surgery.

Comparison between hypersensitivity reactions to cycles of modified FOLFOX6 and XELOX therapies in patients with colorectal cancer.

PURPOSE: Although hypersensitivity reactions (HSRs) to oxaliplatin (L-OHP) therapy are well-documented, few reports have compared different therapies in terms of HSR occurrence. In this study, we compared the frequency and pattern of HSRs to modified FOLFOX6 (mFOLFOX6; 5-fluorouracil, levofolinate calcium and L-OHP infusions) and XELOX (capecitabine and L-OHP) therapies, and sought to identify risk factors associated with HSRs. METHODS: Patients who had received mFOLFOX6 or XELOX chemotherapeutic regimens for unresectable colon or rectal cancer or as adjuvant chemotherapy following colon cancer surgery between April 2012 and August 2015 were included. Potential correlation between treatment modalities (regimen, dosage and route of administration of L-OHP, and injection timing for dexamethasone administration) and HSRs was assessed. RESULTS: Among the 240 patients included in the study, 136 had received mFOLFOX6 therapy and 104 had received XELOX therapy. Although the frequency of HSRs did not differ between the two groups, incidence of HSRs in the first cycle was higher in the XELOX therapy group. Treatment method or cumulative dosage was not identified as a risk factor for HSR; however, the incidence of ≥grade-2 HSR was higher in cases where the cumulative L-OHP dosage was ≥600 mg/m2 and in patients in whom dexamethasone was not co-infused with L-OHP. CONCLUSION: Although HSR rates were comparable among patients treated with mFOLFOX6 and XELOX, HSRs tended to occur more frequently during the first cycle of XELOX therapy as compared to that with mFOLFOX6 therapy. Our findings warrant careful assessment of ≥grade-2 HSRs in patients who are prescribed cumulative L-OHP dosages of ≥600 mg/m2.

Effect of renal function on pemetrexed-induced haematotoxicity.

PURPOSE: Pemetrexed (PEM) is an anticancer agent used for the treatment of non-small cell lung cancer, malignant pleural mesothelioma and thymoma. Reportedly, PEM has higher efficacy and safety when used in combination with platinum-based agents. However, there are only few reports on the safety of PEM in patients with an eGFR of ≤45 mL/min. We examined the effect of renal function on the safety of regimens containing PEM. METHODS: We retrospectively reviewed 221 patients with lung cancer, malignant pleural mesothelioma or thymoma who received treatment with a PEM-containing regimen between 2009 and 2014. Subgroup analyses were performed on the basis of pre-treatment renal function: group A [creatinine clearance (CLcr), <45 mL/min]; group B (CLcr, 45-80 mL/min); and group C (CLcr, ≥80 mL/min). For the purpose of this analysis, the lowest documented blood cell counts and haemoglobin levels, the highest levels of serum creatinine, aspartate aminotransferase, alanine aminotransferase and CLcr from the time of initial administration up to prior to the start of second administration were considered. RESULTS: Groups A, B and C had 8, 123 and 90 patients, respectively. The incidence of grade 2 thrombocytopaenia was significantly higher in group A as compared to that in groups B (P < 0.01) and C (P < 0.05). On multivariate analysis, only a CLcr of <45 mL/min was an independent risk factor for thrombocytopaenia of ≥grade 2. CONCLUSION: When administering a PEM-containing regimen, thrombocytopaenia of ≥grade 2 is more likely to develop in patients with a CLcr of <45 mL/min.

Circulating exosomal microRNAs as biomarkers of colon cancer.

PURPOSE: Exosomal microRNAs (miRNAs) have been attracting major interest as potential diagnostic biomarkers of cancer. The aim of this study was to characterize the miRNA profiles of serum exosomes and to identify those that are altered in colorectal cancer (CRC). To evaluate their use as diagnostic biomarkers, the relationship between specific exosomal miRNA levels and pathological changes of patients, including disease stage and tumor resection, was examined. EXPERIMENTAL DESIGN: Microarray analyses of miRNAs in exosome-enriched fractions of serum samples from 88 primary CRC patients and 11 healthy controls were performed. The expression levels of miRNAs in the culture medium of five colon cancer cell lines were also compared with those in the culture medium of a normal colon-derived cell line. The expression profiles of miRNAs that were differentially expressed between CRC and control sample sets were verified using 29 paired samples from post-tumor resection patients. The sensitivities of selected miRNAs as biomarkers of CRC were evaluated and compared with those of known tumor markers (CA19-9 and CEA) using a receiver operating characteristic analysis. The expression levels of selected miRNAs were also validated by quantitative real-time RT-PCR analyses of an independent set of 13 CRC patients. RESULTS: The serum exosomal levels of seven miRNAs (let-7a, miR-1229, miR-1246, miR-150, miR-21, miR-223, and miR-23a) were significantly higher in primary CRC patients, even those with early stage disease, than in healthy controls, and were significantly down-regulated after surgical resection of tumors. These miRNAs were also secreted at significantly higher levels by colon cancer cell lines than by a normal colon-derived cell line. The high sensitivities of the seven selected exosomal miRNAs were confirmed by a receiver operating characteristic analysis. CONCLUSION: Exosomal miRNA signatures appear to mirror pathological changes of CRC patients and several miRNAs are promising biomarkers for non-invasive diagnosis of the disease.

Ultra-sensitive liquid biopsy of circulating extracellular vesicles using ExoScreen.

Cancer cells secrete small membranous extracellular vesicles (EVs) into their microenvironment and circulation. Although their potential as cancer biomarkers has been promising, the identification and quantification of EVs in clinical samples remains challenging. Here we describe a sensitive and rapid analytical technique for profiling circulating EVs directly from blood samples of patients with colorectal cancer. EVs are captured by two types of antibodies and are detected by photosensitizer-beads, which enables us to detect cancer-derived EVs without a purification step. We also show that circulating EVs can be used for detection of colorectal cancer using the antigen CD147, which is embedded in cancer-linked EVs. This work describes a new liquid biopsy technique to sensitively detect disease-specific circulating EVs and provides perspectives in translational medicine from the standpoint of diagnosis and therapy.

Sudden cardiac arrest immediately after stent graft deployment during treatment of iliac aneurysm with iliocaval fistula.

An 84-year-old woman with heaviness of the right lower extremity had an iliocaval fistula related to a right internal iliac aneurysm. Immediately after deployment of an endovascular device, cardiac arrest occurred because of severely decreased sympathetic activity. After surgery, the patient recovered well and has been followed up with exclusion of the arteriovenous fistula and resolution of the type II endoleak. Endovascular treatment for large arteriovenous fistulas induces rapid closure of the fistula together with restoration of blood supply to the lower extremity. Markedly deactivated sympathetic nerve traffic could result in a critical hemodynamic status in association with endograft deployment.

Intra-operative identification of conjoined lumbosacral nerve roots: a report of three cases.

We report 3 cases of conjoined nerve root anomalies identified during micro-endoscopic discectomy (MED). Between 2009 and 2010, 61 men and 20 women aged 18 to 84 (mean, 42) years underwent MED for symptomatic lumbar disc herniation of L3-4 (n=1), L4-5 (n=44), and L5-S1 (n=36). Magnetic resonance imaging (MRI), myelogram, and postmyelo computed tomography did not identify the anomalies. All 3 patients were male and had type 2A S1 conjoined nerve roots, with a herniated disc at L5-S1. None of them had any preoperative pseudolocalising neurological signs, but all demonstrated stiffer positive straight leg raise sign and deterioration of the Achilles tendon reflex. Postoperatively, all 3 patients achieved excellent clinical outcomes.

Prevention of alveolar air leakage after video-assisted thoracic surgery: comparison of the efficacy of methods involving the use of fibrin glue.

BACKGROUND: The aim of this study was to evaluate the appropriate condition of use of the fibrin glue plus polyglycolic acid (PGA) sheet combination to obtain the optimal sealing effect. METHODS: 126 consecutive patients underwent video-assisted thoracic surgery (VATS) were divided into groups as follows: fibrin glue sprayed on the PGA sheet placed over the pleural defect (Method I); fibrinogen and thrombin solutions sprayed separately on the PGA sheet soaked in thrombin and placed over the pleural defect after rubbing of fibrinogen solution on the area (Method II); fibrin glue sprayed on the PGA sheet placed over the pleural defect after rubbing of fibrinogen solution on the area (Method III). Method II and Method III were also examined in an animal model. RESULTS: Postoperative air leakage was more effectively prevented by Method III than by the other two methods (p < 0.05). In the experimental study, a significantly higher seal-breaking pressure was obtained for Method III than for Method II (p < 0.05). CONCLUSION: Method III was the most effective for preventing alveolar air leakage.

Age, gender, will, and use of home-visit nursing care are critical factors in home care for malignant diseases; a retrospective study involving 346 patients in Japan.

BACKGROUND: We aimed to clarify the factors affecting outcomes of home care for patients with malignant diseases. METHODS: Of 607 patients who were treated in 10 clinics specialized in home care between January and December 2007 at Chiba, Fukuoka, Iwate, Kagoshima, Tochigi and Tokyo prefectures across Japan, 346 (57%; 145 men and 201 women) had malignant diseases. We collected information on medical and social backgrounds, details of home care, and its outcomes based on their medical records. RESULTS: Median age of the patients was 77 years (range, 11-102), and 335 patients were economically self-sufficient. Their general condition was poor; advanced cancer (n = 308), performance status of 3-4 (n = 261), and dementia (n = 121). At the beginning of home care, 143 patients and 174 family members expressed their wish to die at home. All the patients received supportive treatments including fluid replacement and oxygenation. Median duration of home care was 47 days (range, 0-2,712). 224 patients died at home. For the remaining 122, home care was terminated due to complications (n = 109), change of attending physicians (n = 8), and others (n = 5). The factors which inhibited the continuity of home care were the non-use of home-visit nursing care (hazard ratio [HR] = 1.78, 95% confidence interval [CI]: 1.05-3.00, p = 0.03), the fact that the patients themselves do not wish to die at home (HR = 1.83, CI: 1.09-3.07, p = 0.02), women (HR = 1.81, CI: 1.11-2.94, p = 0.02), and age (HR = 0.98, CI: 0.97-1.00, p = 0.02). CONCLUSIONS: Continuation of home care is influenced by patients' age, gender, will, and use of home-visit nursing.

Kinematic evaluation of the adjacent segments after lumbar instrumented surgery: a comparison between rigid fusion and dynamic non-fusion stabilization.

The aim of the current study was to evaluate changes in lumbar kinematics after lumbar monosegmental instrumented surgery with rigid fusion and dynamic non-fusion stabilization. A total of 77 lumbar spinal stenosis patients with L4 degenerative spondylolisthesis underwent L4-5 monosegmental posterior instrumented surgery. Of these, 36 patients were treated with rigid fusion (transforaminal lumbar interbody fusion) and 41 with dynamic stabilization [segmental spinal correction system (SSCS)]. Lumbar kinematics was evaluated with functional radiographs preoperatively and at final follow-up postoperatively. We defined the contribution of each segmental mobility to the total lumbar mobility as the percent segmental mobility [(sagittal angular motion of each segment in degrees)/(total sagittal angular motion in degrees) × 100]. Magnetic resonance imaging was performed on all patients preoperatively and at final follow-up postoperatively. The discs were classified into five grades based on the previously reported system. We defined the progress of disc degeneration as (grade at final follow-up) - (grade at preoperatively). No significant kinematical differences were shown at any of the lumbar segments preoperatively; however, significant differences were observed at the L2-3, L4-5, and L5-S1 segments postoperatively between the groups. At final follow-up, all of the lumbar segments with rigid fusion demonstrated significantly greater disc degeneration than those with dynamic stabilization. Our results suggest that the SSCS preserved 14% of the kinematical operations at the instrumented segment. The SSCS may prevent excessive effects on adjacent segmental kinematics and may prevent the incidence of adjacent segment disorder.

Surgical results of dynamic nonfusion stabilization with the Segmental Spinal Correction System for degenerative lumbar spinal diseases with instability: Minimum 2-year follow-up.

BACKGROUND: When spinal fusion is applied to degenerative lumbar spinal disease with instability, adjacent segment disorder will be an issue in the future. However, decompression alone could cause recurrence of spinal canal stenosis because of increased instability on operated segments and lead to revision surgery. Covering the disadvantages of both procedures, we applied nonfusion stabilization with the Segmental Spinal Correction System (Ulrich Medical, Ulm, Germany) and decompression. METHODS: The surgical results of 52 patients (35 men and 17 women) with a minimum 2-year follow-up were analyzed: 10 patients with lumbar spinal canal stenosis, 15 with lumbar canal stenosis with disc herniation, 20 with degenerative spondylolisthesis, 6 with disc herniation, and 1 with lumbar discopathy. RESULTS: The Japanese Orthopaedic Association score was improved, from 14.4 ± 5.3 to 25.5 ± 2.8. The improvement rate was 76%. Range of motion of the operated segments was significantly decreased, from 9.6° ± 4.2° to 2.0° ± 1.8°. Only 1 patient had adjacent segment disease that required revision surgery. There was only 1 screw breakage, but the patient was asymptomatic. CONCLUSIONS: Over a minimum 2-year follow-up, the results of nonfusion stabilization with the Segmental Spinal Correction System for unstable degenerative lumbar disease were good. It is necessary to follow up the cases with a focus on adjacent segment disorders in the future.

Endogenous angiogenesis inhibitor vasohibin1 exhibits broad-spectrum antilymphangiogenic activity and suppresses lymph node metastasis.

During cancer progression, the angiogenesis that occurs is involved in tumor growth and hematogenous-distant metastasis, whereas lymphangiogenesis is involved in regional lymph node metastasis. Angiogenesis is counterregulated by various endogenous inhibitors; however, little is known about endogenous inhibitors of lymphangiogenesis. We recently isolated vasohibin1 as an angiogenesis inhibitor intrinsic to the endothelium and further demonstrated its anticancer activity through angiogenesis inhibition. Here, we examined the effect of vasohibin1 on lymphangiogenesis. Vasohibin1 exhibited broad-spectrum antilymphangiogenic activity in the mouse cornea induced by factors including VEGF-A, VEGF-C, FGF2, and PDGF-BB. We then inoculated highly lymph node-metastatic cancer cells into mice and examined the effect of vasohibin1 on lymph node metastasis. Tail-vein injection of adenovirus containing the human vasohibin1 gene inhibited tumor lymphangiogenesis and regional lymph node metastasis. Moreover, local injection of recombinant vasohibin1 inhibited lymph node metastasis. These results suggest vasohibin1 to be the first known intrinsic factor having broad-spectrum antilymphangiogenic activity and indicate that it suppresses lymph node metastasis.

[Alteration in antibody-mediated immunity in patients with rituximab-combined chemotherapy and incidence of herpes zoster].

Rituximab, a chimeric monoclonal antibody against the CD20 protein, has an antineoplastic effect resulting from antibody dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). In patients with rituximab-combined chemotherapy, a decline in immunoglobulin can be observed. This is more likely to cause virus reactivation, such as Herpes (H) zoster. However, this fact has not reported in a large-scale study. In order to research immunodeficiency conditions in patients with rituximab-combined therapy, we examined the alteration in immunoglobulin level throughout the treatment among 205 cases with B-cell lymphoma. We also studied the prevalence of H. zoster in those cases. The IgG level throughout the treatment was measured in 89 patients in the research. The median post-chemotherapy IgG level was 41.1% lower than its pre-chemotherapy IgG level. In 58 cases, the IgG level following chemotherapy was below the normal level. In 22 cases, the IgG level dropped to less than half of the pre-chemotherapy level. H. zoster developed in 17 cases (8.3%). There was no significant difference in IgG level between H. zoster-onset cases and non-H. zoster-onset cases. Antibody-mediated immunity can decrease greatly and prolong in cases with rituximab in combination with chemotherapy. Therefore, infection control is considered to be important.

Generation of monoclonal antibodies against a soluble form of lectin-like oxidized low-density lipoprotein receptor-1 and development of a sensitive chemiluminescent enzyme immunoassay.

Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), expressed prominently in atherosclerotic lesions, is cleaved and released as a soluble LOX-1 (sLOX-1), which is a specific biomarker to diagnose acute coronary syndrome (ACS) at an early stage. Although sLOX-1 levels in patient's blood were successfully measured with our previously established enzyme-linked immunosorbent assay (ELISA), the assay was not sensitive enough to detect normal serum levels of sLOX-1 in healthy human subjects. We therefore developed sensitive and specific monoclonal antibodies (mAbs) against sLOX-1 in order to establish a more sensitive immunoassay. Mice were immunized with recombinant human LOX-1 extracellular domain. mAbs were subsequently generated by standard myeloma cell fusion techniques with a novel screening method using time-resolved fluorescence immunoassay. Using two anti-human sLOX-1 mAbs and alkaline phosphatase as a label, a sandwich chemiluminescent enzyme immunoassay (CLEIA) was developed. In total, nine mAbs were obtained. The dissociation constant (K(d)) values of these mAbs for sLOX-1 were 0.12-1.32 nM. Characteristics of these mAbs were estimated and the best combination for CLEIA was selected. The newly established CLEIA could determine sLOX-1 levels as low as 8 pg/mL, and thus, was sensitive enough to measure serum sLOX-1 levels in normal human subjects and to evaluate subtle differences. Values for sLOX-1 measured by monoclonal CLEIA and polyclonal ELISA were highly correlated (r(2)=0.7594, p<0.0001). Area under the curve values of the receiver-operating characteristic curves in detecting ACS were 0.948 and 0.978 for monoclonal CLEIA and polyclonal ELISA, respectively. Thus, a more sensitive sLOX-1 CLEIA was established using newly developed mAbs against sLOX-1. In addition to its advantage in early diagnosis of ACS, this assay may also be useful in predicting cardiovascular disease risk in disease-free subjects.

Vasohibin-1 expression in endothelium of tumor blood vessels regulates angiogenesis.

In this study, we characterized the significance of the vascular endothelial growth factor-inducible angiogenesis inhibitor vasohibin-1 to tumors. In pathological sections of non-small cell lung carcinoma, vasohibin-1 was present in the endothelial cells of blood vessels of the tumor stroma, but not in the lymphatics. In cancer cells, the presence of vasohibin-1 was associated with hypoxia-inducible factor 1alpha/vascular endothelial growth factor and fibroblast growth factor-2 expression. We then examined the function of vasohibin-1 in the mouse by subcutaneously inoculating with Lewis lung carcinoma cells. Resultant tumors in vasohibin-1(-/-) mice contained more immature blood vessels and fewer apoptotic tumor cells than tumors in wild-type mice. In wild-type mice that had been inoculated with Lewis lung carcinoma cells, tail vein injection of adenovirus containing the human vasohibin-1 gene inhibited tumor growth and tumor angiogenesis. Moreover, the remaining tumor vessels in adenoviral human vasohibin-1 gene-treated mice were small, round, and mature, surrounded by mural cells. The addition of adenoviral human vasohibin-1 gene to cisplatin treatment improved cisplatin's antitumor activity in mice. These results suggest that endogenous vasohibin-1 is not only involved in tumor angiogenesis, but when sufficient exogenous vasohibin-1 is supplied, it blocks sprouting angiogenesis by tumors, matures the remaining vessels, and enhances the antitumor effect of conventional chemotherapy.

Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2 in the regulation of angiogenesis.

We recently isolated a novel angiogenesis inhibitor, vasohibin-1, and its homologue, vasohibin-2. In this study we characterize the role of these 2 molecules in the regulation of angiogenesis. In a mouse model of subcutaneous angiogenesis, the expression of endogenous vasohibin-1 was low in proliferating ECs at the sprouting front but high in nonproliferating endothelial cells (ECs) in the termination zone. In contrast, endogenous vasohibin-2 was preferentially expressed in mononuclear cells mobilized from bone marrow that infiltrated the sprouting front. When applied exogenously, vasohibin-1 inhibited angiogenesis at the sprouting front where endogenous vasohibin-1 was scarce but did not influence vascularity in the termination zone where endogenous vasohibin-1 was enriched. Exogenous vasohibin-2 prevented the termination of angiogenesis in the termination zone and increased vascularity in this region. Angiogenesis was persistent in the termination zone in the vasohibin-1 knockout mice, whereas angiogenesis was deficient at the sprouting front in the vasohibin-2 knockout mice. Supplementation of deficient proteins normalized the abnormal patterns of angiogenesis in the vasohibin knockout mice. These results indicate that vasohibin-1 is expressed in ECs in the termination zone to halt angiogenesis, whereas vasohibin-2 is expressed in infiltrating mononuclear cells in the sprouting front to promote angiogenesis.

A case of pancreatic cancer with formation of a mass mimicking alcoholic or autoimmune pancreatitis in a young man. Possibility of diagnosis by hypermethylation of pure pancreatic juice.

CONTEXT: Mass-forming pancreatitis can be divided into two distinct types: alcoholic and autoimmune. There have been some cases of an ambiguous diagnosis although care was taken to differentiate between alcoholic mass-forming pancreatitis, focal type autoimmune pancreatitis and pancreatic cancer. CASE REPORT: We report a case of pancreatic cancer mimicking alcoholic or autoimmune pancreatitis with the formation of a mass in a 32-year-old man with a history of heavy drinking. Although both serum immunoglobulin G and immunoglobulin G4 levels were normal, many serum auto-antibodies, including the antinuclear antibody, were detected. After he stopped drinking, abdominal computed tomography showed a pancreatic head mass 28 mm in diameter with little and weak enhancement in the early and delayed phases, respectively. Endoscopic retrograde cholangiopancreatography showed an obstruction of the main pancreatic duct in the pancreatic head and marked stenosis of the lower common bile duct. Although a percutaneous ultrasound-guided pancreatic biopsy demonstrated no evidence of autoimmune pancreatitis, he was treated with prednisolone to test the efficacy of steroid therapy. However, the pancreatic mass became enlarged after steroid therapy, and he underwent surgery during which the mass was found to be pancreatic cancer. Although the patient was treated with gemcitabine, he died 5 months after surgery. We retrospectively assessed DNA hypermethylation in the patient's pure pancreatic juice obtained on admission. We observed hypermethylation of the cancer-specific gene tissue factor pathway inhibitor 2 (TFPI2). CONCLUSION: This finding suggests that if the DNA hypermethylation of pure pancreatic juice had been assayed before steroid therapy, it would have supported the diagnosis of pancreatic cancer, and steroid therapy could have been avoided.