Outpatient care for facial palsy-a survey on patient satisfaction in uni- and interdisciplinary approaches.

Objective: The various causes of facial palsy, diagnostic methods and treatment approaches frequently involve different medical specialities. Nevertheless, there exist only few specialized consultation and therapy services for patients with facial palsy (FP) in Germany. The aim of the present study was to evaluate factors affecting quality of life (QoL) and treatment satisfaction of patients presenting to an interdisciplinary facial nerve outpatient clinic. Methods: The study analyzed patients presenting to the interdisciplinary facial palsy outpatient clinic in Tuebingen between February 2019 and December 2022. General satisfaction and QoL was estimated by numerous self-rating questionnaires: ZUF-8, SF-36, FDI, FaCE, PHQ-9. An ANOVA was performed to analyze determinants affecting the ZUF-8. Correlation analyses between cause and regeneration of FP as well as questionnaire scores were performed. Results were compared with a group of patients who were managed in an unidisciplinary setting. Results: In total, 66 patients with FP were enrolled. FP patients showed increased levels of depression (PHQ-9: 14.52 ± 3.8) correlating with recovery of the palsy (p = 0.008), FaCE (p < 0.001) and FDI ratings (p < 0.001). There was a high level of satisfaction with the services provided during the uni-and interdisciplinary consultation (ZUF-8: 24.59 ± 6.2), especially among the 12/66 patients who received reconstructive, surgical treatment. However, some patients requested more psychological and ophthalmological support. Conclusion: High levels of treatment satisfaction can be achieved in both an uni-and interdisciplinary setting. However, multimodal therapy approaches should be applied, considering physical and psychological aspects. In the absence of recovery, surgical interventions must be considered as treatment options. Further studies should continue to investigate potential differences between uni-and interdisciplinary treatment.

Predictive value of facial motor-evoked potential and electromyography for facial motor function in vestibular schwannoma surgery.

PURPOSE: Intraoperative neuromonitoring (IONM) aims to preserve facial nerve (FN) function during vestibular schwannoma (VS) surgery. However, current techniques such as facial nerve motor evoked potentials (FNMEP) or electromyography (fEMG) alone are limited in predicting postoperative facial palsy (FP). The objective of this study was to analyze a compound fEMG/FNMEP approach. METHODS: Intraoperative FNMEP amplitude and the occurrence of fEMG-based A-trains were prospectively determined for the orbicularis oris (ORI) and oculi (OCU) muscle in 322 VS patients. Sensitivity and specificity of techniques to predict postoperative FN function were calculated. Confounding factors as tumor size, volume of intracranial air, or IONM duration were analyzed. RESULTS: A relevant immediate postoperative FP was captured in 105/322 patients with a significant higher risk in large VS. While fEMG demonstrated a high sensitivity (77% and 86% immediately and 15 month postoperative, respectively) for identifying relevant FP, specificity was low. In contrast, FNMEP have a significantly higher specificity of 80.8% for predicting postoperative FP, whereas the sensitivity is low. A retrospective combination of techniques demonstrated still an incorrect prediction of FP in ~ 1/3 of patients. CONCLUSIONS: FNMEP and fEMG differ in sensitivity and specificity to predict postoperative FP. Although a combination of IONM techniques during VS surgery may improve prediction of FN function, current techniques are still inaccurate. Further development is necessary to improve IONM approaches for FP prediction.

A comparative study of microsurgery and gamma knife radiosurgery in vestibular schwannoma evaluating tumor control and functional outcome.

Background: Both stereotactic radiosurgery (SRS) and microsurgical resection (SURGERY) are available as treatment options for sporadic vestibular schwannoma (VS). There are very few direct comparative studies comparing both treatment modalities in large cohorts allowing detailed subgroup analysis. This present study aimed to compare the nuances in the treatment of VS by SURGERY and SRS in 2 highly specialized neurosurgical centers. Methods: This is a retrospective bicentric cohort study. Data from patients treated between 2005 and 2011 were collected retrospectively. Recurrence-free survival (RFS) was assessed radiographically by contrast-enhanced magnetic resonance imaging. Results: The study population included N = 901 patients with a mean follow-up of 7 years. Overall, the incidence of recurrence was 7% after SURGERY, and 11% after SRS with superior tumor control in SURGERY in the Kaplan-Meier-analysis (P = 0.031). In small tumors (Koos I and II), tumor control was equivalent in both treatment arms. In large VS (Koos III and IV), however, RFS was superior in SURGERY. The extent of resection correlated with RFS (P < .001). Facial and hearing deterioration was similar in both treatment arms in small VS, but more pronounced in SURGERY of large VS. Tinnitus, vertigo, imbalance, and trigeminal symptoms were more often improved by SURGERY than SRS. Conclusions: SRS can achieve similar tumor control compared to SURGERY in smaller VS (Koos I and II)-with similar postinterventional morbidities. In large VS (Koos III and IV), long-term tumor control of SRS is inferior to SURGERY. Based on these results, we suggest that if combination therapy is chosen, the residual tumor should not exceed the size of Koos II.

Sex Differences in Vestibular Schwannoma.

Vestibular schwannoma (VS) are equally common in men and woman. A number of epidemiological studies have reported on sex-specific aspects of incidence, tumor size, tinnitus and hearing loss. However, data on sex-specific, pre- and post-surgically quality of life (QoL) are rare. The objective of the present study was to determine sex-specific aspects on QoL in VS. Health-related QoL was analyzed in 260 patients (112 male/148 female) with unilateral sporadic VS using general (SF-36: general Short-Form Health Survey), disease-specific (PANQOL: Penn Acoustic Neuroma Quality-of-Life Scale, PANQOL) and symptom-specific (DHI: Dizziness Handicap Inventory; HHI: Hearing Handicap Inventory; THI: Tinnitus Handicap Inventory; FDI: Facial Disability Index) QoL questionnaires. Sex differences were evaluated pre- and postoperative by multi- and univariate analyses based on 200 preoperative and 88 postoperative questionnaires. Female patients were significantly more affected by dizziness, headaches, reduced energy and anxiety. Energy and balance changed similarly in both sexes after surgery. However, postoperative women tended to be more affected by facial palsy and headaches than men. Despite the greater physical impairment, general health improved equivalently or even more in female patients than in males. In conclusion, self-rated QoL in VS is significantly affected by sex and surgery. This should be taken into account when counseling VS patients regarding observation, radiotherapy, and surgery.

Trading mental and physical health in vestibular schwannoma treatment decision.

Objective: Observation, radiotherapy and surgery are treatment options in vestibular schwannomas (VS). Decision making differs between centers and is usually based on tumor characteristics (e.g., size) and the expected physical health (PH) outcome (i.e., hearing and facial function). However, mental health (MH) is often under-reported. The objective of the present study was to ascertain the impact of VS treatment on PH and MH. Methods: PH and MH were assessed in a prospective cross-sectional study including 226 patients with unilateral sporadic VS before and after surgical removal (SURG). Quality-of-life (QoL) was estimated by self-rating questionnaires: general Short-Form Health Survey (SF-36), Penn Acoustic Neuroma Quality-of-Life Scale (PANQOL), Dizziness Handicap Inventory (DHI), Hearing Handicap Inventory (HHI), Tinnitus Handicap Inventory (THI), and Facial Disability Index (FDI). QoL changes over time as well as predictive factors were accessed by multivariate analyses of covariance (MANCOVA). Results: In total, 173 preoperative and 80 postoperative questionnaires were analyzed. There was a significant PH deterioration related to facial function (FDI, PANQOL-face) after surgery. In line with facial rehabilitation, however, FDI improved within the first five years after surgery and did not differ compared to the preoperative patient cohort, eventually. In contrast, MH (i.e., PANQOL-anxiety) and general health (i.e., PANQOL-GH) improved with surgery and correlated with the extent-of-resection. Conclusion: Physical and mental health is significantly influenced by VS surgery. While PH might decrease after surgery, MH potentially increases when patient is cured. Practitioners should take MH into account before advising an incompletely VS treatment (e.g., subtotal resection, observation or radiosurgery).

The Semisitting Retrosigmoid Technique for Removal of Large Vestibular Schwannoma: 2-Dimensional Operative Video.

INDICATIONS CORRIDOR AND LIMITS OF EXPOSURE: The retrosigmoid approach in semisitting position (RS-SSP) is a powerful technique for removal of large vestibular schwannomas. 1 It improves extent of tumor resection and nerve preservation. This video shows the case of a 34-year-old man with a large vestibular schwannoma, treated with the RS-SSP technique. The patient consented to the procedure and to publication of his image. ANATOMIC ESSENTIALS NEED FOR PREOPERATIVE PLANNING AND ASSESSMENT: Preoperative MRI and bone window computed tomography are essential for optimal planning. Intraoperative monitoring throughout the surgery includes somatosensory evoked potential (SSEP) and motor evoked potential (MEP) of limbs, facial MEP and electromyography, and brainstem auditory evoked potention. ESSENTIALS STEPS OF THE PROCEDURE: Major steps are (1) positioning of patient in SSP under SSEP recordings, 2,3 (2) ipsilateral retrosigmoid craniotomy, (3) straight dura incision parallel to sigmoid sinus, (4) opening the basal cisterns and gently elevation of cerebellum, (5) identification of Tübingen line on posterior surface of petrous bone, (6) opening and emptying the internal auditory canal (IAC) under nerves preservation, (7) intracisternal tumor debulking, (8) bimanual nerve dissection of cochlear nerve inferiorly and facial nerve medially/ventrally, (9) endoscopic investigation of IAC fundus, 4 (10) plugging the IAC with bone wax and muscle, (11) jugular vein compression before dura closure, and (12) Closure of craniotomy and wound. PITFALLS/AVOIDANCE OF COMPLICATIONS: Correct positioning in SSP is crucial to minimize the risk of air embolism. 3. VARIANTS AND INDICATIONS FOR THEIR USE: Additional resection of suprameatal tubercle allows extension toward the middle fossa and removal of dumbbell-shaped trigeminal schwannomas and petroclival meningiomas. 4.

Plasma Inflammatory Markers and Ventriculostomy-Related Infection in Patients With Hemorrhagic Stroke: A Retrospective and Descriptive Study.

Background: Diagnosis of ventriculostomy-related infection (VRI) remains difficult due to the various existing definitions. In patients with hemorrhagic stroke, its diagnosis might be further complicated by the presence of intraventricular blood. Furthermore, hemorrhagic stroke per se may cause symptoms compatible with VRI. This study aimed to evaluate the benefit of plasma inflammatory markers for the diagnosis of VRI and its differentiation from patients with non-cerebral infection and patients without infection in a cohort of patients with hemorrhagic stroke. Methods: A total of 329 patients with hemorrhagic stroke and an external ventricular drain (EVD) in situ were admitted to the Neurocritical Care Unit, University Hospital Zurich over a period of 6 years. Of those patients, 187 with subarachnoid hemorrhage and 76 with spontaneous intracerebral hemorrhage were included. Patients with VRI were compared to patients without any infection and to patients with non-cerebral infection, with regards to their clinical characteristics, as well as their inflammatory plasma and cerebrospinal fluid (CSF) markers. For the analysis, peak values were considered. Results: The VRI was diagnosed in 36% of patients with subarachnoid and in 17% of patients with intracerebral hemorrhage. The VRI was diagnosed on an average day 9±6.2 after EVD insertion, one day after the white blood cell count (WBC) peaked in CSF (8 ± 6.3). Plasma inflammatory markers (WBC, C-reactive protein "CRP" and procalcitonin "PCT") did not differ among patients with VRI compared to patients without infection. The CRP and PCT, however, were higher in patients with non-cerebral infection than in patients with VRI. The WBC in CSF was generally higher in patients with VRI compared to both patients without any infection and patients with non-cerebral infection. Conclusions: No differences in plasma inflammatory markers could be found between patients with VRI and patients without any infection. Conversely, CRP/PCT were higher in patients with non-cerebral infection than in patients with VRI. Altogether, CRP, PCT, and WBC are not suitable parameters for VRI diagnosis in neurocritical care unit patients.

Quality of life impairment in adult Moyamoya patients-preoperative neuropsychological assessment and correlation to MRI and H215O PET findings.

Moyamoya angiopathy (MMA) related cerebral perfusion deficits or infarctions might influence quality of life (QoL). This study examines preoperative QoL in adult patients with MMA and correlates these with findings obtained via diagnostic imaging. Sixty-seven adult Moyamoya patients underwent preoperative neuropsychological testing including questionnaires to determine QoL, as well as psychiatric and depressive symptoms. The results were checked for correlation with territorial hypoperfusions seen in H215O PET with acetazolamide (ACZ) challenge (cerebrovascular reserve) and infarction patterns observed in MRI. Each vascular territory was analyzed separately and correlated with QoL. Physical role function was restricted in 41.0% of cases and emotional role function in 34.4% of cases (SF-36). Obsessive-compulsive disorder (39.3%) (SCL-90-R), psychoticism (34.4%) (SCL-90-R), and depression (32.7%) (BDI-II) were also very common. Psychoticism was significantly more frequent in cases where perfusion deficits in PET CT were observed in both MCA territories (left p = 0.0124, right p = 0.0145) and infarctions in MRI were present in the right MCA territory (p = 0.0232). Depression was significantly associated with infarctions in the right MCA territory (SCL-90-R p = 0.0174, BDI-II p = 0.0246). Women were affected more frequently by depression (BDI-II, p = 0.0234). Physical role function impairment was significantly associated with perfusion deficits in the left MCA territory (p = 0.0178) and infarctions in the right MCA territory (p = 0.0428). MMA leads to impairments in different areas of QoL. Approximately one-third of all adult MMA patients suffered from depression, with women being most affected. In addition to depression, presence of executive dysfunctions and mental disorders such as psychoticism, obsessive-compulsive disorder, and impaired physical and emotional role function affected QoL. These patients showed significantly more often infarctions and perfusion deficits in the right MCA territory. Long-term studies with follow-up results are necessary to clarify a possible beneficial impact of early surgical revascularization on QoL and depression in adult MMA patients.

Sensitivity of human meningioma cells to the cyclin-dependent kinase inhibitor, TG02.

Standards of care for meningioma include surgical resection and radiotherapy whereas pharmacotherapy plays almost no role in this disease. We generated primary cultures from surgically removed meningiomas to explore the activity of a novel cyclin-dependent kinase inhibitor, TG02, in meningioma cell cultures. Tumor and cell cultures were characterized by mutation profiling and DNA methylation profiling. DNA methylation data were used to allot each sample to one out of six previously established meningioma methylation classes: benign (ben)-1, 2, 3, intermediate (int)-A, B, and malignant (mal). Four tumors assigned to the methylation class ben-2 showed the same class in culture whereas cultures from five non-ben-2 tumors showed a more malignant class in four patients. Cell cultures were uniformly sensitive to TG02 in the nanomolar range. Assignment of the cell cultures to a more malignant methylation class appeared to be more closely associated with TG02 sensitivity than assignment to a higher WHO grade of the primary tumors. Primary cell cultures from meningioma facilitate the investigation of the anti-meningioma activity of novel agents. TG02, an orally available cyclin-dependent kinase (CDK) inhibitor, warrants further exploration.

Management of brainstem haemorrhages.

Among spontaneous intracranial haemorrhages, primary non-traumatic brainstem haemorrhages are associated with the highest mortality rate. Patients classically present with rapid neurological deterioration. Previous studies have found that the severity of initial neurological symptoms and hydrocephalus are predictors of poor outcomes. In addition, radiological parameters aim to classify brainstem haematomas according to volume, extension and impact on prognosis. However, previous studies have failed to agree on a differentiated radiological classification for outcome and functional recovery. Electrophysiology, including motor, auditory and somatosensory evoked potentials, is used to estimate the extent of the initial injury and predict functional recovery. The current management of brainstem haematomas remains conservative, focusing on initial close neurocritical care monitoring. Surgical treatment concepts exist, but similarly to general intracranial haemorrhage management, they continue to be controversial and have not been sufficiently investigated. This is especially the case for haematomas in the posterior fossa, as these are excluded from most current clinical trials. Existing studies were mostly carried out before the present millennium began, and limitations are evident in the adaptation of those results and recommendations to current management, with today’s technological and diagnostic possibilities. We therefore recommend the re-evaluation of brainstem haemorrhages in the modern neurosurgical and intensive care environment.

Levels of malondialdehyde in the gastric juice: Its association with Helicobacter pylori infection and stomach diseases.

BACKGROUND: Helicobacter pylori (H. pylori) infection causes elevation of lipid peroxidation product malondialdehyde (MDA) and this association may be due to the bacterium causing reactive oxygen species-mediated damage to DNA in the gastric epithelium. The aim of this study was to investigate the gastric juice MDA levels in relation to H. pylori infection and associated gastric diseases. METHODS: Gastric juice samples were obtained from 117 patients undergoing endoscopy, and gastric juice MDA levels were determined by high-performance liquid chromatography (HPLC) system. We compared the MDA levels between patients with and without H. pylori infection and assessed the differences of MDA levels between chronic gastritis, gastric intestinal metaplasia, and gastric cancer postsurgical resection. RESULTS: Malondialdehyde levels in gastric juice were significantly higher in chronic gastritis patients with H. pylori infection than in those without H. pylori infection (P < .0001). In patients without H. pylori infection, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection had significantly higher gastric juice MDA level than patients with chronic gastritis. As a whole, patients with gastric intestinal metaplasia and gastric cancer postsurgical resection also had significantly higher MDA levels in gastric juice as compared to patients with chronic gastritis (P < .01). However, the difference of gastric juice MDA levels between gastric intestinal metaplasia and gastric cancer postsurgical resection was not significant. CONCLUSION: Malondialdehyde in gastric juice could be used as a potential diagnostic biomarker for H. pylori infection and associated gastric diseases. The gastric juice MDA levels increased proportionally with the severity of gastric diseases.

Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells.

Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.

Comparison of 10-day levofloxacin bismuth-based quadruple therapy and levofloxacin-based triple therapy for Helicobacter pylori.

OBJECTIVE: This was a prospective study aiming to investigate whether levofloxacin plus bismuth-based quadruple therapy was more effective than levofloxacin-based triple therapy after failed first-line eradication therapies for Helicobacter pylori (H. pylori) infection. METHODS: Sixty-seven patients infected with H. pylori were randomly assigned to two groups; the levofloxacin plus bismuth-based quadruple therapy group (RBAL [n = 33]; rabeprazole 20 mg twice daily, bismuth subcitrate 120 mg four times daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days) and the levofloxacin-based triple therapy group (RAL [n = 34]; rabeprazole 20 mg twice daily, amoxicillin 1 g twice daily and levofloxacin 500 mg once daily, for 10 days). Endoscopy was performed 4-8 weeks after H. pylori eradication to assess treatment response. We followed up patient response and compliance and checked their resistance to antibiotics. RESULTS: Intention-to-treat analysis revealed that both groups had similar eradication rates (RBAL vs RAL: 84.8% [95% confidence interval {CI} 72.6-97.1%] vs 67.6% [95% CI 51.9-83.4%], P = 0.0987). No significant differences in compliance or adverse events were found (P = 0.9829 and 0.0720). Epsilometer test showed that most eradication failure cases were levofloxacin-resistant. CONCLUSIONS: Adding bismuth subcitrate to levofloxacin-based triple therapy was not more effective than not doing so, but no further side effects were noted. Both eradication therapies were equally safe and patients had the same tolerance to both regimens. Resistance rate to levofloxacin may be important when choosing second-line therapy.

Exploring the expression bar code of SAA variants for gastric cancer detection.

We reported an integrated platform to explore serum protein variant pattern in cancer and its utility as a new class of biomarker panel for diagnosis. On the model study of serum amyloid A (SAA), we employed nanoprobe-based affinity mass spectrometry for enrichment, identification and quantitation of SAA variants from serum of 105 gastric cancer patients in comparison with 54 gastritis patients, 54 controls, and 120 patients from other cancer. The result revealed surprisingly heterogeneous and most comprehensive SAA bar code to date, which comprises 24 SAA variants including SAA1- and SAA2-encoded products, polymorphic isoforms, N-terminal-truncated forms, and three novel SAA oxidized isotypes, in which the variant-specific peptide sequence were also confirmed by LC-MS/MS. A diagnostic model was developed for dimension reduction and computational classification of the 24 SAA-variant bar code, providing good discrimination (AUC = 0.85 ± 3.2E-3) for differentiating gastric cancer group from gastritis and normal groups (sensitivity, 0.76; specificity, 0.81) and was validated with external validation cohort (sensitivity, 0.71; specificity, 0.74). Our platform not only shed light on the occurrence and modification extent of under-represented serum protein variants in cancer, but also suggested a new concept of diagnostic platform by serum protein variant profile.

Positive Feedback Loop of OCT4 and c-JUN Expedites Cancer Stemness in Liver Cancer.

The network of stemness genes and oncogenes in human patient-specific reprogrammed cancer stem cells (CSCs) remains elusive, especially in liver cancer. HepG2-derived induced pluripotent stem cell-like cells (HepG2-iPS-like cells) were generated by introducing Yamanaka factors and the knockdown vector shTP53. They exhibited features of stemness and a higher tumorigenesis after xenograft transplantation compared with HepG2 cells. The cancerous mass of severe combined immunodeficiency (SCID) mice derived from one colony was dissected and cultured to establish reprogrammed HepG2-derived CSC-like cells (designated rG2-DC-1C). A single colony exhibited 42% occurrence of tumors with higher proliferation capacities. rG2-DC-1C showed continuous expression of the OCT4 stemness gene and of representative tumor markers, potentiated chemoresistance characteristics, and invasion activities. The sphere-colony formation ability and the invasion activity of rG2-DC-1C were also higher than those of HepG2 cells. Moreover, the expression of the OCT4 gene and the c-JUN oncogene, but not of c-MYC, was significantly elevated in rG2-DC-1C, whereas no c-JUN expression was observed in HepG2 cells. The positive-feedback regulation via OCT4-mediated transactivation of the c-JUN promoter and the c-JUN-mediated transactivation of the OCT4 promoter were crucial for promoting cancer development and maintaining cancer stemness in rG2-DC-1C. Increased expression of OCT4 and c-JUN was detected in the early stage of human liver cancer. Therefore, the positive feedback regulation of OCT4 and c-JUN, resulting in the continuous expression of oncogenes such as c-JUN, seems to play a critical role in the determination of the cell fate decision from iPS cells to CSCs in liver cancer. Stem Cells 2016;34:2613-2624.

Suppression of IL-8-Src signalling axis by 17ß-estradiol inhibits human mesenchymal stem cells-mediated gastric cancer invasion.

Epidemiologic data show the incidence of gastric cancer in men is twofold higher than in women worldwide. Oestrogen is reported to have the capacity against gastric cancer development. Endogenous oestrogen reduces gastric cancer incidence in women. Cancer patients treated with oestrogens have a lower subsequent risk of gastric cancer. Accumulating studies report that bone marrow mesenchymal stem cells (BMMSCs) might contribute to the progression of gastric cancer through paracrine effect of soluble factors. Here, we further explore the effect of oestrogen on BMMSCs-mediated human gastric cancer invasive motility. We founded that HBMMSCs notably secrete interleukin-8 (IL-8) protein. Administration of IL-8 specific neutralizing antibody significantly inhibits HBMMSCs-mediated gastric cancer motility. Treatment of recombinant IL-8 soluble protein confirmed the role of IL-8 in mediating HBMMSCs-up-regulated cell motility. IL-8 up-regulates motility activity through Src signalling pathway in human gastric cancer. We further observed that 17ß -estradiol inhibit HBMMSCS-induced cell motility via suppressing activation of IL8-Src signalling in human gastric cancer cells. 17ß-estradiol inhibits IL8-up-regulated Src downstream target proteins including p-Cas, p-paxillin, p-ERK1/2, p-JNK1/2, MMP9, tPA and uPA. These results suggest that 17ß-estradiol significantly inhibits HBMMSCS-induced invasive motility through suppressing IL8-Src signalling axis in human gastric cancer cells.

Diagnosis of Helicobacter pylori infection: Current options and developments.

Accurate diagnosis of Helicobacter pylori (H. pylori) infection is a crucial part in the effective management of many gastroduodenal diseases. Several invasive and non-invasive diagnostic tests are available for the detection of H. pylori and each test has its usefulness and limitations in different clinical situations. Although none can be considered as a single gold standard in clinical practice, several techniques have been developed to give the more reliable results. Invasive tests are performed via endoscopic biopsy specimens and these tests include histology, culture, rapid urease test as well as molecular methods. Developments of endoscopic equipment also contribute to the real-time diagnosis of H. pylori during endoscopy. Urea breathing test and stool antigen test are most widely used non-invasive tests, whereas serology is useful in screening and epidemiological studies. Molecular methods have been used in variable specimens other than gastric mucosa. More than detection of H. pylori infection, several tests are introduced into the evaluation of virulence factors and antibiotic sensitivity of H. pylori, as well as screening precancerous lesions and gastric cancer. The aim of this article is to review the current options and novel developments of diagnostic tests and their applications in different clinical conditions or for specific purposes.

The effect of Helicobacter pylori eradication on the levels of essential trace elements.

OBJECTIVE: This study was designed to compare the effect of Helicobacter pylori (H. pylori) infection treatment on serum zinc, copper, and selenium levels. PATIENTS AND METHODS: We measured the serum zinc, copper, and selenium levels in H. pylori-positive and H. pylori-negative patients. We also evaluated the serum levels of these trace elements after H. pylori eradication. These serum copper, zinc, and selenium levels were determined by inductively coupled plasma mass spectrometry. RESULTS: Sixty-three H. pylori-positive patients and thirty H. pylori-negative patients were studied. Serum copper, zinc, and selenium levels had no significant difference between H. pylori-positive and H. pylori-negative groups. There were 49 patients with successful H. pylori eradication. The serum selenium levels were lower after successful H. pylori eradication, but not significantly (P = 0.06). There were 14 patients with failed H. pylori eradication. In this failed group, the serum selenium level after H. pylori eradication therapy was significantly lower than that before H. pylori eradication therapy (P < 0.05). The serum zinc and copper levels had no significant difference between before and after H. pylori eradication therapies. CONCLUSION: H pylori eradication regimen appears to influence the serum selenium concentration (IRB number: KMUH-IRB-20120327).

Acid suppressive agents and risk of Mycobacterium tuberculosis: case-control study.

BACKGROUND: The acid-suppressive agents have been linked with an increased risk of infectious disease. The relationship between these drugs and Mycobacterium Tuberculosis (TB) was not been reported. METHODS: We conducted a case-control study using data from National Health Insurance research database of Taiwan. From 1996 till 2008, and 6541 cases were defined as TB infection/activation (ICD-9 coding plus prescription two of four first-line anti-TB regimen for at least one month). Control subjects who were matched to the TB cases by age and sex were selected with 10:1 ratio. Medical records including acid-suppressive agent prescription and comorbidity, and socioeconomic status were analyzed. RESULTS: TB infection/activation was more frequent to comorbidity with chronic diseases, alcohol abuse, malignancy, immune deficient/suppression status and acid-related disease (peptic ulcer, reflux esophagitis). Among the TB cases, there was higher exposure record to acid-suppressive agents within 3 months before TB index date (OR 2.43(2.06-2.88) and 1.90 (1.68-2.14) for proton pump inhibitor (PPI) and histamine 2 receptor antagonist (H2RA) respectively). After adjusting confounding factors, PPIs prescription 3 months before TB index date had an association of TB infection/activation (adjusted OR 1.63(1.61-1.63)). Similar result was found in H2RA user (adjusted OR 1.51(1.50-1.52)). The association of acid-suppressive agents in TB infection/activation was fade gradually when the drug prescription period extended. CONCLUSIONS: Recent prescription of acid-suppressive agent seems to associate the TB infection/activation. In the society where TB was prevalent, evaluation of pulmonary TB before prescription of PPI or H2RA is warranted.

Detection of genotypic clarithromycin-resistant Helicobacter pylori by string tests.

AIM: To evaluate the utility of the string test to detect genotypic clarithromycin-resistant Helicobacter pylori (H. pylori) by polymerase chain reaction (PCR)-restriction fragment length polymorphism. METHODS: Patients undergoing endoscopic examinations were enrolled in the present study. String tests were done on the next day of endoscopy. Segments of 23S rRNA were amplified from DNA obtained from string tests. PCR-restriction fragment length polymorphism was accomplished by restriction enzymes BbsI and BsaI recognizing the mutation site A to G at 2143 or at 2142 of 23S rRNA domain V, respectively. RESULTS: One hundred and thirty-four patients with H. pylori infection underwent string tests. To compare phenotypic resistance, 43 isolates were successfully cultured in 79 patients in whom 23S rRNA was successfully amplified. Of five patients with clarithromycin-resistant H. pylori, 23S rRNA of H. pylori isolates from four patients could be digested by BsaI. In 38 susceptible isolates, 23S rRNA of H. pylori isolates from 36 patients could not be digested by either BsaI or BbsI. The sensitivity and specificity of the string test to detect genotypic clarithromycin resistance were 66.7% and 97.3%, respectively. Positive and negative predictive values were 80% and 94.7%, respectively. CONCLUSION: String test with molecular analysis is a less invasive method to detect genotypic resistance before treatment. Further large-scale investigations are necessary to confirm our results.