Postprocedure serum amylase or lipase levels predict postendoscopic retrograde cholangiopancreatography pancreatitis: Meta-analysis of diagnostic test accuracy studies and utility assessment.

OBJECTIVES: We aimed to clarify the clinical utility of measuring serum pancreatic enzymes after endoscopic retrograde cholangiopancreatography (ERCP) for the purpose of predicting post-ERCP pancreatitis (PEP) by a meta-analysis of diagnostic test accuracy studies. METHODS: Studies on the prediction accuracy of PEP by serum amylase or lipase measured at 2, 3, and 4 h after ERCP were collected. A literature search was performed in PubMed and the Cochrane Library database for studies published between January 1980 and March 2023. The quality of individual studies was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-2. Data were analyzed using Meta-DiSc 2.0 software. RESULTS: We searched the databases and identified 20 observational studies (12,313 participants). PEPs were defined according to criteria by Cotton or modified Cotton, revised Atlanta criteria, or the Japanese criteria. Meta-analysis of eight studies (4389 participants) showed a pooled sensitivity of 71.1% (95% confidence interval [CI] 56.1-82.5) and pooled specificity of 91.2% (95% CI 85.9-94.6) for the serum amylase cut-off value at 3 times the upper limit of normal (ULN). Another meta-analysis of five studies (1970 participants) showed a pooled sensitivity of 85.8% (95% CI 61.9-95.7) and pooled specificity of 85.3% (95% CI 81.9-88.1) for the serum lipase cut-off value at 3 times ULN. CONCLUSION: Despite a high risk of bias due to various reference standards, this updated meta-analysis and the utility assessment by a decision tree showed the utility of serum amylase or lipase levels more than 3 times ULN measured 2-4 h after ERCP for predicting PEP.

Predictor of primary response to antitumor necrosis factor-α therapy for inflammatory bowel disease: a single-center observational study.

BACKGROUND: It is necessary to find reliable and appropriate predictors of primary response to anti-TNFα therapy (infliximab and adalimumab) in inflammatory bowel disease (IBD) so as to avoid treatment failure and select optimal treatment. The aim of this study is to reveal useful predictors of the response to anti-TNFα treatment from baseline to 2 months after initial administration of anti-TNFα for individual IBD patients using our pharmacokinetic and pharmacodynamic (PK/PD) model at the time of second administration. METHODS: We retrospectively analyzed 26 IBD patients who received anti-TNFα. In the PK/PD model, inflammation was assumed to be suppressed based on the action of anti-TNFα at the rate constant of Kanti-TNFα (day-1). Kanti-TNFα0 (day-1) is Kanti-TNFα in the absence of anti-TNFα. We expressed inflammation caused by factors not affected by the action of anti-TNFα using the rate constant Kelse (day-1). Using univariate and multivariate linear regressions, we statistically analyzed factors related to the improvement of disease activity index. RESULTS: The significant correlation between Kanti-TNFα0/Kelse and the improvement of disease activity index was shown in Crohn's disease patients (univariate: estimated value 2.4; P = 0.003; and multivariate: 1.8; P = 0.012) and ulcerative colitis patients (univariate: 0.12; P = 0.011), and no other factors were significant. CONCLUSION: This is the first study to present a useful predictor of primary response to anti-TNFα of individual IBD patients at second administration. The Kanti-TNFα0/Kelse ratio may help to select the optimal therapeutic drug and avoid the improper continuous administration of anti-TNFα in the induction phase.

Serum PR3-ANCA Is a Predictor of Primary Nonresponse to Anti-TNF-α Agents in Patients with Ulcerative Colitis.

BACKGROUND: Anti-tumor necrosis factor-α (TNF-α) agents are effective for moderately to severely active ulcerative colitis (UC). Nonetheless, a proportion of patients fail to respond to these agents as therapy for induction of remission. Recent studies indicated that perinuclear anti-neutrophil cytoplasmic antibody (p-ANCA) may predict response to anti-TNF-α agents in UC patients. However, whether PR3-ANCA can predict primary nonresponse (PNR) to anti-TNF-α agents has not yet been evaluated. The aim of this study was to examine whether PR3-ANCA can predict PNR to anti-TNF-α in UC patients. METHODS: This was a single-center retrospective study. Data were extracted from 50 patients with UC who had measurements of PR3-ANCA and received anti-TNF-α agents for the first time as induction therapy. The primary endpoint of this study was a proportion of patients with PNR stratified by PR3-ANCA positivity. PNR to anti-TNF-α agents was defined as failure to achieve reduction in partial Mayo score by 2 or more points and change to other therapeutics within 6 weeks. RESULTS: Fourteen (28%) of the 50 patients were PR3-ANCA positive. Seventeen (34%) of the 50 patients demonstrated PNR. Eleven (78.6%) of the 14 PR3-ANCA-positive patients demonstrated PNR, while 6 (16.7%) of the 36 PR3-ANCA-negative patients demonstrated PNR. Multivariate analysis demonstrated that PR3-ANCA positivity was associated with PNR to anti-TNF-α agents (odds ratio 19.29, 95% CI: 3.30-172.67; p = 0.002). CONCLUSION: PR3-ANCA positivity can predict PNR to anti-TNF-α agents in UC patients.

Early hemodynamics of hepatocellular carcinoma using contrast-enhanced ultrasound with Sonazoid: focus on the pure arterial and early portal phases.

To clarify the early hemodynamics of hepatocellular carcinoma (HCC), we defined the early portal phase of contrast-enhanced ultrasound (CEUS) and examined the reliability of this modality for determining HCC differentiation. Starting in 2007, we performed Sonazoid CEUS in 146 pathologically confirmed hepatic nodules; 118 HCC (8 poorly [Pd], 73 moderately [Md] and 37 well-differentiated [Wd]) and 28 benign nodules. We focused on the pure arterial and early portal phases up to 45 seconds after Sonazoid injection, and then the subsequent phase up to 30 minutes. We calculated covariance-adjusted sensitivities for nodule enhancement combinations of these three phases. Nodule enhancements were divided into hypo, iso and hyper. A positive predictive value of 100% was obtained for the following patterns: iso-iso-hypo, hypo-iso-iso, and hypo-hypo-hypo for Wd, hyper-iso-hypo and hyper-hypo-hypo for Md, hypo-hyper-hypo for Pd, and hyper-hyper-hyper for benign nodules. In Wd HCC (early HCC), there were seven enhancement patterns, thought to be characterized by various hemodynamic changes from early to advanced HCC. Two patterns allowing a diagnosis of Wd HCC were hypo in the pure arterial phase. Subsequent iso-enhancement in the early portal phase indicated a portal blood supply. Decreased enhancement in the early portal phase allows a diagnosis of Md HCC. However, gradual enhancement observed from the pure arterial to the early portal phase allows a diagnosis of Pd HCC. Therefore, even in the early portal phase, hemodynamic changes were visible not only in Wd but also in Md and Pd HCC. In conclusion, with division of the early phase hemodynamics into pure arterial and early portal phases, CEUS can provide information useful for determining the likely degree of HCC differentiation and for distinguishing early stage HCC from benign nodules.

A Patient with KL-6 Elevation with Anti-TNFα Who Could Receive Long-Term Use without Interstitial Pneumonia after Class Switch of Anti-TNFα.

A 40-year-old man with refractory ulcerative colitis (UC) was treated with tumor necrosis factor α inhibitor (anti-TNFα), infliximab. One month later, the chest computed tomography and laboratory test showed noninfectious interstitial lung disease (ILD) and elevation of serum Krebs von den Lungen-6 (KL-6). Fortunately, ILD disappeared after the discontinuation with anti-TNFα. Two and a half years after his first UC treatment, he was treated again with another anti-TNFα, adalimumab, for relapse and he had a second ILD. This course suggested anti-TNFα induced ILD. The characteristics of anti-TNFα-induced ILD in inflammatory bowel disease (IBD) are not well understood. We summarized and investigated the characteristics of such patients based on a literature review including 15 cases. It suggested that anti-TNFα-induced ILD in IBD might be rare and tends to have a better outcome compared with ILD in rheumatoid arthritis.

Risk Factors for Mortality in Pneumocystis jirovecii Pneumonia in Patients with Inflammatory Bowel Disease.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is highly fatal once infection is established. In this study, we investigated the risk of PJP mortality in patients with inflammatory bowel disease (IBD). METHODS: We conducted a retrospective observational study of case data from IBD patients who developed PJP, compiled from 17 collaborating institutions. Parameters such as age, sex, medications used, and blood test results were analyzed to identify risk factors for mortality. RESULTS: The mortality rate among the 28 IBD patients who developed PJP was 17.9%. A low serum albumin level at the start of IBD treatment was identified as a risk factor for mortality and showed the following association with probability of death (P): P = 1/[1 + exp(-5.5 + 2.4 × Alb). The probability of death exceeded 0.5 when serum albumin was 2.2 g/dL or lower. CONCLUSION: Patients with IBD who develop PJP have a high mortality rate and often cannot continue treatment with medication alone. Therefore, it is necessary to pay attention to albumin levels at the start of immunosuppressive therapy when creating a treatment plan.

Interleukin-6 as a diagnostic marker for infection in critically ill patients: A systematic review and meta-analysis.

BACKGROUND: The ability of blood levels of interleukin (IL)-6 to differentiate between infection and non-infection in critically ill patients with suspected infection is unclear. We assessed the diagnostic accuracy of serum IL-6 levels for the diagnosis of infection in critically ill patients. METHODS: We systematically searched the PubMed, MEDLINE, Cochrane Resister of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL, and Igaku Chuo Zasshi databases for studies published from 1986 to August 2016 that evaluated the accuracy of IL-6 levels for the diagnosis of infection. We constructed 2 × 2 tables and calculated summary estimates of sensitivity and specificity using a bivariate random-effects model. RESULTS: The literature search identified 775 articles, six of which with a total of 527 patients were included according to the predefined criteria. The pooled sensitivity, specificity, and diagnostic odds ratio were 0.73 (95% confidence interval [CI], 0.61-0.82), 0.76 (95% CI, 0.61-0.87), and 2.31 (95% CI, 1.20-3.48), respectively. The area under the curve (AUC) of the summary receiver operator characteristic (SROC) curve was 0.81 (95% CI, 0.78-0.85). In the secondary analysis of two studies with a total of 263 adult critically ill patients with organ dysfunction, the pooled sensitivity, specificity, and diagnostic odds ratio were 0.81 (95% CI, 0.75-0.86), 0.77 (95% CI, 0.67-0.84), and 2.87 (95% CI 2.15-3.60), respectively. CONCLUSIONS: Blood levels of IL-6 have a moderate diagnostic value and a potential clinical utility to differentiate infection in critically ill patients with suspected infection.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Clinical practice guideline for post-ERCP pancreatitis.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERPC) is used for the diagnosis and treatment of pancreatic and biliary diseases. Post-ERCP pancreatitis (PEP) is a complication which needs special care and clinical practice guideline for this morbidity is also needed. METHODS: The key clinical issues of diagnosis and treatment of PEP were listed and checked, and then the clinical questions were formulated. PubMed (MEDLINE) and Ichushi-web (Japanese medical literature) were used as databases. For the study of diagnostic test accuracy, items similar to QUADAS-2, i.e., random selection from a population to which the diagnostic test is applied, blinding of index tests and reference tests, completeness of reference standard, completeness of test implementations, the same timing of tests, and missing data were assessed as well as the indirectness of the study subjects, index tests, reference standard, and outcomes. Grading of recommendations was determined as strong or weak. In clinical practice, the judgment of attending doctors should be more important than recommendations described in clinical practice guidelines. Gastroenterologists are the target users of this clinical practice guideline. General practitioners or general citizens are not supposed to use this guideline. The guideline committee has decided to include wide clinical issues such as etiological information, techniques of ERCP, the diagnosis, treatments, and monitoring of PEP in this guideline. RESULTS: In this concise report, we described ten clinical questions, recommendations, and explanations pertaining to risk factors, diagnosis, prognostic factors, treatments, and preventive interventions in the medical practice for PEP. CONCLUSIONS: We reported here the essence of the clinical practice guideline for PEP.

Asian Perspectives on Diagnostic and Therapeutic Strategies in Inflammatory Bowel Disease: Report and Analysis of a Survey with Questionnaires.

BACKGROUND: Diagnostic and therapeutic strategies in inflammatory bowel disease (IBD) vary among countries in terms of availability of modalities, affordability of health care resource, health care policy and cultural background. This may be the case in different countries in Eastern Asia. The aim of this study was to determine and understand the differences in diagnostic and therapeutic strategies of IBD between Japan and the rest of Asian countries (ROA). METHODS: Questionnaires with regard to clinical practice in IBD were distributed to members of the International Gastroenterology Consensus Symposium Study Group. The responders were allowed to select multiple items for each question, as multiple modalities are frequently utilized in the diagnosis and the management of IBD. Dependency and independency of selected items for each question were evaluated by the Bayesian network analysis. RESULTS: The selected diagnostic modalities were not very different between Japan and ROA, except for those related to small bowel investigations. Balloon-assisted enteroscopy and small bowel follow through are frequently used in Japan, while CT/MR enterography is popular in ROA. Therapeutic modalities for IBD depend on availability of such modalities in clinical practice. As far as modalities commonly available in both regions are concerned, there seemed to be similarity in the selection of each therapeutic modality. However, evaluation of dependency of separate therapeutic modalities by Bayesian network analysis disclosed some difference in therapeutic strategies between Japan and ROA. CONCLUSION: Although selected modalities showed some similarity, Bayesian network analysis elicited certain differences in the clinical approaches combining multiple modalities in various aspects of IBD between Japan and ROA.

Effects of preoperative proton pump inhibitor administration on bleeding after gastric endoscopic submucosal dissection: A systematic review and meta-analysis.

BACKGROUND AND AIM: The efficacy of using proton pump inhibitors (PPIs) prior to gastric endoscopic submucosal dissection (ESD) to reduce gastric bleeding remains controversial. This study aimed to systematically review the literature to evaluate the efficacy of preoperative PPI use to reduce post-ESD bleeding. METHODS: PubMed, the Cochrane library, and the Igaku-Chuo-Zasshi database were searched to identify randomized trials eligible for inclusion in the systematic review. Data from four studies (406 patients) were combined to calculate a pooled risk difference (RD) for developing post-ESD bleeding. RESULTS: Compared with patients who received no premedication, the pooled RD for post-ESD bleeding in patients who received preoperavive PPI was -0.027 (95% confidence interval: -0.070-0.017, p = 0.228), without significant heterogeneity. Preoperavive PPI use significantly increased gastric pH (weighted mean difference: 1.289, 95% CI: 0.227-2.352, p = 0.0174). CONCLUSIONS: This systematic review and meta-analysis showed that premedication with PPI had no advantage for the prevention of post-ESD bleeding, despite increasing gastric pH.

Placement of a triple-layered covered versus uncovered metallic stent for palliation of malignant gastric outlet obstruction: a multicenter randomized trial.

BACKGROUND: Usually, uncovered self-expandable metallic stents (SEMS) are used for palliation of malignant gastric outlet obstruction (GOO). A triple-layered covered SEMS is reported to be efficacious, but its performance has not been compared with uncovered SEMS. The present study is the first to compare the efficacy and safety of a triple-layered covered versus uncovered SEMS. PATIENTS AND METHODS: A multicenter randomized study was conducted in two tertiary referral centers, with 62 eligible patients with symptomatic GOO to receive covered (n = 31) or uncovered SEMS (n = 31). The primary endpoint was SEMS patency, and secondary endpoints were success rate and adverse events after complete follow up. RESULTS: Both groups had a technical success rate of 100% and comparable clinical success rates (P = 0.67). There was nostatistically significant difference in stent patency and adverse events between the two groups (P = 0.52 and P = 0.38, respectively). Although the occurrence rate of persistent obstructive symptoms was comparable (P = 0.42), that of recurrent obstructive symptoms was higher in the uncovered group (29% vs 3.6%, P = 0.0125). Patient survival did not differ between groups (P = 0.34). CONCLUSION: There was no statistically significant difference in stent patency, but use of a triple-layered covered SEMS was associated with less frequent stent dysfunction more than 4 weeks after stenting, despite similar short-term outcomes.

Customized chemotherapy based on epidermal growth factor receptor mutation status for elderly patients with advanced non-small-cell lung cancer: a phase II trial.

BACKGROUND: Elderly patients are more vulnerable to toxicity from chemotherapy. Activating epidermal growth factor receptor (EGFR) mutations in non-small-cell lung cancer (NSCLC) are associated with enhanced response to EGFR tyrosine-kinase inhibitors. We studied patients with advanced NSCLC for whom treatment was customized based on EGFR mutation status. METHODS: We screened 57 chemotherapy-naïve patients with histologically or cytologically confirmed NSCLC, stage IIIB or IV, aged 70 years or older, and with an Eastern Cooperative Oncology Group performance status 0 or 1, for EGFR exon 19 codon 746-750 deletion and exon 21 L858R mutation. Twenty-two patients with EGFR mutations received gefitinib; 32 patients without mutations received vinorelbine or gemcitabine. The primary endpoint was the response rate. RESULTS: The response rate was 45.5% (95% confidence interval [CI]: 24.4%, 67.8%) in patients with EGFR mutations and 18.8% (95% CI: 7.2%, 36.4%) in patients without EGFR mutations. The median overall survival was 27.9 months (95%CI: 24.4 months, undeterminable months) in patients with EGFR mutations and 14.9 months (95%CI: 11.0 months, 22.4 months) in patients without EGFR mutations. In the gefitinib group, grade 3/4 hepatic dysfunction and dermatitis occurred in 23% and 5% of patients, respectively. In patients treated with vinorelbine or gemcitabine, the most common grade 3 or 4 adverse events were neutropenia (47%; four had febrile neutropenia), anemia (13%), and anorexia (9%). No treatment-related deaths occurred. CONCLUSIONS: Treatment customization based on EGFR mutation status deserves consideration, particularly for elderly patients who often cannot receive second-line chemotherapy due to poor organ function or comorbidities. TRIAL REGISTRATION: This trial is registered at University hospital Medical Information Network-clinical trial registration (http://www.umin.ac.jp/ctr/index/htm) with the registration identification number C000000436.

Weight-based high- and low-dose ribavirin in combination with peginterferon α-2b therapy for genotype 2 chronic hepatitis C: A randomized trial.

AIM: The optimal ribavirin dose in the treatment of patients infected with hepatitis C virus (HCV) genotype 2 remains to be elucidated. We aimed to seek the optimal ribavirin dose required for this genotype in a randomized trial. METHODS: We compared the efficacy and tolerability of the 24-week peginterferon α-2b (1.5 µg/kg/week) therapy in combination with a weight-based higher dose (600-1000 mg) and lower dose (400-800 mg) of ribavirin for genotype 2 patients. Noninferior margin was set at 10%. RESULTS: A total of 120 patients were randomized to a higher-dose or a lower-dose group. Sustained virological response (SVR) by intention-to-treat analysis was achieved in 47/58 (81.0%, 90% confidential interval [CI]: 72.6-89.5) patients in the higher-dose group and 41/60 (68.3%, 90% CI: 58.5-78.2) patients in the lower-dose group (difference, -12.7%; 90% CI, -25.7 to 0.3). Relapse rates were 10% and 21.6% in the higher-dose and the lower-dose groups, respectively. Multiple logistic regression analysis showed that ribavirin dose/kg body weight was the only significant predictor of SVR (≥9.5 mg/kg per day vs <9.5 mg/kg per day; odds ratio = 3.34; 95% CI, 1.41-7.92; P = 0.006). Twenty-one (36.2%) in the higher-dose group required ribavirin dose reduction because of anemia, whereas seven patients (11.7%) did in the lower-dose group (P < 0.01). Three of the higher-dose group and two of the lower-dose group required premature termination of therapy. CONCLUSIONS: Weight-based lower-dose ribavirin regimen was not equivalent to the higher-dose counterpart in the treatment of HCV genotype 2. We discourage treating these patients with low-dose ribavirin regimens. The peginterferon therapy in combination with ribavirin at a weight-based higher dose (600-1000 mg) remains the standard-of-care treatment for this genotype.

The performance of Cochlin-tomoprotein detection test in the diagnosis of perilymphatic fistula.

BACKGROUND: Perilymphatic fistula (PLF), defined as an abnormal communication between the inner and middle ear, presents with a symptomatology of hearing loss and vestibular disorder that is indistinguishable from a number of other inner ear diseases. Methods of diagnosis remain controversial. We have previously shown that Cochlin-tomoprotein (CTP) is selectively detected in the perilymph. To establish a definite diagnostic test for PLF using CTP as a biochemical marker, we examined the diagnostic performance of the CTP detection test. METHODS: CTP detection test was performed by Western blot using recombinant human CTP (rhCTP) as a spiked standard. We evaluated the specificity of the CTP detection test by testing non-PLF cases. To describe the limitations of the test, we tested samples from patients with middle ear infection. We also studied the stability of CTP protein by storing the samples at room temperature (25 degrees C) or 4 degrees C for 55 days. The effects of repeated freezing and thawing were also evaluated. Serially diluted perilymph was tested to find out the detection limit of CTP. FINDINGS: We have established a standardized CTP detection test using high (0.27 ng) and low (0.13 ng) spiked standards of rhCTP in Western blotting. Middle ear lavages (MEL) from 54 of 55 non-PLF cases were negative in the CTP detection test, i.e. the specificity of the test is 98.2%. MEL from 43 out of 46 cases with chronic suppurative otitis media or middle ear cholesteatoma were negative for CTP. CTP is a stable protein and detection was not affected by the storage, or freezing and thawing. The detection limit of perilymph was 0.161 microl/lane in an average of 5 samples. INTERPRETATION: CTP is a stable perilymph-specific protein, and this CTP detection could be the first clinically established diagnostic tool to detect PLF with a high specificity. PLF is surgically correctable by sealing the fistula. Appropriate recognition and treatment of PLF can improve hearing and balance in afflicted patients.

[Drug interactions in medical oncology].

Cytotoxic anti-neoplastic drugs are some of the strongest acting drugs. They have a complex pharmacological profile, narrow therapeutic window, steep dose-toxicity curve, and many pharmacokinetic and pharmacodynamic differences both within and between patients. This makes it difficult to avoid adverse effects. These drugs are approved for usage based on their clinical benefit to risk ratio. The recommended dose is usually close to the maximally-tolerated dose in order to achieve maximum therapeutic effect. Therefore, there is more concern about drug interactions affecting the pharmacokinetics of anti-neoplastic drugs than drugs in general. Any physician taking care of oncology patients must understand not only the pharmacokinetic profile(absorption, protein binding, metabolism and excretion)of the anti-neoplastic drugs their using, but also the many factors that affect the pharmacokinetic profile such as hepatic and renal function, and co-administered drugs. Expertise to achieve a good balance between safety and efficacy in medical treatment with proper knowledge in supportive care as well as an understanding of pharmacokinetics, pharmacodynamics and pharmacogenomics is essential for medical oncologists. In this review, we have summarized the drug-drug interactions important for the management of cancer patients. The types of interactions covered are pharmaceutical interactions and interactions at the level of absorption, protein binding, metabolism and excretion.

Cochlin-tomoprotein: a novel perilymph-specific protein and a potential marker for the diagnosis of perilymphatic fistula.

BACKGROUND: Perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear. A procedure for obtaining definite proof of a PLF remains elusive, and methods of diagnosis remain controversial. To date, there is no clinically relevant biochemical marker for perilymph leakage. Using proteomic analysis of inner ear proteins, we have previously found unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms (p63s, p44s and p40s) in the inner ear tissue and a short 16-kDa isoform of cochlin-tomoprotein (CTP) in the perilymph. Since cochlin was found to be highly specific to the inner ear, we speculated that CTP might also be specific to the perilymph. The aim of this study was to determine whether CTP, a novel perilymph-specific protein, could be used as a marker for the diagnosis of PLF. METHODS: By Western blotting, we investigated the specificity of CTP expression in a range of body fluids that included perilymph, serum, saliva and cerebrospinal fluid. To elucidate the detection limit of CTP, serially diluted recombinant human (rh)CTP as well as human perilymph was tested. RESULTS: CTP was selectively expressed in all 20 perilymph samples tested, but not in 77 samples of the other body fluids. The detection limit of rhCTP was 0.27 ng or 0.022 microl of perilymph per well on Western blot analysis. CONCLUSION: The results strongly suggest that CTP can be a specific marker of perilymph leakage. Moreover, CTP has the potential to be a biochemical marker that allows a definitive diagnosis of the etiology of PLF-related hearing loss and vestibular disorders.