Relapse rate and predictors of relapse after cessation of glucocorticoid maintenance therapy in type 1 autoimmune pancreatitis: a multicenter retrospective study.

BACKGROUND: Type 1 autoimmune pancreatitis responds well to glucocorticoid therapy with a high remission rate. Moreover, glucocorticoid maintenance therapy can help prevent relapse. However, the relapse rate following cessation of long-term glucocorticoid therapy is unknown. The aim of this study was to clarify the relapse rate and predictors of relapse following long-term glucocorticoid therapy cessation. METHODS: We analyzed 94 patients who achieved remission after undergoing glucocorticoid therapy, discontinued treatment after at least 6 months of maintenance therapy, and were subsequently followed up for at least 6 months. The patients were divided into three groups based on treatment duration (< 18, 18-36, and ≥ 36 months), and their relapse rates were compared. Univariate and multivariate analyses of clinical factors were conducted to identify relapse predictors. RESULTS: After discontinuing glucocorticoid therapy, relapse was observed in 43 (45.7%) patients, with cumulative relapse rates of 28.2% at 1 year, 42.1% at 3 years, 47.0% at 5 years, and a plateau of 77.6% at 9 years. Of the 43 patients who relapsed, 25 (58.1%) relapsed within 1 year after after cessation of glucocorticoid therapy. Relapse and cumulative relapse rates did not differ significantly according to treatment duration. In the multivariate analysis, an elevated serum IgG4 level at the time of glucocorticoid cessation was found to be an independent predictor of relapse (hazard ratio, 4.511; p < 0.001). CONCLUSIONS: A high relapse rate occurred after cessation of glucocorticoid maintenance therapy, regardless of the duration of maintenance therapy, especially within the first year after cessation. However, the normalization of long-term serum IgG4 levels may be a factor in considering cessation.

Efficacy of vonoprazan 10 mg compared with 20 mg for the initial treatment in patients with erosive esophagitis: a randomized pilot study.

BACKGROUND: The study aimed to investigate the efficacy of vonoprazan 10 mg compared with 20 mg in patients with erosive esophagitis. METHOD: Seventy-three patients with erosive esophagitis were randomly divided into two groups either vonoprazan 20 mg (n = 37) or 10 mg (n = 36). They were administered each dose for 4 weeks as the initial treatment followed by maintenance treatment with 10 mg for 8 weeks. The primary endpoints were mucosal healing rate and symptom relief at 4 weeks. The secondary endpoint was symptom relief at 12 weeks after the maintenance treatment. Mucosal healing was assessed endoscopically, and symptom relief was assessed using the FSSG score. RESULTS: At 4 weeks, the endoscopic healing rates of the 20 mg and 10 mg groups were 94.6% and 94.4%, respectively. The FSSG scores of the 20 mg and 10 mg groups were significantly decreased in both treatment groups from 13 (4-39) to 4 (0-25) and 14 (4-40) to 3 (0-29), respectively. At 12 weeks, the scores further decreased to 2 (0-13) and 2 (0-26), respectively. The vonoprazan 10 mg group showed a similar therapeutic effect to the 20 mg group in mucosal healing at 4 weeks and in symptom relief throughout the study period. When stratified by esophagitis grading, these findings were still demonstrated in grade A/B patients but not in grade C/D patients. CONCLUSION: Our findings suggest that initial treatment with vonoprazan 10 mg might be useful especially in patients with mild erosive esophagitis. Large controlled studies are warranted to confirm our investigation.

Repeated bronchoconstriction attenuates the cough response to bronchoconstriction in naïve guinea pigs.

BACKGROUND: Cough variant asthma (CVA) is recognized as a precursor of bronchial asthma (BA). However, the cough response to bronchoconstriction differs between these similar diseases. Repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators may impact the cough response. METHODS: We investigated the influence of repeated bronchoconstriction on the cough response to bronchoconstriction using naïve guinea pigs. Bronchoconstriction was induced for 3 consecutive days and changes in the cough response and lipid mediators, such as PGE2, PGI2, and cysteinyl-LTs (Cys-LTs), in BAL fluid (BALF) were assessed. We investigated the effect of endogenous PGI2 on the cough response by employing a PGI2 receptor antagonist. In order to investigate the cough response over a longer period, we re-evaluated the cough response 2 weeks after repeated bronchoconstriction. RESULTS: The number of coughs induced by bronchoconstriction were significantly decreased by repeated bronchoconstriction. The levels of PGE2, PGI2, and Cys-LTs, and the ratio of PGI2/PGE2 were significantly increased, following repeated bronchoconstriction. This decrease in the cough response was suppressed by pretreatment with a PGI2 receptor antagonist. Two weeks after repeated bronchoconstriction, the cough response returned to the same level as before repeated bronchoconstriction along with a concomitant return of lipid mediators, such as PGE2, PGI2, and Cys-LTs and the ratio of PGI2/PGE2. CONCLUSIONS: Our results suggest that repeated bronchoconstriction and the resulting imbalance of endogenous lipid mediators contribute to the difference in cough responses to bronchoconstriction in CVA and BA.

[Effective treatment of POEMS syndrome accompanied by plasmacytoma with lenalidomide, dexamethasone, and local irradiation].

A 70-year-old woman experienced pain in both gastrocnemius muscles, numbness in the toes, and muscle weakness in both the legs that lasted for two months. After getting admitted to our hospital, the muscle weakness extended to both her arms, and nerve conduction studies revealed decreased nerve conduction velocity, which was more prominent in the elbow and the axilla than in the wrist. A magnetic resonance imaging revealed a tumor in the right femoral neck, which was histologically diagnosed as plasmacytoma. Laboratory findings revealed IgA lambda type M protein and an elevated VEGF level of 2,320 pg/ml; edema was present in both the legs. After a diagnosis of POEMS syndrome, lenalidomide and dexamethasone treatment were initiated simultaneously, along with irradiation. The treatment improved polyneuropathy, along with a decrease in the VEGF level. Increased vascular permeability due to elevated VEGF led to the development of neuropathy of POEMS syndrome, and treatment against proliferating monoclonal plasma cells is effective. In the present case, we believe that a prompt control of the plasmacytoma with novel therapeutic agents for myeloma with irradiation resulted in the improvement of the neurological symptoms.

Impact of sclerosing dacryoadenitis/sialadenitis on relapse during steroid therapy in patients with type 1 autoimmune pancreatitis.

OBJECTIVES: Steroids are the first-line drugs for induction of remission in patients with type 1 autoimmune pancreatitis (AIP), and the usefulness of steroid maintenance therapy to prevent relapse has recently been reported. However, even during steroid therapy, a relatively large percentage of patients relapse and the predictive factors for relapse have not yet been elucidated. The aim of this study was to clarify the predictive factors for relapse of AIP patients during steroid therapy. MATERIALS AND METHODS: The medical records of 76 patients with type 1 AIP with continued steroid therapy after induction of remission were analyzed retrospectively. The relapse rate during steroid therapy was evaluated, and the risk factors for relapse were investigated by univariate and multivariate analysis of clinical factors. RESULTS: Relapse occurred in 28.9% (22/76) of the patients. The cumulative relapse rates were 10.5% at 1 year, 25.0% at 3 years, 34.9% at 5 years, and 43.0% at 10 years. In multivariate analysis, presence of sclerosing dacryoadenitis/sialadenitis at the time of initial diagnosis of AIP was an independent risk factor for relapse (HR 3.475, p = .009). The cumulative relapse rates of patients with sclerosing dacryoadenitis/sialadenitis reached 21.4% at 1 year, 56.0% at 3 years, and 78.0% at 5 years. CONCLUSIONS: Sclerosing dacryoadenitis/sialadenitis was a predictive factor for relapse in type 1 AIP during steroid therapy; in such cases, strict follow-up is necessary with relapse in mind.

Curative thoraco-systemic therapy plus local treatment to the brain for extensive disease-small-cell lung cancer with metastasis only to the brain.

We reviewed 11 cases of extensive disease (ED)-SCLC and metastasis only to the brain treated during 2011-14. All patients underwent definitive therapy similar to that for limited disease (LD), combined with local treatment for BM. We compared the survival outcomes of these patients to those of patients with LD (n = 29) or other ED (n = 38) during the same period. Three patients had progression of BM at completion of chemotherapy. Ten patients received whole-brain radiotherapy (4 prophylactic, 6 therapeutic), and remaining one elderly patient underwent stereotactic radiosurgery. Finally, 8 and 3 patients achieved a CR or PR of BM, respectively. Five remained free of progression for 21.1-73.2 months. The progression-free and overall survival outcomes of ED-SCLC with brain only metastases were comparable to those of LD and superior to those of other ED. In conclusion, ED-SCLC with metastasis limited to the brain could be treated with curative intent.

Role of prostaglandin E2 in bronchoconstriction-triggered cough response in guinea pigs.

A feature of cough variant asthma is a heightened cough response to bronchoconstriction. The mediators of this response are unknown. This study was designed to elucidate the role of lipid mediators in bronchoconstriction-triggered cough response in an experimental animal model. We examined the influence of bronchoconstriction on cell components and mediators including prostaglandin E2 (PGE2) in bronchoalveolar lavage fluid (BALF). We studied the cough response to bronchoconstriction (CRB) by measuring the correlation between the increase in enhanced pause (Penh), an index of bronchoconstriction, and cough counts induced by methacholine (Mch) inhalation in conscious guinea pigs. We then examined the effects of intraperitoneal pretreatment with 16, 16-dimethyl-prostaglandin E2 (dm-PGE2) on CRB and cough counts. The total number of cells and cell components in the BALF were not influenced by bronchoconstriction. While levels of PGE2, prostaglandin I2, and cysteinyl leukotrienes were significantly increased, levels of prostaglandin D2, thromboxane B2, and substance P in the BALF were not. Dm-PGE2 significantly decreased the Mch-induced increase in Penh. Following bronchoconstriction by additional Mch inhalation, dm-PGE2 produced an increase in CRB and cough counts in a dose-dependent manner. Additionally, the heightened CRB following dm-PGE2 treatment was suppressed by pretreatment with PGE2 receptor (E-prostanoid EP) -1 and EP-3 antagonists in a dose-dependent manner, but not by EP-2 and EP-4 antagonists. The EP-1 antagonist also decreased cough counts. These results suggest that PGE2 acts as an exacerbating factor for bronchoconstriction-triggered cough. EP1 and EP3 may provide new therapeutic targets for cough variant asthma.

Role of prostaglandin I2 in the bronchoconstriction-triggered cough response in guinea pigs.

Purpose/Aim of the study: Methacholine chloride (MCh) inhalation causes bronchoconstriction and cough. Following MCh-induced bronchoconstriction, metabolic products of prostaglandin I2 (PGI2) increase in bronchoalveolar lavage fluid (BALF), suggesting that PGI2 plays a role in the cough response. Accordingly, we used an experimental guinea pig model to evaluate the role of PGI2 in the bronchoconstriction-triggered cough response. MATERIALS AND METHODS: Experiment 1: The concentration of PGF1α, a stable metabolite of PGI2, in BALF was assessed in animals exposed to nebulized MCh and animals exposed to nebulized saline. Experiment 2: Bronchoconstriction and cough were assessed in 3 groups of animals after MCh inhalation (a saline group, low-dose PGI2 group, and high-dose PGI2 group). Enhanced pause (Penh) was used as a measure of bronchoconstriction. Experiment 3: Bronchoconstriction and cough were assessed in 3 groups of animals (groups administered saline, a low dose of a specific antagonist of the PGI2 receptor (IP antagonist), and a high dose of a specific IP antagonist). RESULTS: The PGF1α concentration in BALF was significantly higher in the bronchoconstriction group than in the control group. In animals administered high-dose PGI2, the MCh-induced increase in Penh was significantly suppressed, and the number of coughs induced by bronchoconstriction was significantly decreased. In animals treated with a high dose of an IP antagonist, the MCh-induced increase in Penh was not affected, and the number of coughs increased. CONCLUSIONS: Our results suggest that PGI2 ameliorates a bronchoconstriction-triggered cough. The measurement and administration of PGI2 may assist in the diagnosis and treatment, respectively, of the cough response triggered by bronchoconstriction.

Bronchoconstriction-triggered cough in atopic cough: A retrospective study.

BACKGROUND: Atopic cough (AC) and cough variant asthma (CVA) were identified as major causes of chronic non-productive cough in a Japanese study. A characteristic feature of CVA is the presence of a heightened cough response to bronchoconstriction. On the other hand, the cough response to bronchoconstriction in AC remains unclear. METHODS: Methacholine (Mch)-induced cough in AC was measured and compared with that in CVA. Diagnoses of AC and CVA were made based on patient history, physical examination, response to bronchodilator therapy, cough reflex sensitivity to capsaicin, spirometry, and airway responsiveness to methacholine. RESULTS: Thirteen AC patients and 12 CVA patients in whom the criteria were met were recruited to the study. After inhalation of Mch at PC35-PEF40 that means milder bronchoconstriction than PC20-FEV1, cough was triggered a few times in AC. [cough number: 1/ 32 min (0-40)]. Conversely, significantly greater number of coughs was provoked in CVA, compared with AC [cough number: 35.5/ 32 min (25-125), p < 0.05]. CONCLUSIONS: The cough response to bronchoconstriction is reduced in AC compared to CVA. This feature may be useful in the diagnosis of chronic cough.

Paradoxical reaction to antituberculosis therapy after 6 months of treatment for pulmonary tuberculosis: A case report.

Paradoxical reactions (PRs) to antituberculosis (anti-TB) drugs during treatment are well known phenomena, but a PR presenting as a new pulmonary lesion after completion of treatment is extremely rare, and little is known about the management of such cases. A 44-year-old man was diagnosed with pulmonary TB. His sputum cultures became negative 45 days after the initiation of standard anti-TB treatment. Upon the patient's completion of 6 months of anti-TB therapy, computed tomography revealed a new irregularly shaped mass in the lower left pulmonary lobe. A transbronchial lung biopsy (TBLB) revealed caseous necrosis and granulomatosis surrounded by epithelioid and multinucleated giant cells. Cultures of both the TBLB specimen and bronchoalveolar lavage fluid remained negative for TB. The CT shadow disappeared 6 months later without further administration of anti-TB drugs. Careful observation without therapy may be sufficient for a patient treated for TB who develops a PR upon completion of treatment, if the patient has achieved a bacteriological remission.

A case report on metastatic pancreatic tumor from pulmonary adenocarcinoma that difficult to differentiate from primary pancreatic ductal carcinoma.

A woman was admitted to our department for lung adenocarcinoma and she was treated with left upper lobectomy. The carcinoembryonic antigen level had increased. Enhanced computed tomography showed a hypovascular tumor in the pancreatic tail and in the extension of the distal main pancreatic duct. Endoscopic ultrasonography (EUS) clearly showed a low echoic lesion, and histological examination revealed adenocarcinoma. On immunostaining, the lesion was diagnosed as metastatic adenocarcinoma of the lungs. The patient was treated with chemotherapy for lung cancer and survived for 4 years after diagnosis. Differentiating a metastatic lesion to the pancreas from pancreatic ductal adenocarcinoma is very important. Accurate diagnosis enables administration of appropriate treatment. In this case, EUS was especially useful for assessing the tumor in the pancreas. When patients with a history of extra-pancreatic cancer present with a pancreatic lesion, pancreatic metastases should be considered, regardless of the time elapsed since occurrence of the primary cancer. EUS-fine needle aspiration (FNA) with histological examination is the best method for definitive diagnosis of pancreatic disease in this group of patients. This approach has very high sensitivity and accuracy for the diagnosis of pancreatic metastases.

Evaluation of antibiotic use to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis.

BACKGROUND/AIMS: The purpose of this study was to evaluate the relationship between prophylactic antibiotic use and complications following endoscopic retrograde cholangiopancreatography (ERCP). METHODOLOGY: We retrospectively evaluated 605 consecutive patients who underwent ERCP in our hospital between September 2009 and November 2011. The antibiotic group included patients who underwent their procedure before October 2010, while the control group included patients after October 1, 2010, who did not receive antibiotics. We compared the incidence of postoperative pancreatitis and cholangitis between the groups. RESULTS: There were no significant differences in the backgrounds of the 304 control and the 301 antibiotic-treated patients. The incidence of post-ERCP pancreatitis was 4.9% in the control group and 4.3% in the antibiotic group (p = 0.72). The incidence of postoperative cholangitis was 2.0% in the control group and 1.7% in the antibiotic group (p = 0.99). Choledocholithiasis, pancreatic duct injection, and female gender were detected as significant risk factors for postoperative pancreatitis by multivariate analysis; sclerosing cholangitis and incomplete biliary drainage were significant risk factors for postoperative cholangitis. Even in cases with these risk factors, prophylactic antibiotic use did not influence the incidence of pancreatitis or cholangitis. CONCLUSION: Prophylactic antibiotics do not reduce the incidence of either pancreatitis or cholangitis following ERCP.

[COMBINED USE OF INTERFERON-GAMMA RELEASE ASSAY AND LOW-DOSE COMPUTED TOMOGRAPHY FOR TUBERCULOSIS SCREENING PROGRAM OF HEALTH CARE WORKERS].

OBJECTIVE: To evaluate the value of the interferon-gamma release assays and low-dose computed tomography for the pulmonary tuberculosis screenings program of health care workers. DESIGN: For the pulmonary tuberculosis (TB) screenings program, T-SPOT.TB (one of interferon-gamma release assays: IGRA) were performed on 332 health care workers (HCWs) with normal chest roentgenogram and without the history of TB treatment. Low-dose computed tomography (LDCT) was also performed on IGRA positive HCWs. RESULTS: Ten of 332 subjects were positive IGRA. LDCT was performed on IGRA positive 10 subjects. Abnormal findings were noted in 2 of 10 subjects by LDCT. One had CT findings compatible with active TB and finally diagnosed as active TB. Another had scarring shadow at right S5 and lingular segment. Nine of 10 IGRA positive subjects were judged as latent tuberculosis infection (LTBI). Three hundred twenty-one subjects with negative and borderline IGRA of 332 HCWs were judged as not infected with TB. CONCLUSION: Combined use of IGRA and LDCT for tuberculosis screening program of HCWs was found to be effective for early diagnosis of TB, accurate diagnosis of LTBI and judgment of non-infective subjects.

Timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis.

OBJECTIVE: We retrospectively studied the timing of radiological improvement after steroid therapy in patients with autoimmune pancreatitis (AIP). MATERIAL AND METHODS: Patients with AIP (n = 31) received steroids followed by diagnostic imaging within 1 month. Pancreatic swelling, pancreatic and bile duct features, and apparent diffusion coefficient (ADC) were compared before and after treatment. The period from treatment initiation to evaluation was divided into five phases: early phase (days 3-5), week 1 (days 6 and 7), week 2 (days 8-14), week 3 (days 15-21), and week 4 (days 22-28). Five gastroenterologists evaluated pancreatic swelling and duct features (good/intermediate/no response), and the "good response" rate (response rate) was calculated for each phase. In addition, pancreatic volumes were measured with a 3D workstation before and after treatment, and the percentage change in volume was calculated. ADC values were calculated in 14 patients. RESULTS: The median ratio of pancreatic volume after relative to before treatment was 0.89, 0.79, 0.67, 0.59, and 0.47 for early phase, week 1, week 2, week 3, and week 4, respectively. The response rate of the pancreatic swelling was 37.5%, 57.1%, 83.3%, 100%, and 100%; response rate of the pancreatic duct was 0%, 20%, 75%, 75% and 100%; and response rate of the bile duct was 0%, 66.7%, 83.3%, 100%, and 80%. The ADC increased after treatment in all 14 patients, including the 7 patients evaluated in the early phase. CONCLUSIONS: Evaluation of pancreatic swelling and duct features is recommended in week 2 and thereafter. The ADC increased soon after treatment initiation, suggesting its usefulness for evaluating early treatment responses.

Comparative study of 4 Fr versus 6 Fr nasobiliary drainage catheters: a randomized, controlled trial.

BACKGROUND AND AIM: Despite the benefits of endoscopic nasobiliary drainage (NBD) in endoscopic retrograde cholangiopancreatography (ERCP), post-ERCP pancreatitis (PEP) and nose/throat discomfort can result. We aimed to determine whether the use of a smaller catheter alleviates these complications. METHOD: A randomized, controlled trial at a tertiary care center compared 4 Fr and 6 Fr NBD catheters; 165 ERCP patients with naïve papillae were randomly assigned to a catheter-size group. RESULTS: The prevalence of PEP was significantly lower in the 4 Fr group (3.7%; 3/82) than in the 6 Fr group (15.7%; 13/83; P = 0.019). No spontaneous catheter displacement occurred within 24 h. Discomfort visual analog scores were 2.6 and 4.3 in the 4 Fr and 6 Fr groups, respectively (P = 0.0048) on procedure day; on the following day, the scores were 2.3 and 3.6 (P = 0.028). Bile output was 16.3 mL/h and 21.4 mL/h in the 4 Fr and 6 Fr groups (P = 0.051). On obstructive jaundice subgroup analysis, bile drainage was 19.2 mL/h and 22.1 mL/h in the 4 Fr and 6 Fr groups (P = 0.40). The 4 Fr group required 5.6 days to reduce bilirubin levels versus 6.1 days in the 6 Fr group (P = 0.51). CONCLUSIONS: In patients with naïve papillae, lower rates of PEP and less nose/throat discomfort are associated with the use of 4 Fr NBD catheters. In patients with obstructive jaundice, 4 Fr and 6 Fr catheters are comparable with regard to bile output and bilirubin level reduction.

Characteristic Features of Cholangiocarcinoma Complicating Primary Sclerosing Cholangitis.

BACKGROUND/AIMS: Primary sclerosing cholangitis (PSC) is often complicated by cholangiocarcinoma (CCA); thus, early detection of CCA is an important way to improve PSC prognosis. METHODOLOGY: In a retrospective study, 23 cases of PSC were included. Seven cases were complicated by CCA (CCA group) and 16 cases were not (control group). Blood examinations, bile duct imagings from direct cholangiography, intraductal ultrasonography (IDUS) findings and pathological diagnosis results (bile juice cytology, brush cytology, and forceps biopsy) were referenced. RESULTS: Blood examinations showed that serum carbohydrate antigen 19-9 (CA19-9), total bilirubin, and aspartate aminotransferase were significantly higher in the CCA group, whereas cholangiography showed that the dominant stricture was significantly longer in the CCA group. No significant difference in the IDUS findings was observed between the 2 groups. Cholangioscopy enabled CCA diagnosis via identification of the papillary mucosa in sites other than the stricture. Forceps biopsy was the most useful pathological diagnostic technique, with a sensitivity of 86% and a specificity of 100%. CONCLUSIONS: The CA19-9 level and bile duct stricture morphology were useful for diagnosing CCA complicating PSC. Aggressive performance of cholangioscopy and pathological diagnostic techniques, such as brush cytology and forceps biopsy, are essential for identification.