Chronic rhinitis and stress: the possible culprits of midfacial segment pain.

BACKGROUND: Bilateral symmetrical pain in the midfacial region without evidence of sinonasal disease is termed midfacial segment pain (MSP), about which little is known. The present study explored the prevalence of facial pain and the risk factors for MSP. METHODS: We analysed cross-sectional data from the Korea National Health and Nutrition Examination Survey (KNHANES). Those who reported facial pain or pressure lasting at least three months with no evidence of a sinonasal disease on nasal endoscopy were considered to have MSP. The participants were categorised according to the presence of facial pain and chronic rhinosinusitis. Basic demographic data and medical conditions, including hypertension, diabetes mellitus, and dyslipidemia, were compared between subject groups. We also evaluated psychological stress, depressive episodes, and suicidal thoughts, as well as physician-diagnosed nasal diseases, including chronic rhinitis and symptomatic nasal septal deviation. Univariate and multivariate logistic regression analyses were performed to determine risk factors for MSP. RESULTS: Of 31,999 participants, the prevalence of facial pain was 0.59%. A total of 58 (0.18%) respondents had MSP, of whom 40 (73.5%) were female. On univariate analysis, female sex, chronic rhinitis, and psychological stress were more prevalent in the subjects with MSP than the control subjects. However, in the multivariate analysis, only chronic rhinitis and psychological stress remained significant, while the female sex exhibited only marginal significance. CONCLUSION: Chronic rhinitis and psychological stress may be significant risk factors for MSP.

Increased risk of cardiovascular diseases in patients with chronic rhinosinusitis: a longitudinal follow-up study using a national health screening cohort.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most common chronic inflammatory diseases and is characterized by sinonasal inflammation that lasts longer than 12 weeks. Whether the effect of chronic inflammation caused by CRS on cardiovascular diseases (CVDs) is similar to its effect on other inflammatory disorders has not been thoroughly evaluated. We aimed to demonstrate whether CRS patients have a higher prevalence of CVDs, including stroke and ischemic heart disease (IHD). METHODOLOGY: We compared the prevalence of various comorbidities between CRS and control participants through a case-control cohort study from 2002 to 2015 that included 514,866 participants. CRS (n=6,552) and control (n=26,208) participants who were over 40 years old were selected by matching age, sex, income, and area of residence at a 1:4 ratio. RESULTS: A stratified Cox proportional hazards model was utilized to assess the hazard ratio (HR) of CRS for stroke and IHD. The HRs for stroke and IHD were significantly increased in CRS patients compared to controls after adjusting for obesity, alcohol consumption, smoking, systolic and diastolic blood pressure, fasting blood glucose, total cholesterol, hemoglobin, and Charlson Comorbidity Index (CCI) scores. The HR of stroke was significantly higher in the absence of nasal polyps than in the presence of nasal polyps. The HR of IHD was significantly increased in the CRS group regardless of the presence of nasal polyps. CONCLUSIONS: This study showed that CRS participants had a significantly higher prevalence of stroke and IHD.

Surgical morbidity and mortality in patients after microvascular reconstruction for head and neck cancer.

OBJECTIVES: The aim was to evaluate the importance of clinical factors in the prediction of postoperative complications in patients with microvascular reconstruction for head and neck squamous cell cancer (HNSCC). DESIGN: A retrospective review of case notes was performed. SETTING: Patients treated at a single institute. PARTICIPANTS: This study included 259 patients with HNSCC treated with radical surgery and microvascular reconstruction between 1993 and 2014. MAIN OUTCOME MEASURES: We allocated the patients to three groups using a preoperative comorbidity score based on risk factors: group A (≥3 risk factors, n = 16), group B (2 risk factors, n = 49) and group C (0 or 1 risk factor, n = 194). RESULTS: Surgical mortality in this cohort was 1.9% (5 of 259 patients). The preoperative comorbidity score was associated with surgical mortality (P < .001). Pharyngocutaneous fistula (P = .001) and flap compromise (P = .023) were more frequent as preoperative comorbidity score increased. Preoperative comorbidity score (P < .001), advanced age (P = .007), advanced pathologic T stage (P = .028), advanced pathologic N stage (P = .005), preoperative (chemo) radiotherapy (P < .001), history of cardiovascular disease (P = .015) and pulmonary disease (P = .007), and diabetes (P < .001) had significant adverse effects on 5 year disease-specific survival (DSS) in a univariate analysis. The 5-DSS rates of groups A, B and C were 30%, 37% and 70%, respectively. Multivariate analysis showed that preoperative comorbidity score was significantly correlated with 5 year DSS (hazard ratio [HR], 3.56; 95% confidence interval [CI], 1.81-6.99; P < .001 for group A and HR, 1.91; 95% CI, 1.15-3.18; P = .013 for group B compared with group C). CONCLUSION: Patients with a high preoperative comorbidity score have an increased risk of surgical mortality and morbidity after microvascular reconstruction for HNSCC.

Association Study of 60 Candidate Genes with Antipsychotic-induced Weight Gain in Schizophrenia Patients.

INTRODUCTION: This study aimed to investigate the association of multiple candidate genes with weight gain and appetite change during antipsychotic treatment. METHODS: A total of 233 single nucleotide polymorphisms (SNPs) within 60 candidate genes were genotyped. BMI changes for up to 8 weeks in 84 schizophrenia patients receiving antipsychotic medication were analyzed using a linear mixed model. In addition, we assessed appetite change during antipsychotic treatment in a different group of 46 schizophrenia patients using the Drug-Related Eating Behavior Questionnaire. RESULTS: No SNP showed a statistically significant association with BMI or appetite change after correction for multiple testing. We observed trends of association (P<0.05) between 19 SNPs of 11 genes and weight gain, and between 7 SNPs of 5 genes and appetite change. In particular, rs696217 in GHRL showed suggestive evidence of association with not only weight gain (P=0.001) but also appetite change (P=0.042). Patients carrying the GG genotype of rs696217 exhibited higher increase in both BMI and appetite compared to patients carrying the GT/TT genotype. DISCUSSION: Our findings suggested the involvement of a GHRL polymorphism in weight gain, which was specifically mediated by appetite change, during antipsychotic treatment in schizophrenia patients.

Relationship between tinnitus and suicidal behaviour in Korean men and women: a cross-sectional study.

OBJECTIVES: This study investigated the prevalence of suicidal ideation and behaviour in a representative sample of South Koreans with or without tinnitus. DESIGN: A cross-sectional study. SETTING: Based on data from the 2010 to 2012 Korean National Health and Nutrition Examination Survey (KNHANES). PARTICIPANTS: The study included 17 446 Korean individuals. MAIN OUTCOME MEASURES: Participants provided demographic, socio-economic and behavioural information, as well as responses to questionnaires assessing the presence and severity of tinnitus, mental health status regarding stress, depression, and suicidal ideation and attempts. In the univariate analysis, the Rao-Scott chi-square test and logistic regression analysis were used to test the association between tinnitus and risk factors. Simple and multiple linear regression analyses were used to examine the association between tinnitus and mental status. RESULTS: A total of 20.9% and 1.2% of participants with tinnitus, and 12.2% and 0.6% of those without, reported suicidal ideation and attempts, respectively (P < 0.0001 and P = 0.001). Participants reporting suicide attempts showed a higher proportion of severe annoying (6.0%) and irritating (11.8%) tinnitus than those with suicidal ideation (1.4% and 10.2%, respectively). Risks for experiencing tinnitus were significantly associated with suicidal ideation and attempts after adjusting for confounding variables. CONCLUSION: This study has important implications for enhanced screening and evaluation of mental health status and suicidal ideation/behaviour among tinnitus patients.

The value of preoperative 18F-FDG PET/CT for the assessing contralateral neck in head and neck cancer patients with unilateral node metastasis (N1-3).

OBJECTIVES: The purpose of this study was to determine whether preoperative (18) F-FDG PET/CT is useful in assessing contralateral lymph node metastasis in the neck. DESIGN: A retrospective review of medical records was performed. SETTING: Patients treated at a single institute. PARTICIPANTS: One hundred and fifty-seven patients whose pathology results were positive for unilateral node metastasis (N1-3) involvement and underwent preoperative (18) F-FDG PET/CT for head and neck squamous cell carcinoma (HNSCC) were reviewed. MAIN OUTCOME MEASURES: Prognostic factors and nodal SUVmax were studied to identify the risk of contralateral disease. RESULTS: Thirty-six (22.9%) patients had contralateral cervical lymph node metastases. The (18) F-FDG PET/CT had a sensitivity of 80% and a specificity of 96% in identifying the contralateral cervical lymph node metastases on a level-by-level basis. The median SUVmax values of the ipsilateral and contralateral lymph nodes were 3.99 ± 3.36 (range, 0-20.4) and 2.94 ± 2.04 (range, 0-8.7), respectively (P = 0.001). There was a significant difference in the median SUVmax of contralateral nodes between the benign and malignant cervical lymph nodes (2.31 ± 0.62 versus 3.28 ± 2.43, P = 0.014). The cut-off value of contralateral median SUVmax in the context of contralateral cervical metastasis was 2.5 with the sensitivity of 75% and the specificity of 94%. A median contralateral lymph node SUVmax  ≥ 2.5 was associated with 5-year disease-specific survival (P = 0.038). CONCLUSION: (18) F-FDG PET/CT median SUVmax cut-off values of contralateral lymph nodes ≥2.5 were associated with contralateral cervical lymph node metastases and 5-year disease-specific survival in HNSCC patients with unilateral metastases.

Effects of microbial additives on chemical composition and fermentation characteristics of barley silage.

This study examined the effects of bacterial inoculants on chemical composition and fermentation indices of barley silage. Barley forage (Youngyang) was harvested at 24% dry matter (DM) and wilted to 47.9% DM. The wilted barley forage was chopped to 3-5 cm length and applied with no inoculant (CON), L. plantarum (1×10(10) cfu/g, LP) or Effective Microorganisms (0.5×10(9) cfu/g, EM). Then the forages were ensiled in four replications for each treatment in 20 L mini silos and stored for 100 days. The contents of crude protein and ether extract were higher in CON silage ensiled for 100-d, while the contents of DM and crude ash were higher in EM silage (p<0.05). The contents of ADF, NDF and hemicellulose as well as the in vitro DM digestibility were not affected by microbial inoculation (p>0.05). The pH, ammonia-N concentration and lactate to acetate ratio were higher (p<0.05) in CON silage, while lactate concentrations were higher (p<0.05) in CON and LP silage. Acetate concentration and lactic acid bacteria was increased (p<0.05) by both inoculants (LP and EM), but propionate concentration and yeast was increased (p<0.05) by EM and LP, respectively. These results indicated that the fermentation quality of barley silage was improved by the application of bacterial inoculants.

Pathological validation of supracricoid partial laryngectomy in laryngeal cancer.

OBJECTIVES: To validate pathologically whether supracricoid partial laryngectomy is an oncologically sound procedure in cases with invasion of the thyroid cartilage, paraglottic space, pre-epiglottic space, anterior commissure, or subglottis. DESIGN: A retrospective review of case notes was performed. SETTING: Patients treated at a single institute in the Republic of Korea. PARTICIPANTS: Sixty-three patients who underwent supracricoid partial laryngectomy for laryngeal squamous cell carcinoma between June 1994 and May 2005 who were followed for at least 2 years. MAIN OUTCOME MEASURES: Local control and overall survival rates. Pathological invasion of the thyroid cartilage, anterior commissure, pre-epiglottic space, paraglottic space, or subglottis was also investigated as a cause of recurrence. Prognostic factors for local control and survival were evaluated with univariate and multivariate models. RESULTS: Invasion of the anterior commissure, paraglottic space, thyroid cartilage, pre-epiglottic space, or subglottis had no significant impact on the recurrence or overall survival rates. The presence of a positive resection margin was significantly associated with recurrence in the univariate and multivariate analyses (P = 0.026, 0.028, respectively). When considering the prognostic factors influencing survival, the univariate analysis showed that N stage, a positive resection margin and recurrence had significant influences on the overall survival rate (P = 0.010, 0.0004 and 0.000 respectively). In the multivariate analysis, only recurrence affected the survival rate (P = 0.002). CONCLUSION: Supracricoid partial laryngectomy can be used with oncological safety in selected cases of laryngeal cancer with invasion of the anterior commissure, thyroid cartilage, pre-epiglottic space, paraglottic space, or subglottis.

Insulin Resistance is Associated with Chronic Laryngitis in Korean Women.

OBJECTIVES: The aim of this study was to investigate the association between chronic laryngitis (CL) and insulin resistance (IR) in South Korea using data from the 2010 Korea National Health and Nutrition Examination Surveys (KNHANES). DESIGN, SETTING AND PARTICIPANTS: Cross-sectional data of 4,261 adults who completed KNHANES were analyzed. CL was considered when participants experienced a voice change and demonstrated flexible laryngoscopic findings of diffuse laryngeal inflammation. All participants were assessed for IR using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Among the Korean population older than 19 years, the prevalence of chronic laryngitis was 3.8±0.7%. Univariate analysis demonstrated that CL was significantly associated with smoking and systolic and diastolic blood pressure in men and with age, diastolic blood pressure, HDL cholesterol, insulin, and HOMA-IR in women. Multiple regression analysis demonstrated that the mean value of HOMA-IR was significantly associated with CL in women only. In addition, CL was more prevalent in the highest compared with the lowest HOMA-IR quartile (OR [95% CI]: 2.268 [1.053-4.884] after adjusting for age, OR [95% CI]: 2.235 [1.040-6.181] after adjusting for confounding factors of age, body mass index, smoking status, alcohol intake, regular exercise, education, and income). CONCLUSIONS: These findings indicate that IR characterized by HOMA-IR is significantly associated with CL in Korean women only. Our results suggest that HOMA-IR could be an early predictive factor of increased risk of CL in Korean women.

DNA pooling: a comprehensive, multi-stage association analysis of ACSL6 and SIRT5 polymorphisms in schizophrenia.

Many candidate gene association studies have evaluated incomplete, unrepresentative sets of single nucleotide polymorphisms (SNPs), producing non-significant results that are difficult to interpret. Using a rapid, efficient strategy designed to investigate all common SNPs, we tested associations between schizophrenia and two positional candidate genes: ACSL6 (Acyl-Coenzyme A synthetase long-chain family member 6) and SIRT5 (silent mating type information regulation 2 homologue 5). We initially evaluated the utility of DNA sequencing traces to estimate SNP allele frequencies in pooled DNA samples. The mean variances for the DNA sequencing estimates were acceptable and were comparable to other published methods (mean variance: 0.0008, range 0-0.0119). Using pooled DNA samples from cases with schizophrenia/schizoaffective disorder (Diagnostic and Statistical Manual of Mental Disorders edition IV criteria) and controls (n=200, each group), we next sequenced all exons, introns and flanking upstream/downstream sequences for ACSL6 and SIRT5. Among 69 identified SNPs, case-control allele frequency comparisons revealed nine suggestive associations (P<0.2). Each of these SNPs was next genotyped in the individual samples composing the pools. A suggestive association with rs 11743803 at ACSL6 remained (allele-wise P=0.02), with diminished evidence in an extended sample (448 cases, 554 controls, P=0.062). In conclusion, we propose a multi-stage method for comprehensive, rapid, efficient and economical genetic association analysis that enables simultaneous SNP detection and allele frequency estimation in large samples. This strategy may be particularly useful for research groups lacking access to high throughput genotyping facilities. Our analyses did not yield convincing evidence for associations of schizophrenia with ACSL6 or SIRT5.

Impact of pre-operative body mass index in head and neck cancer patients undergoing microvascular reconstruction.

OBJECTIVES: To analyse the relationship of pre-operative body mass index with surgical complications and oncological outcomes in patients undergoing microvascular reconstruction for head and neck squamous cell cancer. METHOD: A retrospective review was conducted of 259 patients who underwent microvascular free flap reconstruction after head and neck ablative surgery. RESULTS: Mean body mass index was 22.48 kg/m2. There were no correlations between body mass index and: flap failure (p = 0.739), flap ischaemia (p = 0.644), pharyngocutaneous fistula (p = 0.141) or wound infection (p = 0.224). The five-year disease-specific survival rate was 63 per cent. On univariate analysis, the five-year disease-specific survival rate was significantly correlated with pre-operative body mass index, based on Kaplan-Meier survival curves (p = 0.028). The five-year disease-specific survival rates in underweight, normal weight, overweight and obese groups were 47 per cent, 55 per cent, 65 per cent and 80 per cent, respectively. CONCLUSION: Pre-operative body mass index was a useful predictor for recurrence and survival in patients who underwent microvascular reconstruction for head and neck squamous cell cancer.

Lateral neck dissection affects the voice in thyroid cancer patients.

OBJECTIVE: This study aimed to identify the effect of lateral neck dissection on voice change in thyroidectomised patients. METHODS: Medical records from 264 patients who underwent thyroidectomy with (n = 65) or without (n = 199) lateral neck dissection were reviewed. Clinical and voice evaluation data were compared between the two groups. RESULTS: Patients who underwent surgery that included lateral neck dissection had lower fundamental frequencies and speaking fundamental frequencies. They also had a higher incidence of asymmetric mucosal wave and vocal fold oedema on videostroboscopy during the first month after surgery, with the incidence of vocal fold oedema remaining significantly higher at three months. Self-assessed voice quality scores were significantly higher in lateral neck dissection patients at both one and three months after surgery. CONCLUSION: In thyroidectomised patients, lateral neck dissection lowers the vocal pitch in the initial period after surgery and induces vocal fold oedema that persists for several months. Although most objective parameters improved within a month, subjective symptoms lasted for longer.

Are neurologic examination abnormalities heritable? A preliminary study.

BACKGROUND: Neurologic examination abnormalities (NEA) are more prevalent among patients with schizophrenia as well as their unaffected relatives when compared with healthy controls, suggesting that NEA may be endophenotypes for schizophrenia. We estimated the heritability of NEA in moderately sized pedigrees. We also evaluated correlations between NEA and cognitive performance in order to examine their construct validity. METHODS: Members of eight extended families, each consisting of two first degree relatives with schizophrenia/schizoaffective disorders, as well as available first- to fifth-degree relatives were examined (n=96 participants). A modification of the Neurological Evaluation Scale (NES) was employed, augmented with localizing signs. Where feasible, we used untransformed data such as error counts and completion time, rather than ordinal measures. Heritability was estimated using the variance component method, implemented in SOLAR. RESULTS: Statistically significant heritability (h2) estimates were obtained for several measures (p<0.05, h2+/-standard error: rapid alternating movements, right-sided completion time, 0.99+/-0.19; alternating fist-palm test, completion time, 0.77+/-0.19 s, errors, 0.70+/-0.32; fist-ring test, right-sided completion time, 0.53+/-0.23 s, left-sided completion time, 0.70+/-0.21 s; go-no go task, correct responses, 0.93+/-0.33; audio-visual integration, correct responses, 0.79+/-0.54). For most items, heritability analysis was hampered by insufficient data variability (infrequent errors). Correlational analyses show some degree of divergence among types of NEA, repetitive motor tasks being associated with most domains of cognitive functioning other than executive functioning, and cognitive-perceptual tasks being associated with memory and executive functioning. CONCLUSIONS: Significant familial influences on certain aspects of neurologic performance were detected. These heritable measures were also correlated with heritable neurocognitive measures.

Induction of tetradecanoyl phorbol acetate-inducible sequence (TIS) genes by electroconvulsive shock in rat brain.

We studied the induction of tetradecanoyl phorbol acetate-inducible sequences (TIS)1, 7, 8, 11, and 21 in rat cerebral cortex, hippocampus, and cerebellum after electroconvulsive shock (ECS). These genes were reported to be induced by depolarization in PC-12 cells. Single ECS induced TIS1, 8, 11, and 21, but not TIS7 genes in the rat brain regions examined. In cerebral cortex and hippocampus, induction of TIS1, TIS8, and TIS21 reached peak at 30 or 45 min after ECS. The induced mRNA of TIS1 and 21 decreased rapidly and returned almost to the basal level by 90 min after ECS, whereas those of TIS8 and 11 lasted longer. In cerebellum, TIS genes were induced and disappeared more rapidly than in the other two regions. The 10 and 20 daily ECSs did not affect the inducibility of TIS1, 11, and 21 in cerebellum, but the induction of TIS8 was attenuated by 35% after 20 daily ECSs. Our study indicated that ECS could induce some of the TIS genes in various rat brain regions, but the induction patterns were different depending on the TIS genes and brain regions. Our study also suggested that chronic ECS could not attenuate the induction of some immediate early genes.

The activation of B-Raf and Raf-1 after electroconvulsive shock in the rat hippocampus.

We demonstrated that ECS activates the kinase activity of B-Raf and Raf-1 in the rat hippocampus. The activity was maximal at one minute after ECS and temporally coincided with the increased membrane translocation of Rafs and the reported activity of MAPK, but not with the phosphorylation of Rafs.

Electroconvulsive shock does not induce c-fos and junB, but TIS1 and TIS8/zif-268, in neonatal rat hippocampus.

The induction in the animal brain of immediate early genes (IEGs) is known to be age-dependent, and it was suggested that, during neonatal period, signaling pathways for the induction of IEGs are immature. In this study, we investigated the induction of various IEGs in neonatal rat hippocampus after electroconvulsive shock (ECS). ECS did not induce c-fos and junB in the hippocampus of 7-day-old rat, but these genes were weakly induced at postnatal 14 days and to an adult level at postnatal 21 days; two other IEGs, TIS1 (NGFI-B, nur77) and TIS8 (zif-268, Egr-1, Krox-24, NGFI-A), were induced at postnatal 7 days, however. Our results suggested that during the neonatal period, signaling pathways for TIS1 and TIS8 induction in rat hippocampus after ECS are complete, while those for c-fos and junB are immature.

Extracapsular spread and FDG PET/CT correlations in oral squamous cell carcinoma.

The purpose of this study was to evaluate the use of (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT) to identify extracapsular spread (ECS) with histologic correlations in oral squamous cell carcinoma (OSCC). The medical records of 80 patients who underwent of FDG PET/CT for OSCC before surgery were reviewed. ECS was present in 60% (24/40) dissected necks and in 55% (39/71) of dissected cervical levels. A significant difference was found between the maximum standardized uptake (SUVmax) values of cervical lymph nodes with ECS and without ECS (3.33±1.91 vs. 1.12±1.24, p<0.001). When receiver operating characteristic (ROC) curve analysis and SUVmax values were used to detect ECS, the area under the ROC curve was 0.864±0.045 (p<0.001). At an optimal SUVmax cut-off value of 2.25 the sensitivity and specificity were 85% and 88%, respectively. The presence of ECS and a SUVmax>2.25 had a significant adverse effect on 5-year disease specific survival. A SUV(max)>2.25 was found to be associated with a greater risk of cervical lymph node metastasis in OSCC.

Microbial characterization of toluene-degrading denitrifying consortia obtained from terrestrial and marine ecosystems.

The degradation characteristics of toluene coupled to nitrate reduction were investigated in enrichment culture and the microbial communities of toluene-degrading denitrifying consortia were characterized by denaturing gradient gel electrophoresis (DGGE) technique. Anaerobic nitrate-reducing bacteria were enriched from oil-contaminated soil samples collected from terrestrial (rice field) and marine (tidal flat) ecosystems. Enriched consortia degraded toluene in the presence of nitrate as a terminal electron acceptor. The degradation rate of toluene was affected by the initial substrate concentration and co-existence of other hydrocarbons. The types of toluene-degrading denitrifying consortia depended on the type of ecosystem. The clone RS-7 obtained from the enriched consortium of the rice field was most closely related to a toluene-degrading and denitrifying bacterium, Azoarcus denitrificians (A. tolulyticus sp. nov.). The clone TS-11 detected in the tidal flat enriched consortium was affiliated to Thauera sp. strain S2 (T. aminoaromatica sp. nov.) that was able to degrade toluene under denitrifying conditions. This indicates that environmental factors greatly influence microbial communities obtained from terrestrial (rice field) and marine (tidal flat) ecosystems.

Risk factors for recurrence of primary bile duct stones after endoscopic biliary sphincterotomy.

BACKGROUND: Endoscopic biliary sphincterotomy (EST) is a well-established procedure for bile duct stone extraction. Bile duct stones can be classified as primary or secondary. However, few data are available on the recurrence of primary and secondary bile duct stones after EST. Therefore risk factors for the recurrence of primary bile duct stones after EST were prospectively studied. METHODS: Between 1991 and 1997, 61 patients underwent EST for primary bile duct stones. All met the following criteria: (1) previous cholecystectomy without bile duct exploration, (2) detection of bile duct stones at least 2 years after initial cholecystectomy. Mean follow-up was 2.2 years. Fourteen patients were lost to follow-up. The recurrence of primary bile duct stones was defined as the detection of bile duct stones no sooner than 6 months after complete clearance of primary bile duct stones. RESULTS: The overall recurrence rate of primary bile duct stones was 21% (10 of 47). Two significant risk factors for recurrence were identified by multivariate analysis: (1) patients with a bile duct diameter of 13 mm or greater after stone removal had recurrences more frequently than those with a duct diameter of 13 mm or less, and (2) patients whose papilla was located on the inner rim or deep within a diverticulum, so that the papillary orifice was not visible endoscopically, had more frequent recurrences than patients with a papilla outside the diverticulum, or no peripapillary diverticulum. CONCLUSION: The independent risk factors for recurrence of primary bile duct stones were sustained dilation of the bile duct even after complete removal of stones and location of the papilla on the inner rim or deep within a diverticulum.