Research Article ___________________________________________________ ____________________ J Res Adv Dent 2013; 2:1:20-30 Evaluation of Association Between Periodontitis and Prostate Specific Antigen Levels in Chronic Prostatitis Patients Chakrapani Swarna1 Vijay Prasad Koganti2* Ramanarayana Boyapati3 Kishore K. Katuri4 DN. Swamy5 D. Ravindranath6 ABSTRACT Back ground: Prostate specific antigen (PSA) is the most important of all tumor markers in men with prostatic disease. In the presence of inflammation or malignancy, PSA levels are raised to ≥4 ng/ml. This study was conducted to evaluate an association between periodontitis and PSA levels in chronic prostatitis patients. Materials and methods: A total of 47 chronic prostatitis patients with periodontal disease were divided into four groups based on the type of prostatitis and clinical attachment level. The four groups were group 1A (CAL < 2.7 mm and mild prostatitis), group 2A (CAL ≥ 2.7 mm and mild prostatitis), group 1B (CAL < 2.7 mm and moderate/severe prostatitis), group 2B (CAL ≥ 2.7 mm and moderate/severe prostatitis). PSA values were calculated and correlation with periodontal parameters was done. Results: The mean gingival and plaque index scores in group 1B and group 2B were significantly higher than group 1A and group 2A (p< 0.05). Pocket depth, clinical attachment level and the mean PSA values in group 2B were higher when compared with other groups. Subjects with CAL≥2.7 mm had higher mean PSA values (16.27±25.96 ng/ml) than those with CAL≤2.7 mm (2.24± 1.51mm), which is significant (p< 0.05) suggesting a positive correlation between PSA and CAL. Conclusion: In cases where CAL≥2.7 mm and moderate/severe prostatitis there are higher PSA values than those with either condition alone. Keywords: Periodontitis, Prostatitis, Prostate specific antigen levels. INTRODUCTION Prostatitis is a condition that involves inflammation of the prostate gland, which is especially seen among men younger than 50 years, with a variety of complaints referring to the lower urogenital tract and perineum.1,2 Symptoms of Prostatitis include pain during urination, difficulty in emptying the bladder completely, urinary frequency and pain in penis, testicles, pelvic area and during or after ejaculation.3 Prostate specific antigen is a 33kDa serine protease enzyme, which is a biological marker or a tumor marker, synthesized primarily by the epithelial cells that line the acini and ducts of the prostate gland.4 The major function of PSA is to liquefy the gel proteins (seminogelin I and II and fibronectin) in the semen and help in the lyses of seminal clots for the release of motile sperm _______________________________________________________________________________________ Copyright ©2013 eISSN 3898-6473 needed for fertilization.5 A normal level of PSA in the circulation is 4ng/ml, but the disruption of the prostatic architecture, by inflammation or malignancy, causes the increased serum PSA levels.6 Gram- negative bacteria like Escherichia coli and Klebsiella spp, have been implicated in the etiology of prostatic infection.7 There is substantiating evidence to support the role of the immune system in the pathogenesis of prostatitis, which is likely to be mediated through proinflammatory cytokines, such as interleukin -1β (IL1β) and tumor necrosis factor- (TNF – ). 8, 9 Study was approved by Institutional ethical committee. A total of 47 prostatitis patients with periodontal disease were included in the study based on the above criteria. After obtaining the patients consent, periodontal examination was performed. The periodontal parameters assessed are: Gram-negative bacteria have been suggested as etiologic agents for periodontitis and category I and II prostatitis.10 Cytokine imbalance towards increased pro-inflammatory and decreased anti-inflammatory cytokines has been implicated in the pathogenesis of both periodontitis and prostatitis.11 Given the similarity in etiopathogenesis of prostatitis and periodontitis, it is possible that an association between the two conditions exists which may manifest elevated PSA levels in the circulating blood7. The prostatespecific antigen (PSA) test is routinely used as a screening tool in the diagnosis of prostate cancer. The purpose of this study is to evaluate any association between periodontitis and PSA levels in chronic prostatitis patients. 1) Probing depth (PD) and clinical attachment level (CAL) at six sites per tooth using UNC-15 Probe. 2) Gingival Index (Silness and Loe 1963). 3) Plaque Index (Loe and Silness 1967). 12 4) Percentage of sites with bleeding on probing (Ainamo and Bay Bleeding index 1975). Methodology: Patients are divided into four groups based on type of prostatitis and clinical attachment level. The groups are: Group 1A - CAL < 2.7 with mild prostatitis, Group 2A - CAL≥ 2.7 with mild prostatitis, Group 1B - CAL < 2.7 with moderate or severe prostatitis and Group 2B is CAL ≥ 2.7 mm with moderate or severe prostatitis. 5 ml of intra venous blood sample was collected from each patient and the blood sample was sent for estimation of serum PSA levels to the laboratory. Prostate needle biopsy of the Prostate gland had been taken and sent for histological sectioning. 13 Among these, 32 patients were non-malignant and 15 were malignant. MATERIALS & METHODS RESULTS Study design: Patients attending the department of Urology, Government General Hospital, Guntur, who complained of lower urinary tract infections and diagnosed as Prostatitis with chronic periodontitis were examined. Among 47 patients, 16 patients were with mild prostatitis (34.05%) and 31 patients were with severe prostatitis (65.95 %), 15 patients were malignant (31%). The clinical attachment level among these patients ≤ 2.7 was seen in 10 patients (21.3%) and ≥2.7 was in 37 patients (78.7%) (Table 1 and Graph 1). A significant difference was observed between mild and moderate and severe types of prostatitis in relation to status of malignancy (Chi square=9.2533, p<0.05) (Table 2 and Graph 2). The mean gingival index score and plaque index scores in group 1A was 1.63±1.27 and 1.59±1.23, in group 1B was 1.40±0.50 and 1.56±0.69, in group 2A was 1.37±0.47 and 1.35±0.42 and in group 2B was 1.89±0.53 and 1.83±0.49 respectively. A significant difference (p<0.05) was observed between the groups IA and 2B (Table 3 and Graph 3). Inclusion criteria: 1. Patients aged 21 years or above 2. Prostate needle biopsy performed within the last 6 months or with elevated serum PSA levels ≥4 ng/ml 3. Patients with ≥12 teeth present 4. Patients who had not undergone oral prophylaxis in the last six months were recruited into the study. Exclusion criteria: 1. Age <21years 2. Periodontal treatment within the last 3 months 3. History of other systemic diseases 21 22 23 The mean bleeding index score in group 1A was 0.80±0.31, in group 1B it was 1.00 and in 2A group was 0.97±0.006 and 2B group it was 1.0 respectively. When compared with other groups, the subjects in group 2B had significant higher percentage of bleeding on probing (p<0.05) (Table 4 and Graph 4). Subjects in group 2B had significantly higher (p<0.05) CAL and probing depth scores 5.69±1.34mm and 3.76±0.96mm respectively when compared with group 1A (1.90±0.61mm and 3.26±0.55mm) group 1B (2.28±0.03mm and 3.72±0.01mm) and group 2A (3.61±0.87mm and 3.49±0.71mm) (Table 5 and Graph 5). 24 16 18.00 15 16 16.00 Number 14.00 12.00 10.00 8.00 6.00 4.00 2.00 0 0.00 Mild Moderate/severe Malignant No malignant 25 2.25 1.9 Mean value 2.00 1.75 1.8 1.6 1.6 1.6 1.4 1.4 1.4 1.50 1.25 1.00 0.75 0.50 0.25 0.00 Group 1A Group 1B Group 2A GI scores Group 2B PI scores 1.25 1.0 1.0 1.0 Mean value 1.00 0.8 0.75 0.50 0.3 0.25 0.1 0.0 0.0 0.00 Group 1A Group 1B Mean PSA Group 2A Group 2B Std.Dev. PSA 26 7.00 5.7 Mean value 6.00 5.00 3.7 4.00 3.3 3.00 3.6 3.8 3.5 2.3 1.9 2.00 1.00 0.00 Group 1A Group 1B CAL scores Group 2A Group 2B PD scores 25.00 Mean value 19.5 20.00 15.00 10.00 4.2 5.00 4.7 1.8 0.00 Group 1A Group 1B Group 2A Group 2B 27 18.5 20.00 18.00 Mean value 16.00 14.00 12.00 10.00 8.00 3.2 6.00 4.00 2.00 0.00 Mild The PSA levels were higher in subjects with CAL ≥2.7mm than those with CAL≤2.7mm. The PSA level in group 1A was 1.75±1.24ng/ml, in group 1B it was 4.23±0.32ng/ml, in group 2A it was 4.73±1.53ng/ml and in group 2B it was 19.46±28.60ng/ml respectively. No statistically significant (F=1.8265, p>0.05) difference in PSA levels was observed in between the groups (Table 6 and Graph 6). Subjects with moderate or severe prostatitis had significantly higher (t=-2.1715, p<0.05) PSA levels (18.47±27.88ng/ml) than those with none or mild prostatitis (3.23±2.04ng/ml) (Table 7 and Graph 7). Moderate/severe and the extent and aggressiveness of prostate inflammation in biopsy specimens.14,7 DISCUSSION Hasui et al and Irani et al also supported the same finding and attributed that increased serum PSA is due to disruption of epithelial integrity of the prostate gland. 6,15 Kuzner et al found less PSA staining in inflamed areas than in non-inflamed areas and concluded that increased PSA levels in prostatitis patients was caused because of inflammatory response which disrupts glandular epithelium and causes leakage of PSA into blood stream not because of glandular hyperactivity or hyperplasia.16 Prostate-specific antigen has been extensively studied and widely used in monitoring the growth of prostatic malignancies (Oesterling, 1991). Prostate-specific antigen (PSA) concentration levels have become an essential tool in the diagnosis of early, curable prostate cancer. Morote et al showed that serum PSA levels were directly related to the prostate volume and not the extent or type of inflammatory infiltrate and stated that there might be another non-prostatitic source of PSA such as periodontium which is responsible in the increasing serum PSA levels.17 The higher PSA levels are found in patients with moderate/severe compared to no/mild prostatitis in agreement with previous study by Kandirali et al and Joshi et al, who reported a positive correlation between the serum PSA levels In our study, a higher PSA values are seen in patients with CAL≥2.7 mm compared to CAL<2.7 mm. A positive correlation was observed between periodontal parameters with elevated PSA levels stating that all the individual periodontal 28 parameters were significantly increased with increase in PSA levels. This is in contrast with the earlier study conducted by Nishant Joshi et al7. However bleeding index scores were not significant among the groups. When the Probing depth and clinical attachment level were compared, all the four study groups showed a direct relationship with Prostate Specific Antigen levels. Although the relationship between periodontitis and prostatitis are yet to be proved but there is substantial evidence that supports the role of the immune system in the pathogenesis of both prostatitis and periodontitis, which is mainly mediated through pro-inflammatory cytokines such as interleukin (IL)- 1β and tumor necrosis factor-α (TNF-α). Current evidence suggests that periodontal disease contributes to the increased levels of various pro-inflammatory cytokines and other acute phase proteins which regulate inflammatory response. Elevated levels of IL-1, TNF-α and IL-6 in serum of men with prostatitis is well documented.18 Therefore, it is possible that periodontitis indirectly contributes to the inflammation of prostate gland or disruption of epithelium with increased production of inflammatory cytokines. The present study was done on small sample size and cross-sectional in nature which will not give us cause and effect relationship. So, a large sample size with long term evaluation with the assessment of other risk factors will determine the level of relationship between PSA levels and periodontitis. Change in the PSA levels and prostate volume were not evaluated in this study. Therefore, PSA density (PSA value divided by prostate volume) assessment gives more accurate values considering the variations in the size of prostate gland enlargement. Further studies should emphasize more on the relationship of periodontitis with prostatitis considering all the inflammatory markers for further association. CONCLUSION: With the increasing severity of prostatitis and periodontitis, the Prostate Specific Antigen levels are also increasing, showing that in subjects where there is CAL≥2.7 mm and moderate/severe prostatitis, there are higher PSA values than those with either condition alone. 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