Polymorphisms in LRP2 and CUBN genes and their association with serum vitamin D levels and sleep apnea.

PURPOSE: Vitamin D deficiency has been associated with the occurrence of obstructive sleep apnea syndrome (OSAS). Megalin (LRP2) and cubilin (CUBN) are implicated in vitamin D metabolism, whereas LRP2 and CUBN polymorphisms have been previously associated with variable serum vitamin D levels. The present study aimed to evaluate the role of LRP2 rs2228171 c.8614C > T and CUBN rs1801222 c.758A > G polymorphisms in OSAS susceptibility, independently or in synergy with vitamin D levels. METHODS: Vitamin D serum concentration of consecutive individuals was measured. PCR-RFLP was used for LRP2 rs2228171 and CUBN rs1801222 genotyping. RESULTS: A total of 176 individuals was enrolled, including 144 patients with OSAS and 32 controls. Frequency of LRP2 rs2228171 c.8614 T and CUBN rs1801222 c.758G alleles was estimated at 22.4% and 79.8%, respectively. LRP2 and CUBN polymorphisms were not associated with OSAS occurrence (rs2228171Τ allele: 22.9% in OSAS group vs. 20.3% in controls, p = 0.651; rs1801222A allele 19.4% in OSAS group vs. 23.4% in controls, p = 0.471). Frequency of CUBN rs1801222A allele carriers was increased in patients with moderate or severe OSAS compared to mild OSAS (p = 0.028). Patients with OSAS homozygous for LRP2 CC and CUBN GG genotypes had lower vitamin D serum concentration compared to controls carrying the same genotype (18.0 vs 27.0 ng/mL, p = 0.006 and 19.0 vs 27.5 ng/mL, p = 0.007, respectively). CONCLUSION: CUBN rs1801222 polymorphism may affect OSAS severity. Among other factors, low vitamin D concentration is associated with OSAS occurrence, irrespectively of LRP2 and CUBN polymorphisms.

Reduced Serum Vitamin D Levels Are Associated with Insulin Resistance in Patients with Obstructive Sleep Apnea Syndrome.

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (ß = -0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913-0.995, p = 0.030) and a positive association of BMI (ß = 0.110, OR: 1.116, 95% CI: 1.007-1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Can tumor necrosis factor a (TNF-a) and interleukin 6 (IL-6) be used as prognostic markers of infection following ureteroscopic lithrotripsy and extracorporeal shock wave lithotripsy for ureteral stones?

OBJECTIVE: Ureteroscopic lithotripsy (URS) and Extracorporeal shock wave lithotripsy (ESWL) are highly effective for the treatment of uretral lithiasis and remain the treatment option for the majority of patients for more than two decades. In the present study we aimed to evaluate the levels of serum tumor necrosis factor A (TNFa) and interleucin 6 (IL6) in patients undergoing ESWL and URS. SUBJECTS AND METHODS: A total number of seventy patients were involved in our study. Thirty patients (17 males, 13 females), with a mean age of 43 had underwent ESWL and thirty patients (19 males, 11 females), with a mean age of 47 (range: 26-68) underwent URS lithotripsy. Ten healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-a and IL-6 were obtained before URS and ESWL and after the procedure at 1, 24, and 48 hours and at 2, 24, and 48 hours, respectively. The pre ESWL/URS and post ESWL/URS levels were compared and correlated with possible tissue damage. According to ESWL procedure we found that serumTNF-a levels were significantly increased after one hour (P<0,001) and after 24 hours (P=0.007). Furthermore, IL-6was significantly increased at 2 (P< 0,001), 24 and 48 hours post ESWL (P=0,003 and 0,002) respectively. For URS serum TNF-a levels were statistical significantly correlated preoperatively with one hour (P=0,0083) and 48 hours (P<0,001) after URS and IL-6 with 2 and 24 hours (P<0,001). In 3 patients for URS and 1 for ESWL we observed post procedure fever (>38.5C(o)). All those patients had preoperatively high values of TNF-a and Il-6 that increased at 1 and 2-hours respectively. In conclusion, high pre ESWL/URS levels of serum TNF-a and IL-6 may indicate a predisposition for post ESWL/URS inflammation and infection following URS lithotripsy or ESWL procedure.

Tumor necrosis factor A and interleucin 6 serum values in patients undergoing extracorporeal shock wave lithotripsy for ureteral stones.

OBJECTIVE: Extracorporeal shock wave lithotripsy (ESWL) is highly effective for the treatment of uretral lithiasis and remains the first treatment option for the majority of patients when ureteral lithiasis can not be treated otherwise for more than two decades. In the present study we aim to evaluate the levels of serum tumor necrosis factor a (TNF-a) and interleucin 6 (IL-6) in patients undergoing ESWL and investigate whether preESWL levels of serum TNF-a and IL-6 correllate with any possible infectious complications after ESWL. SUBJECTS AND METHODS: Thirty patients (17 males and 13 females), with a mean age of 43 who underwent ESWL for ureteral stones and 10 healthy volunteers serving as the control group were enrolled in this study. Serum samples for TNF-a and IL-6 were obtained before ESWL and after ESWL, 1, 24, and 48 hours and 2, 24, and 48 hours, respectively. The preESWL and postESWL serum TNF-a levels and IL-6 were compared and correlated with possible tissue damage and infectious complications. RESULTS: We found that serum TNF-a levels were significantly decreased one hour (P<0,001) and increased 24 hours (P=0.007) after ESWL. Furthermore IL-6 was also significantly increased 2 hours (P<0,001), 24 and 48 hours after ESWL (P=0,003 and 0,002 respectively). In 3 patients we observed fever (39 (o)C) postESWL procedure with negative urine culture and high serum values of TNF-a and IL6 preESWL. IN CONCLUSION: A high specific markers such as serum TNF-a levels (15-25pg/ml) and IL-6 (25-35pg/ml) might be useful to identifying patients with possible infection following ESWL lithotripsy. However, further studies are needed to get more accurate results.

Chromogranin A as a biomarker of disease activity and biologic therapy in inflammatory bowel disease: a prospective observational study.

OBJECTIVE: To access the correlation of Chromogranin A (CgA) with inflammatory bowel disease (IBD) activity and responsiveness to medical therapy. MATERIAL AND METHODS: A prospective observational study was conducted in 56 patients with moderate ulcerative colitis (UC) or Crohn's disease (CD) (UC, n = 29, CD, n = 27), 17 patients with irritable bowel syndrome and predominant diarrhea (IBS-D) and 40 healthy volunteers. IBD patients were treated by biologics (infliximab or adalimumab) or conventional agents (aminosalicylates, thiopurines or methotrexate and steroids) and were classified according to their treatment in two groups. Serum CgA was measured at baseline and 4-week posttreatment period. RESULTS: Serum CgA was significantly higher in IBD patients than in those with IBS-D or healthy volunteers (p < 0.01). Furthermore, serum CgA was markedly increased in CD patients than in UC patients (p < 0.01). CgA value was significantly reduced in 'biologic' group (24 IBD patients, UC, n = 15, CD, n = 9) at 4-week posttreatment period (p < 0.01), while 18/24 (72%) patients were already in remission during that time. In contrast, CgA value was significantly increased in the 'conventional' treatment group (32 IBD patients, UC, n = 14, CD, n = 18) between the two visits (p < 0.01), although 22/32 (69%) patients were in remission during the 4-week posttreatment period. CONCLUSION: CgA appears to be a reliable marker of disease activity in IBD patients and especially in those who received biologic therapy. IBS-D patients presented normal CgA values.

Serum cytocines values in patients after endoscopic surgery for ureteral lithiasis.

Obstructive uropathy due to ureteral stones can cause renal infection and, if left untreated, can cause impairment of renal function. Endoscopic surgery such as ureteroscopy (URS) and laser lithotripsy are the primary therapeutic approach. Cytokines as non invasive markers may have a role to diagnose ureteral damage and infection. We aimed to evaluate serum cytokine levels of tumor necrosis factor-a (TNFa) and interleukin-6 (IL6) in patients undergoing URS and holmium laser lithotripsy. The study included 40 patients (male 25 and 15 female) with a mean age of 47 years and 10 healthy blood donors serving as the control group. None of them had any additional systemic diseases, previous insertion of a ureteral double "j" stent or of a nephrostomy tube, neoplasmatic disease ot renal insufficiency. Routine urine examination and urine culture were obtained to exclude urinary infection. Preoperatively and 1h, 2h, 24h and 48h postoperatively serum samples of TNF-a and IL-6 were collected and measured. Serum TNFa and IL-6 values were correlated with the other variables measured from blood samples after the URS using paired samples Students t-test with confidence interval 95%. A P value of less than 0.01 was considered statistically significant. Correlation between serum TNF-a and IL6 levels with healthy donors were statistically significant in 1h (0.004), 2h (0.001), 24h (0.001) and 48h (0.001 and 0.001) postoperatively, respectively. In conclusion, our study shows that cytokines could be helpful as markers of renal tissue damage. However, further studies are needed to get more accurate results.

Minimal invasive treatment options in pregnant women with ovarian vein syndrome.

PURPOSE: To describe the treatment modalities of symptomatic ovarian vein syndrome in pregnancy. METHODS: In our study, we included 12 pregnant women with right ureter and kidney dilatation; caused by ureteric obstruction. In 11 out of 12, we insert a DJ stent and in one woman we applied percutaneous nephrostomy, because of intermittent abdominal pain, resistant on analgetic therapy or feverish pyelonephritis. DJ stents and nephrostomy were inserted under ultrasound guidance without anaesthesia. RESULTS: After insertion of DJ stents, respective percutaneous nephrostomy colic attacks went back immediately and the feverish pyelonephritis in few days. At no time during these procedures, there was a risk for pregnancy. CONCLUSION: Ovarian vein syndrome in pregnancy can lead to violent colic pain and can become complicated by accompanied pyelonephritis. In these cases insertion of a DJ stent or percutaneous nephrostomy under ultrasound guidance is possible and safe, and leads to an improvement of complaints immediately.

Single inguinal node metastasis of stage I testicular seminoma shown by scrotal scintigraphy, 6 months following radical orchiectomy.

Lymphatic drainage of the testes is known to follow a predictable pathway that usually involves the retroperitoneal, paraaortic, paracaval and interaortocaval nodal chains. Herein we report the case of a 41 years old man with a stage I testicular seminoma, with an unexpected inguinal lymph node metastasis. During his routine follow-up visit, 6 months after radical orchiectomy, a spherical mass in the right inguinal region was palpated. Thoraco-abdominal CT did not reveal any evidence of retroperitoneal enlarged lymph nodes or distant metastases, but showed a 2cm right inguinal mass. Scrotal scintigraphy with technetium-99m pertechnetate was performed in order to evaluate the local vascularity of the right inguinal area. The angiographic phase (0-1min) and the blood pool images at 15, 30, 45 and 60min revealed high uptake in the right inguinal region, suggesting a hyperemic mass suspicious for tumor recurrence. The excised mass was found to be an enlarged lymph node infiltrated with seminoma. The patient received adjuvant radiotherapy to which he showed a complete response and has been disease free at 2 years follow-up. In conclusion, in the case presented scrotal scintigraphy showed a hyperemic mass at the right inguinal region that proved to be the sentinel node of a stage I testicular seminoma and was treated accordingly.

Radiobiological analysis of preliminary results of a phase II study of pelvic hypofractionated and accelerated radiotherapy for high-risk prostate cancer patients.

PURPOSE: Conventionally fractionated radiotherapy (CRT) is widely applied for the treatment of high-risk prostate cancer. Pelvic node irradiation improves control of the disease. Although the therapeutic guidelines support the use of hypofractionated and accelerated radiotherapy (HypoAR), this is addressed to prostate and seminal vesicles. At the same time, the safety and efficacy of HypoAR for pelvic node irradiation remain obscure. Material and Methods: In a phase II study, we evaluated the feasibility of pelvic HypoAR in 22 high-risk prostate cancer patients. The RT scheme delivers 14 consecutive fractions of 3.67 Gy (total 51.38 Gy) to the prostate, 3.5 Gy (total 49 Gy) to the seminal vesicles, and 2.7 Gy (total 37.8 Gy) to the lymph nodes, using image-guided volumetric modulated arc therapy. A comparative radiobiological analysis of dose-volume histogram is performed (HypoAR vs. hypothetical equivalent CRT regimens, without and with time correction). RESULTS: Our clinical experience shows impressively low early and short-term late toxicities, without any grade III events, within a median follow-up of 30 months. Only one biochemical relapse was recorded 30 months after irradiation. In radiobiological analysis, considering an α/ß-value of 4 Gy and a λ-value of 0.2 Gy/day for late effects, all comparisons predicted significantly lower toxicity for the HypoAR regimen (p < 0.05). For early toxicities (α/ß = 10 Gy), a λ-value lower than 0.4 Gy/day favors the HypoAR regimen, which is along with the clinical results. CONCLUSION: Radiobiological analysis favors HypoAR as a safe and effective regimen for high-risk prostate cancer patients, which is confirmed in the current phase II clinical study.

Vitamin D Levels in Patients with Overlap Syndrome, Is It Associated with Disease Severity?

Background: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) has been defined as overlap syndrome (OVS). Recently, a link between OSA, COPD and Vitamin D (Vit D) serum concentration was reported, however, evidence regarding Vit D status in patients with OVS is scarce. The aim of the present study was to evaluate Vit D serum levels and to explore the association of those levels with anthropometric, pulmonary function and sleep parameters in patients with OVS. Methods: Vit D serum levels were measured in patients diagnosed with OVS, as confirmed by overnight polysomnography and pulmonary function testing. Results: A total of 90 patients (79 males and 11 females) were included in the analysis. The patients were divided into three groups matched for age, gender, and BMI: the control group that included 30 patients (27 males and 3 females), the OSA group that included 30 patients (26 males and 4 females), and the OVS group that included 30 patients (26 males and 4 females). Patients with OVS exhibited decreased serum 25(OH)D levels compared with OSA patients and controls (14.5 vs. 18.6 vs. 21.6 ng/mL, p < 0.001). In the OVS group, multiple linear regression analysis identified AHI and FEV1, as predictors of serum 25(OH)D levels (p = 0.041 and p = 0.038, respectively). Conclusions: Lower Vit D levels have been observed in patients with OVS compared with OSA patients and non-apneic controls, indicating an increased risk of hypovitaminosis D in this population which might be associated with disease severity.

Positive lymphoscintigraphy (ILS) and negative computed tomography for metastatic penile cancer.

Penile carcinoma usually occurs in older than 40 years men with an incidence in western communities of 0.5 to 1.6 per 100,000 men per year while in developing countries the rate is much higher in men. Extensive lymph node dissection of lymphatic inguinal metastases evident by inguinal lymphoscintigraphy (ILS) induces improved overall survival. A 75 years old male with penile squamous cell carcinoma stage pT2N0M0 of less than 2cm diameter, with tumor invasion of the penis corpora underwent partial penectomy with a 2-cm disease-free margin. Three months postoperation, computed tomography (CT) was negative for local recurrence or distant metastases. A dynamic ILS was performed after local anaesthesia and intradermal injection of 80MBq of (99m)Tc-nanocolloid at the lower edge of the left and right inguinal ducts. The lymphatic chain and a hot spot suggestive of a first draining lymph node appeared after 15min on the right inguinal region in the second zone according to Daseler mapping. The left inguinal area was negative for sentinel node (SN). In view of this finding an exploratory laparotomy was performed and pathology showed that this lymph node that was probably a SN was infiltrated by the squamous cell carcinoma. The patient was upstaged to T2N1M0 and scheduled to receive adjuvant chemotherapy with two courses of cisplatin and 5-fluorouracil. While T1 and T2 tumours of diameters <2cm are best treated with penile-preserving methods such as circumciand/or local excision. Tumours of T2 >2cm, T3 tumours, and T4 tumours are treated with glans amputation and/or partial or total penile amputation. Imaging with magnetic resonance imaging (MRI) or computed tomography (CT) scan do not always give accurate staging information, because positive findings are usually found only in patients with clinically palpable, enlarged inguinal lymph nodes. Computed tomography and MRI have low sensitivity to identify occult metastases, because they present criteria for malignant involvement mainly based on the size of the lesions. The main pitfall of these diagnostic modalities is due to occult metastatic disease occurring within normal sized nodes. Approximatively 20% of the patients with non palpable lymph nodes harbour occult inguinal metastases, and there is evidence that this group of patients may benefit from early surgical dissection of the inguinal nodes, compared to a wait-and-see policy. It is understood that current imaging techniques cannot accurately detect occult metastases, while ILS is more reliable. In 80% of patients with penile cancer, after ILS, drainage to both groins is observed. Bilateral nodes are often visualized early, sometimes asynchronously with one of the lymph nodes filling late. This is why delayed images are recommended. Pitfalls of ILS are: a) Contamination of the skin with the tracer and b) radiopharmaceutical entering the blood. There are also several reasons that may account for absent or faint SN uptake: low dose of the tracer or low tracer quality, patient's age (better in young patients), tumor involvement of the sentinel node, and finally too short or too long interval between tracer injection and ILS. The ILS can be mapped according to Daseler's inguinal zones. Penile cancer drains directly to the nodes in the superior and central Daseler zones. According to others, the majority (73%) of SN was located in the medial superior, 8.7% in the lateral superior, and 18.3% in the central zone. No drainage was seen on the two inferior quadrants. The majority (62.1%) of higher-tier nodes was found in the external iliac zone. Inguinal LS can save us from watchful waiting in cases of otherwise occult metastases. In conclusion, ILS has shown lymph node metastases while clinical and CT examinations were negative. The false positive and false negative results of ILS are mentioned.

Tissue polypeptide antigen in the follow-up of patients with urinary bladder cancer compared with conventional urine cytology.

The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

The prognostic value of serum chromogranin A and prostate specific antigen in prostate cancer patients for progression to the hormone resistance state.

Prostate adenocarcinomas (PAC) consist mainly of tumour cells of luminal immunophenotype and scattered neuroendocrine (NE) cells. NE cells are defined by chromogranin A (CgA) immunoreactivity. T he aim of this study is the evaluation of CgA serum levels in monitoring prostate cancer (PC) patients under complete androgen deprivation (CAD) in comparison with the prostate specific antigen (PSA) as a prognostic marker of androgen resistance and bone metastases. Ninety-two patients with newly diagnosed PAC and 30 healthy blood donors serving as the control group were enrolled in the study. Serum CgA and PSA values were measured. All patients had locally advanced or metastatic disease and received CAD treatment. In the group of PAC patients bone scanning with 925MBq (99m)Tc-MDP revealed the presence of bone metastatic lesions in 50 patients (29 with more than 3 lesions and 21 with less than 3 lesions). The other 42 patients had no bone metastases. The patients and the control group were re-evaluated after 1 year. Our results showed that serum CgA positively correlated with multiple bone metastases and higher Gleason score, serum levels of CgA and PSA. Levels of PSA were significantly higher in patients with PAC and bone metastases compared with those with no bone metastases (P<0.001). In patients with multiple bone metastases and Gleason Score >7 elevated serum levels of CgA higher than those of PSA were found. In conclusion, serum CgA levels is a valuable marker for predicting the presence of multiple bone metastases in PAC patients. Combined with PSA, CgA can predict disease progression in patients with advanced PAC under CAND treatment and is correlated with poor prognosis.

Genetics of Obstructive Sleep Apnea: Vitamin D Receptor Gene Variation Affects Both Vitamin D Serum Concentration and Disease Susceptibility.

Obstructive sleep apnea syndrome (OSAS) is a multifactorial and common disorder affecting 10-17% of men and 3-9% of women. A low vitamin D serum concentration has been reportedly linked to OSAS susceptibility, but the underlying molecular genetic mechanisms are poorly understood thus far. We report here original findings on the ways in which vitamin D receptor (VDR) gene polymorphic variation (FokI, BsmI, ApaI, and TaqI polymorphisms) impacts serum vitamin D concentration and, additionally, susceptibility to OSAS. In a sample of 176 consecutive subjects (144 patients with OSAS and 32 healthy controls) phenotyped by full polysomnography (PSG), we characterized human genetic variation in VDR using the Sequenom MassARRAY iPLEX platform. A logistic regression analysis was employed to account and correct for covariates such as sex, age, body mass index, and comorbidities. Importantly, we observed that the FokI CC genotype frequency was markedly higher in patients with OSAS compared with controls (50.7% vs. 28.1%; p = 0.027). VDR FokI polymorphism explained 14.5% of vitamin D serum concentration variability. Moreover, the VDR FokI polymorphism was also associated with excessive daytime sleepiness (p = 0.016). To the best of our knowledge, this is the first clinical genetics study examining the role of VDR polymorphic variation on OSAS as phenotyped using full PSG. We call for further studies of vitamin D-related mechanisms that might contribute to OSAS risk in independent populations.

Four prognostic indices in advanced prostate cancer patients, under palliative androgen deprivation treatment.

Prostate cancer (PCa) is the second leading cause of death in men aged 40 years and older ]and prognostic indices are useful in suggesting its proper treatment. The aim of this study was to evaluate the prognostic value of Gleason score (GS), TNM staging system, initial serum prostate specific antigen (PSA) and bone scintigraphy (BS) in patients with PCa under hormonal palliative treatment, in the development and progression of recurrent PCa. Our methods were as follows: Between January 2005 and December 2007, we have studied at the University General Hospital of Alexandroupolis fourty patients of mean age 77+/-7.2 years with advanced PCa under palliative treatment with antiandrogens and luteinizing hormone-releasing hormone analogues. PCa was diagnosed histologically, based on the TNM system after transrectal ultrasonography guided biopsy. The Gleason score assessment was made as described by others. Metastases were confirmed by a positive bone scintigraphy with 925 MBq (99m)Tc-MDP using a tomographic gamma camera, computerized axial tomography or magnetic resonance imagining. Measurements of PSA were conducted by the radioimmunoassay method. We also examined 20 healthy blood donors (median age 45+/-6.1 years) as controls, in order to estimate the cut-off value of PSA. Our results show the following: Thirteen of our patients had 1-6 "hot" spots and 27 had more than 6 "hot" spots in the bone scan. The median Gleason score was 7 (modal Gleason score 3+4). Serum PSA levels were higher in patients with PCa and bone metastases in comparison to those with PCa without bone metastases. Very high values of PSA (more than 50 ng/ml) were found in patients with multiple bone metastases (>6 "hot" spots). In conclusion, our findings demonstrate that the prognostic value of GS (P=0.043), TNM staging (P=0.1410), serum PSA levels (P=0.002) and BS (P=0.0135) when used alone, not always improve the prognosis to hormone indepentent but when combined (P<0.001) increase the prognosis in patients with advanced PCa under hormonal palliative treatment.

Metabolic Syndrome and Vitamin D Levels in Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Numerous studies have indicated that obstructive sleep apnea syndrome (OSAS), may contribute to the development of metabolic syndrome (MetS) and diabetes. Moreover, OSAS has been associated with lowered vitamin D (Vit D) levels, but reports are inconclusive. Aim of the study was to compare Vit D levels according to the presence of MetS and its components in OSAS patients. METHODS: The presence of MetS was evaluated and serum 25-hydroxy vitamin D [25(OH)D] levels were measured in consecutive newly diagnosed, by polysomnography, subjects with OSAS. RESULTS: A total of 107 subjects (88 men) with OSAS were included in the study. Patients were divided into group A (OSAS with MetS group: 55 subjects) and group B (OSAS without MetS: 52 subjects). There were no differences between the two groups in terms of age, body mass index, and sleep parameters. Patients in group A exhibited higher levels of daytime sleepiness, as expressed by Epworth Sleepiness Scale score (12 ± 5.5 vs. 9.3 ± 4.8 for groups A vs. B, p = 0.008). Serum 25(OH)D levels were significantly decreased in group A, as compared with group B (18 ± 8.6 ng/mL vs. 23.9 ± 14.1 ng/mL, respectively, p = 0.012). Group A was then subdivided in two smaller groups, according to patients' metabolic index: OSAS patients with metabolic score = 3 and OSAS patients with metabolic score >3. Serum 25(OH)D levels were higher in OSAS patients with metabolic score = 3 compared with OSAS patients with metabolic score >3 (19.8 ± 8.9 ng/mL vs. 15.1 ± 7.3 ng/mL respectively, p = 0.038). CONCLUSIONS: OSAS patients with concurrent MetS exhibit lower serum Vit D levels, as compared with those without MetS.

[The importance of the tumor marker CYFRA 21-1 in patients with lung cancer after surgery or chemotherapy].

Lung cancer is the most common cancer worldwide with 900,000 new cases each year in men and 330,000 in women, being also the major cause of death from cancer. In Greece about 4,000 persons die every year due to lung carcinoma. One of the major problems in the follow up of these patients is the difficulty of early detection of recurrent disease. Tumor markers are of particular interest in this respect. Cytokeratines, especially fragment 19, are specified epithelial tissue-proteins that show increased levels in patients with carcinomas. CYFRA 21-1 assays determine the serum cytokeratin 19 fragment. The aim of our study was to evaluate the importance of serum CYFRA 21-1 studied by immunoradiometric assay in patients with various types of lung cancer after surgery or chemotherapy. Ninety-six consecutive patients were studied during a two years period. Forty-five of them had small cell lung cancer (SCLC) and 51 had non-small cell lung cancer (NSCLC). Moreover, 52 healthy individuals were studied to estimate the cut off value of CYFRA 21-1. Increased serum levels of the marker were found in patients with lung cancer compared to controls (P<0.001). The cut off value was estimated as 3.3 ng/ml with 96% specificity. Before the treatment there was no difference in the sensitivity of CYFRA 21-1 for patients with SCLC (21/45 patients had increased CYFRA 21-1 levels, 47%) and for patients with NSCLC (27/51 had increased levels, 52%). Also, before treatment there was a higher sensitivity in NSCLC than in SCLC and especially in SCC among other histotypes of NSCLC when different stages of the disease were compared. Patients with extended disease, metastatic or recurrent disease had also more increased levels of the marker (P<0.001). One month after surgical ablation of the primary lung lesion, 28/58 patients showed a drop in the levels of the marker as an indication of the tumor ablation. From the 58 operated patients 35 relapsed and 31/35 showed an increase in CYFRA-21-1 levels with a sensitivity of 92% and specificity of 95%. From the 38 patients that underwent chemotherapy treatment, 24 had a depravation of the disease and 21/24 had a great increase of serum CYFRA 21-1 with a sensitivity of 89% and specificity of 94%. In conclusion, CYFRA 21-1 is a useful tumor marker before and after surgical treatment in lung cancer.

Second-look Flexible Nephroscopy Combined With Holmium: Yttrium-Aluminum-Garnet Laser Lithotripsy Under Local Anesthesia: A Prospective Study.

OBJECTIVE: To present a prospectively studied series of patients who underwent second-look flexible nephroscopy combined with holmium:yttrium-aluminum-garnet (Ho:YAG) laser lithotripsy under local anesthesia for residual stone removal after percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: Thirty consecutive eligible patients who underwent a PCNL procedure in the previous 48-96 hours were included. The inclusion criteria were the following: (1) 1 or 2 residual stones 0.8-1.5 cm in diameter and (2) age >18 years. Approximately 15 mL of a 2% solution of lidocaine hydrochloride was injected through the nephrostomy tube, which was then clamped for 15 minutes. Flexible nephroscopy was combined with Ho:YAG laser lithotripsy set at 0.8 Joules and 8 Hz. Patients were asked to rate their pain intensity using the numeric rating scale (NRS). RESULTS: There were 14 (46.7%) men and 16 (53.3%) women in the study, with a mean age of 45.2 ± 17.5 years. Twenty-one (70%) patients had 1 stone and 9 (30%) had 2 stones needing fragmentation. Twenty-eight (93.3%) patients successfully underwent the procedure under local anesthesia. The mean NRS value was 1.39 ± 1.08 (range 0-5). For the entire group, there was a statistically significant difference between those patients with 1 stone vs 2 stones needing fragmentation (NRS scores of 1.1 ± 0.77 vs 2.1 ± 1.36, respectively, P = .033). Operative time >30 minutes was associated with higher NRS score. The stone-free rate under local anesthesia was 86.7%. CONCLUSION: For patients with a minimal to moderate residual stone burden after PCNL, second-look flexible nephroscopy can be combined with Ho:YAG laser lithotripsy using only local anesthesia.

Survival and Quality of Life Benefit after Endoscopic Management of Malignant Central Airway Obstruction.

BACKGROUND: Although interventional management of malignant central airway obstruction (mCAO) is well established, its impact on survival and quality of life (QoL) has not been extensively studied. AIM: We prospectively assessed survival, QoL and dyspnea (using validated EORTC questionnaire) in patients with mCAO 1 day before interventional bronchoscopy, 1 week after and every following month, in comparison to patients who declined this approach. Material/Patients/Methods: 36 patients underwent extensive interventional bronchoscopic management as indicated, whereas 12 declined. All patients received full chemotherapy and radiotherapy as indicated. Patients of the 2 groups were matched for age, comorbidities, type of malignancy and level of obstruction. Follow up time was 8.0±8.7 (range 1-38) months. RESULTS: Mean survival for intervention and control group was 10±9 and 4±3 months respectively (p=0.04). QoL improved significantly in intervention group patients up to the 6(th) month (p<0.05) not deteriorating for those surviving up to 12 months. Dyspnea decreased in patients of the intervention group 1 month post procedure remaining reduced for survivors over the 12th month. Patients of the control group had worse QoL and dyspnea in all time points. CONCLUSIONS: Interventional management of patients with mCAO, may achieve prolonged survival with sustained significant improvement of QoL and dyspnea.

Coexistence of squamous cell tracheal papilloma and carcinoma treated with chemotherapy and radiotherapy: a case report.

BACKGROUND: Papillomatosis presents, most frequently, as multiple lesions of the respiratory tract, which are usually considered benign. Malignant degeneration into squamous cell carcinoma is quite common, although curative approaches vary a lot in modern literature. CASE REPORT: We report a case of a 66-year-old male patient with the coexistence of multiple squamous cell papilloma and carcinoma in the upper trachea with severe airway obstruction that was diagnosed through bronchoscopy and treated by performing an urgent tracheostomy, followed by concurrent chemotherapy and radiotherapy. There was no evidence of recurrence after a 12-month follow-up period. CONCLUSION: This study underlines the diagnostic and therapeutic value of bronchoscopy as well as multimodality palliative treatment in such cases. To the best of our knowledge, this is the first study to describe an immediate treatment protocol with tracheostomy and concurrent chemotherapy/radiotherapy in a patient with squamous cell tracheal papilloma and carcinoma.