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Shock Wave Lithotripsy Not Associated With Development of Diabetes Mellitus at 6 Years of Follow-up
Abstract
To investigate the hypothesis that extracorporeal shock wave lithotripsy (ESWL) increases the incident risk of new-onset diabetes mellitus (DM). Studies have suggested that ESWL predisposes to DM.
Using a mail survey, we collected data on the presence and onset of DM in 1947 patients treated with the Medstone-STS electrohydraulic lithotripter from 1999 to 2002. These patients were matched by age, sex, and body mass index to controls from the National Health and Nutrition Examination Survey (NHANES) database. Of the 1947 patients, 4% could not be matched and were excluded, leaving 1869 for analysis, of whom 60.0% were men. The mean age was 51.9 years at ESWL and the median follow-up was 6 years. The mean body mass index at the end of the study was 28.6 kg/m(2).
At ESWL, 8.67% of matched patients had a diagnosis of DM. This had increased to 13.9% at the time of survey. In the NHANES group, 8.34% had DM at the time the ESWL group underwent treatment, and this had increased to 14.1% at the NHANES survey. Therefore, the rate of new DM cases in the ESWL group was similar to that in the NHANES group (5.2% vs 5.8%, respectively; P = .47). Multivariate analysis of the patient cohort confirmed that age, sex, body mass index, and family history correlated with development of DM and that the laterality of treatment and number of treatments or shocks given were not significant predictors of DM.
The results of our study have shown that patients treated with ESWL do not develop DM at a greater rate than does the general population at 6 years of follow-up.
... Prior studies on this topic have shown conflicting results, with literature both supporting [1] and opposing [6][7][8] a link between DM and ESWL for kidney stones. However, careful review of the existing literature shows several key limitations, including selection bias, lack of generalisability, and flawed comparison groups. ...
... Unfortunately, three of those studies relied on questionnaire/ telephone interview to determine the outcome of DM and also had low response rates, both of which are major limitations [6][7][8]. Furthermore, three of those four had other key limitations. The study by Sato et al. [6] included patients who were treated with a low number of shocks (900) and the control group comprised patients who had ESWL for ureteric stones (which if located in the proximal ureter could theoretically result in pancreatic damage). ...
... A major strength of the present study was the use of administrative data (ODD) to determine the outcome of DM; this consistent and validated data source addresses a major limitation of prior studies [1,[6][7][8]. Another strength of our present study was the selection of our comparator group. ...
Objective
To determine if patients treated with extracorporeal shockwave lithotripsy (ESWL) are at a greater risk of developing diabetes mellitus (DM) than those treated with ureteroscopy (URS).
Patients and Methods
A retrospective population‐based cohort study was performed of all ESWL and URS stone treatments done in Ontario between January 1994 and March 2014, utilising linked encoded healthcare databases. The primary outcome was the development of DM >90 days after treatment. The Kaplan–Meier method was used for unadjusted survival analysis and multivariable analysis with Cox proportional hazards regression was used to assess the risk of DM between the ESWL and URS groups whilst controlling for age, gender, region of residence, income quintile, year of treatment, and comorbidity index. A sensitivity analysis with a subset of ESWL patients treated for left renal or proximal ureteric stones was completed.
Results
We identified 106 963 patients who underwent ESWL or URS over the study period with a median follow‐up of 6.6 years (ESWL 8.5 years, URS 5.6 years). Unadjusted survival analysis showed an increased risk of developing DM in the ESWL group compared to the URS group (P < 0.001); however, multivariable analysis showed no increased risk of DM in the ESWL cohort (hazard ratio [HR] 0.97, 95% confidence interval [CI] 0.91–1.02; P = 0.25). Similarly, sensitivity analysis showed no increased risk of DM in the left renal/proximal ureteric stone ESWL cohort compared to the URS cohort (HR 1.04, 95% CI 0.96–1.13; P = 0.35).
Conclusions
Our population‐based cohort study demonstrated no increased risk of DM in patients undergoing ESWL compared to URS.
... It has been reported that hormonal treatment (hCG and GnRH) may harm the germ cells in 1 to 3-year-old boys with cryptorchidism who did not respond to the hormones used to induce testicular descent. 30 No reports on long-term fertility outcomes following isolated hormonal therapy (no surgery at any time) 127 were found in our literature search. Hormonal therapy may have some value to optimize germ cell maturation and/ or sperm production. ...
... 124 Several other studies have failed to show an increase in hypertension or diabetes mellitus. [125][126][127][128][129][130] Multivariate analysis of 727 patients with a 20year follow-up at our institution revealed no increased rate of diabetes or hypertension in those with kidney stones compared to prevalence of these diseases in the general population. 131 Any new onset of diabetes or hypertension after SWL is most likely due to the association of kidney stones with the metabolic syndrome. ...
... Krambeck et al., in a retrospective review, proposed that there was an association between diabetes and ESWL that was dependent on the number and intensity of shocks [49]. However in 2009, Makhlouf et al. found no association between ESWL and diabetes in a retrospective survey of 1869 patients who underwent ESWL compared to a case-controlled population at a 6 year follow-up [56]. In 2012, de Cógáin et al. also demonstrated no significant relationship between ESWL and DM [57]. ...
Purpose of review:
Since its introduction, extracorporeal shock wave lithotripsy (ESWL) has undergone a variety of changes; however, it remains one of the most utilized treatment modalities for urolithiasis. The goal of this review is to provide the practicing urologist an update on contemporary trends, new technologies, and related controversies in utilizing ESWL for stone treatment.
Recent findings:
ESWL use has come under scrutiny with a shift in focus to cost-effectiveness and healthcare outcomes. Fortunately, advances in lithotripter technology have spawned several generations of devices that strive to improve stone-free rates and decrease complications. Most of all, a focus on patient selection criteria has helped improve procedural success. Years of experience utilizing ESWL for stone treatment have helped urologists better optimize its use and minimize complications. Improvements in technique along with more stringent patient and stone selection have helped ESWL remain a mainstay in the treatment of stone disease.
... Later studies compared patients with ureteropelvic junction and renal stones and patients with distal ureteric calculi and did not find an association between lithotripsy and DM or HTN [17]. Makhlouf et al. also failed to find an association between lithotripsy and HTN or diabetes [18]. All these controversial studies evaluated treatments performed with the HM-3 lithotripter, and the long-term effects of more advanced devices have not been determined. ...
To assess the incidence of long-term side effects after shock-wave lithotripsy treatment performed with an electromagnetic Dornier Lithotripter S device. A specific follow-up was undertaken on a cohort of 100 selected patients that underwent SWL for a single renal stone in our center from 2002 to 2004. Previous and current data were compared using the Student t test. Factors associated with the incidence of hypertension and diabetes mellitus were determined. Ten years after treatment, mean serum creatinine level and glomerular filtration rate remained similar to previous values (serum creatinine level: 0.96 ± 0.22 vs. 0.92 ± 0.19 mg/dL; glomerular filtration rate: 92.8 ± 17.8 vs. 88.1 ± 21.7 mL/min). There were marked increases in blood cholesterol, blood pressure, and blood glucose levels, while smoking decreased. Age, glomerular filtration rate, body mass index, blood glucose and blood pressure at the time of treatment were significantly associated with the presence of hypertension and diabetes mellitus at follow-up; blood cholesterol was associated with diabetes mellitus development. After 10 years, overall renal function appeared to have been unaffected by shock-wave lithotripsy treatment. The increased rate of hypertension and diabetes mellitus were consistent with the incidence in the global population. This is the first report on the long-term safety of a third generation electromagnetic lithotripter, and indicates that there are no long-term sequelae.
... Nevertheless, a study involving a large population with 6 years follow-up indicated no association between diabetes mellitus risk and ESWL. [3] Knowing whether this follow-up period is long enough is difficult to establish. ...
... versus 5.8%; p=0.47). 38 A study of 5,287 patients with calculi and without diabetes monitored for an average of 8.7 years found no association between ESWL and the appearance of diabetes in both univariate and multivariate analyses, including age, sex and obesity (hazard ratio = 0.92; 95% CI 0.71-1.18). 39 The association between ESWL and the development of chronic diseases (hypertension and diabetes) is unclear and studies with higher levels of evidence are needed to confirm or rule out this association (Level of evidence 2b; Grade of recommendation B). ...
The use of certain technical principles and the selection of favorable cases can optimize the results of extracorporeal shock wave lithotripsy (ESWL). The aim of this study is to review how ESWL works, its indications and contraindications, predictive factors for success, and its complications. A search was conducted on the Pubmed® database between January 1984 and October 2013 using "shock wave lithotripsy" and "stone" as key-words. Only articles with a high level of evidence, in English, and conducted in humans, such as clinical trials or review/meta-analysis, were included. To optimize the search for the ESWL results, several technical factors including type of lithotripsy device, energy and frequency of pulses, coupling of the patient to the lithotriptor, location of the calculus, and type of anesthesia should be taken into consideration. Other factors related to the patient, stone size and density, skin to stone distance, anatomy of the excretory path, and kidney anomalies are also important. Antibiotic prophylaxis is not necessary, and routine double J stent placement before the procedure is not routinely recommended. Alpha-blockers, particularly tamsulosin, are useful for stones >10mm. Minor complications may occur following ESWL, which generally respond well to clinical interventions. The relationship between ESWL and hypertension/diabetes is not well established.
... Shortly after the publication of the Mayo Clinic report 2 retrospective studies with followup of 17 years or less in patients with stones treated with SWL showed no higher incidence of T2D. 11,12 With this background of clinical information we performed an animal study to address whether SWL treatment would increase the risk of T2D. We used the Ossabaw miniature swine model in which features similar to those of human MetS develop, 13,14 including cluster of factors such as obesity, insulin resistance, impaired glucose tolerance, dyslipidemia and hypertension. ...
Purpose
To determine whether shock wave lithotripsy (SWL) treatment of the kidney of metabolic syndrome (MetS) pigs worsens glucose tolerance or increases the risk of developing diabetes mellitus.
Materials and Methods
Nine-month-old female Ossabaw miniature pigs were fed a hypercaloric atherogenic diet to induce MetS. At 15 months of age, pigs were treated with 2000 SWs or 4000 SWs (24 kV at 120 SWs/min) using the unmodified Dornier HM3 lithotripter. SWs were targeted to the upper pole calyx of the left kidney so as to model treatment that would also expose the tail of the pancreas to SWs. Intravenous glucose tolerance tests (IVGTTs) were performed on conscious, fasting pigs before SWL and at 1 month and 2 months post-SWL with blood samples taken for glucose and insulin measurement.
Results
Pigs fed the hypercaloric atherogenic diet were obese, dyslipidemic, insulin resistant and glucose intolerant—consistent with the development of MetS. Assessment of insulin resistance, glucose tolerance and pancreatic beta cell function from fasting plasma glucose and insulin levels, and the glucose and insulin response profile to IVGTTs, were similar before and after SWL.
Conclusions
The MetS status of SWL treated pigs was unchanged 2 months following treatment of the kidney with 2000 high-amplitude SWs or overtreatment with 4000 high-amplitude SWs. These findings do not support a single SWL treatment of the kidney as a risk factor for the onset of diabetes mellitus.
... 38 However, in a matched case-control study by Makhlouf et al. to investigate the incident risk of new-onset diabetes mellitus following SWL, no statistical difference was identified between the case group and the controls at long term follow up of 6 years. 39 El-Nahas et al. also concluded that no effect on renal growth and no development of hypertension or diabetes was observed in a paediatric population in long-term follow-up after SWL for treatment. 40 On the contrary, in a recent study, shockwave treatment appeared to be beneficial in treating chronic diabetic foot ulcers. ...
In the past decade, the field of urology has been one of the most rapidly progressing in applied technological advancements at the level of both medical diagnostics and treatment. The introduction of modern robotic laparoscopy has changed the face of minimally invasive surgery. For endourology specialists, stone surgery continues to be in the forefront of daily practice and innovations and new technologies are constantly being developed, aiming towards ever higher stone free rates and earlier recovery for the patient. But, is there a price? Indeed, in addition to advances in conservative treatment and prevention, modern endourology and stone disease management in particular enjoys a large variety of sophisticated new equipment and disposables, used either alone or in combination, developed from various companies at considerable cost. It is more than often that even expert professionals are not totally familiar with the whole range of treatment options and devices that are available in the market, as they commonly bear different names despite being used for the same purpose. Furthermore, a question of integrity might arise when using newly developed equipment directly in the operating theatre, with respect to the efficacy of the device as well as the learning curve required by the operator. In this review, we shall outline the latest advances in interventional lithotripsy technology and also demonstrate the most effective ways to use each particular modality efficiently and safely, with respect to the latest published guidelines and evidence-based recommendations.
... Two recent retrospective studies conducted after publication of the Mayo Clinic report have found no association between SWL and the development of diabetes mellitus. 66,67 However, limitations in the experimental design of these studies leaves the question of potential for development of diabetes mellitus following SWL unanswered. 68 That is, in the study by Makhlouf and colleagues the duration of the follow-up period was only 6 years-likely too short a period to be relevant to the development of chronic disease. ...
... 14,15 Similarly, the association between SWL and an increased risk of developing diabetes mellitus or hypertension was not proved by other investigators. 16,17 In contrast, Barbosa et al observed new onset hypertension in 15% of patients who were treated with SWL in a median follow-up of 6 years, whereas this rate was 6.25% in the matched control group. 18 The long-term effects of SWL on renal function have also been studied in patients with a solitary kidney by several investigators. ...
... Patients who receive multiple sessions of SWL may be at increased risk of long-term effects such as the transition from calcium oxalate stones to stones of calcium phosphate and brushite [119], and also hypertension [120]. Most recently there has been a report associating the onset of diabetes mellitus with SWL dose [121] although other studies contest this association [122,123]. However, assessment of these long-term effects is complicated owing to the varied natural history of recurrent stone formers and by differences in treatment protocols (see section 5.3) [110]. ...
Shock wave lithotripsy (SWL) is the process of fragmentation of renal or ureteric stones by the use of repetitive shock waves generated outside the body and focused onto the stone. Following its introduction in 1980, SWL revolutionized the treatment of kidney stones by offering patients a non-invasive procedure. It is now seen as a mature technology and its use is perceived to be routine. It is noteworthy that, at the time of its introduction, there was a great effort to discover the mechanism(s) by which it works, and the type of sound field that is optimal. Although nearly three decades of subsequent research have increased the knowledge base significantly, the mechanisms are still controversial. Furthermore there is a growing body of evidence that SWL results in injury to the kidney which may have long-term side effects, such as new onset hypertension, although again there is much controversy within the field. Currently, use of lithotripsy is waning, particularly with the advent of minimally invasive ureteroscopic approaches. The goal here is to review the state of the art in SWL and to present the barriers and challenges that need to be addressed for SWL to deliver on its initial promise of a safe, effective, non-invasive treatment for kidney stones.
Extracorporeal shock wave lithotripsy (SWL) remains the only noninvasive modality in lithotripsy and still contributes to more than half of all urinary stone treatments worldwide; however, success rates vary significantly because different equipment and protocols are used. An overview of shock wave generation methods for SWL and comments on some representative modern lithotripters are given in the first part of the chapter. Descriptions of few old lithotripter models were included due to their historical importance. Furthermore, some interesting shock wave sources that remained as experimental devices are mentioned. Recommendations to perform efficient SWL treatments are given in the second part of the chapter. Contraindications, treatment of pediatric and obese patients, the influence of the focal size, shock wave rate, shock wave coupling, stone size, composition, and location on treatment outcomes, as well as the convenience of voltage-stepping and the use of prophylactic shock waves are discussed. SWL for gallbladder, pancreatic common bile duct, and salivary gland stones was also included. Although SWL is a routine in urology and millions of treatments have been performed successfully, improvements to increase stone fragmentation efficiency and reduce tissue damage are still being sought. The final section of this chapter deals with a few developments that might be incorporated into commercial devices in the future.
Injudicious use of shock wave lithotripsy can lead to unwanted effects. The acute bioeffects of shock waves such as renal hemorrhage can be reduced by a number of measures, which include pretreatment with shockwaves, slowing the firing rate, and reducing the total number of shock waves delivered and the power of the shock. Improving the coupling between the patient and machine also improves effectiveness and reduces harm. Long-term effects include renal scarring and new-onset hypertension. This chapter explores the mechanisms by which these bioeffects are produced.
Aim: To investigate the effect of extracorporeal shock wave lithotripsy (ESWL) on the pancreatic exocrine functions related to the number of high-energy shock waves and the ESWL-applied kidney side for upper urinary tract stones. Materials and methods: Included in the study were 76 patients undergoing ESWL for proximal ureteral or kidney stones. The right kidney group (RKG) consisted of 40 patients who underwent ESWL for right kidney stones and the left kidney group (LKG) consisted of 36 patients who underwent ESWL for left kidney stones. Results: The observed changes in plasma amylase and lipase levels were not statistically significant compared with the pre-ESWL values in both groups. The relationship between the number of applied shock waves (SWs) and the serum amylase and lipase after ESWL showed a statistically significant positive correlation in the RKG but not in the LKG. Conclusion: There were no statistically significant differences between the pre- and post-ESWL serum amylase and lipase levels. However, a statistically significant positive correlation was found between the number of SWs applied and the post-ESWL amylase and lipase levels in the RKG. Although clinical and experimental studies have shown the safety of ESWL, avoiding excess sessions and an unnecessarily high number of SWs may be helpful in the prevention of the potential risks of ESWL.
The role of shock-wave lithotripsy (SWL) in the management of ureteral calculi has been challenged following the development of more minimally invasive ureteroscopic techniques. Evidence, however, suggests that equivalent stone clearance rates are achieved using SWL without routine retrograde manipulation and stenting, and thus patient morbidity and cost may be less with this therapy. Patient positioning may be modified to permit optimal treatment of mid- and distal ureteral stones. Predictive factors for single-treatment stone clearance, including stone size and density, obesity and stone location, may be assessed using nomograms. Clearance rates after SWL tend to be higher for ureteral than renal calculi, and higher for proximal than distal ureteral stones. The use of medical expulsive therapy can also improve stone-fragment clearance. Little conclusive evidence exists to suggest long-term metabolic consequences of SWL for ureteral calculi. SWL remains a central option in the management of ureteral calculi.
The purpose of the study was to evaluate the association between shock wave lithotripsy (SWL) for urinary stone and new-onset diabetes mellitus (DM). A comprehensive data collection was performed in the Pubmed database, Embase database, Chinese Biomedical database, Chinese National Knowledge Infrastructure database and VIP database. Difference in incidence of new-onset DM after SWL between cases and controls was evaluated by odds ratio (OR) with its 95 % confidence interval (CI). And summary adjusted risk ratios (RRs) and 95 % CIs were calculated to assess the strength of association between SWL and new-onset DM, and then subgroup analyses were conducted. Five studies were included in this meta-analysis. The incidence of new-onset DM after SWL is not higher than that in the population who do not receive SWL [OR = 1.59, 95 % CI (0.92, 2.74), P = 0.10]. And statistical association between SWL and new-onset DM could not be found significantly [RR = 1.33, 95 % CI (0.83, 2.13), P = 0.24], either. However, body mass index (BMI) [RR = 1.09, 95 % CI (1.04, 1.14), P < 0.001] and family history of DM (FHx DM) [RR = 0.35, 95 % CI (0.15, 0.80), P = 0.013] were found significantly associated with the development of DM in subgroup analyses. Our data suggests that there is no association between SWL for urinary stone and new-onset DM.
Background
Nobiletin is a non-toxic dietary flavonoid that possesses anti-cancer properties. Nobiletin has been reported to reduce the risk of prostate cancer, but the mechanism is not well understood. In this study, we investigated the effects of nobiletin in prostate cancer cell lines PC-3 and DU-145.
Methods
Nobiletin was isolated from a polymethoxy flavonoid mixture using HPLC, cell viability was analyzed with MTS-based assays. Protein expression was examined by ELISA and western blotting. Gene expression was examined by luciferase assay. And the pathways were examined by manipulating genetic components with plasmid transfection.
Results
Data showed that nobiletin decreased cell viability in both prostate cell lines, with a greater reduction in viability in PC-3 cells. HIF-1α expression and AKT phosphorylation were decreased in both cell lines. The VEGF expression was inhibited in PC-3 but not DU-145 cells. cMyc expression was decreased in DU-145 cells. Nobiletin down-regulated NF-κB (p50) expression in nuclei of DU145 cells but not whole cells. It also suppressed NF-κB expression in both whole cells and nuclei of PC-3 cells. Increasing HIF-1α levels reversed nobiletin’s inhibitory effects on VEGF expression, and up-regulating AKT levels reversed its inhibitory effects on HIF-1α expression. We speculate that AKT influences cell viability probably by its effect on NF-κB in both prostate cells. The effect of nobiletin on VEGF expression in PC-3 cell lines was through the AKT/HIF-1α pathway.
Conclusion
Taken together, our results show that nobiletin suppresses cell viability through AKT pathways, with a more profound effect against the more metastatic PC-3 line. Due to this enhanced action against a more malignant cell type, nobiletin may be used to improve prostate cancer survival rates.
To evaluate regional differences in adaptation of best practice recommendations for extracorporeal shock wave lithotripsy (SWL) across 4 distinct geographic regions.
A retrospective study was performed using a prospective database maintained by a mobile lithotripsy provider (ForTec Medical, Streetsboro, OH). SWL cases performed in Ohio, Northern Illinois/Southern Wisconsin, Florida, and New York were included. Treatment parameters evaluated included treatment rate, use of a power ramp-up protocol, use of a pretreatment pause after the initial 100 shocks, ancillary procedures, and need for retreatment. Regional and physician-specific patterns were examined. Statistical analyses using chi-square and analysis of variance were performed with a significance of P <.05.
Data from 2240 SWL procedures were included in the study. Overall adaptation of power ramp-up protocols and treatment rates were high (93% and 93%), whereas use of pause was lower (75%, P <.001). Retreatment rates were low (4.3%), although ancillary procedures were performed in 34% of patients, and 8.3% of patients received stents for stones <1 cm. Regional differences were present in all parameters: Florida physicians used power ramp-up less (83%, P <.001) but had good use of pretreatment pause (98%, P <.001), both Wisconsin/Illinois and New York were less likely to use slow rate (87% and 84%, respectively, P <.001).
The recommendations for slower shock wave rates and power ramp protocols have reached high penetration in urologic practices; however, the more recent recommendation for a pause after the initial 100 shocks has been less uniformly implemented. Inconsistencies in regional adaptation of best practices may identify opportunities for further education.
Background:
Prostate cancer is the second leading cause of cancer death in men worldwide. Several factors such as availability of screening tests, and dietary, other lifestyle, environmental and genetic influences contribute to worldwide disparities in prostate cancer incidence and mortality rates. Our aims were to investigate patient characteristics at the time of diagnosis, common treatment strategies employed and survival in an Iranian male population with prostate cancer.
Materials and methods:
Archives of Pathology Departments of five referral centers affiliated with the School of Medicine of Shahid Sadoughi University in Yazd province were reviewed. Paraffin-embedded blocks were reviewed by two independent pathologists to confirm the diagnosis. The latest modification of the Gleason Scoring System was adopted to determine pathological grading. Following pathological evaluation, patients were contacted via telephone to acquire information regarding their current status.
Results:
Pathology blocks were available for 113 patients. However, upon phone contacts, we were unable to determine the survival status in 23 patients (response rate=83%). Therefore, 90 patients were enrolled in the final analysis. The median follow-up time was 6.0 years (ranging from 0.3 to 8.8 years). There were 30 death attributed to prostate cancer in the study group. Kaplan-Meier analysis revealed that patient age at the time of diagnosis was a significant predictor of survival. Another significant predictor of poorer survival was higher tumor grade.
Conclusions:
Our observations indicate that age and pathological grade can negatively affect survival of individuals with prostate cancer in Iran.
Unlabelled:
WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Extracorporeal shockwave lithotripsy is effective for the treatment of paediatric renal stones with favourable short-term safety. Extracorporeal shockwave lithotripsy for treatment of paediatric renal stones is also safe for the kidney and the child on long-term follow-up.
Objective:
To evaluate the long-term effects of extracoporeal shockwave lithotripsy (SWL) for treatment of renal stones in paediatric patients.
Patients and methods:
A database of paediatric patients who underwent SWL monotherapy for treatment of renal stones from September 1990 through to January 2009 was compiled. This study included only patients with follow-up for more than 2 years. The long-term effects of SWL were evaluated at the last follow-up with measurement of patients' arterial blood pressure, estimation of random blood sugar and urine analysis. The results of diastolic blood pressure were plotted against a standardized age reference curve. The treated kidney was examined by ultrasonography for measurement of renal length and detection of stones. The measured renal lengths were plotted against age-calculated normal renal lengths in healthy individuals.
Results:
The study included 70 patients (44 boys (63%) and 26 girls) with mean age at the time of SWL 6.5 ± 3.6 years (range 1-14). The mean follow-up period was 5.2 ± 3.6 years (range 2.1-17.5). The mean age at last follow-up was 11.7 ± 5.3 years (range 4.4-27.5). No patients developed hypertension or diabetes. Only one treated kidney was smaller than one standard deviation of the calculated length. The cause of this was obstruction by a stone in the pelvic ureter 3 years after SWL.
Conclusion:
The long-term follow-up after SWL for treatment of renal stones in paediatric patients showed no effect on renal growth and no development of hypertension or diabetes.
A 42-year-old man without a history of kidney stones had intermittent left flank pain for several weeks before being seen by his primary care doctor. Urinalysis revealed microhematuria. Computed tomography (CT) of the abdomen and pelvis without contrast enhancement identified a calcification 12 mm in diameter in the left renal pelvis, associated with mild hydronephrosis and a normal-caliber ureter. The attenuation coefficient of the stone was 790 Hounsfield units, and the skin-to-stone distance was 8.5 cm. He was referred to a urologist, who reviewed the CT scan and recommended treatment with extracorporeal shock-wave lithotripsy.
Cadmium, a widespread toxic pollutant of occupational and environmental concern, is a known human carcinogen. The prostate is a potential target for cadmium carcinogenesis, although the underlying mechanisms are still unclear. Furthermore, cadmium may induce cell death by apoptosis in various cell types, and it has been hypothesized that a key factor in cadmium-induced malignant transformation is acquisition of apoptotic resistance. We investigated the in vitro effects produced by cadmium exposure in normal or tumor cells derived from human prostate epithelium, including RWPE-1 and its cadmium-transformed derivative CTPE, the primary adenocarcinoma 22Rv1 and CWR-R1 cells and LNCaP, PC-3 and DU145 metastatic cancer cell lines. Cells were treated for 24 hours with different concentrations of CdCl(2) and apoptosis, cell cycle distribution and expression of tumor suppressor proteins were analyzed. Subsequently, cellular response to cadmium was evaluated after siRNA-mediated p53 silencing in wild type p53-expressing RWPE-1 and LNCaP cells, and after adenoviral p53 overexpression in p53-deficient DU145 and PC-3 cell lines. The cell lines exhibited different sensitivity to cadmium, and 24-hour exposure to different CdCl(2) concentrations induced dose- and cell type-dependent apoptotic response and inhibition of cell proliferation that correlated with accumulation of functional p53 and overexpression of p21 in wild type p53-expressing cell lines. On the other hand, p53 silencing was able to suppress cadmium-induced apoptosis. Our results demonstrate that cadmium can induce p53-dependent apoptosis in human prostate epithelial cells and suggest p53 mutation as a possible contributing factor for the acquisition of apoptotic resistance in cadmium prostatic carcinogenesis.
Biochanin-A, a major dietary isoflavone in soy and red clover, possesses anticancer and chemopreventive properties. Induction of apoptosis by naturally occurring dietary agents is an important event for cancer chemoprevention. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) triggers apoptosis selectively in cancer cells but not in normal cells. Soluble or expressed in immune cells, molecules TRAIL plays a significant role in surveillance and defense mechanisms against tumours. Prostate cancer is an ideal disease for nutritional prevention. The TRAIL-mediated apoptosis pathway in prostate cancer cells is an attractive target for chemopreventive activities of dietary agents. LNCaP and DU145 prostate cancer cells are resistant to TRAIL-induced apoptosis. We showed that biochanin-A markedly augmented TRAIL-induced cytotoxicity and apoptosis in both prostate cancer cell lines. Then, we investigated the mechanisms by which biochanin-A enhanced TRAIL-mediated apoptosis using the LNCaP cell line. The isoflavone sensitized the TRAIL-resistant LNCaP cells through the inhibition of transcription factor NF-κB(p65) activity, increased the expression of the death receptor TRAIL-R2 (DR5), and disrupted mitochondrial membrane potential (ΔΨm). Our study confirmed that biochanin-A overcame TRAIL-resistance by engaging both intrinsic and extrinsic apoptotic pathways and by regulating the NF-κB activity. The results suggested a potential role of biochanin-A in prostate cancer chemoprevention through the enhancement of TRAIL-mediated apoptosis.
To compare the prevalence of hypertension and diabetes mellitus (DM) in patients treated with an unmodified HM-3 lithotripter (USWL) and a second-generation modified HM-3 lithotripter (MSWL) 20 years ago at our Centre with that in the provincial population. To determine whether the type of lithotripter was differentially associated with the development of these sequelae.
Retrospective review of 727 patients at Vancouver General Hospital who underwent shock-wave lithotripsy (SWL) between 1985 and 1989. Our study group was compared with Statistics Canada data describing the provincial prevalence of these diseases. Multivariate analysis was performed.
The response rate was 37.3%. There was a greater proportion of overweight and obese individuals in the study group compared with the provincial average. In univariate analysis, lithotripsy with an unmodified HM-3 (USWL) was associated with a higher rate of DM than the provincial rate, whereas lithotripsy with the modified HM-3 (MSWL) was not. Hypertension was more prevalent in all lithotripsy subjects. On multivariate analysis the type of lithotripter was not associated with the development of either sequela.
No association between lithotripsy and the development of either DM or hypertension in a multivariate analysis Metabolic syndrome may have elevated the prevalence of DM and hypertension observed in our subjects on univariate analysis, which is in keeping with the fact that our study population had statistically higher body mass indices than the provincial rate. Lithotripsy using the HM-3 was not associated with increased DM or hypertension.
Numerous compounds detected in medical plants and dietary components or supplements possess chemopreventive, antitumor and immunomodulatory properties. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an important endogenous anticancer factor that induces apoptosis selectively in cancer cells. However, some tumor cells are resistant to TRAIL-mediated apoptosis. Naturally occurring agents could sensitize TRAIL-resistant cancer cells and augment their apoptotic activity.We examined the cytotoxic and apoptotic effects of neobavaisoflavone and psoralidin in combination with TRAIL on LNCaP prostate cancer cells. The cytotoxicity was evaluated by MTT and LDH assays. The apoptosis was detected using Annexin V-FITC by flow cytometry and fluorescence microscopy. The LNCaP cells were shown to be resistant to TRAIL-induced apoptosis. Our study demonstrated that neobavaisoflavone and psoralidin sensitized TRAIL-resistant cells and markedly augmented TRAIL-mediated apoptosis and cytotoxicity in prostate cancer cells. Cotreatment of LNCaP cells with 100 ng/ml TRAIL and 50 μM neobavaisoflavone or 50 μM psoralidin increased the percentage of the apoptotic cells to 77.5±0.5% or 64.4±0.5%, respectively. The data indicate the potential role of the bioactive compounds isolated from the medicinal plant Psoralea corylifolia (neobavaisoflavone and psoralidin) in prostate cancer chemoprevention through enhancement of TRAIL-mediated apoptosis.
To determine whether shock wave lithotripsy (SWL) increases the prevalence of hypertension (HTN) at intermediate follow-up.
All patients were treated with the Medstone STS electrohydraulic lithotripter, and the data were recorded prospectively in a centralized database. The data on the development of HTN after SWL was obtained from a questionnaire mailed to the patients who had undergone SWL from November 1999 and January 2002. Controls matched for age, sex, and body mass index were obtained from the National Health and Nutrition Examination Survey, using the demographic, body measurements, medical conditions, and blood pressure data sets. Two sets of matching controls were used to compare the prevalence of HTN between our patients and the NHANES population at SWL and at the follow-up point.
A total of 2041 patients responded to the questionnaire, with a median follow-up of 6 years. No statistically significant difference was found in the HTN prevalence between the patients and matched controls at SWL (26.7% vs 28.0%). At the follow-up point, the prevalence of HTN was greater in our patients (37.8%) than in the controls (32.5%, P=.0009). Of our patients, 15% have developed de novo HTN compared with the predicted rate of 6.25% from the matched controls. Male gender, age, and a greater body mass index were associated with the development of HTN, but none of the SWL parameters (number of shocks, bilateral vs unilateral, and multiple SWL sessions) were significantly associated with HTN.
The results of our study have indicated a small, but significant, increase in the risk of developing HTN after SWL using a third-generation electrohydraulic lithotripter at intermediate follow-up.
To complete a prospective evaluation of serum amylase and lipase levels before and after shock wave lithotripsy (SWL) for renal stones. We also compared these serum levels to those of patients undergoing percutaneous and ureteroscopic stone surgery. SWL injury to the pancreas should be noted by an increase in serum amylase and lipase.
A prospective evaluation of 38 patients (16 who underwent SWL, 15 who underwent percutaneous nephrostolithotomy, and 7 who underwent ureteroscopic stone manipulation) who underwent treatment of renal calculi at our institution was completed. The control group was the combined group of patients who had undergone percutaneous nephrostolithotomy or ureteroscopic stone manipulation. The serum amylase and lipase levels were measured before the procedure, immediately after the procedure (2 hours), and ≥30 days after the procedure.
No statistically significant difference was found in the change from before to immediately after the procedure between the SWL group and the controls in amylase (median decrease 6 U/L vs 11 U/L, P = .45) or lipase (median decrease 4 U/L vs 9 U/L, P = .31). Also, no statistically significant evidence was seen in the change from before to >30 days after the procedure between the SWL group and controls in the amylase level (median increase 0 U/L vs 2 U/L, P = 1.00) or lipase (median change 2 U/L increase vs 1 U/L decrease, P = .96).
SWL does not appear to noticeably increase the serum amylase and lipase level directly postoperatively or >30 days after the procedure compared with baseline or compared with the controls.
Interventions to prevent type 2 diabetes should be directed toward individuals at increased risk for the disease. To identify such individuals without laboratory tests, we developed the Diabetes Risk Score.
A random population sample of 35- to 64-year-old men and women with no antidiabetic drug treatment at baseline were followed for 10 years. New cases of drug-treated type 2 diabetes were ascertained from the National Drug Registry. Multivariate logistic regression model coefficients were used to assign each variable category a score. The Diabetes Risk Score was composed as the sum of these individual scores. The validity of the score was tested in an independent population survey performed in 1992 with prospective follow-up for 5 years.
Age, BMI, waist circumference, history of antihypertensive drug treatment and high blood glucose, physical activity, and daily consumption of fruits, berries, or vegetables were selected as categorical variables. Complete baseline risk data were found in 4435 subjects with 182 incident cases of diabetes. The Diabetes Risk Score value varied from 0 to 20. To predict drug-treated diabetes, the score value >or=9 had sensitivity of 0.78 and 0.81, specificity of 0.77 and 0.76, and positive predictive value of 0.13 and 0.05 in the 1987 and 1992 cohorts, respectively.
The Diabetes Risk Score is a simple, fast, inexpensive, noninvasive, and reliable tool to identify individuals at high risk for type 2 diabetes.
The purpose of this study was to examine the prevalences of diagnosed and undiagnosed diabetes, and impaired fasting glucose (IFG) in U.S. adults during 1999-2002, and compare prevalences to those in 1988-1994.
The National Health and Nutrition Examination Survey (NHANES) contains a probability sample of adults aged > or =20 years. In the NHANES 1999-2002, 4,761 adults were classified on glycemic status using standard criteria, based on an interview for diagnosed diabetes and fasting plasma glucose measured in a subsample.
The crude prevalence of total diabetes in 1999-2002 was 9.3% (19.3 million, 2002 U.S. population), consisting of 6.5% diagnosed and 2.8% undiagnosed. An additional 26.0% had IFG, totaling 35.3% (73.3 million) with either diabetes or IFG. The prevalence of total diabetes rose with age, reaching 21.6% for those aged > or =65 years. The prevalence of diagnosed diabetes was twice as high in non-Hispanic blacks and Mexican Americans compared with non-Hispanic whites (both P < 0.00001), whereas the prevalence of undiagnosed diabetes was similar by race/ethnicity, adjusted for age and sex. The prevalence of diagnosed diabetes was similar by sex, but prevalences of undiagnosed diabetes and IFG were significantly higher in men. The crude prevalence of diagnosed diabetes rose significantly from 5.1% in 1988-1994 to 6.5% in 1999-2002, but the crude prevalences were stable for undiagnosed diabetes (from 2.7 to 2.8%) and IFG (from 24.7 to 26.0%). Results were similar after adjustment for age and sex.
Although the prevalence of diagnosed diabetes has increased significantly over the last decade, the prevalences of undiagnosed diabetes and IFG have remained relatively stable. Minority groups remain disproportionately affected.
We performed extracorporeally induced destruction of kidney stones on 72 patients. No complications have resulted from the tissue exposure to high energy shock waves. Clearance studies before and after the shock wave treatment indicate no changes in renal function. The method was used successfully in all patients with stones in the renal pelvis. In none of these patients was an open operation required. Two patients with ureteral stones also were treated with shock waves but had to be operated upon because of insufficient destruction of the stone.
We performed extracorporeally induced destruction of kidney stones on 72 patients. No complications have resulted from the tissue exposure to high energy shock waves. Clearance studies before and after the shock wave treatment indicate no changes in renal function. The method was used successfully in all patients with stones in the renal pelvis. In none of these patients was an open operation required. Two patients with ureteral stones also were treated with shock waves but had to be operated upon because of insufficient destruction of the stone.
Some reports have shown a decreased effectiveness of extracorporeal shock wave lithotripsy (ESWL*) with newer lithotriptors. We used a first generation unmodified Dornier HM3 lithotriptor to treat 5,698 patients with renal and ureteral calculi and a second generation Medstone STS device to treat 8,166 patients with renal and ureteral calculi. The treatment results were compared using the chi-square test to determine statistical significance. The stone-free rate, retreatment rate and post-ESWL secondary procedure rate were 69.5%, 4.4% and 3.1%, respectively, with the Dornier HM3 device and 72.1%, 4.9% and 2.3%, respectively, with the Medstone lithotriptor for single renal stones, and 81.5%, 5.2% and 5.5%, respectively, with the Dornier HM3 and 83.2%, 5.2% and 5.0%, respectively, with the Medstone device for single ureteral stones. There were no statistically significant different results between a second generation tubless Medstone STS lithotriptor and the gold standard unmodified Dornier HM3 instrument.
Some reports have shown a decreased effectiveness of extracorporeal shock wave lithotripsy (ESWL*) with newer lithotriptors. We used a first generation unmodified Dornier HM3 lithotriptor to treat 5,698 patients with renal and ureteral calculi and a second generation Medstone STS device to treat 8,166 patients with renal and ureteral calculi. The treatment results were compared using the chi-square test to determine statistical significance. The stone-free rate, retreatment rate and post-ESWL secondary procedure rate were 69.5%, 4.4% and 3.1%, respectively, with the Dornier HM3 device and 72.1%, 4.9% and 2.3%, respectively, with the Medstone lithotriptor for single renal stones, and 81.5%, 5.2% and 5.5%, respectively, with the Dornier HM3 and 83.2%, 5.2% and 5.0%, respectively, with the Medstone device for single ureteral stones. There were no statistically significant different results between a second generation tubless Medstone STS lithotriptor and the gold standard unmodified Dornier HM3 instrument.
A retrospective multicenter survey was performed to evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) as a treatment of pancreatic stones.
A survey was sent to 11 institutions belonging to the Japanese Association of Extracorporeal Shock Wave Lithotripsy in Digestive Diseases, and data were collected on 555 patients who underwent ESWL for pancreatic stones between January 1990 and September 2002. The male:female ratio was 5.2:1, and the mean age was 52.5 years. The etiology was alcohol related in 425 patients (76.6%) and idiopathic in 111 patients (20.0%); 204 patients (36.8%) had a single stone and 470 patients (84.7%) were symptomatic.
Mean frequency of the procedure was 5.0 times (range, 1-29). Fragmentation of stones was achieved in 513 patients (92.4%), and the complete stone clearance rate after ESWL alone or in combination with interventional endoscopy was 72.6%. Symptom relief was achieved in 428 (91.1%) of 470 patients. Thirty-five patients (6.3%) developed complications, including 30 patients (5.4%) who developed acute pancreatitis. Five hundred four (90.8%) patients were followed for a mean of 44.3 months, during which 122 (22.0%) suffered stone recurrence (mean time to recurrence, 25.1 months). Twenty-two (4.1%) of the 504 patients who were followed required surgery. Pancreatic exocrine function improved in 65 patients (38.0%), was unchanged in 49 patients (28.7%), and progressed in 57 patients (33.3%). Pancreatic endocrine function improved in 44 patients (24.3%), was unchanged in 85 patients (47.0%), and progressed in 52 patients (28.7%).
ESWL is the treatment of choice for clearing pancreatic stones.
SWL has revolutionized the management of nephrolithiasis and it is a preferred treatment for uncomplicated renal and proximal ureteral calculi. Since its introduction in 1982, conflicting reports of early adverse effects have been published. However, to our knowledge the long-term medical effects associated with SWL are unknown. We evaluated these adverse medical effects associated with SWL for renal and proximal ureteral stones.
Chart review identified 630 patients treated with SWL at our institution in 1985. Questionnaires were sent to 578 patients who were alive in 2004. The response rate was 58.9%. Respondents were matched by age, sex and year of presentation to a cohort of patients with nephrolithiasis who were treated nonsurgically.
At 19 years of followup hypertension was more prevalent in the SWL group (OR 1.47, 95% CI 1.03, 2.10, p = 0.034). The development of hypertension was related to bilateral treatment (p = 0.033). In the SWL group diabetes mellitus developed in 16.8% of patients. Patients treated with SWL were more likely to have diabetes mellitus than controls (OR 3.23, 95% CI 1.73 to 6.02, p <0.001). Multivariate analysis controlling for change in body mass index showed a persistent risk of diabetes mellitus in the SWL group (OR 3.75, 95% CI 1.56 to 9.02, p = 0.003). Diabetes mellitus was related to the number of administered shocks and treatment intensity (p = 0.005 and 0.007).
At 19 years of followup SWL for renal and proximal ureteral stones was associated with the development of hypertension and diabetes mellitus. The incidence of these conditions was significantly higher than in a cohort of conservatively treated patients with nephrolithiasis.
Unlabelled:
There has been controversy over whether extracorporeal shock wave lithotripsy (ESWL) can cause damage to the endocrine cells of the pancreas, leading to the later development of diabetes mellitus. Authors from Germany prospectively evaluated acute endocrine pancreatic injury as collateral damage caused by the ESWL for treating upper urinary tract stones. In a careful study they showed that there was no effect on serum levels of variables indicating exocrine and endocrine pancreatic tissue damage, suggesting that the idea that ESWL might lead to future diabetes mellitus is unlikely to be correct.
Objective:
To detect acute damage to pancreatic cells by extracorporeal shock wave lithotripsy (ESWL), with a focus on endocrine function, as recently the development of diabetes mellitus has been suggested to be a late complication of treatment of upper urinary tract stones, and injury to pancreatic tissue by ESWL, leading to insufficient endocrine function, has been proposed as an explanation of this effect.
Patients and methods:
The study included 12 consecutive patients treated with ESWL for proximal ureteric or kidney stones, using a third-generation electromagnetic lithotripter. To evaluate pancreatic tissue injury caused by ESWL we determined blood variables known to indicate exocrine and endocrine pancreatic cell damage; blood samples were taken before, during, immediately after, and 1 h and 24 h after ESWL to determine the serum levels of amylase, lipase, insulin, glucose, c-peptide and glucagon. Eight patients treated with ESWL for distal ureteric stones were evaluated in the same way and served as the control group.
Results:
Neither the variables indicating islet cell damage (c-peptide, insulin and glucagon), nor those indicating damage of exocrine pancreatic cells (amylase and lipase) changed significantly over the time course in both groups.
Conclusion:
We could detect no immediate effect on the serum levels of variables indicating exocrine or endocrine pancreatic tissue damage caused by ESWL for urinary tract stones. The hypothesis that ESWL leads to pancreatic trauma with consecutive development of diabetes mellitus therefore seems unlikely.
Prevalence of diabetes and impaired fasting glucose in adults in the US population: National Health and Nutrition Examination Survey
- Rust Kf Byrd-Holt
- Dd
Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and impaired fasting glucose in adults in the US population: National Health and Nutrition Examination Survey 1999-2002. Diabetes Care. 2006;29:1263-1268.
Aus-tria: R Foundation for Statistical Computing
- Vienna
Vienna, Aus-tria: R Foundation for Statistical Computing; 2005.