Indian Journal of Urology Users online:1673  
IJU
Home Current Issue Ahead of print Editorial Board Archives Symposia Guidelines Subscriptions Login 
Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
  Table of Contents 
SYMPOSIUM
Year : 2014  |  Volume : 30  |  Issue : 2  |  Page : 202-207
 

Surgical therapy for benign prostatic hypertrophy/bladder outflow obstruction


Department of Urology, Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom

Date of Web Publication29-Mar-2014

Correspondence Address:
Nikesh Thiruchelvam
Addenbrookes Hospital, Cambridge University Hospitals NHS Trust, Cambridge
United Kingdom
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0970-1591.126907

Rights and Permissions

 
   Abstract 

Monopolar transurethral resection of the prostate (TURP) with endoscopic electrocautery remains the gold standard surgical technique for benign prostatic hypertrophy (BPH) by which all new procedures are compared. We reviewed the current literature, and international urological guidelines and consensus opinion on various surgical options for BPH and present a brief overview of alternative techniques including bipolar TURP, transurethral incision of the prostate, transurethral vaporization of the prostate, laser prostatectomy (with holmium, thulium and potassium titanyl phosphate greenlight lasers) and open prostatectomy (with mention of new techniques including laparoscopic and robotic prostatectomy). Emerging, experimental and less established techniques are also described including endoscopic heat generation (transurethral microwave thermotherapy, radiofrequency transurethral needle ablation of the prostate, high intensity focused ultrasound, hot water induced thermotherapy, pulsed electromagnetic radiofrequency), injection therapy (transurethral ethanol ablation and botulinum toxin) and mechanical devices (intraprostatic stents and urethral lift devices). Despite a plethora of surgical options, none have realistically improved outcomes in the long-term compared with TURP. Improvements have been made on improving surgical morbidity and time in hospital. Questions remain in this area, including what specific elements of bladder outflow obstruction (BOO) result in damage to the urinary tract, how does BPH contribute to BOO and how much prostate volume reduction is necessary to relieve BOO or lower urinary tract symptoms. Given these unanswered questions and the multitude of procedures available, it is clear that appropriate counselling is necessary in all men who undergo BPH surgery.


Keywords: Green light laser, holmium laser enucleation of the prostate, laser prostatectomy, prostatectomy, thulium laser, transurethral resection of the prostate


How to cite this article:
Thiruchelvam N. Surgical therapy for benign prostatic hypertrophy/bladder outflow obstruction. Indian J Urol 2014;30:202-7

How to cite this URL:
Thiruchelvam N. Surgical therapy for benign prostatic hypertrophy/bladder outflow obstruction. Indian J Urol [serial online] 2014 [cited 2019 Aug 26];30:202-7. Available from: http://www.indianjurol.com/text.asp?2014/30/2/202/126907



   Introduction Top


Conservative and medical therapy for male lower urinary tract symptoms (LUTS) secondary to benign prostatic hypertrophy (BPH) is now well established. Management is largely established in terms of alpha-blocker and 5-alpha reductase inhibitor treatment. This is in contrast to the large number of surgical treatment options available. This article highlights the alternative procedures available in widespread usage and also describes uncommon, historic and experimental options.


   Endoscopic electrocautery Top


Monopolar transurethral resection of the prostate (TURP) remains the gold standard treatment for the surgical management of BPH and bladder outflow obstruction (BOO). TURP rates have declined over the past two decades due to the significant benefits of medical therapy and, to a lesser extent, the proliferation of alternative surgical techniques.

Recommended indications for TURP include:

  • Moderate to severe LUTS (either not controlled with medical therapy or by patient choice)
  • Acute urinary retention (AUR) (despite the use of an alpha-blocker)
  • Recurrent urinary tract infection
  • Recurrent haematuria
  • Obstructive uropathy.


BPH resulting in BOO can be inferred by patient's obstructive symptoms, flow-rates, post-void residual urine measurements and cystoscopic findings, but the diagnosis on BOO can only be firmly made by urodynamic investigation. The latter studies should be performed in a man under 50 or over 80 with LUTS, in a patient with neurological disease and LUTs, in a man with on-going symptoms of BOO after bladder outlet surgery, in a man with disproportionately significant storage LUTS and in a man who cannot void greater than 150 ml.

TURP involves resecting the prostate gland in small chips and washing out the prostate chips and subsequent rollerball diathermy for haemostasis [Figure 1]. A urinary catheter may or may not be irrigated and is usually removed after 24-48 h. TURP is effective in reducing symptoms scores and in improving quality of life (QOL) score. [1] The reduction in symptoms score and improvement in QOL scores remain high after this operation and has not been bettered by any endoscopic technique. Mortality risk is low with this operation and results remain durable with published data up to 22 years. [2] Complications include problematic incontinence (this is less than 2% in contemporary series), retrograde ejaculation (in two-thirds) and a third reported erectile dysfunction (it is important to stress that the natural history of impotence in elderly men remains unknown). Reoperation, usually with another TURP, is around 1-2% per year. The risk of TUR syndrome (dilutional hyponatremia from fluid absorption) has dramatically decreased (better awareness, reduced operating times and better perioperative assessment and care) and is less than 1%. Younger men with BOO, may only need an incision at the bladder neck or transurethral incision of the prostate, usually at the 5 and 7 0'clock positions rather than undergoing a complete TURP to alleviate BOO. This incision technique has been recommended for use in men with prostate gland volume of less than 30 ml and without significant prostatic middle lobes.
Figure 1: Endoscopiv view during TURP a) resection, b) diathermy

Click here to view


In an attempt to improve hemostasis, decrease length of catheterization and reduce TUR syndrome, bipolar TURP has become popular. The technique uses a specialized resectoscope loop, which contains both the active and return electrodes and allows resection in saline irrigation. Prostate tissue is heated indirectly by the heat from the ignition of the spark that occurs between the electrode loops. Contemporary results suggest there are lower rates of clot retention, catheterization, operating time, irrigation and TUR syndrome, but with similar surgical outcomes (international prostate symptom score (IPSS) scores, reoperation rates, etc.,) to TURP. Results appear to be durable and comparable to TURP up to 5 years. [3]

Transurethral vaporization of the prostate involves vaporization (by steam), subsequent desiccation and resultant coagulation [Figure 2] of prostatic tissue. This bipolar technique allows surgery with saline irrigation. There are many electrode designs available, for example a rollerball, and various loop configurations. At 1 year, complication rates are similar to TURP. Similar to TURP, vaporization-resection of the prostate has also been described.
Figure 2: Endoscopic view during TUVP

Click here to view



   Laser surgery Top


Types of lasers used for BPH surgery by either coagulating, vaporizing or enucleating the prostate:

  • Potassium titanyl phosphate (KTP): neodymium (Nd): yttrium-aluminum-garnet (YAG) and lithium borate (LBO): Nd: YAG
  • Diode lasers
  • Holmium (Ho): YAG (Holmium laser enucleation of the prostate [HoLEP])
  • Thulium (Tm): YAG (Thulium laser enucleation of the prostate [ThuLEP] or Thulium vapoenucleation of the prostate [ThuVEP]).


KTP lasers have been used for photoselective vaporization of the prostate (PVP). The power of these lasers has increased since their introduction into prostate surgery, rising from 60 watt (W) to 80 W and more recently 180 W. Two randomized controlled trials (RCT) comparing TURP and 80 W PVP show similar [4] or improved flow rates [5] at up to 1 year follow-up. KTP PVP with 80 W has also shown comparative results with open prostatectomy. [6] LBO PVP has shown similar short-term equivalence to TURP. Both KTP and LBO emit green light and have been shown to reduce intraoperative blood loss and have reduced post-operative blood transfusion rates when compared to TURP. Stricture, retrograde ejaculation, and retreatment rates appear similar to TURP.

Much of the data on diode lasers refer to the 980 nm laser diode. These prospective studies with follow-up to 1 year show improvement in flow rates and a reduction in post-void residuals and prostate specific antigen. However, as this technique is associated with higher rates of bladder neck stricture or obstruction from necrotic tissue, it is rarely performed.

The high temperatures generated by the holmium laser create bubbles of steam which tears tissue apart but with resultant excellent hemostasis. Initially holmium lasers were used to vaporize or ablate the prostate (HoLAP), then used to resect the prostate (HoLRP) and now enucleation of prostate lobes (HoLEP). In the latter technique, the lobes are pushed into the bladder and then morcellated [Figure 3]. There have been 6 RCT'S comparing HoLEP with TURP and one comparing HoLEP with open prostatectomy. Essentially there is no statistically significant difference between HoLEP and TURP in improving symptom scores and QOL scores at up to 7 years. [7],[8] HoLEP showed greater improvement in flow rates at 1 year, but not at 7 years. Less blood loss and transfusion rates have been observed with HoLEP, but there is a significant learning curve. [9] HoLEP has a significantly longer operating time than TURP but this may be offset by shorter catheterization or hospital stay in some centers. At 5 years follow-up, HoLEP is also comparable with open prostatectomy. [10]
Figure 3: Endoscopic view during HoLEP

Click here to view


Thulium laser radiation allows better tissue vaporization than holmium and has also undergone similar evolution of techniques with vaporization, vaporesection (ThuVARP), vapoenucleation and laser enucleation (ThuVEP). At 1 year follow-up, currently there seems to be no difference in the outcome or complication rates between TURP and ThuVARP [11] and between HoLEP and ThuVEP [12] or HoLEP and ThuLEP. [13]

Laser techniques for treating BPH appear to have equivalent results to TURP with limited long-term data. They have superiority to TURP in anticoagulated patients where risks of bleeding and the need for post-operative blood transfusion remain low. As with bipolar TURP, saline irrigation can be used with laser surgery and this limits the development of hyponatremia (however, this is still possible following use of large volumes of irrigant, inappropriate post-operative fluid management and inappropriate SIADH release). The advantages of shorter catheterization and possible length of stay with laser surgery need to be offset against the increased operating costs (in terms of equipment and operating time) and learning curve. Prostate enucleation or megaresection is also possible using bipolar electrocautery. [14],[15]


   Open prostatectomy Top


Open prostatectomy allows enucleation of the hyperplastic prostatic adenoma. Initially performed by a perineal approach, this was superseded by Freyer's suprapubic transvesical approach, [16] Millin's retropubic transcapsular prostatectomy [17] and more recently laparoscopic [18] and robotic-assisted [19] approaches.

Prostatectomy still holds a strong place in BPH surgery in many countries where resources, endourological equipment and experience is not available. Simple prostatectomy provides good functional outcome with excellent long-term improvements in flow rates, postvoid residuals, and symptom scores. [20] Disadvantages include a longer operating time, and hospital stay and recovery, need for a lower midline incision and higher post-operative bleeding potential. In men with very large prostates, this type of surgery has largely been replaced by endourological laser techniques. However, in men with urethral disease (e.g.following hypospadias repair and/or on-going stricture disease), or with large bladder calculi or in men with fixed hips that do not allow flexion, open prostatectomy maybe necessary.


   Heat generation Top


A number of minimally invasive techniques have been tried and have fallen out of general use, but they do have a role in the office setting. These techniques involve applying various heat sources to the prostate to cause necrosis and sloughing of prostate tissue. These techniques have been marred by significant post-operative irritative urinary symptoms and dysuria and high re-operation rates and are therefore not in common practice or appear within recommended guidelines. Heat sources that have been tried include transurethral microwave thermotherapy (TUMT), transurethral needle ablation (TUNA), high intensity focused ultrasound and water induced thermotherapy. Pulsed electromagnetic radiofrequency has also been investigated. [21] This investigational study showed a greater improvement (than an alpha-blocker) in symptom scores and prostate volume when patients attended 30 min session daily for 2 weeks. TUNA and TUMT result in less favorable outcome when compared to TURP and have a higher retreatment rate in low quality cohort studies; however given that these procedures are safe with low peri-operative complications, they have a role in the office setting and have been recommended in American Urological and European Urological Association guidelines.


   Injection therapy Top


Transurethral ethanol ablation involves endoscopic injection of dehydrated ethanol (98% concentration) at 4-8 sites in the prostate. This can be delivered transurethrally, transperineally or transrectally. As above, this results in coagulative necrosis and subsequent prostate gland volume reduction. As above, symptom scores and flow rates do improve but again, a high reintervention rate is observed (single center series with short follow-up only have been described). [22],[23] Significant adverse events have been noted with this technique including bladder neck necrosis and ureteric injury requiring reimplantation. Botulinum toxin has also been injected into the prostate. Administration routes described include transperineal ultrasound guided injection as well as transurethral and transrectal routes. Short-term improvement has been observed in symptom scores in medically unfit patients. [24] Mechanism of action of the toxin for prostatic injection remains unknown; it may work locally or centrally, through muscle relaxation or by prostate apoptosis and longer term volume reduction. Potential adverse effects of the need for repeated injection into prostate tissue is also unknown and potentially alarming. Hence, currently this therapy is experimental.


   Mechanical devices Top


Initially, intraprostatic stents were used for patients who were not fit enough for surgical intervention and did not want to stay permanently catheterized. A variety of stent material exists and this includes self-retaining spiral stents, malleable stents and heat-expandable stents. Early results suggested reasonable longevity in improvement in symptoms scores, but this was offset by high rates of stent repositioning and stent removal with symptoms of hematuria and perineal pain. Urolume is a permanent stent that promotes epithelialization of the urethra over the stent and has been used with reasonable success in medically unfit patients with AUR or with marked LUTS. Complications include irritative LUTS and painful ejaculation necessitating device removal. [25]

The urethral lift technique pulls the lateral lobes of the prostate laterally toward the capsule to increase the size of the urethral lumen. Its advantage is that this technique causes immediate relief of obstruction with minimal morbidity. With a cystoscope and a custom implant delivery device (The UroLift System ® ), a non-absorbable monofilament suture with a nitinol capsular tab is inserted in an anterolateral fashion to compress the lateral prostatic lobes. Additional implants are then placed as required to achieve a visually open urethral lumen [Figure 4]. A key advantage of this emerging technique is that it can be performed with local anesthesia and oral sedation. Complications include hematuria, dysuria and irritative urinary symptoms; retrograde ejaculation is rare. Later complications uncommonly include UTI and prostatitis and transient erectile dysfunction. TURP is still possible at a later stage. Short-term results show a 40% reduction in IPSS, 40-50% improvement in QOL scores and 30% improvement in peak flow rates. This improvement occurs at 2 weeks and appears to be sustained at 2 years. [26],[27],[28]
Figure 4: Diagrammatic representation of UroLift

Click here to view



   Conclusions Top


A number of surgical treatment options exist for BPH [Table 1]. None have realistically improved outcomes in the long-term compared with TURP although improvements have been made on improving surgical morbidity and time in hospital. Indications for BOO surgery are well-defined, but questions remain in this area. [29] We do not what specific elements of BOO result in damage to the urinary tract, how does BPH contribute to BOO and how much prostate volume reduction is necessary to relieve BOO or LUTS. BOO surgery is more successful in men who suffer from confirmed BOO, [30] but untreated BOO does not always result in long-term loss of bladder function or improvement in LUTS. [31] Finally, those with underactivity prior to surgery may continue to suffer from bladder underactivity and its associated LUTS after BOO surgery. [32] It is clear that appropriate counselling is necessary in all men who undergo BPH surgery.
Table 1: Summary of BPH surgical techniques (see text for explanation of abbreviations; levels of evidence is listed in brackets for the place in current common management pathways)

Click here to view


 
   References Top

1.Emberton M, Neal DE, Black N, Harrison M, Fordham M, McBrien MP, et al. The National Prostatectomy Audit: The clinical management of patients during hospital admission. Br J Urol 1995;75:301-16.  Back to cited text no. 1
    
2.Reich O, Gratzke C, Stief CG. Techniques and long-term results of surgical procedures for BPH. Eur Urol 2006;49:970-8.  Back to cited text no. 2
    
3.Xie CY, Zhu GB, Wang XH, Liu XB. Five-year follow-up results of a randomized controlled trial comparing bipolar plasmakinetic and monopolar transurethral resection of the prostate. Yonsei Med J 2012;53:734-41.  Back to cited text no. 3
    
4.Bouchier-Hayes DM, Anderson P, Van Appledorn S, Bugeja P, Costello AJ. KTP laser versus transurethral resection: Early results of a randomized trial. J Endourol 2006;20:580-5.  Back to cited text no. 4
    
5.Horasanli K, Silay MS, Altay B, Tanriverdi O, Sarica K, Miroglu C. Photoselective potassium titanyl phosphate laser vaporization versus transurethral resection of the prostate for prostates larger than 70 mL: A short-term prospective randomized trial. Urology 2008;71:247-51.  Back to cited text no. 5
    
6.Skolarikos A, Papachristou C, Athanasiadis G, Chalikopoulos D, Deliveliotis C, Alivizatos G. Eighteen-month results of a randomized prospective study comparing transurethral photoselective vaporization with transvesical open enucleation for prostatic adenomas greater than 80 cc. J Endourol 2008;22:2333-40.  Back to cited text no. 6
    
7.Lourenco T, Armstrong N, N›Dow J, Nabi G, Deverill M, Pickard R, et al. Systematic review and economic modelling of effectiveness and cost utility of surgical treatments for men with benign prostatic enlargement. Health Technol Assess 2008;12:iii, ix-x, 1-146, 169-515.  Back to cited text no. 7
    
8.Gilling PJ, Wilson LC, King CJ, Westenberg AM, Frampton CM, Fraundorfer MR. Long-term results of a randomized trial comparing holmium laser enucleation of the prostate and transurethral resection of the prostate: Results at 7 years. BJU Int 2012;109:408-11.  Back to cited text no. 8
    
9.Martin AD, Nunez RN, Humphreys MR. Bleeding after holmium laser enucleation of the prostate: Lessons learned the hard way. BJU Int 2011;107:433-7.  Back to cited text no. 9
    
10.Kuntz RM, Lehrich K, Ahyai SA. Holmium laser enucleation of the prostate versus open prostatectomy for prostates greater than 100 grams: 5-year follow-up results of a randomised clinical trial. Eur Urol 2008;53:160-6.  Back to cited text no. 10
    
11.Xia SJ, Zhuo J, Sun XW, Han BM, Shao Y, Zhang YN. Thulium laser versus standard transurethral resection of the prostate: A randomized prospective trial. Eur Urol 2008;53:382-89.  Back to cited text no. 11
    
12.Bach T, Xia SJ, Yang Y, Mattioli S, Watson GM, Gross AJ, et al. Thulium: YAG 2 mum cw laser prostatectomy: Where do we stand? World J Urol 2010;28:163-8.  Back to cited text no. 12
    
13.Zhang F, Shao Q, Herrmann TR, Tian Y, Zhang Y. Thulium laser versus holmium laser transurethral enucleation of the prostate: 18-month follow-up data of a single center. Urology 2012;79:869-74.  Back to cited text no. 13
    
14.Liao N, Yu J. A study comparing plasmakinetic enucleation with bipolar plasmakinetic resection of the prostate for benign prostatic hyperplasia. J Endourol 2012;26:884-8.  Back to cited text no. 14
    
15.Geavlete B, Stanescu F, Iacoboaie C, Geavlete P. Bipolar plasma enucleation of the prostate vs open prostatectomy in large benign prostatic hyperplasia cases-A medium term, prospective, randomized comparison. BJU Int 2013;111:793-803.  Back to cited text no. 15
    
16.Freyer PJ. Total enucleation of the prostate: A further series of 550 cases of the operation. Br Med J 1919;1:121-1202.  Back to cited text no. 16
[PUBMED]    
17.Millin T. Retropubic prostatectomy; a new extravesical technique; report of 20 cases. Lancet 1945;2:693-6.  Back to cited text no. 17
[PUBMED]    
18.Mariano MB, Tefilli MV, Graziottin TM, Morales CM, Goldraich IH. Laparoscopic prostatectomy for benign prostatic hyperplasia: A six-year experience. Eur Urol 2006;49:127-31.  Back to cited text no. 18
    
19.Sotelo R, Clavijo R, Carmona O, Garcia A, Banda E, Miranda M, et al. Robotic simple prostatectomy. J Urol 2008;179:513-5.  Back to cited text no. 19
    
20.Varkarakis I, Kyriakakis Z, Delis A, Protogerou V, Deliveliotis C. Long-term results of open transvesical prostatectomy from a contemporary series of patients. Urology 2004;64:306-10.  Back to cited text no. 20
    
21.Giannakopoulos XK, Giotis C, Karkabounas SCh, Verginadis II, Simos YV, Peschos D, et al. Effects of pulsed electromagnetic fields on benign prostate hyperplasia. Int Urol Nephrol 2011;43:955-60.  Back to cited text no. 21
    
22.Sakr M, Eid A, Shoukry M, Fayed A. Transurethral ethanol injection therapy of benign prostatic hyperplasia: Four-year follow-up. Int J Urol 2009;16:196-201.  Back to cited text no. 22
    
23.El-Husseiny T, Buchholz N. Transurethral ethanol ablation of the prostate for symptomatic benign prostatic hyperplasia: Long-term follow-up. J Endourol 2011;25:477-80.  Back to cited text no. 23
    
24.Sacco E, Bientinesi R, Marangi F, Totaro A, D'Addessi A, Racioppi M, et al. Patient-reported outcomes in men with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia treated with intraprostatic OnabotulinumtoxinA: 3-month results of a prospective single-armed cohort study. BJU Int 2012;110:E837-44.  Back to cited text no. 24
    
25.Bajoria S, Agarwal SA, White R, Zafar F, Williams G. Experience with the second generation UroLume prostatic stent. Br J Urol 1995;75:325-7.  Back to cited text no. 25
    
26.Chin PT, Bolton DM, Jack G, Rashid P, Thavaseelan J, Yu RJ, et al. Prostatic urethral lift: Two-year results after treatment for lower urinary tract symptoms secondary to benign prostatic hyperplasia. Urology 2012;79:5-11.  Back to cited text no. 26
    
27.Barkin J, Giddens J, Incze P, Casey R, Richardson S, Gange S. UroLift system for relief of prostate obstruction under local anesthesia. Can J Urol 2012;19:6217-22.  Back to cited text no. 27
    
28.McNicholas TA, Woo HH, Chin PT, Bolton D, Fernández Arjona M, Sievert KD, et al. Minimally invasive prostatic urethral lift: Surgical technique and multinational experience. Eur Urol 2013;64:292-9.  Back to cited text no. 28
    
29.Oelke M, Kirschner-Hermanns R, Thiruchelvam N, Heesakkers J. Can we identify men who will have complications from benign prostatic obstruction? ICI-RS 2011. Neurourol Urodyn 2012;31:322-6.  Back to cited text no. 29
    
30.Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P. The natural history of lower urinary tract dysfunction in men: Minimum 10-year urodynamic followup of transurethral resection of prostate for bladder outlet obstruction. J Urol 2005;174:1887-91.  Back to cited text no. 30
    
31.Thomas AW, Cannon A, Bartlett E, Ellis-Jones J, Abrams P. The natural history of lower urinary tract dysfunction in men: Minimum 10-year urodynamic follow-up of untreated bladder outlet obstruction. BJU Int 2005;96:1301-6.  Back to cited text no. 31
    
32.Al-Hayek S, Thomas A, Abrams P. Natural history of detrusor contractility - Minimum ten-year urodynamic follow-up in men with bladder outlet obstruction and those with detrusor. Scand J Urol Nephrol Suppl 2004;(215):101-8.  Back to cited text no. 32
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]

This article has been cited by
1 Photoactive dye-enhanced tissue ablation for endoscopic laser prostatectomy
Minwoo Ahn,Nguyen Trung Hau,Nguyen Van Phuc,Junghwan Oh,Hyun Wook Kang
Lasers in Surgery and Medicine. 2014; : n/a
[Pubmed] | [DOI]



 

Top
Print this article  Email this article
 

    

 
   Search
 
  
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Article in PDF (3,480 KB)
    Citation Manager
    Access Statistics
    Reader Comments
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
   Introduction
    Endoscopic elect...
   Laser surgery
   Open prostatectomy
   Heat generation
   Injection therapy
   Mechanical devices
   Conclusions
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed4117    
    Printed57    
    Emailed4    
    PDF Downloaded302    
    Comments [Add]    
    Cited by others 1    

Recommend this journal

HEALTHWARE INDIA