This document summarizes intralesional treatments for Peyronie's disease, including interferon, verapamil, and collagenase clostridium histolyticum (CCH). It describes the pathophysiology of PD and reviews definition, epidemiology, and standard treatment options. Two large randomized controlled trials of CCH showed statistically significant improvements in penile curvature deformity and bother scores compared to placebo. However, CCH treatment requires up to 8 injections over 8 months and is associated with adverse events like pain, hematoma, and swelling. Overall, intralesional therapies may provide benefit for select PD patients but require consideration of treatment burden and costs.
Case Study: Recurrent myoma with menorrhagiaLyndon Woytuck
A case study on a patient presenting with menorrhagia in a history of recurrent myomatous disease. The patient details have been changed to anonymize the individual.
Dermoscopy or epiluminescence microscopy
A simple, noninvasive method to examine the subsurface features of the skin.
Structures seen
Epidermis
Dermoepidermal junction
Superficial dermis
3 types of dermoscope
1.Nonpolarized devices
2.Polarized devices
3.Hybrid devices
Dermoscopy is used in:
1.Evaluating pigmented skin lesions
2.Evaluating nonpigment skin lesions
3.Entomodermoscopy
4.Trichoscopy
5.Onychoscopy
different dermoscopic patterns are used to diagnose the dermatological diseases are
1. melanocytic patterns:
Pigmentary patterns: typical pigment pattern, atypical pigment patter, pseudonetwork
dots and globules
Blue white veil
star brust pattern
2, Non melanocytic pattern:
milia like cyst
comedo like opening
3. vascular patterns:
lacunae
arborizing vessels
comma like vessels
corkscrew vessel
red dots
glomerular vessels
linear vessels
etc
Case Study: Recurrent myoma with menorrhagiaLyndon Woytuck
A case study on a patient presenting with menorrhagia in a history of recurrent myomatous disease. The patient details have been changed to anonymize the individual.
Dermoscopy or epiluminescence microscopy
A simple, noninvasive method to examine the subsurface features of the skin.
Structures seen
Epidermis
Dermoepidermal junction
Superficial dermis
3 types of dermoscope
1.Nonpolarized devices
2.Polarized devices
3.Hybrid devices
Dermoscopy is used in:
1.Evaluating pigmented skin lesions
2.Evaluating nonpigment skin lesions
3.Entomodermoscopy
4.Trichoscopy
5.Onychoscopy
different dermoscopic patterns are used to diagnose the dermatological diseases are
1. melanocytic patterns:
Pigmentary patterns: typical pigment pattern, atypical pigment patter, pseudonetwork
dots and globules
Blue white veil
star brust pattern
2, Non melanocytic pattern:
milia like cyst
comedo like opening
3. vascular patterns:
lacunae
arborizing vessels
comma like vessels
corkscrew vessel
red dots
glomerular vessels
linear vessels
etc
Melasma| Melasma and its Treatment| Facial Pigmentation| Post-Pregnancy Pigm...Dr. Rajat Sachdeva
Melasma, Pigmentation on facial skin, most commonly occur on the face of female and in Dark Skin Races.
Treatment for melasma, Sun protection, avoid waxing, Tretinoin, Hydroquinone, Corticosteroid, Azeloic Acid, Glycolic Acid, Chemical Peels, Microdermabrasion, Laser Intensed Pulse Light,
A powerpoint presentation that I presented during my class reporting. The pictures and the informations found in this ppt were gathered from different sources in internet and from a powerpoint presentation uploaded in the slideshare by Brian Cosby.
A discussion on various photodermatoses including sun burns, porphyria, actinic chelitis, hydroa vacciniforme and chronic actinic dermatitis. Sun tan and skin color types. Affect of Sunlight on the skin. Useful for medical residents, dermatologists and nurse. Useful in exam preparation.
Glands in skin | Skin Specialist in Zirakpur | Dr. Isha V.Mittal | +91-72-93-...Dr. Isha V.Mittal
Gland in skin are accessory structure of skin. It originate in dermis layer of skin. Protrude through the epidermis layer of the skin resulting in sweat and sebum emerging from skin surface.
Type- exocrine gland ....
Dr. Isha V. Mittal is one of the top skin specialist Doctor / dermatologist in zirakpur, Panchkula and Dhakoli region. She is a Gold Medalist in Dermatology/ Skin Speciality and is a leading Dermatologist , Cosmetologist , Laser specialist and hair transplant expert.
CHRONIC PELVIC PAIN can affect men, MORE common (60%) in women, lifelong vs. acquired, generalized vs. situational, psychological factors, physical Contact SlenderImage@gmail.com for Consulting & Speaking - P.Anderson 323-486-3770
Melasma| Melasma and its Treatment| Facial Pigmentation| Post-Pregnancy Pigm...Dr. Rajat Sachdeva
Melasma, Pigmentation on facial skin, most commonly occur on the face of female and in Dark Skin Races.
Treatment for melasma, Sun protection, avoid waxing, Tretinoin, Hydroquinone, Corticosteroid, Azeloic Acid, Glycolic Acid, Chemical Peels, Microdermabrasion, Laser Intensed Pulse Light,
A powerpoint presentation that I presented during my class reporting. The pictures and the informations found in this ppt were gathered from different sources in internet and from a powerpoint presentation uploaded in the slideshare by Brian Cosby.
A discussion on various photodermatoses including sun burns, porphyria, actinic chelitis, hydroa vacciniforme and chronic actinic dermatitis. Sun tan and skin color types. Affect of Sunlight on the skin. Useful for medical residents, dermatologists and nurse. Useful in exam preparation.
Glands in skin | Skin Specialist in Zirakpur | Dr. Isha V.Mittal | +91-72-93-...Dr. Isha V.Mittal
Gland in skin are accessory structure of skin. It originate in dermis layer of skin. Protrude through the epidermis layer of the skin resulting in sweat and sebum emerging from skin surface.
Type- exocrine gland ....
Dr. Isha V. Mittal is one of the top skin specialist Doctor / dermatologist in zirakpur, Panchkula and Dhakoli region. She is a Gold Medalist in Dermatology/ Skin Speciality and is a leading Dermatologist , Cosmetologist , Laser specialist and hair transplant expert.
CHRONIC PELVIC PAIN can affect men, MORE common (60%) in women, lifelong vs. acquired, generalized vs. situational, psychological factors, physical Contact SlenderImage@gmail.com for Consulting & Speaking - P.Anderson 323-486-3770
Prematür Ejakülasyon (erken boşalma) erkeklerde en sık görülen cinsel fonksiyon bozukluğudur. Bu sunumda prematür ejakülasyon nedenleri ve sınıflaması anlatılacaktır.
Erektil Disfonksiyon (sertleşme bozukluğu, iktidarsızlık), özellikle orta yaşın üzerindeki erkeklerde sık rastlanılan bir sorundur. Bu sunuda ereksiyon problemi yaşayan hastalar hekime başvurduklarında yapılacak işlemler özetlenmektedir.
Sexual function is essential to good health and well-being in men. The relationship between male sexual function, pelvic floor function, and pelvic pain is complex and only beginning to be appreciated.
Presentation on "Medical and Non-surgical Treatment of Peyronie's Disease" by David Ralph, BSc, MS, FRCS (Men's Health International Surgical Center in Switzerland) at the 5th Emirates International Urological Conference in Dubai. (Decembre 2016)
Presentation on "Peyronie's disease: a tailored surgical procedure for every patient" by Carlo Bettocchi, M.D, FECSM (Men's Health International Surgical Center in Switzerland) at the 5th Emirates International Urological Conference in Dubai. (Decembre 2016)
Darren M. Brenner, MD, Assistant Professor of Medicine and Surgery at Northwestern University's Feinberg School of Medicine discusses fecal incontinence in scleroderma patients including its prevalence, diagnostics, types and therapeutics.
2020 OA Vision: Emerging Therapeutics on the OA landscapeOARSI
Philip Conaghan MBBS PhD FRACP FRCP
Director, Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds
Deputy Director, NIHR Leeds Biomedical Research Centre
Premature Ejaculation is the most common form of sexual dysfunction and currently available therapies are not optimal. Recently, several biotech companies and researchers developed mechanical devices for the treatment of premature ejaculation but further clinical data are warranted.
Treatment of spinal tuberculosis - presented at the Postgraduate teaching course held at KEM Hospital, Mumbai in March 2016.
The talk highlights steps in diagnostic workup and treatment algorithm for management of spinal tuberculosis.
Please see notes attached to clinical slides. They contain details about clinical presentation and treatment approach chosen for the case presented
Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms.
Presented at AHA by: Faiez Zannad, M.D., Ph.D., John J.V. McMurray, M.D., Henry Krum, M.B., PhD., Dirk J. van Veldhuisen, M.D.,Ph.D., Karl Swedberg, M.D., Ph.D, Harry Shi, M.S., John Vincent, M.B., PhD., Stuart J Pocock, Ph.D. and Bertram Pitt, M.D. for the EMPHASIS-HF Study Group * Eplerenone in Mild Patients Hospitalization And SurvIval Study in Heart Failure
Courtesy of http://www.cardiovascularbusiness.com
Eletro Stimulation of Lower Esophageal Sphincter on GERD treatment Manoel Galvao Neto
First in man Studies in a novel, unique and disruptive technology to surgicaly treat Reflux desease (GERD) without anatomical changes by laparoscopic implant of leads on the esophagi-gastric junction (EGJ) followed by stimulation of a pace=maker
Similar to Intralesional treatment in Peyronie's Disease (20)
Erkek infertilitesi (kısırlığı) son yıllarda sıklığı giderek artan bir sağlık sorunudur ve her yıl infertilite nedeniyle yardımcı üreme tekniklerine başvuran çiftlerin sayıları artmaktadır. Batı ülkelerinde yaşayan erkeklerin sperm sayılarının son 50 yılda yaklaşık olarak yarı yarıya azaldığı dikkate alındığında, çevresel faktörlerin sperm sayı ve kalitesi üzerindeki etkisi önem kazanmaktadır.
Postprostatectomy sexual problems are not limited to erectile dysfunction. Patients and surgeons must also pay attention to orgasmic problems, ejaculatory pain, infertility, climacturia and etc.
Penile Rehabilitation after Prostate Cancer Treatment: Is there an Analogy to...Ege Can Serefoglu MD FECSM
Sexual dysfunction follows radical pelvic surgery in both sexes. Nerve sparing surgery is possible for both male and female pelvic cancers. Nature and pathophysiology of sexual dysfunction varies in men and women. Clinical evidence for rehabilitation is limited in men, and absent in women. However, every cancer survivor women deserves sex. It is our responsibility to help them
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
HOT NEW PRODUCT! BIG SALES FAST SHIPPING NOW FROM CHINA!! EU KU DB BK substit...GL Anaacs
Contact us if you are interested:
Email / Skype : kefaya1771@gmail.com
Threema: PXHY5PDH
New BATCH Ku !!! MUCH IN DEMAND FAST SALE EVERY BATCH HAPPY GOOD EFFECT BIG BATCH !
Contact me on Threema or skype to start big business!!
Hot-sale products:
NEW HOT EUTYLONE WHITE CRYSTAL!!
5cl-adba precursor (semi finished )
5cl-adba raw materials
ADBB precursor (semi finished )
ADBB raw materials
APVP powder
5fadb/4f-adb
Jwh018 / Jwh210
Eutylone crystal
Protonitazene (hydrochloride) CAS: 119276-01-6
Flubrotizolam CAS: 57801-95-3
Metonitazene CAS: 14680-51-4
Payment terms: Western Union,MoneyGram,Bitcoin or USDT.
Deliver Time: Usually 7-15days
Shipping method: FedEx, TNT, DHL,UPS etc.Our deliveries are 100% safe, fast, reliable and discreet.
Samples will be sent for your evaluation!If you are interested in, please contact me, let's talk details.
We specializes in exporting high quality Research chemical, medical intermediate, Pharmaceutical chemicals and so on. Products are exported to USA, Canada, France, Korea, Japan,Russia, Southeast Asia and other countries.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
3. Financial and Other Disclosures
Off-label use of drugs, devices, or other agents: None or FILL IN HERE; including your local
regulatory agency, such as FDA, EMA, etc.
Data from IRB-approved human research is presented [or state: “is not”]
3
I have the following financial interests or
relationships to disclose:
Disclosure code
No financial relationships N
6. Definition & Epidemiology of PD
Peyronie's disease (PD) is a fibrotic disorder of the tunica
albuginea of the penis.
Naming has been attributed to François Gigot de la Peyronie
(surgeon to king Louis XIV of France)
Memoire sur quelques obstacles qui s'opposent d l'Ejaculation
naturelle de la semence (Memoires de l'Academie royale de chirurgie - 1743)
7. Definition & Epidemiology of PD
Scarring/plaque of the tunica albuginea with excessive abnormal
collagen deposition
Potential symptoms:
• Curvature – 80-91%
• Nodule – 15%
• Pain – 3-22%
• ED – 15-28%
• Penile shortening – 14%
8-9% report preceding trauma
More common in white males (OR 8.47)
15-58% of patients are unaware of disease (incidental discovery)
Bella A. J Sex Med 2007; Kadioglu A, et al. J Uro 2002; Rhoden EL, et al. J Sex Med 2010; Kadioglu A, et al. IJIR 2004; Chung E, et al. BJUI 2012.
8. Definition & Epidemiology of PD
Prevalence varies:
In the general population: 0.4-13%
Among patients:
ED 7.9%
DM 8.1%
ED + DM 20.3%
Post-RP 15.9%
4 – Rhoden EL, et al: 2001 IJIR.
5– La Pera G, et al: 2001 Eur Urol.
6 – Mulhall JP, et al: 2004 J Urol.
1 – Lindsay MB, et al: 1991 J Urol.
2 – DiBenedetti DB, et al: 2011 Adv Urol.
3 - Schwarzer U, et al: 2001 BJU Int.
10. Pathophysiology: What Is Collagen?
• Primary extracellular structural component
• All collagens contain a triple helix:
• Composed of three polypeptide chains
• Contains Gly-X-Y motifs (X and Y normally proline or
hydroxyproline)
• The triple helix
• Requires extensive post-translational modification (“hard to
make”)
• Is extremely stable (“hard to break”)
14. • Clinicians should NOT offer:
• Vitamin E, tamoxifen, procarbazine, omega-3
fatty acids, or Vit E w/ L-carnitine
• Electromotive therapy w/ verapamil
• Shock wave therapy for curvature or plaque
size (may offer for pain)
• Radiotherapy
Treatment
AUA Guidellines on PD 2015
15. Clinicians may administer collagenase w/ modeling
for pts with:
• Stable disease
• 30-90°
• Intact erectile function w/ or w/o meds
Clinicians may offer intralesional interferon or
verapamil
Treatment
AUA Guidellines on PD 2015
18. Intralesional Interferon Alpha-2b
1 RCT, 1 randomized study (w/o placebo), 8
observational studies
Single-blind, multicenter, placebo controlled, parallel arm
N=103, age 55, PD >12 mo, curvature > 30°
Bi-weekly x 12 injections
Curvature reduction: 13.5° (IFN) vs 4.5°
Plaque size reduction: 2.6 cm2 (IFN) vs 0.9 cm2
Pain improvement: 67.7% (IFN) vs 28.1%
Hellstrom WJ, et al: 2006 J Urol.
19. Intralesional Interferon Alpha-2b
Role in men w/
Stable disease
Curvature >30°
Non-calcified plaque
ventral curvatures, penile pain
Pts should be informed regarding expected average curvature
reduction of 13.5 degrees (only 9 degrees different than
placebo)
Clinicians should counsel pts prior to tx about potential
adverse events
sinusitis, flu-like symptoms, and minor penile swelling.
AUA Guidellines on PD 2015
20. Intralesional Verapamil
2 RCTs, 8 observational studies
1. 10 – 27 mg intralesional verapamil weekly for 6 months1
N=14
Randomized, single-blind, placebo controlled
significant decrease in plaque length, width, and volume in the
verapamil group (but not in the placebo group)
2. 10 mg verapamil, twice weekly for 12 weeks2
N=80,
Randomized, single-blind, placebo controlled
No significant differences in curvature, pain, plaque size, or sexual
function
1- Rehman J et al. Urology 1998
2 – Shirazi M, et al. Int Urol Nephrol. 2009
21. Intralesional Verapamil
Clinicians who consider the use of intralesional
verapamil as a treatment for symptoms of PD should
fully consider the weakness of the evidence
demonstrating its efficacy.
Clinicians should counsel pts prior to tx about potential
adverse events,
penile bruising, dizziness, nausea, and pain at the injection site.
AUA Guidellines on PD 2015
22. 2014 – The Year of Collagenase
Clostridium Histolyticum
23. Surgical specimens of excised plaque & normal tunica
Injection into dorsal tunica (400 U clostridial collagenase in 0.2 mL)
Incubation for 24 h before tissue processing
Localized complete lysis of collagen (note sharp demarcation from normal tissue)
Gelbard MK, et al. Urol Res 1982
Hematoxylin & eosin stain
(collagen = dense pink stain)
Van Gieson’s stain
(collagen = dark red stain)
CCH injection into the Plaque
24. Amino acid release to buffer (ninhydrin) after CCH
injection into the plaque
Gelbard MK, et al. Urol Res 1982
25. Complete disruption of plaque collagen
• Surgically excised plaque bisected:
• Half was treated with collagenase (400 U in 0.1 mL)
• Half was injected with saline (0.1 mL)
• Incubation for 24 h before tissue processing
• Note difference in size & morphology (both are same magnification)
Saline Collagenase
Gelbard MK, et al. Urol Res 1982
27. CCH in PD
Investigation for Maximal Peyronie’s Reduction Efficacy
and Safety Studies (IMPRESS I + II)
2 large double-blind, randomized, placebo controlled phase 3
studies
Conducted at 64 sites in the U.S. and Australia
417 + 415 subjects with penile curvature deformity from 20 to
90o
Randomized to receive up to 8 injections of XIAFLEX 0.58
mg or placebo in 2:1 ratio
maximum of 4 treatment cycles, each separated by 6 weeks
Gelbart M, et al. J Urol. 2013
28.
29. CCH Improved Penile Curvature Deformity
over 52 Weeks
20
25
30
35
40
45
50
55
XIAFLEX Placebo XIAFLEX Placebo
Baseline
EOS
37.6%
21.3%
15.2%
30.5%
DegreesofCurvatureDeformity
P=0.0005 P=0.0059
IMPRESS I IMPRESS II
N=199 N=104 N=202 N=107
30. CCH Improved Penile Curvature Deformity
over 52 Weeks
Baseline curvature deformity – 48o
End of study curvature deformity – 28o (38% improvement)
Gelbart M, et al. J Urol. 2013
31. CCH Improved PDQ Bother
Domain Score over 52 Weeks
PDQBotherScale
P=0.0451 P=0.0496
IMPRESS I IMPRESS II
2.4
(32.4%)
1.6
(20.7%
)
N=199 N=104 N=202 N=107
Gelbart M, et al. J Urol. 2013
32. Most Common Adverse Events > 5%
ITT analysis/Preferred term listed
IMPRESS I IMPRESS II
XIAFLEX Placebo XIAFLEX Placebo
N = 277
n (%)
N = 140
n (%)
N = 274
n (%)
N = 141
n (%)
Any non-serious AE 256 (92.4) 81 (57.9) 252 (92.0) 88 (62.4)
Penile hematoma 171 (61.7) 19 (13.6) 165 (60.2) 22 (15.6)
Penile Pain 119 (41.2) 11 (7.9) 96 (35.0) 8 (5.7)
Penile swelling 114 (41.2) 1 (0.7) 95 (34.7) 2 (1.4)
Injection site pain 70 (25.3) 5 (3.6) 41 (15.0) 4 (2.8)
Penile hemorrhage 60 (21.7) 14 (10.0) 43 (15.7) 1 (0.7)
Injection site hematoma 45 (16.2) 14 (10.0) 61 (22.3) 16 (11.3)
33. Most Common Adverse Events > 5%
ITT analysis/Preferred term listed
IMPRESS I IMPRESS II
XIAFLEX Placebo XIAFLEX Placebo
N = 277
n (%)
N = 140
n (%)
N = 274
n (%)
N = 141
n (%)
Penile edema 45 (16.2) 1 (0.7) 40 (14.6) 0 (0.0)
Injection site swelling 30 (10.8) 0(0.0) 35 (12.8) 2 (1.4)
Contusion 28 (10.1) 0 (0.0) 27 (9.9) 1 (0.7)
Ecchymosis 26 (9.4) 0 (0.0) 12 (4.4) 0 (0.0)
Blood blister 9 (3.2) 0 (0.0) 17 (6.2) 0 (0.0)
Injection site hemorrhage 15 (5.4) 10 (7.1) 10 (3.6) 3 (2.1)
34. Serious Adverse Events
ITT analysis/Preferred term listed
IMPRESS I IMPRESS II
XIAFLEX Placebo XIAFLEX Placebo
N = 277
n (%)
N = 140
n (%)
N = 274
n (%)
N = 141
n (%)
Treatment emergent SAE 27 (9.7) 7 (5.0) 12 (4.4) 4 (2.8)
Treatment related SAE 3 (1.1) 0(0.0) 3 (1.1) 0 (0.0)
XIAFLEX Treatment Related SAEs
Hematoma 2 (0.7) 0 (0.0) 1 (0.4) 0 (0.0)
Corporal Rupture
(penile fracture)
1 (0.4) 0 (0.0) 2 (0.7) 0 (0.0)
35. Conclusions of IMPRESS trials
• CCH showed statistically significant improvements in
• penile curvature deformity (physical) [p-values of 0.0005 and
0.0059]
• PD bother (psychosocial) [p-values of 0.0451 and 0.0496]
• XIAFLEX is an effective FDA-approved biological therapy for the
treatment of PD
• How many pts drop out the study???
(pain, hematoma, swelling, 8 mo tx)
• Is a mean curvature reduction of 17° is “functionally” significant
for the patient?
• If the whole course of 8 injections is used, the cost would be >£8
000 (€11 200). (more than double compared with a tariff of £1
856 for a Nesbit procedure) (NHS England).
36. Conclusions
• PD is a common condition that can be both
physically and psychologically devastating for men
and their partners
• Intralesional interferon and verapamil treatment
may be effective.
• CCH showed statistically significant improvements
(17°) in penile curvature and PD bother
• It can be effective in PD patients with
• Dorsal curvature <50-60 degrees
• Without calcified plaque
• Reducing the number of treatment cycles needed
would make the treatment significantly more cost
effective.