Download infections-marek-szymanski-ed-2015

Uniwersytet Mikołaja Kopernika w Toruniu
Collegium Medicum w Bydgoszczy
Infections of the Urinary &
Reproductive Systems
dr hab. n. med. Marek Szymański
KATEDRA i KLINIKA POŁOŻNICTWA,
CHORÓB KOBIECYCH i GINEKOLOGII ONKOLOGICZNEJ
Structures of Reproductive System
• Females
– Urinary and reproductive systems
are distinct
23.2 Normal Biota of the Urinary
Tract
• Outer region of the urethra harbors some normal
biota
• Nonhemolytic streptococci, staphylocci,
corynebacteria, and some lactobacilli
• Normal Biota of the Male Genital Tract
– Same as described for urethra, since the urethra is the
terminal “tube”
• Normal Biota of the Female Genital Tract
– The vagina harbors a normal population of microbes
• Lactobacillusi species
• Candida albicans at low levels
Cystitis
• Cystitis: sudden onset of symptoms
– Pain in the pubic area
– Frequent urges to urinate even when the bladder is
empty
– Burning pain accompanying urination (dysuria)
– Cloudy urine
– Orange tinge to the urine (hematuria)
– Fever and nausea
– Back pain indicates kidneys may also be involved
23.4 Reproductive Tract Diseases
Caused by Microorganisms
• Many are transmitted through sexual
contact, but not all are
• Three broad categories of sexually
transmitted diseases
– Discharge diseases
– Ulcer diseases
– Wart diseases
Vaginitis and Vaginosis
•
•
•
•
Inflammation of the vagina
Vaginal itching to some degree
Burning and sometimes a discharge occurs
Symptoms depend on the etiologic agent
Candida albicans
• Normal biota living in low numbers
• If grows rapidly and causes a yeast
infection, white vaginal discharge occurs
Gardnerella species
• Infection called vaginosis rather than
vaginitis because inflammation in the
vagina does not occur
• Vaginal discharge with a very fishy odor,
especially fater sex
• Itching is common
Trichomonas vaginalis
• Asymptomatic infections in approximately
50% of females and males
• Some people experience long-term negative
effects
Discharge Diseases with Major
Manifestation in the Genitourinary
Tract
• Increase in fluid discharge in male and female
reproductive tracts
• Includes trichomoniasis, HIV, gonorrhea, and
Chlamydia infection
Gonorrhea
• N. gonorrhoeae is the etiologic agent- also
known as the gonococcus
• Symptoms in the male
– Urethritis, painful urination and a yellowish
discharge
– Can occasionally spread from the urethra to the
prostate gland and epididymis
– Scar tissue in the spermatic ducts during
healing can render a man infertile (rare)
Symptoms in the Female
• Likely that both urinary and genital tracts will
be infected
• Mucopurulent or bloody vaginal discharge
• Painful urination if urethra is affected
• Major complications occur when the infection
ascends from the vagina and cervix to higher
reproductive structures
– Salpingitis
– Pelvic inflammatory disease
Chlamydia
• Most common reportable infectious disease in the U.S.
• Majority of cases are asymptomatic
• Symptoms in males
– Inflammation of the urethra
– Symptoms mimicking gonorrhea
– Untreated infections may lead to epididymitis
• Symptoms in females
–
–
–
–
Cervicitis
Discharge
Salpingitis
May lead to PID
Genital Ulcer Diseases
• Three common infectious conditions
resulting in lesions on a person’s genitals
• Syphilis, chancroid, and genital herpes
• Having one of these diseases increases the
chances of infection with HIV because of
the open lesions
Syphilis
• Three distinct clinical stages: primary,
secondary, and tertiary
• Latent periods of varying duration also occur
• Transmissible during the primary and
secondary stages, and the early latency period
between secondary and tertiary
• Largely nontransmissible during late latent and
tertiary stages
Primary Syphilis
• Appearance of a hard chancre at the site of
entry of the pathogen (after an incubation
period of 9 days to 3 months)
• Lymph nodes draining the affected region
become enlarged and firm
• Chancre filled with spirochetes
• Chancre heals spontaneously in 3 to 6 weeks
but by then the spirochete has moved into the
circulation
Secondary Syphilis
• 3 weeks to 6 months after the chancre heals
• Many systems have been invaded
• Fever, headache, sore throat, followed by
lymphadenopathy and a red or brown rash that
breaks out on all skin surfaces
• Hair often falls out
• Lesions contain viable spirochetes and disappear
spontaneously in a few weeks
• Major complications occur in bones, hair follicles,
joints, liver, eyes, and brain
Latency and Tertiary Syphilis
• Highly varied latent period, can last for 20
years or longer
• Tertiary syphilis is rare because of the use of
antibiotics
• Major complications occur by this stage
• Cardiovascular syphilis- weakens the arteries
in the aortic wall
• Gummas develop in tissues such as the liver,
skin, bone, and cartilage
Congenital Syphilis
• From a pregnant woman’s circulation into
the placenta and fetal tissues
• Inhibits fetal growth
• Disrupts critical periods of development
Chancroid
• No systemwide effects
• Infection usually begins as a soft papule at
the point of contact
• Develops into a soft chancre (painful in
men, but may be unnoticed in women)
• Inguinal lymph nodes can become swollen
and tender
Wart Diseases
• Human papillomavirus (HPV)
– Causative agents of genital warts
– An individual can be infected with HPV without
having warts, however
• Molluscum Contagiosum
– Unclassified virus in the pox family
– Can take the form of skin lesions
– Wartlike growths on the mucous membranes or
skin of the genital area
Group B Streptococcus
“Colonization”- Neonatal Disease
• 10% to 40% of women in the U.S. are
colonized asymptomatically by group B
Streptococcus
• When these women become pregnant, about
half of their infants become colonized by the
bacterium during passage through the birth
canal
• Small percentage of infected infants
experience life-threatening bloodstream
infections, meningitis, or pneumonia
• Normally urine and urinary tract above bladder
are sterile
– Urethra contains normal resident flora
• Lactobacillus, Staphylococcus, Corynebacterium and
Streptococcus
• Normal flora varies in female genital tract
– Depends on hormones
• Lactobacillus
Urinary Tract Infections
May include any or all of the organs
•
•
•
•
Urethritis – inflammation of urethra
Cystits – inflammation of the urinary bladder
Ureteritis –inflammation of the ureters
Pyelonephritis – inflammation of the kidneys
• Causative agents:
– Usually intestinal flora
• E. coli – most common
• Proteus and Klebsiella
• Psudomonas
– Typically nosocomial
– Non-enteric bacteria
– Non-invasive and opportunistic
• Signs and Symptoms
– Dysuria – frequent, painful urination
– cloudy urine with foul odor; may have pale red color 9due to
blood in urine)
– Tenderness of pelvic area
– May have slight fever
• Prevention
–
–
–
–
Adequate fluid intake (2-4 liters daily)
Cranberry juice may help prevent attachment of bacteria
Void urine immediately after sex
Proper personal hygiene
• Treatment
– Sulfonamides or cephalosporins
Bacterial Vaginosis
• Causative agent:
– May be caused by multiple anaerobic bacteria
– Gardnerella vaginalis
• Change in vaginal flora
– pH increases and allows
overgrowth of pathogen
• Signs & Symptoms
– Thin, grayish-white vaginal discharge
• Can be slightly bubbly
– Pungent ‘fishy’ odor
– Some itching and irritation
– 50% asymptomatic
• Prevention
– No proven prevention
– Associated with multiple sexual partners, vaginal douching,
anti-microbial therapy
• Treatment
– Metronidazole
– Vinegar douche
– Reestablishment of lactobacilli
Vaginal Candidiasis
• Causative agent
– Candida albicans
• Normal flora for up to 80%
women
• Opportunistic pathogen
• Dimorphic
of
• Signs & Symptoms
– White mucoid colonies on vaginal mucus membranes and
labia
– Severe itching and burning
– White curd-like discharge
Vaginal Cancer
Vaginal Cancer
• Rare tumor representing only 1-2% of all
gynecologic malignancies
• 80-90% are metastatic
• Mean age of patients with primary vaginal
cancer is 60-65 years
• Most primary tumors are squamous cell in
origin
• HPV DNA identified in VAIN
Vaginal Cancer precursors
•
•
•
•
VAIN – avg age of VAIN 3 is 53
Ratio of VAIN to CIN is 1:23
5% progress to Vaginal Ca
Hallmark of VAIN
– cytologic atypia-Pleomorphisim, irreg nuclear
contours and chromatin clumping
– Abnormal maturation
– nuclear enlargement
Vaginal Cancer precursors
• VAIN 3
– usually occurs in upper third of vagina and is
multifocal and diffuse in half the cases.
– 1/3 of patients have a hx/o CIN
– CIN coexists w/ VAIN in 10-20% of pts
– Colposcopic findings are similar to those of
CIN (aceto white epithelium with punctations
and mosaic patterns)
Vaginal Cancer precursors
VAIN 1Proliferation of basal layer
Koilocytotic atypia
Enlarged pleomorphic
nuclei
vacuolated cytoplasm
Vaginal Cancer precursors
VAIN 2Proliferation of basal
layer,crowding
and loss of polarity
Koilocytotic atypia
Enlarged pleomorphic
nuclei
vacuolated cytoplasm
Vaginal Cancer precursors
VAIN 3
Increased proliferation of
abnormal basal and parabasal
cells replacing full
thickness of epithelium
Vaginal Cancer precursors
• Treatment Options for VAIN
–
–
–
–
Excisional Bx for small lesions
Partial Vaginectomy
Laser Vaporization
Intravaginal 5FU cream
Vaginal Cancer: Predisposing
Factors
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•
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•
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Low socioeconomic status
History of genital warts
Vaginal discharge or irritation
Previously abnormal Pap smear
Early hysterectomy
Previous pelvic radiation (?)
In-utero exposure to DES
Anatomy of the Vagina
• Muscular dilatable tube averaging 7.5 cm in length
• Vaginal wall composed of three layers: mucosa,
muscularis, adventitia.
• Epithelium normally contains no glands and
changes little during reproductive cycle
• Lymphatic drainage of upper vagina via pelvic
nodes while lower vagina drains via femoral and
inguinal nodes.
Natural History and Patterns of
Spread
• Lesions usually found in the upper vagina
on the posterior wall
• Vaginal primary tumors may spread along
mucosa to cervix or vulva (changes
diagnosis)
• Direct extension to bladder, parametria,
paracolpos, rectum, cardinal ligaments,
uterosacral ligaments
Gross and microscopic Findings
• 50% of Vag Ca ulcerative
• 30% are exophytic
• 20%are annular and constricting
Natural History and Patterns of
Spread
• Any of the nodal groups may be involved
regardless of the location of the tumor
• Inguinal nodes most often involved if lesion
is in the lower 1/3 of the vagina
• Clinically apparent inguinal node mets seen
in 5-20% of patients
• Incidence of pelvic nodes varies with stage
and location of the tumor
Lymphatic Drainage of Vagina
Clinical Presentation
• Abnormal vaginal bleeding
– 50-75% of patients with primary tumors
• Dysuria
• Pain
Diagnostic Work-up
• Complete history and physical
• Speculum examination and palpation of the
vagina
• Bimanual pelvic and rectovaginal
examination
• Pap smear, colposcopy, directed biopsies
Diagnostic Work-up
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•
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•
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•
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Cystoscopy
Proctosigmoidoscopy
Chest X-ray
IVP
Barium enema
Computed Tomography
MRI (84% PPV, 97% NPV)
Staging
• Stage I - Lesions confined to the mucosa
• Stage II- Subvaginal tissue involved but no
extension to pelvic sidewall
– IIA: Subvaginal infiltration only
– IIB: Parametrial extension
• Stage III- Pelvic sidewall extension
• Stage IV- Bladder or rectal extension and/or direct
extension outside of true pelvis
Staging
Natural History and Patterns of
Failure
• Stage I
– 10-20% pelvic recurrence, 10-20% distant
• Stage II
– 35% pelvic recurrence, 22% distant
• Stage III
– 25-37% pelvic recurrence, 23% distant
• Stage IV
– 58% pelvic recurrence, 30% distant
Pathology
• Squamous Cell CA represents 80-90% of
primary tumors
• Vaginal SCCA may be considered primary
if there is neither cervical or vulvar CA at
diagnosis or for 10 years prior
• No correlation between grade and survival
Verrucous Carcinoma
• Variant of well-differentiated SCCA that
rarely occurs in the vagina
• Relatively large, well-circumscribed, soft
cauliflower-like mass
• Cytologic features of malignancy are
lacking
• May recur locally after surgery but rarely, if
ever, metastasizes
Pathology
• Melanoma
– 2nd most common vaginal cancer
– Most frequently found in the lower third
– Cells may be spindle shaped, epithelioid, or
small lymphocyte-like, pigmented or nonpigmented
– Junctional activity helps exclude the possibility
of a metastasis
– Depth of invasion best predictor of survival
Pathology
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•
•
•
•
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Smooth muscle tumors
Small Cell Carcinoma
Endodermal Sinus Tumor
Rhabdomyosarcoma (Sarcoma Boytrioides)
Malignant lymphoma
Clear Cell Adenocarcinoma
Management
• Radiation therapy is the preferred treatment
for most carcinomas of the vagina
• Surgical therapy
– Irradiation failures
– Non-epithelial tumors
– Stage I Clear cell adenocarcinomas in young
women
Management
• Surgery
– Stage I tumors of the middle or upper third of
vagina treated with radical hysterovaginectomy
and PLND
– Stage I tumors of the lower third of vagina
which may encroach on the vulva treated with
radical vulvovaginectomy and bilat. groin node
dissection
– Pelvic exenteration possible for more invasive
lesions
Management
• Stage I
– Usually managed with RT
– Superficial lesions (<1cm) may be treated with
vaginal cylinder covering the entire vagina (6-7
Gy mucosal dose + 2-3 Gy dose to tumor)
– Thicker lesions may be treated with vaginal
cylinder + single plane implant
– EBRT reserved for aggressive lesions
(infiltrating or poorly differentiated)
Vaginal Cylinder + Single Plane
Implant
Management
• Stage I
– Radical hysterectomy, partial vaginectomy,
PLND may be used for lesions of the posterior
and lateral vaginal fornices
• Stage IIA
– WPRT (2000cGy) + parametrial boost for
4500cGy-5,000cGy total
Management
• Stage IIA
– WPRT (2000cGy) + parametrial boost for
4500cGy-5,000cGy total
– WPRT + combination of intracavitary and
interstitial implants for 5000 to 6000 cGy total
• Stage IIB, III, IVA
– WPRT (4000 cGy) + parametrial boost (2500
cGy)
Management
• Small Cell Carcinoma
– Reasonable local control may be obtained with
surgery or irradiation followed by systemic
chemo
– Cyclophosphamide, Adriamycin, Vincristine
(CAV) X 12 cycles (some prior to initiation of
RT)
– Doses of RT similar to SCCA
Management
• Rhabdomyosarcoma
– Generally treated with a combination of
surgery, RT, and chemotherapy
– Vincristine, Dactinomycin, Cyclophosphamide
(VAC) X 1-2 years effective adjuvant treatment
for stage 1 dz
– Local excision + interstitial/intracavitary RT +
systemic chemo has replaced radical pelvic
surgery as therapy of choice
Sarcoma Botryoides
Sarcoma Botryoides
Strap cell
Management
• Malignant Lymphoma
– Vaginectomy and radical hysterectomy or
pelvic exenteration has been used for localized
vaginal tumors
– Satisfactory results with pelvic RT (tele and
brachytherapy) + systemic chemo
– Cyclophosphamide, adriamycin, vincristine,
prednisone (CHOP) X 6 cycles most often used
Clear Cell Adenocarcinoma and
DES Exposure
• Incidence is between 0.14 to 1.4/1000
women exposed to DES
• Median age at diagnosis 19 years
• Lesions found mainly in the upper 1/3 of
the anterior vaginal wall
• 90% of patients with early stage disease (I
and II) at diagnosis
Management
• Clear Cell Adenocarcinoma
– Surgery for stage I lesions has advantage of
ovarian preservation and better vaginal function
following skin graft
– Vaginectomy, radical hysterectomy PLND,
paraaortic LNBx (frozen section of distal
margin)
– Intracavitary or transvaginal radiation can be
used for small lesions
– More extensive lesions: EBRT
Clear cell adenocarcinoma
FAVORABLE FACTORS IN SURVIVAL OF
PATIENTS WITH CLEAR CELL
ADENOCARCINOMA
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•
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•
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•
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Low stage
Older age
Tubulocystic Pattern
Small tumor diameter
Reduced depth of invasion
Negative nodal mets
Positive ho/o DES
Radiation Therapy Techniques
• EBRT delivered through AP:PA portals or using 4
field “box technique”
• 15 cm X 15 cm or 15 cm X 18 cm portals usually
adequate
• Inguinal nodes should be electively covered
(4500-5000cGy) for tumors of the lower 1/3 of
vagina
• Additional 1500cGy (4-5cm depth) delivered for
palpable inguinal nodes
Radiation Therapy Techniques
Portal for pelvic RT
and elective groin
coverage
Portal for groin
coverage with
palpable inguinal
Radiation Therapy Techniques
• Intracavitary therapy utilizes vaginal cylinders
(Burnett, Bleodorn, Delclos, or MIRALVA
applicators)
• Upper 1/3 lesions can be treated with tandem and
ovoids
• Interstitial therapy with 137Cs, 226Ra, or 192Ir
needles have been used
• High dose rate brachytherapy (>1200cGy/hour)
also used
Summary
• Superficial stage I lesions may be treated
with RT or radical hysterovaginectomy
• Stage IIA-IVA treated with WPRT and
intracavitary RT
• Role of chemotherapy in advanced SCCA
presently unknown
• Pelvic failures and distant metastases occur
in 1/2 of pts with advanced dz
5 Year Survival
80
70
60
50
40
30
20
10
0
Stage I
Stage II Stage III Stage IV
• Epidemiology
– Can be spread person to person
• Mother to newborn
• Rarely sexually transmitted
– Antibacterial medications increases risk
– Other risk factors include birth control, hormone therapy,
AIDS, diabetes, invasive hospital procedures and cancers
– Changes in vaginal flora and pH
• Prevention
– minimizing risk factors
• Treatment
– Intra-vaginal treatment with nystatin and
clotrimazole
• Cream azoles may weaken latex condoms
– Oral fluconazole
Vulvar cancer
Vulvar cancer is a rare disease in
which malignant (cancer) cells form
in the tissues of the vulva.
Vulvar cancer forms in the external
genitalia.
The vulva includes:
Vulvar Carcinoma
• Majority are of epidermal
origin
• Age: 60-75 years.
• 90-95% of Vulval cancer
are of Squamous origin.
• Melanoma of the vulva is
second most common type
(4-9%).
Aetiology
• Vulval dermatomes (lichen sclerosis): a common Vulval
inflammatory dermatosis (HPV 16 & 33) affecting older
women with ↑chance of malignant progression.
• Vulval Intraepithelial Neoplasia (VIN) : 80% will lead to
invasive cancer at 10 years if not treated & 7-8% if treated.
VIN3 is a pre-invasive condition.
• Human papilloma virus (HPV): associated with 30% of Vulval
cancer & with 80-90% of Vulval cancer in women less than 50
years of age.
• Smoking: co-factor of HPV & VIN development.
 VIN affects mainly L.minora & perineum.
Classification of VIN
• VIN I - mild dysplasia with
hyperplastic vulvar dystrophy with
mild atypia
• VIN II - Moderate dysplasia,
hyperplastic vulvar dystrophy with
moderate atypia
• VIN III - Severe dysplasia;
hyperplastic vulvar dystrophy with
severe atypia (it replaces the term
carcinoma in situ, Bowen’s disease).
Carcinoma in situ
VIN Dx & Rx
• Dx: colposce + biopsies
• Rx:
- low grade VIN: observation.
- VIN3: local excision or laser vaporization
- Topical immunomodulator: imiquimod
Vulval Carcinoma
Clinical Staging (F.I.G.O.):
• Stage I :
1a: confined to vulva with <1mm invasion.
1b: confined to vulva with a diameter < 2 cm & no inguinal
lymph nodes affection.
• Stage II : limited to vulva with diameter > 2 cm) & no
inguinal lymph nodes affection.
• Stage III : adjacent spread to the lower urethra and/or vagina
and/or anus and/or unilateral lymph nodes affection.
• Stage IV :
A. Bilateral inguinal nodes metastases, involvement of mucosa
of rectum, urinary bladder, upper urethra or pelvic bones.
B. Distant metastasis.
Treatment of Vulval Carcinoma
• Stage I & II :
Radical local excision with 1cm disease–free margin.
• Stage III & IV :
- According to the general health.
- Chemotherapy & radiotherapy to shrink the tumour to permit
surgery which may preserve the urethral & anal sphincter function.
- radical vulvectomy + inguinal L. nodes dissection.
- reconstructive surgery with skin grafts or myocutaneous flaps for
healing.
Vaginal Intraepithelial Neoplasia (VaIN)
• Extremely uncommon (150 times < CIN).
• 70% associated with CIN (extension of the transformation
zone into the vaginal fornices).
• Predisposing factors: similar to those of CIN (HPV), but the
age of VaIN is higher than CIN, diethylstilboesterol in utero
(metaplastic transformation into the vagina), previous history
of CIN), radiotherapy of CA cervix.
• VaIN is graded 1-3 but is less invasive than CIN:
- VaIN1: mild dysplasia.
- VaIN2: moderate dysplasia.
- VaIN3: severe dysplasia.
• Dx: V. smear, colposcopy, biopsy (even after hysterectomy).
• Rx: low grade: observation. high grade: excision, 5fluoroyracil, diathermy. Alternatively, Radiotherapy.
Vaginal Carcinoma
• Incidence: 1-2% of all gyn. Cancer.
• Classification:
1. primary: squamous (common, 85%), adenocarcinoma (17-21
years of age, metastasis to L.Ns), clear cell adenocarcinoma
(DES).
2. secondary: metastasis from the cervix, endometrium,…..others.
• 50% in the upper 3rd, 30% in lower 3rd & 19% in middle 3rd.
• Posterior V. lesions more common than anterior & the anterior
are more common than lateral lesions.
• Spread: direct & lymphatic.
Vaginal Carcinoma
Clinical Staging (F.I.G.O.):
• Stage I: tumour confined to vagina.
• Stage II : tumour invades paravaginal tissue but not
to pelvic sidewall.
• Stage III : tumour extends to pelvic sidewall.
• Stage IV :
a) tumour invades mucosa of bladder or rectum
and/or beyond the true pelvis.
b) Distant metastasis.
TREATMENT
• Stage 1:
1. Tumour < 0.5 cm deep:
a. surgery: local excision or total vaginectomy with reconstruction.
b. radiotherapy.
2. Tumour > 0.5 cm deep: (a) wide vaginectomy, pelvic
lymphadenectomy + reconstruction of vagina. (b) radiotherapy
• stage 2: (a) radical vaginectomy, lymphadenectomy (b)
radiotherapy
• Stage 3: radiotherapy.
Risk factors
•Having vulvar intraepithelial neoplasia (VIN).
•Having human papillomavirus (HPV) infection.
•Having a history of genital warts.
•Having many sexual partners.
•Having first sexual intercourse at a young age.
•Having a history of abnormal Pap tests (Pap smears).