Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5258_Библиотеки_им_академика_М_И_Перельмана.pdf
217
(60.9%). Of the episodes with identiable causes, the most common etiologic agent was
C. difcile (13.3%), followed by norovirus (8.1%), and CMV (6.3%). Co-infection was
detected in 1.9% of community-onset diarrhea admissions [109].
8.4.1 Diagnostic Considerations
A good history is important when assessing diarrhea in SOT recipients. Fever more
commonly indicates a viral, or invasive bacterial etiology, and rarely is caused by
parasitic infections. Blood in the stool can be caused by invasive bacterial infec-
tions, CMV or Entamoeba. Watery diarrhea with or without emesis suggests C. dif-
cile, viral or medication-induced diarrhea or other parasitic infections [110].
In both immunosuppressed and immunocompetent patients, fecal studies have a
low overall diagnostic yield [111] but are often a necessary part of the evaluation.
The American Society of Transplantation Infectious Diseases Community of
Practice guidelines, last updated in 2019, recommended a tiered approach: stopping
any non-immunosuppressive medications, and performing rst line microbiologic
testing consisting of bacterial stool culture, C. difcile PCR, and serum CMV PCR
or nucleotide acid amplication test (NAAT) [107].
In clinical practice, however, there is now increased use of multiplex enteric
pathogen panel PCR (EPP) as rst step in diagnosis, to detect a broad range of bac-
terial, parasitic, and viral pathogens [112]. It should be noted that sensitivity for
each pathogen varies across PCR assays and is often inferior to single probe assays
[113]. In addition, PCR cannot distinguish between colonization and pathogenic
causes of diarrhea, hence caution is advised when interpreting results, especially for
diarrheagenic gram negative organisms and toxin-negative C. difcile [114]. In the
hematopoietic stem cell transplant population, results have suggested that EPP is
most useful when performed on an outpatient basis or at hospital admission [115].
It is important to be know which organisms are included in the EPP available at
individual institutions. Although uncommon causes of diarrhea in the SOT recipient
[109], it should be noted that Cystisospora, Isospora, and Microsporidia are not
typically found on these tests. Therefore, if EPP is unrevealing and suspicion for
infectious etiology persists, one may consider sending stool ova and parasites
(O&P), special stains (Auramine and Trichrome), and/or pathogen specic PCR.
A step-wise approach to diagnosis is suggested below in Fig.8.2, along with an
example of organisms included in a commonly used EPP in Table8.6.
8.4.2 Clostridioides difcile
Clostridioides difcile (C. diff) is a spore-forming, gram positive anaerobic bacte-
rium that produces two exotoxins (toxin A and toxin B). It is a common cause of
inammatory diarrhea and colonic mucosal injury in the SOT population.
8 Infections intheAdult Solid Organ Transplant Recipient
218
Fig. 8.2 Diagnostic approach to diarrhea in SOT recipients. The diagnostic and treatment
approach should be adjusted for local epidemiology, the overall clinical likelihood of infectious
diarrhea, the severity of presentation, pattern of diarrhea (duration, relationship with intake), and
the availability of EPP.For further discussion, see Chap. 9. *Consider need for invasive diagnostics
especially if concern for post-transplant lymphoproliferative disorder (PTLD), graft-versus-host
disease (GVHD), inammatory bowel disease (IBD), or poor response to CMV therapy; or con-
cern for less common pathogens. **Limited data, with a Cochrane review from 2022 concluding
no evidence to support or refuse use of probiotics in SOT recipients [116]. Rare cases of
Lactobacillus infection associated with probiotics in SOT population has been reported [117].
CMV cytomegalovirus, C. difcile Clostridium difcile, EGD esophagogastroduodenoscopy, GI
gastroenterology, ID infectious diseases, IV intravenous, NAT nucleic acid test, O+P ova and para-
site, PO per os, qPCR quantitative polymerase chain reaction, SOT solid organ transplant, SIBO
small intestinal bacterial overgrowth
8.4.2.1 Epidemiology
SOT recipients are more vulnerable to C. diff infection due to a combination of immu-
nosuppression, frequent hospitalizations, and antibiotic use for prophylactic or thera-
peutic purposes [118]; particularly with the use of multiple antimicrobial agents with
extended courses [119]. In a meta-analysis including 21,683 SOT recipients, the over-
all estimated prevalence was 7.4% (95% 5.6–9.5%), and varied based on the type of
organ transplant, with highest risk in multi-organ recipients, and lowest risk in pan-
creas transplant and kidney transplant recipients. Unfortunately, there is an increasing
trend of C. diff infection in SOT recipients, with the 1-year incidence increasing in
annual cohorts from 23.1 per 1000 person-years in 2003 (95% CI 12.8–41.8) to 46.7
per 1000-person-years in 2017 (95% CI 35.0–62.3) [120]. Recurrence is also com-
mon, with estimated rates approximately 20%; this has been attributed to unstable
colonization of intestines with physiologic microbiota, and less so due to resistance to
antimicrobials or the failure to produce IgG antibodies against toxins A and B [121].
Typically, C. diff infection occurs most frequently in the immediate post-
transplant period, with a multi-national prospective study by Blumberg et al.
J. Hu et al.
219
Table 8.6
Organisms included in GI panel from BioFire Diagnostics, Salt Lake City, UT, USA
Bacterial
Campylobacter (C. jejuni, C. coli, C. upsaliensis)
Clostridium difcile toxin A/B
Plesiomonas shigelloides
Salmonella spp
Vibro (V. parahaemolyticus, V. vulnicus, V. cholerae)
Yersinia enterolitica
Enteroaggregative Escherichia coli (EAEC)
Enteropathogenic Escherichia coli (EPEC)
Enterotoxogenic Escherichia coli (ETEC)
Shiga-like toxin producing Escherichia colia (STEC) stx1/stex2, including O157
Shigella/Enteroinvasie Escherichia coli (EIEC)
Viral
Adenovirus F40/41
Astrovirus
Norovirus
Rotavirus A
Sapovirus (genogroups I, II, IV, and V)
Parasitic/Other
Cryptosporidium
Cyclospora caytanensis
Entamoeba histolytica
Giardia lamblia (also known as G. intestinalis and G. duodenalis)
reporting a median of 20days from transplant to C. diff infection [122], although
SOT recipients remain at longitudinal risk. Late-onset C. diff infection, dened as
occurring 90days or more post-transplant, is also associated with a greater risk of
short and long-term mortality, compared with early onset C. diff infection. In a
cohort study including 10,724 patients, post-transplant C. diff infection was associ-
ated with a 90-day mortality incidence of 17% [120].
8.4.2.2 Diagnosis
Diagnosis of C. diff infections is based on both clinical and laboratory data. There
is an increasing number of people who are colonized with C. diff and no current
laboratory tests can distinguish between colonization and infection. Hence, the
diagnosis of C. diff is made when a patient experiences new onset or unexplained,
clinically signicant (3 loose stool/day) diarrhea in the presence of laboratory con-
rmation of free C. diff toxin (toxin A or B via EIA), or toxigenic C. diff bacteria
(C. diff NAAT) in the stool. In the 2019 American Society of Transplantation
Community of Practice guidelines for C. diff in solid organ transplant recipients,
additional recommendations include not automatically repeating negative C. diff
tests, and not “testing for cure” after an infection [123]. Uncommonly, C. diff may
present without diarrhea, and this infection should be also considered in SOT recipi-
ents who present with fever, leukocytosis, abdominal pain, and ileus. If there is
8 Infections intheAdult Solid Organ Transplant Recipient
220
negative C. diff standard testing and a high clinical suspicion for C. diff infection,
then further workup should be considered, including abdominal/pelvic CT imaging,
colonoscopy, and repeat standard testing, although this is most relevant among hos-
pitalized and/or critically ill patients [124].
8.4.2.3 Treatment (Table8.7)
Treatment of C. diff infection is similar in SOT recipients and the general population.
For an initial episode of non-fulminant disease, the 2021 IDSA C. difcile guide-
line update prefers using daxomicin 200 mg BID for 10 days, rather than PO
vancomycin 125mg q6H for 10days, although both are acceptable rst-line options.
This recommendation places a high value on safety of daxomicin, as well as a
small benet with regard to recurrence rates. However, initial clinical cure rates are
comparable, and the use of daxomicin may have cost implications [125–128]. The
American College of Gastroenterology guidelines suggest that both PO vancomycin
and daxomicin are acceptable options [129].
In our clinical practice, for an initial episode of non-fulminant disease, we utilize
PO daxomicin in patients at very high risk for recurrence.Patients at highest risk
of recurrence include those with three or more of the following risk factors: age
≥65years, history of C. diff infection in the previous 6months (for recurrent cases),
severely compromised immunity based on NIH criteria (including SOT recipients),
or severe C. diff infection based on Zar score (score ≥2). The Zar score assigns
Table 8.7 Treatment options for C. diff infection
Initial C. diff infection OR reinfection (>8weeks after initial episode)
• Preferred therapy by IDSA: daxomicin 200mg BID×10days
• Alternate: PO vancomycin 125mg PO/NG q6H×10days
• If all above agents are not available, for non-severe infection, consider PO metronidazole
500mg TID×10–14days
• In our clinical practice, we historically considered using PO vancomycin 125mg PO/NG
q6H×10days + IV bezlotoxumab for patients with high risk for recurrence. Bezlotoxumab
was discontinued in January 2025 and is no longer available.
First recurrence
• PO doxamicin 200mg BID×10days
• PO daxomicin 200mg BID×5days, followed by once every other day for 20days
• Alternate: PO vancomycin pulse/taper: 125mg PO q6H×10–14days, 125mg PO
BID×7days, 125mg PO every 2–3days×2–8weeks
Second or more recurrences
• Fidaxomicin pulse or pulse/extenced taper regimen as mentioned above
• PO vancomycin pulse/taper regimen as mentioned above
• PO vancomycin 125mg q6H×10days followed by rifaximin 400mg TID×20days
• Consider FMT with GI consultation
J. Hu et al.
221
different points to the following criteria: age>60, fever, low albumin level, leukocy-
tosis, endoscopic evidence of pseudomembranous colitis, and ICU admission.
Historically, we would also consider combination therapy with PO vancomycin and
IV bezlotoxumab, a monoclonal antibody targeting toxin B; however, since January
2025, bezlotoxumab is no longer manufactured.
Fulminant disease, as dened by the presence of hypotension, shock, ileus, and/
or megacolon should be managed as inpatient and is beyond the scope of this chap-
ter. Generally, it is treated with a combination of high-dose PO/nasogastric (NG)
vancomycin, IV metronidazole, consideration of rectal vancomycin, as well as sur-
gical consultation.
Recurrent C. diff infection is dened by resolution of symptoms while on appro-
priate therapy, followed by re-emergence of symptoms within 8weeks of treatment
discontinuation. Treatment depends on the number of recurrences; summarized in
Table 8.7.
Fecal microbiota transplant (FMT) has been used in immunosuppressed and
SOT recipients in limited studies [130–132]. A multi-center study of 94 SOT recipi-
ents with recurrent C. diff (78%) or severe fulminant C. diff (22%) found an overall
cure rate of 91% with FMT, and a 3-month primary cure rate of 58.7% [133].
Adverse events were experienced in 22%, consisting of mostly self-limited diarrhea
or abdominal pain. However, 3.2% experienced severe adverse events including two
hospitalizations for ares of inammatory bowel disease (IBD). The same study
found that in SOT recipients with IBD, 25% experienced post-FMT IBD exacerba-
tions. In CMV seropositive patients, 14% experienced reactivation of CMV after
FMT.The 2019 AST guidelines notes similar efcacy and safety outcomes of FMT
in SOT recipients compared to immunocompetent hosts based on this limited, retro-
spective data [123]. No randomized controlled trials of FMT in SOT recipients have
been published as of 2024. It is advisable to consult a transplant infectious disease
specialist when considering FMT following recurrent or severe C. diff infection.
In April 2023, the FDA approved the rst orally administered fecal microbiota
product for recurrence of C. diff infection (VOWST, Seres Therapeutics, Cambridge
MA, USA) based on the multicenter, randomized, placebo-controlled ECOSPOR
III study [134]. This product consists of a puried collection of Firmicutes spores,
obtained from fecal matter from healthy donors, and is thought to restore intestinal
ora. Other available products include Rebyota (Ferring Pharmaceuticals, Malmo,
Sweden) approved in 2022, and VE303 (Vedanta Biosciences, Cambridge MA,
USA). As of 2024, data remains lacking in SOT recipients.
8.4.3 Cytomegalovirus
Cytomegalovirus (CMV) is a double stranded DNA virus that is part of the herpes
virus family. It has varying gastrointestinal manifestations including esophagitis,
gastritis, enteritis, colitis and typically presents with diarrhea, abdominal pain and
fever. It can also cause hepatitis, cholangitis and pancreatitis, as well as non-GI
manifestations discussed separately.
8 Infections intheAdult Solid Organ Transplant Recipient
222
8.4.3.1 Risk Factors
In the SOT population, CMV-negative recipients who receive an organ from a
CMV-positive donor (D+/R−) are at the highest risk for CMV disease. This is dif-
ferent from the hematopoietic stem cell transplant population, in whom D−/R+ con-
fers the highest risk.
Other factors associated with risk for CMV disease include the net state of
immunosuppression (in particular, lymphocyte-depleting agents such as anti-
thymocyte globulins and alemtuzumab, or high doses of maintenance immunosup-
pression [135], allograft rejection and its treatment [136], and type of
transplantation—with lung, small intestine transplants at the highest risk) [7]. This
may potentially be explained by the intensity of immunosuppression and the amount
of transplanted lymphoid tissue [137].
8.4.3.2 Diagnosis
As per the guidelines for work-up of diarrhea in SOT recipients, plasma CMV test-
ing with either PCR or quantitative nucleic acid amplication testing (QNAT) is a
rst-line test. There is some data that suggest a stool CMV PCR may be highly
specic (but not sensitive), but this test may not be widely available [138]. Older
(2013) guidelines [137] recommend QNAT for both diagnosis and monitoring of
CMV infections, although this test has largely been supplanted by PCR, if available.
The pp65 CMV antigenemia test has historically been used for diagnosis and moni-
toring of CMV infections but is less standardized and more labor-intensive. Repeat
serologic testing has a limited role post-transplantation, as SOT recipients may have
impaired ability to mount robust antibody response due to immunosuppression, and
there is potential for false positive results from passively transferred antibodies
through blood products or intravenous immunoglobulin (IVIG). Accordingly, test-
ing for seroconversion is not recommended for the diagnosis of CMV disease after
SOT, although it may be used with modest predictive ability to determine ongoing
susceptibility among CMV-seronegative recipients [139]. We rarely if ever test for
CMV IgG or IgM post-transplant in our practice for any indication.
Viral culture of the blood and urine has poor sensitivity and specicity, respec-
tively, and are not currently recommended to diagnose CMV.Tissue-invasive dis-
ease is diagnosed via CMV inclusion bodies or CMV antigens detected via
immunohistochemistry on biopsy specimens obtained during endoscopy, along with
evidence of viral cytopathic effect on pathology. Tissue cultures and QNAT can be
difcult to interpret as both infection and shedding can create positive results but
may have a limited role in diagnosis [140]. Tissue diagnosis via colonoscopy should
be pursued if needed to conrm the diagnosis even with a positive change in serum
PCR (e.g., if there are competing diagnoses, the patient tolerates anti-CMV therapy
poorly, or if empiric therapy against CMV was attempted and the patient did not
respond) or if the serum CMV PCR is negative but the clinical suspicion of CMV
gastrointestinal disease is still high.
J. Hu et al.
223
8.4.3.3 Treatment
SOT recipients with CMV gastrointestinal disease should receive consultation with
an infectious disease specialist.
First line medications for treatment of CMV disease are IV ganciclovir and
oral valganciclovir, along with consideration of cautious reduction in immuno-
suppression. Oral valganciclovir achieves blood levels comparable to IV ganci-
clovir and has been used in mild/moderate CMV disease [141]. Ganciclovir is
preferable in severe/life-threatening disease, for those with high viral loads, and
those with impaired absorption, including high-frequency diarrhea or vomiting
[7]. For refractory/resistant disease, medications such as foscarnet, cidofovir, and
maribavir are utilized with the guidance of a transplant infectious disease
expert [142].
During treatment for CMV disease, kidney function must be monitored care-
fully, and doses of antiviral medication adjusted accordingly. In general, virologic
response is monitored once weekly using PCR, and the duration of therapy is indi-
vidualized based on symptom resolution and virologic clearance, with minimum
duration of 2weeks. It is notable that the half-life of CMV DNA in plasma ranges
from 3 to 8days with an average of 5–5.5days [143], hence it may take ~2weeks
to identify response to antiviral treatment. After at least 2weeks of appropriately
dosed antiviral treatment, at least a one-log decline in viral load is anticipated. If this
response is not observed, one must consider the possibility of refractory disease,
including antiviral resistance, over-immunosuppressed status, or subtherapeutic
antiviral drug concentrations.
After treatment, there is no clear evidence for benet of secondary prophylaxis
of CMV, except to complete a planned duration of initial prophylaxis following
transplantation [144].
8.4.4 Norovirus, Sapovirus andAstrovirus
Norovirus is a single-stranded RNA virus that causes 90% of non-bacterial diar-
rhea, resulting in 19–21 million cases per year in the USA.Routes of infection
include fecal/oral, inhalation of aerosolized emesis, or direct contact. Most immu-
nocompetent people experience self-limited acute diarrhea and vomiting followed
by up to 2weeks of asymptomatic shedding. While some SOT recipients may pres-
ent similarly, several studies suggest that chronic diarrhea is also a common presen-
tation [107, 145, 146].
Norovirus in SOT recipients frequently presents with dehydration, kidney insuf-
ciency, graft dysfunction, and chronic diarrhea; it rarely causes mortality. Treatment
is supportive and focuses heavily on rehydration and anti-motility agents. Reducing
immunosuppressive medications has not improved the recovery for Norovirus
chronic diarrhea. There are some controversial data for role of nitazoximide in this
setting [147].
8 Infections intheAdult Solid Organ Transplant Recipient
224
Sapovirus and Astroviruses may present similarly and may or may not be
detected by EPP.
8.4.5 Parasites
Other important causes of infectious diarrhea in SOT recipients include parasitic
infections. Some notable parasitic infections beside Entamoeba and Giardia, which
are the most common diarrheagenic parasites in the general population, include
Cryptosporidium, Cystoisospora, Cyclospora, and Microsporidium.
Cryptosporidium is a water-borne parasite which has been known to infect immu-
nosuppressed and SOT recipients in epidemic outbreaks from environmental expo-
sures. Because some of these parasites are not detected in standard EPPs, additional
testing may be required, as discussed in Sect. 8.4.1. Avoidance of exposure to water
sources that could be contaminated by waste products should be encouraged for all
SOT recipients and use of in-line water lters recommended for those whose water
source is not treated by a public utility [148]. (See Chap. 14.) Treatment for parasitic
infections should follow standard guidelines, with infectious disease specialist con-
sultation for cases that do not respond to treatment.
8.4.6 Non-infectious Causes
There are many non-infectious causes of diarrhea in a SOT recipient.
Immunosuppressive and other medications commonly cause diarrhea—mycophe-
nolate causes dose dependent, direct enterocyte toxicity, while calcineurin inhibi-
tors such as tacrolimus cause diarrhea via a macrolide promotility effect. Severe
diarrhea is also associated with elevations in tacrolimus exposure with the potential
for tacrolimus nephrotoxicity, due to not only dehydration but also decreased
metabolism by the intestinal P-glycoprotein and CYP3A4 systems that become dys-
functional in the setting of diarrhea [149]. Sirolimus and everolimus may also cause
diarrhea [150, 151]. A thorough medication history should be obtained. Less com-
mon causes include graft versus host disease (GVHD) and post-transplant lympho-
proliferative disorder (PTLD). GVHD is rare in solid organ transplantation, except
in small bowel transplants. GVHD may present with chronic diarrhea, abdominal
pain, fevers, and sometimes rash. PTLD, when it involves the gastrointestinal tract,
may present with chronic diarrhea, weight loss, abdominal pain, gastrointestinal
bleeding, and anorexia. The risk for PTLD, associated with active replication of
EBV either after primary infection or reactivation during treatment with immuno-
suppression, is thought to increase with increased immunosuppression, and is high-
est in multiorgan and intestinal transplants, and lowest in kidney and liver transplants.
Mortality rates historically for PTLD in SOT recipients are 50–70% [152]. See
Chaps. 9 and 10).
J. Hu et al.
225
8.4.7 Esophagitis
Esophagitis presents a diagnostic and management challenge in SOT recipients.
In addition to the risk of opportunistic infections (Table8.8), non-infectious causes
are common. For instance: there are reports of increased incidence of erosive esoph-
agitis associated with the type and duration of immunosuppression [153]. In the
pediatric SOT population, remarkably high rates of eosinophilic esophagitis have
been reported [154–156]. Uncommon causes such as PTLD can also rarely manifest
as esophagitis [157]. Overall, early endoscopic evaluation and biopsy should be
considered in this vulnerable population.
8.4.8 Oral Lesions intheSOT Recipient
The infectious differential diagnosis for oral lesions in the SOT recipient is very
similar to the causes of esophagitis outlined above (other than parasitic causes such
as Cryptosporidium or Ascaris that are not associated with oral manifestations)
[162]. The most common viral pathogen is HSV, with lesions characterized initially
Case
A 50-year-old woman with history of kidney-pancreas transplant 1year ago
presents with intractable nausea and vomiting, along with odynophagia, dys-
phagia to solids that progressed to liquids. She recently completed therapy for
Helicobacter pylori. She remains on immunosuppressive medications includ-
ing mycophenolate mofetil, tacrolimus, and prednisone. Initial examination is
without thrush nor other oral lesions; abdominal examination was benign.
Laboratory ndings revealed an acute renal injury with creatinine 2.0mg/dL
from baseline of 1.2mg/dL, therapeutic tacrolimus level, H. pylori IgG>8U/
mL (normal <0.89), CMV PCR negative, and EBV viral load was log 4.2IU/
mL.What are the next appropriate steps?
Comment
In the setting of intractable nausea and vomiting and acute renal injury,
this patient should be admitted to the hospital for supportive care and expe-
dited evaluation including GI consultation with consideration of esophago-
gastroduodenoscopy (EGD). In general, when there is concern for esophagitis
in an immunocompromised host, involvement of subspecialty colleagues is
prudent for early consideration of invasive testing. There are myriad infec-
tious and non- infectious causes of esophagitis, with the former summarized in
Table 8.8. If there is presence of oral thrush, consideration may be made for
empiric treatment with systemic uconazole. Should symptoms not improve in
3–5days, EGD should be pursued.
8 Infections intheAdult Solid Organ Transplant Recipient
226
Table 8.8
Infectious causes of esophagitis [80, 158, 159]
Etiology Diagnosis and notes Treatment
Herpes simplex virus
(HSV)
• Endoscopy: biopsy or brushing
from ulcer edge demonstrating
viral cytopathic effects
• PCR testing on biopsy sample
• Typically, it is a consequence of
reactivation of HSV with spread
of virus to the esophagus through
the vagus nerve or direct
extension of infection from the
oral cavity
Acyclovir 400mg q8H
Alternate: valacyclovir 1gm
BID or famciclovir 500mg
BID
If unable to take PO: IV
acyclovir 5mg/kg q8H
If no improvement consider
resistant virus
a
Cytomegalovirus (CMV) • Endoscopy with tissue biopsy for
CMV inclusions or positive
CMV-specic
immunohistochemistry staining,
qualitative PCR
• Positive tissue culture or PCR
consistent but can represent
contamination from blood or
secretions
• Plasma or whole blood for CMV
PCR; negative result does not
exclude tissue-invasive disease
IV ganciclovir always at
initiation, often followed by
PO valacyclovir only after
clinical improvement
Varicella zoster virus
(VZV)
• Rare, suspect in ill patients with
dermatologic manifestations
• Endoscopy with biopsy
• PCR testing on biopsy sample
• Histology with ballooning
degeneration, multinucleated
giant cells
Acyclovir or valacyclovir; IV
may be required by symptom
severity, dosing higher than
for HSV (ID consult
recommended)
Epstein–Barr virus (EBV)
• Endoscopy with biopsy
• EBV is also associated with
post-transplant
lymphoproliferative disorder
(PTLD) in the esophagus
Acyclovir to suppress oral
hairy leukoplakia, long-term
maintenance therapy may be
required
Human papilloma virus
(HPV)
• HPV manifestations typically
asymptomatic
• Endoscopy with tissue biopsy;
diagnosis based on
histopathology and
immunohistochemical stains.
Koilocytosis, giant cells, and
cytologic atypia may be visible
• HPV can be associated with
development of esophageal
cancer
Typically, no specic
treatment required;
endoscopic options exist as
well as reports of interferon
alpha
Preventative HPV vaccination
may reduce risk of infection
and lesions, though is
unlikely to lead to viral
clearance or lesion regression
based on data from anal
cancer [160, 161]
(continued)
J. Hu et al.