GI Kaposi Sarcoma

1. MORBIDITY AND MORTALITY

2. CHIEF COMPLAINT:
Difficulty and painful swallowing x ten days.
HISTORY OF PRESENT ILLNESS:
A 48-year-old Hispanic homosexual male with history of HIV/ AIDS recently
diagnosed in early June treated for Pneumocystis pneumonia as well as diagnosed with
Kaposi sarcoma/genital HSV/herpes zoster/oral thrush presented to the ED complaining of
severe difficulty in swallowing insidious in onset, gradually progressive to both solids and
liquids, not been able to tolerate solid food as it is causing extreme pain in the retrosternal
epigastric area. Only been able to take thin liquids and take pills. Reports a temperature
on and off, losing weight and poor appetite, improved shortness of breath and cough.
Denied headache, blurring of vision, nausea, vomiting, choking, chest pain, palpitations,
diarrhea, pain abdomen, bleeding per rectum/dark stools, dysuria, burning urination

3. Past Hospitalisation :
 Diagnosed to have HIV disease on 06/02/2014 when he was tested positive for
evaluation of "feeling unwell" for the past several months. Hospitalized for a week in
first week of june when he presented initially with progressive dyspnea associated with
cough and fever & multiple violaceous rashes involving the upper and lower extremities.
Had a bronchoscopy proven Pneumocystis jiroveci pneumonia. Bronchoscopy did not
report any endobronchial lesion or any signs of malignancy. A skin biopsy was
performed. Viral load was 4,13,585 and a CD4 count of 54. He did fairly well while on
trimethoprim sulfa, along with prednisone, and was discharged on prophylactic
Azithromycin home to follow up in the EIP clinic.

4.  Skin biopsy confirmed HHV8 positive lesions consistent with Kaposi sarcoma. Staging workup, and a CT scan of
the abdomen and pelvis revealed a proximal small-bowel distention with a possible mass involving the ileocecal
valve(2.5 cm)and multiple retroperitoneal lymph nodes. The patient'ssensitivity came up quite favorable and the
virus is sensitive to all given antiretroviral spectra and was started on highly active antiretroviral therapy
consisting of tenofovir/emtricitabine/elvitegravir/cobicistat. Was sent for Oncology evaluation.Returned to the
HIV Clinic about a week ago, and he was doing well until the day before followup when he noticed dysphagia to
solids and liquids and recorded a low grade temperature. The examination showed a morbilliform rash
involving the trunk and upper extremities, as well as extensive whitish patches involving the hard palate and
theposterior pharyngeal wall. At that time, the trimethoprim sulfa was stopped, as a drug allergy was
entertained, and it was switched to atovaquone along with prednisone for continuation of his Pneumocystis
treatment. Oral fluconazole was started.
 The patient was compliant to given instructions. He started to take Fluconazole and the rest of the medications
but he still has difficulty swallowing. Dysphagia did not improve although his rash disappeared.
 Past medical history: Herpes zoster 2 years ago
 Past surgical history: skin biopsy,bronchoscopy
 Allergies : Bactrim(skin rash)

5. SOCIAL HISTORY:
 originally from Colombia, lived in United States for the past 14 years.
 worked in inventory
 Lives in Union,NJ with his significant other.
 Not a current smoker. Stopped smoking cigarettes approximately 5
years ago. 20 pack years history.
 Does not drink alcohol. No use of illicit drugs.
 Homosexual with one partner for the last 5 years(recently tested
negative for HIV) not sexually active for the last 1 year.
 pet dogs at home.
 no recent significant travel.
FAMILY HISTORY:
 Father deceased from pancreatic cancer at age 69.
 Mother is alive at age 62 with thyroid disease, cardiac arrhythmias.
 Three sisters 42, 43 and 49 healthy

6. PHYSICAL EXAMINATION
General: age inappropriate Hispanic male who looks chronically ill and older than his stated age,not in acute distre
Vital Signs: Blood pressure is 92/68. Temperature is 100. Pulse is
109, respiratory rate is 20.
Head: mild pallor but no icterus. Oral thrush is resolved already.
Neck: Supple, without any signs of meningeal irritation, submandibular lymphadenopathy present.
Chest: Symmetrical expansion with fairly clear lungs anteriorly.
Heart: S1, S2, Regular rate.No Murmers/rubs/gallops
Abdomen: Soft, positive for bowel sounds, no tenderness on
palpation in all quadrants, no organomegaly/masses appreciated.
GenitoUrinary: no suprapubic or CVA tenderness, uncircumcised penis without any urethral discharge or ulcer, anus
shows multiple exophytic, verrucous warts around the anal verge, with a 3 x 2 cm painful ulcer at the superior
aspect of the gluteal fold with some granulation tissue.
Extremities: toenail onychomycosis +.
Skin: violaceous papular subcentimeter rash in lower
and upper extremities.
Extremities: No clubbing, no varicosities, edema or tremor.
Neurological Exam: Normal. No focal neurologic deficits.

7. Violaceous
maculopapular skin
lesions

9. This 48-year-old Caucasian male with HIV/AIDS (viral load
413,585 copies and CD4 count of 52) and Kaposi sarcoma, who
has been recently hospitalized for Pneumocystis jiroveci
pneumonia, nowis readmitted for dysphagia and failure to
thrive while being treated for oropharyngeal candidiasis.
Presently worsening dysphagia and severe odynophagia. Not
responding to oral Fluconazole.

10. :
1.Worsening dysphagia and severe odynophagia.
Possible candida esophagitis Other concerns for dysphagia in
this
AIDS patient include opportunistic infections like herpes
simplex
virus or cytomegalovirus versus noninfectious etiology like
aphthous
Ulcer, esophageal lymphoma or Kaposi sarcoma but it is less
likely compared
to above mentioned etiology.
s/p fluconazole po trial as outpatient for approx 6 days.
fluconazole and acyclovir IV GI consult for EGD
2.Recent episode of Pneumocystis pneumonia.
continue the
completed course of Pneumocystis pneumonia treatment.
Infectious
disease will be consulted and follow his recommendations.
3.AIDS/HIV. CD4 count is 52, viral load is above 400,000.
MAC prophylaxis medications
held HAART.

11. 4.Kaposi sarcoma.
The patient was followed by hematology/oncologist.
Considering to
start local radiation versus chemotherapy. Also he was found
to have
ileocecal mass 2.5 cm. The patient will require colonoscopy to
diagnose the etiology of this mass to rule out involvement of
the gastrointestinal tract of Kaposi sarcoma.
5. Perianal lesions
- Most likely herpes ulcers.
- Obtain HSV 1-2 PCR rectal swab along with HSV Cx of lesions
margin an base of ulcer.
6. Severe malnutrition.
7. Anemia of chronic disease. This is most likely multifactorial
anemia of chronic disease. Gastrointestinal loss of iron should
be

12. 7. Anemia of chronic disease. This is most likely
multifactorial anemia of chronic disease. Gastrointestinal
loss of iron should beruled out. The patient will be
started on oral supplement up to the
esophagogastroduodenoscopy and after he tolerated.
8. Hyponatremia could be secondary to Pneumocystis
pneumonia although other possibilities will be ruled out.
Will follow theserum osmolarity and urine sodium.
9. Gastrointestinal and deep venous thrombosis
prophylaxis measures
will be implemented.

13.  Had 1 episode of loose diarrhea non bloody non mucoid of
small amount. Tmax 101.2f. SIRS 2/4, sepsis. Blood cx
negative x1 day.
- O&P x3, stool cx to r/o OIs.
 Pt was noted to have severe dysphagia not even tolerating
clear liquids which were tolerated before.
 Increased productive cough of whitish sputum and bedside
vital signs revealed a O2 sat of 83-88% with borderline
hypotension BP 99/55. Pt denied SOB, chest pain,
palpitations, lower extremity pain. Pt saturating better at 98-
99% on 50% Non rebreather mask.

14.  Pt desat to 85% AGAIN on non rebreather 50%. Pt in severe
respiratory distress, use of accessory muscles of
respiration.Bilateral worsening infiltrates in the CXR
 ICU TRANSFER FOR VDRF, INTUBATED
 Started on Vancomycin and Zosyn
 Acute hypoxemic ventilator dependent respiratory failure with
ARDS - secondary to IRIS with PJP vs r/o HSV pneumonitis and
concern for superimposed bacterial infections/ HCAP and will
be at risk for VAP now. requiring PEEP of 12 and FiO2 to 100%
- on broad spectrum coverage with clindamycin +
primaquine/acyclovir/zosyn and vancomycin respectively.

15.  Bronchoscopy done blood, respiratory and BAL cultures
as well. culture so far is negative. legionella and
pneumococcal antigen is negative. ID and pulm on
board.
 Severe septic shock- on phenylephrine + Levophed now
with aggressive IV hydration. possible source as # 1 and
will c/w the management as # 1.
 Urine cx revealed Enterococcus faecali, Blood cx
negative 3 days, Pancytopenia - neutropenia -
neutropenic precautions/ given neupogen

18. p.jeruvici(gms)
afb negative
Negative for malignancy

21. perivascular proliferation
Promontory sign
perivascular lymphocyte infiltrate

24.  AFB cultures from 6/7/14 positive s/o
disseminated MAC vs TB as the underlying cause
for ARDS with IRIS.
 Had prbc transfusion while in ICU .
 Started on anti MAC & Tb therapy as discussed with
ID.
 Patient off pressor on day 7 .

30.  VDRF for 9 days,extubated on 7/5/14 as
discussed with pulmonary team after successful
weaning.on high flow oxygen.
 pt failed swallow evaluation secondary to
dysphagia.secondary to voluminaous diarrghea(c
diff ,cx,cryptosporidia,isospora negative)
 Pt to be further evaluated by GI ,Dr.Bhaghal for
persistent voluminous diarrhea,endoscopy for
dysphagia,colonoscopy for ileocaecal mass
 Transfer to medical floor

31.  Awaiting results of quantiferon,DNA probe studies.
 Patient desaturated to 85%, acutely became tachypneic and
tachycaric on high flow O2. Returned to 99%. Pt c/o
generalized weakness unable to use hands.
 EGD was cancelled due to the risk of aspiration during the
procedure.
 NG feeding restarted at low rate. At that time he is
hemodynamically stable is on anti MAC & Tb therapy.
Improved voluminous diarrhea put over 24 hrs 360 cc off
tube feeds.(C-diff, cx, cryptosporidia negative)

32.  He developed bloody melenic stool on the floor and he was
subsequently upgraded to the intensive care unit for further
monitoring and for endoscopy.
 Had EGD, indicating erosive gastritis, large amount of brown
liquid content in stomach, no active bleeding seen, pt needs
colonoscopy when stable. and no evidence of any esophagitis,
candidiasis d patient was monitored for hemoglobin and
vitals. and no evidence of any esophagitis, candidiasis and
patient was monitored closely in the ICU with followup of
hemoglobin and vitals. pt. was started back on TF as per GI.
 pt no longer with bloody stool. Depleted lytes noted and
replaced. Ca 5.7 (L), Mg 1.5 (L), Phos 1.2 (L), K 2.0 (L).
 The patient's guarded prognosis was discussed with the
partner and mother at length.

33.  He had another bright red blood per rectum, hemoglobin
started dropping and emergent colonoscopy in AM was planned
as per Dr. Baghal.
 Overnight the patient's blood pressure continued to drop, not
responding to IV fluids and his blood pressure was dropping and
then he was started on pressors and then patient had asystole
andpatient was coded
 He did have a little spontaneous circulation after 5 minutes and
he started bleeding from the mouth and rectum, and he was
maxed out on 4 pressors and he was getting blood transfusions
in the meantime,
 and then he coded again. Family at this time requested for DNR
DNI and the patient was pronounced dead at 9:03 AM on 07/13.
The patient's family refused autopsy.

35. Kaposi sarcoma (KS) is a vascular tumor that is
etiologically associated with human
herpesvirus 8 (HHV-8)
Although KS has been reported among all risk
groups for HIV infection, it is most common
in homosexual or bisexual men.

36.  Since the introduction of combined antiretroviral
therapy (ART), the incidence of KS has declined
markedly in HIV-infected patients
 The incidence of KS is particularly high during
the first six months following the initiation of
ART, and then falls dramatically with continued
treatment.
 The high incidence immediately following ART
initiation may be attributable to the relatively
severe immunosuppression that led to ART or to
unmasking of KS by the immune reconstitution
inflammatory syndrome.

37.  Corticosteroid therapy has been associated with the induction of
KS and the exacerbation of preexisting KS in HIV-infected
persons.
 The association of corticosteroids with KS is important because
of the frequent use of these agents in HIV-infected patients with
a variety of disorders including immune thrombocytopenia (ITP)
and Pneumocystis jirovecii pneumonia. In such patients, KS
lesions may regress upon reduction or withdrawal of steroids.
 Opportunistic infections have also been associated with the
induction of KS and with the exacerbation of preexisting KS. High
levels of proinflammatory cytokines, which have been
demonstrated in the setting of opportunistic infections, may
account for these effects on KS.

39. Three histologic features that are characteristic of KS, both in
cutaneous and visceral sites:
 angiogenesis,
 inflammation,
 proliferation.
The lesions generally show two major abnormalities:
whorls of spindle-shaped cells with leukocytic infiltration and
neovascularization with aberrant proliferation of small vessels.
 These small vessels lack a basement membrane and display
leaky behavior with microhemorrhages and hemosiderin
deposition. As the disease progresses, it evolves from patches to
plaques, and then to a nodular form.
 The characteristic histologic pattern of KS does not differ among
the affected epidemiologic groups

40.  KS involvement has been observed in almost all
visceral sites, including lymph nodes, liver,
pancreas, heart, the testes, bone marrow, bone,
and skeletal muscle.
 The most frequent sites of noncutaneous disease
are the oral cavity, gastrointestinal tract, and
respiratory system.
 However, visceral involvement as the initial
manifestation of KS is relatively uncommon.
Furthermore, visceral disease now appears to be
much less frequent, given the use of
antiretroviral therapy as well as multiple
treatment options

41.  Prior to the widespread introduction of ART, the gastrointestinal
tract was involved in approximately 40 percent of patients with
KS at initial diagnosis and in up to 80 percent at autopsy.
 Gastrointestinal involvement can occur in the absence of
cutaneous disease.
 Gastrointestinal lesions may be asymptomatic or may cause
weight loss, abdominal pain, nausea and vomiting, upper or
lower gastrointestinal bleeding, malabsorption, intestinal
obstruction, and/or diarrhea .
 Gastrointestinal KS lesions are easily recognized by the
endoscopist. They are typically hemorrhagic nodules that can be
either isolated or confluent and may occur in any portion of the
gastrointestinal tract.

45.  The initial evaluation of a patient with KS consists of a thorough
physical examination with special attention paid to those areas
typically affected by the disease
 Evaluation for visceral involvement is guided by symptomatology
and basic laboratory testing.
 ●Testing the stool for occult blood is the simplest way to screen
for gastrointestinal involvement. Endoscopy is usually reserved
for patients who test positive for occult blood or have
gastrointestinal symptoms.
 ●Chest x-ray is useful to screen for pulmonary lesions.
Bronchoscopy should be reserved for those with an abnormal
radiograph and persistent respiratory symptoms in the absence
of another cause.
 CT scanning of the chest, abdomen, and pelvis is typically not
necessary.
 The CD4 cell count and HIV viral load are important for staging
and prognosis, and thus may be useful in making treatment
decisions.

46. The diagnosis of KS should be confirmed by
biopsy whenever possible, although biopsies
may not demonstrate KS because the lesions
tend to be submucosal.

47.  antibodies directed against CD31 (JC70/A)
and CD34 (QBEND/10 and anti-HPCA-1)
more extensively in Kaposi sarcoma; to
assess their value in routine diagnosis; and to
compare them with the traditional endothelial
cell markers Ulex europaeus agglutinin 1
(UEA-1) and factor VIII related antigen.

48.  Combined antiretroviral therapy
 - Immune reconstitution inflammatory
syndrome
 Local symptomatic therapy
 Systemic chemotherapy
 - Liposomal anthracyclines
 - Taxanes
 Experimental approaches
 Anti-HHV-8 therapy

49. IRIS is a collection of host responses that can occur
following the initiation of ART.
In addition to worsening of symptoms from preexisting
infections with IRIS, the initiation of ART has been
associated with progression of KS within three to six
weeks after starting antiretroviral therapy.
Factors associated with an increased risk of IRIS in patients
initiating ART for HIV include more extensive (T1) KS, a
higher HIV viral load, and the use of ART without
chemotherapy .
Progression of KS in patients with IRIS can be severe and has
been associated with death in some cases

50.  Intralesional chemotherapy — Intralesional
chemotherapy can induce regression of injected
tumors and is preferred for small lesions.
Vinblastine is the most widely used agent.
 Radiation therapy — The primary role of radiation
therapy is to treat symptomatic disease that is
too extensive to be treated with intralesional
chemotherapy, but is not extensive enough to
require systemic therapy.
 Topical — Alitretinoin (9-cis retinoic acid to treat
cutaneous KS lesions.

51.  indications for adding systemic chemotherapy to ART
include:
 ●Widespread skin involvement (eg, more than 25 lesions)
 ●Extensive cutaneous KS that is unresponsive to local
treatment
 ●Extensive edema
 ●Symptomatic visceral involvement
 ●Immune reconstitution inflammatory syndrome (IRIS)
treatment withpegylated liposomal
doxorubicin or liposomal daunorubicin is generally
recommended as the first-line treatment for KS. Other
agents that have been used
include paclitaxel, bleomycin, vinblastine,vincristine,
and etoposide

52. targets include angiogenesis, sex hormones, vitamin D and
its analogs, and cellular differentiation
●Imatinib— Activation of the platelet-derived growth factor
(PDGF) and c-kit receptors (both receptor tyrosine kinases)
are important in the growth of KS lesions and imatinib
inhibits both of these receptors.
●Inhibitors of mTOR pathway — Rapamycin
and temsirolimus are inhibitors of the mTOR pathway and
appear to have activity in patients with KS
●Bevacizumab — Bevacizumab is a monoclonal antibody
directed against vascular endothelial growth factor, which
contributes to the pathogenesis of KS.
●Vitamin D and its analogs — Primary KS tumors and cell
lines derived from KS lesions express high levels of the
vitamin D receptor
● fumagillin and thalidomide

53.  Case-control studies of historical cohorts of
HIV-seropositive subjects suggest that there
is a lower incidence of KS in patients treated
with ganciclovir or foscarnet but not acyclovir

54.  Friedman SL, Wright TL, Altman DF.
Gastrointestinal Kaposi's sarcoma in patients with
acquired immunodeficiency syndrome.
Endoscopic and autopsy findings.
Gastroenterology 1985; 89:102.
 Ioachim HL, Adsay V, Giancotti FR, et al. Kaposi's
sarcoma of internal organs. A multiparameter
study of 86 cases. Cancer 1995; 75:1376.
 Danzig JB, Brandt LJ, Reinus JF, Klein RS.
Gastrointestinal malignancy in patients with
AIDS. Am J Gastroenterol 1991; 86:715.

55. DISCUSSION
What could have been done differently?
Are there any changes to our hospital
protocols that we can change to facilitate
better outcomes for patients?
Thoughts?
Questions?