CASE REPORT
Periphera l obst ruct ive a rt eria l disea se w orsened by use of gem cit a bine for
t he t rea t m ent of pa ncrea t ic ca ncer: ca se report a nd review of t he lit era t ure
Edua rdo Licht e nfe lsI; Te lm o Pedro Bona m igoI I; Vinícius C. PiresI I I; M á r cio Luis Luca sI V; Da ia ne Schlindw e inV
IVascular surgeon. Graduat e st udent in Medicine, Pat hology, Fundação Faculdade Federal de Ciências
Médicas de Port o Alegre ( FFFCMPA) , Port o Alegre, RS, Brazil.
I IAssociat e professor, Vascular surgery, FFFCMPA, Port o Alegre, RS, Brazil. Head, Vascular Surgery
Service, I rm andade Sant a Casa de Misericórdia de Port o Alegre ( I SCMPA) , Port o Alegre, RS, Brazil.
I I IResident in Vascular Surgery, FFFCMPA, Port o Alegre, RS, Brazil. I SCMPA, Port o Alegre, RS. I VVascular surgeon. Graduat e st udent , Medicine, Hepat ology, FFFCMPA, Port o Alegre, RS, Brazil. VMedical st udent , Universidade Lut erana do Brasil ( ULBRA) , Canoas, RS, Brazil.
Correspondence
J Vasc Bras. 2007; 6( 3) : 293- 6.
ABSTRACT
We report a case of lower lim b crit ical ischem ia associat ed wit h chem ot herapy wit h gem cit abine. This report present s a case of a 68- year- old m an who underwent pancreat oduodenect om y due t o
pancreas t um or. One m ont h lat er, t he pat ient was subm it t ed t o four chem ot herapy sessions wit h gem cit abine for 1 m ont h. I n addit ion, 30 days lat er he developed sym pt om s of peripheral art erial obst ruct ive disease, and crit ical ischem ia of t he right lower lim b 2 weeks lat er. An im aging st udy showed diffuse art erial disease associat ed wit h fem oropoplit eal occlusion and poor dist al bed. The pat ient was subm it t ed t o a revascularizat ion procedure, which was unsuccessful due t o local condit ions, result ing in above- knee am put at ion.
Keyw ords:Chem ot herapy, t hrom bosis, neoplasm s.
RESUM O
isquem ia crít ica do m em bro inferior direit o. O exam e por im agem dem onst rou doença art erial difusa associada à oclusão fem oropoplít ea com reenchim ent o dist al precário. O pacient e foi subm et ido a um a t ent at iva de revascularização que, devido às condições locais, foi m alsucedida, result ando na am put ação do m em bro no nível da coxa.
Pa la vr a s- cha ve:Quim iot erapia, t rom bose, neoplasias.
I nt roduct ion
Dist al art erial ischem ia is a rare com plicat ion caused by chem ot herapy and probably associat ed wit h preexist ing organic diseases.1 The chem ot herapeut ic agent s used for t he t reat m ent of cancer have
been associat ed wit h t hree form s of vascular t oxicit y: hepat ic and pulm onary venoocclusive disease,2
venous and art erial t hrom bosis3 and brain, m yocardial and lim b ischem ia.4 There is a large num ber
of drugs causing vascular t oxicit y ( Table 1) .1 , 5 , 6 The exact pat hogenesis of vascular lesions has not
been com plet ely cleared so far.1 Ot her causes of vascular disease should be st udied, since neoplasm s alone can cause vascular t oxicit y. I n addit ion, previous vascular diseases associat ed wit h t obacco are frequent .1 , 5
Gem cit abine is an act ive nucleoside analogue t hat act s against a wide range of solid t um ors. Toxicit y is low, and t he m ost frequent com plicat ions are m yelosuppression and nausea.7 - 1 0 Throm bot ic
m icroangiopat hy is a report ed, alt hough rare com plicat ion.1
Case descript ion
A 68- year- old m ale pat ient wit h diagnosis of pancreat ic adenocarcinom a. He report ed being a sporadic sm oker and hypert ensive for long t im e, and denied diabet es m ellit us or ot her diseases.
Over t he 3 m ont hs previous t o diagnosis, t he pat ient developed ast henia and lost 11 kg. He did not have cachexia, only weight loss. I n addit ion, he report ed abdom inal discom fort over t he past 3 weeks. On vascular exam inat ion, t he pat ient had present and full fem oral and poplit eal pulses and reduced, but present dist al pulses. Com put ed t om ography showed a 2- cm t um or in t he pancreas head. The pat ient was subm it t ed t o duodenopancreat ect om y wit h good surgical and oncological out com e. I n t he following m ont h, he was subm it t ed t o four sessions of chem ot herapy wit h
gem cit abine for 30 days. Two weeks aft er t he last chem ot herapy session, t he pat ient had right lower lim b cooling and pain. Crit ical ischem ia wit h rest pain was diagnosed t hree weeks aft er t he end of chem ot herapy. Poplit eal and dist al pulses were not palpable, and t he foot was cold and pale. The pat ient had norm al coagulogram and slight ly increased inflam m at ory m arkers ( globular
sedim ent at ion velocit y = 32) . Art eriography showed diffuse art erial disease associat ed wit h fem oropoplit eal occlusion wit h ankle recanalizat ion ( Figure 1) . The pat ient was t hen subm it t ed t o explorat ory surgery wit h t he aim of revascularizing t he lower lim b, but t he lim b had no local condit ions t o perform t he procedure. He was t hen subm it t ed t o right lower lim b am put at ion at t he t high level. The art eries, t hrough t he whole fem oropoplit eal and dist al ext ension, had m uch adherence, significant inflam m at ory process, t hickening and lum en t hrom bosis.
The anat om opat hological exam inat ion of t he right lower lim b showed diffuse at herosclerosis, fibrous plaques, art erial lum en t hrom bosis and art erial t hickening due t o t he inflam m at ory process of t he m edial layer.
Discussion
I schem ic com plicat ions of t he lower lim bs in oncological pat ient s are rare. Vascular disease is m ore frequent ly associat ed wit h sm oking, dyslipidem ia, hypert ension and diabet es m ellit us.1 Vasculopat hy
is also relat ed t o t um ors t hat produce m ucin or not , as well as t o ant icancer t reat m ent .1 , 5 , 6 , 1 0 Art erial com plicat ions relat ed t o pancreat ic neoplasia are rare and m ore frequent ly m icroangiopat hic.1 I t is hard t o at t ribut e t he genesis of vascular disease t o only one fact or when all fact ors are present .1 , 1 1
However, different ly from venous t hrom boem bolic com plicat ions, art erial t hrom boses are rare.
duodenopancreat ect om y. However, even in t hat procedure survival is low. Adj uvant chem ot herapy is used in m ost cases, especially in m ore advanced st ages. Gem cit abine is one of t he chem ot herapeut ic drugs used in adj uvant t reat m ent .1 2 , 1 3
Art erial t hrom bot ic com plicat ions have been described in cisplat in- based chem ot herapeut ic regim es for t he t reat m ent of germ inat ive cell t um ors. Vos et al. described t hree cases com plicat ed due t o art erial occlusion and one due t o silent m yocardial infarct ion. These event s occurred 10 days aft er t he beginning of chem ot herapy and im proved wit h t reat m ent cessat ion.6 There are m any report s
describing t hrom boem bolic com plicat ions relat ed t o chem ot herapy for germ inat ive cell t um ors.1 1 , 1 4 - 1 6
Chem ot herapy for breast neoplasia has a 1.3% incidence of art erial t hrom bosis during t he t reat m ent . Use of t am oxifen and reduct ion in levels of C and S prot ein seen during t he t reat m ent seem t o be fact ors relat ed t o art erial com plicat ions, but t heir m echanism s rem ain unknown.1 , 1 5
Gem cit abine, which is an analogue of t he ant im et abolit e ara- C, has not been associat ed wit h art erial ischem ia, t hrom bosis or vascular spasm . However, t hrom bot ic m icroangiopat hy is one of t he art erial com plicat ions relat ed t o gem cit abine.1 I t is a drug wit h few collat eral effect s, such as pulm onary
t oxicit y wit h alveolar lesion, venoocclusive disease wit h hepat ic failure, changes in glom erular filt rat ion and hem olyt ic urem ic syndrom e.1 8 - 2 2
Barceló et al. report ed four cases of pat ient s who developed dist al ischem ic com plicat ions associat ed wit h com bined chem ot herapy wit h cisplat in and gem cit abine. Two of t hese pat ient s were subm it t ed t o infracondylar am put at ion, one t o t hrom bect om y, and t he last was t reat ed wit h plat elet
ant iaggregat ing agent s and vasoact ive drugs. I n t hose four cases, dist al ischem ia was at t ribut ed t o chem ot herapy. I t is im port ant t o st ress t hat all pat ient s had hist ory of sm oking.1
I n t he present case, t he pat ient had few risk fact ors for vascular disease before t he
chem ot herapeut ic t reat m ent . Sporadic sm oking and hypert ension, when under cont rol, do not generally cause sudden art erial occlusive event s, but at herosclerosis and chronic vascular disease wit h insidious evolut ion. Therefore, diffuse at herosclerosis dem onst rat ed in art eriography could be at t ribut ed t o sm oking and hypert ension. The likely associat ion bet ween ischem ic alt erat ions and t reat m ent using gem cit abine is due t o t he sequence of event s and period of sym pt om occurrence. Mechanism and pat hogenesis rem ain unexplained. I n addit ion, t he inflam m at ory process of t he art erial wall diagnosed by anat om opat hological exam inat ion indicat es an inflam m at ion t hat could have it s origin in chem ot herapeut ic drugs.
Crit ical ischem ia of t he lower lim bs in oncological pat ient s is a rare event . Peripheral ischem ic sym pt om s, especially when associat ed wit h chem ot herapy wit h gem cit abine, should be st rict ly followed. As a result of dem ocrat izat ion of chem ot herapeut ic t reat m ent s, ischem ic alt erat ions should always be considered due t o risk of evolut ion for crit ical ischem ia and lim b am put at ion. Furt her st udies are needed t o confirm t his associat ion and it s respect ive im pact on clinical pract ice.
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Correspondence:
Eduardo Lichtenfels
Rua Hon„rio Silveira Dias, 1500/305 CEP 90540-070 – Porto Alegre, RS, Brazil Tel.: (51) 3325.5379
Fax: (51) 3314.3599
Email: [email protected]
This study was carried out at the Course of Vascular Surgery, Department of Surgery, FFFCMPA, and at Vascular Surgery Service, ISCMPA.
