ORIGINALES Practice Of Central Nervous System

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ORIGINALES
Practice of central nervous system prophylaxis
and treatment in acute leukemias in Spain.
Prospective registry study
210.658
Juan-Manuel Sanchoa, Mireia Morgadesa, Reyes Arranzb, Pascual Fernández-Abellánc,
Guillermo Debend, Natalia Alonsoe, Margarita Blanesf, María José Rodríguezg, Concepción Nicolásh,
Eva Sánchezi, Alberto Fernández de Sevillaj, Eulogio Condek and Josep-Maria Riberaa, on behalf of
investigators of QUIT Study (PETHEMA, GELTAMO and GOTEL Groups)
a
Servicio de Hematología Clínica. ICO-Hospital Germans Trias i Pujol. Badalona. Universitat Autònoma de Barcelona. Barcelona.
Servicio de Hematología. Hospital Universitario de la Princesa. Madrid.
c
Servicio de Hematología. Hospital General Universitario de Alicante. Alicante.
d
Servicio de Hematología. Hospital Juan Canalejo. La Coruña.
e
Servicio de Hematología. Complejo Hospitalario Universitario de Santiago. Santiago de Compostela. La Coruña.
f
Servicio de Hematología. Hospital La Fe. Valencia.
g
Servicio de Hematología. Hospital Universitario de Canarias. Santa Cruz de Tenerife.
h
Servicio de Hematología. Hospital Universitario Central de Asturias. Oviedo. Asturias.
i
Servicio de Hematología. Hospital Vall d’Hebron. Barcelona.
j
Servicio de Hematología. ICO-Hospital Duran i Reynals. L’Hospitalet de Llobregat. Barcelona.
k
Servicio de Hematología. Hospital Marqués de Valdecilla. Santander. Cantabria. España.
b
BACKGROUND AND OBJECTIVE: Central nervous system (CNS) involvement in patients diagnosed with acute leukemias (AL) is an uncommon complication with poor prognosis. The indication and the schedules of prophylaxis
and treatment of CNS involvement in AL are not homogenous among countries and within the same country.
The aim of this prospective longitudinal study was to analyze and report the practice of CNS prophylaxis and
treatment in patients with AL in Spain.
PATIENTS AND METHOD: Prospective study conducted from June 2005 to June 2006. Adult patients (ⱖ 18 yr.)
diagnosed with AL who received CNS prophylaxis or treatment were consecutively included through online registration.
RESULTS: 265 patients from 32 hospitals were included. Mean (standard deviation) age was 44 (16) yr. and
133 (50%) were males. For acute lymphoblastic leukemia patients (n = 158), CNS therapy was given to 12
cases (10 at diagnosis and 2 at relapse) and consisted of triple intrathecal therapy (TIT, methotrexate, cytarabine and hydrocortisone) in 11 and liposomal depot cytarabine in one. CNS prophylaxis (n = 146) consisted
of TIT in 135 cases, intrathecal methotrexate in 7, intrathecal cytarabine in 2 and intrathecal liposomal depot
cytarabine in 2. No cranial irradiation either for prophylaxis or therapy was given in any case. In acute myeloblastic leukemia patients (n = 107), CNS therapy was administered to 17 cases (9 at diagnosis and 8 at relapse). Intrathecal therapy consisted of TIT in 11, intrathecal liposomal depot cytarabine in 5 and intrathecal
cytarabine in one. One patient also received craniospinal irradiation. CNS prophylaxis (n = 90) consisted of
TIT in 68 cases and intrathecal methotrexate in 22.
CONCLUSIONS: In Spain, the patterns of CNS prophylaxis and therapy for AL are homogeneous. TIT was the most
frequent schedule for CNS prophylaxis and therapy. The lack of use of cranial or craniospinal irradiation and
the administration of new drugs (i.e.: liposomal depot cytarabine) for CNS therapy and prophylaxis is of note.
Key words: Acute leukemia. Central nervous system involvement. Intrathecal. Liposomal depot cyitarabine.
Práctica habitual de profilaxis y tratamiento de la infiltración neuromeníngea en pacientes
con leucemia aguda en España. Estudio de registro prospectivo
FUNDAMENTO Y OBJETIVO: La infiltración del sistema nervioso central (SNC) en pacientes diagnosticados de leucemia aguda (LA) es una complicación infrecuente que comporta un mal pronóstico. La indicación y las pautas
de profilaxis y tratamiento de la infiltración neuromeníngea en la LA no son homogéneas en los diferentes países, y tampoco en los diferentes centros de un mismo país. El objetivo de este estudio longitudinal y prospectivo ha sido describir la práctica real de profilaxis y tratamiento de la infiltración neuromeníngea en pacientes
con LA en España.
PACIENTES Y MÉTODO: Se trata de un estudio prospectivo llevado a cabo desde junio de 2005 a junio de 2006.
Se incluyó, mediante registro electrónico, a los pacientes adultos (edad ⱖ 18 años) diagnosticados de LA que
recibieron profilaxis o tratamiento de la infiltración del SNC.
RESULTADOS: Se incluyó a un total de 265 pacientes procedentes de 32 hospitales. La media (desviación estándar) de edad fue de 44 (16) años y 133 (50%) eran varones. Entre los 158 pacientes con leucemia linfoblástica aguda, 12 (10 en el momento del diagnóstico y 2 en recaída) recibieron tratamiento del SNC por infiltración neuromeníngea, que consistió en tratamiento intratecal triple (TIT: metotrexato, citarabina e hidrocortisona)
en 11 casos y citarabina liposómica de liberación lenta por vía intratecal en uno. La profilaxis del SNC administrada en los 146 pacientes restantes incluyó TIT en 135 casos, metotrexato intratecal en 7, citarabina intratecal en 2 y citarabina liposómica de liberación lenta por vía intratecal en 2. No se administró radioterapia
craneal ni craneoespinal a ningún paciente. Entre los 107 pacientes con leucemia mieloblástica aguda, 17
tenían infiltración del SNC (9 en el momento del diagnóstico y 8 en la recaída). El tratamiento intratecal consistió en TIT en 11 casos, citarabina liposómica de liberación lenta en 5 y citarabina intratecal en uno. Un
paciente recibió además radioterapia craneoespinal. La profilaxis del SNC en los 90 pacientes restantes incluyó TIT en 68 casos y metotrexato intratecal en 22.
CONCLUSIONES: En España las pautas de profilaxis y tratamiento de la infiltración neuromeníngea en pacientes
con LA son homogéneas. El TIT fue el esquema usado con mayor frecuencia tanto para la profilaxis como para
el tratamiento del SNC. Llama la atención la escasa utilización de la radioterapia holocraneal o craneoespinal,
así como la administración de nuevos fármacos, como la citarabina liposómica de liberación lenta, en el tratamiento y la profilaxis de la meningosis leucémica.
Palabras clave: Leucemia aguda. Infiltración del sistema nervioso central. Intratecal. Citarabina liposómica de
liberación lenta.
Meningeal involvement in patients diagnosed with acute leukemia (AL) is associated
with poor prognosis. In patients diagnosed
with acute lymphoblastic leukemia (ALL),
this is a well-recognized complication that
appears in about 5% of the patients at the
time of the diagnosis, and in 3-8% of patients at relapse, despite central nervous
system (CNS) prophylaxis1-3. In patients
with acute myeloid leukemia (AML), CNS
involvement is a more infrequent event.
Risk factors for leukemic meningeosis in
both AML and, specially, ALL patients have
been identified, which has led to the development of prophylaxis schedules based on
the administration of CNS-directed therapies such as cranial irradiation, intrathecal
drugs and systemic therapy with drugs
able to cross the blood-brain barrier4-7. However, the schedules of prophylaxis and
treatment of CNS involvement in AL are not
homogeneous in different countries and
even within the same country.
The QUIT (Registro Español de Pacientes
que Reciben Quimioterapia Intratecal) registry was an initiative of the PETHEMA
(Programa para el Estudio y Tratamiento
de las Hemopatías Malignas, Asociación
Española de Hematología y Hemotera-
Study supported in part by grant P-EF/06 from the
José Carreras International Leukemia Foundation. The
study was also partially supported by an unrestricted
grant from Mundipharma Pharmaceuticals SL, and
RD06/0020/1056 from RETICS.
Correspondence: Dr. J.M. Ribera.
Servicio de Hematología Clínica.
Institut Català d’Oncologia-Hospital Germans Trias i Pujol.
Ctra. Canyet, s/n. 08916 Badalona. Barcelona. España.
E-mail: jribera@iconcologia.net
Recibido el 29-5-2007; aceptado para su publicación
5-6-2007.
Med Clin (Barc). 2008;131(11):401-5
401
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SANCHO JM ET AL. PRACTICE OF CENTRAL NERVOUS SYSTEM PROPHYLAXIS AND TREATMENT IN ACUTE LEUKEMIAS IN SPAIN.
PROSPECTIVE REGISTRY STUDY
pia), GEL/TAMO (Grupo Español de Linfomas/Trasplante Autólogo de Médula
Ósea) and GOTEL (Grupo Oncológico
para el Tratamiento y Estudio de los Linfomas) groups designed to prospectively
know the current practice of CNS prophylaxis and therapy in patients diagnosed
with hematological malignancies (AL and
lymphoproliferative disorders) in Spain.
The objective of this study was to report
the practice of CNS prophylaxis and treatment in patients with AL.
Patients and method
This prospective study was conducted from June
2005 to June 2006 in 32 Spanish hospitals. Adult patients (ⱖ 18 yr.) diagnosed with AL who received CNS
prophylaxis or CNS treatment were consecutively included through online registration. Each patient was
included only once. The questionnaire included sociodemographic variables (age, sex, hospital), AL subtype (ALL, AML, and risk group in ALL patients) and
date of diagnosis, presence or absence of meningeal
involvement at diagnosis, timing of the CNS involvement (at diagnosis or at relapse), date of diagnosis of
leukemic meningeosis, neurological symptoms at the
time of CNS involvement, and the method used for
diagnosis of CNS involvement (detection of blast cells
in a sample of cerebrospinal fluid [CSF] by cytology or
by flow cytometry, computed tomography [CT] scan or
magnetic resonance imaging [MRI]).
The following data of CNS therapy were recorded: reason of CNS-directed therapy (prophylaxis or treatment, and in case of prophylaxis, the reason: protocol
requirement, hyperleukocytosis, conditioning regimen
for stem cell transplantation [SCT] and others), date
of the start of intrathecal drugs administered (methotrexate, cytarabine, and triple intrathecal therapy
[TIT], including methotrexate, cytarabine and hydrocortisone), route (intrathecal through lumbar puncture or intraventricular) and schedule of administration,
as well as other CNS-directed therapies such as cranial irradiation or the use of new drugs.
An intermediate analysis after 6 months of start of registry was performed and their results were reported
at meetings of PETHEMA, GEL/TAMO and GOTEL
groups. Results were expressed as crude frequencies
and percentages, and were analyzed separately for
ALL and AML.
Results
A total of 265 patients diagnosed with AL
from 32 hospitals were included. The
mean (standard deviation) age was 44
(16) yr. (range: 18-78) and 133 (50%)
were males. Distribution according to AL
subtype was: ALL in 158 cases (59.6%)
and AML in 107 (40.4%).
Regarding ALL patients (table 1), intrathecal therapy was administered for leukemic
meningeosis in 12 cases and as CNS
prophylaxis in 146. Ten out of 12 patients
with CNS involvement had blast cells at
CSF at the time of the diagnosis, and 2
showed first CNS relapse. Diagnosis of
CNS involvement was established by the
observation of blast cells in CSF in 9 cases, flow cytometry in 8, and MRI or CT
scan in 4. Neurological symptoms included: mental status impairment in 4 cases,
cranial nerve palsy in 5, muscle weakness
in 5, headache in 5, diplopy in 3, sensorial
neuropathy in 2, impairment in march in 2
402
Med Clin (Barc). 2008;131(11):401-5
and loss of vision in one. As shown in table
1, TIT was the most common CNS-directed therapy administered, followed by depot liposomal cytarabine (as compassionate use). Lumbar puncture was the
preferred route for intrathecal administration (11 out of the 12 patients), whereas in
the remaining patient an intraventricular
administration through an Ommaya reservoir was used. Cranial irradiation was not
used in any case. With respect to CNS
prophylaxis (n = 146), TIT was also the
most frequent schedule (table 1), but the
use of intrathecal depot liposomal cytarabine in 2 patients is of note. The reasons
reported by the investigators for the compassionate use of this drug were the development of arachnoiditis due to intrathecal
methotrexate in one case, and a high white blood cell count in the remaining patient. As occurred in patients with CNS involvement, lumbar puncture was the most
frequent route for intrathecal administration (144 cases; 98.6%), whereas an Ommaya reservoir was used in only 2 patients
(1.4%). Cranial or craniospinal radiotherapy was not administered as CNS prophylaxis in any case.
Patients with AML (table 2) received intrathecal therapy for leukemic meningeosis in 17 cases and as CNS prophylaxis in
the remaining 90. Nine out of these 17
patients showed CNS leukemia at the
TABLE 1
Main characteristics of the acute
lymphoblastic leukemia patients
(n = 158) included in the QUIT Registry
Variable
Age (yr)*
40 (16)
Gender (M/F)
82/76
Subtype ALL
High-risk non-Ph ALL
Intermediate-risk ALL
Mature B ALL (Burkitt’s leukemia)
Ph ALL
Not specified
90
22
15
27
4
Therapy for CNS involvement (n = 12)
TIT
Methotrexate
Cytarabine
Depot liposomal cytarabine
Cranial or craniospinal irradiation
11
0
0
1
0
Therapy for CNS prophylaxis (n = 146)
TIT
Methotrexate
Cytarabine
Depot liposomal cytarabine
Cranial or craniospinal irradiation
135
7
2
2
0
Reason for CNS prophylaxis (n = 146)
Protocol requirement
Relapse
Conditioning regimen for SCT
136
5
5
*Mean (standard deviation). ALL: acute lymphoblastic leuke-
mia; CNS: central nervous system; F: female; M: male; Ph
ALL: Philadelphia chromosome-positive acute lymphoblastic
leukemia; QUIT Registry: Registro Español de Pacientes que
Reciben Quimioterapia Intratecal; SCT: stem cell transplantation; TIT: triple intrathecal therapy (including methotrexate, cytarabine and hydrocortisone).
time of diagnosis and 8 as relapse. Diagnosis of CNS involvement was established by: cytology (n = 10), flow cytometry
(n = 6), and CT scan or MRI (n = 8).
Neurological symptoms included: headache in 9 patients, vomiting in 7, impairment in march in 6, muscle weakness in
4, sensorial neuropathy in 4, cranial nerve palsy in 3, mental status impairment
in 2, diplopy in 2 and loss of vision in 1.
TIT was the most frequent CNS-directed
therapy, but 5 patients received intrathecal depot liposomal cytarabine (as compassionate use). Only 2 patients received
intrathecal therapy through an Ommaya
reservoir. Craniospinal irradiation was given to one patient. The remaining 90 patients with AML received intrathecal therapy as prophylaxis (in all cases by
lumbar puncture), with TIT again being
the most frequent schedule reported (table 2). Similar to ALL patients, radiotherapy was not administered in any case.
Tables 1 and 2 show that protocol requirement was the most frequent reason for
CNS prophylaxis, followed by the administration of intrathecal therapy as part of
the conditioning regimen for SCT.
Discussion
This is the first study that prospectively
describes the current practice of prophylaxis and therapy for leukemic meningeosis in Spain. This study demonstrates
that, in the Spanish population with AL,
CNS prophylaxis and therapy schedules
are homogeneous, with TIT through lumbar puncture being the most frequent
therapy for CNS involvement or CNS
prophylaxis. Two additional features are
of note: the lack of use of cranial or craniospinal irradiation for prophylaxis or
therapy of leukemic meningeosis, and
the compassionate use of new formulations of drugs, such as liposomal depot
cytarabine, in CNS involvement and even
for CNS prophylaxis.
Most of the information on CNS prophylaxis or therapy in patients diagnosed with
hematological malignancies is provided
by the analysis of patients treated according to local or multicenter protocols, but
systematic reviews on the current practice of CNS chemoprophylaxis have only
been reported in non-Hodgkin’s lymphoma patients8,9, but not in patients with
AL.
The uniform results of CNS prophylaxis in
ALL are due to the wide use of the riskadapted protocols from the PETHEMA
group in Spain10-16, which only included
TIT as CNS prophylaxis and limited the
use of CNS irradiation for selected cases
of T-cell ALL in children with hyperleukocytosis in the early studies. With respect to the type of intrathecal therapy,
two features should be pointed out. First,
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SANCHO JM ET AL. PRACTICE OF CENTRAL NERVOUS SYSTEM PROPHYLAXIS AND TREATMENT IN ACUTE LEUKEMIAS IN SPAIN.
PROSPECTIVE REGISTRY STUDY
TABLE 2
Main characteristics of the acute
myeloid leukemia patients (n = 107)
included in the QUIT Registry
Variable
Age (yr)a
49 (14)
Gender (M/F)
51/57
AML subtype
AML
Relapse of AML
APL
Relapse of APL
96
4
4
3
Therapy for CNS involvement (n = 17)
TIT
Methotrexate
Cytarabine
Depot liposomal cytarabine
Cranial or craniospinal irradiation
11
0
1
5
1
Therapy for CNS prophylaxis (n = 90)
TIT
Methotrexate
Cytarabine
Depot liposomal cytarabine
Cranial or craniospinal irradiation
68
22
0
0
0
Reason for CNS prophylaxis (n = 90)
AML subtypeb and/or protocol
requirement
Conditioning regimen for SCT
High WBC count
Extramedullary involvement
69
14
6
1
a
Mean (standard deviation); bmyelomonocytic or monocytic
subtypes. AML: acute myeloid leukemia; APL: acute promyelocytic leukemia; CNS: central nervous system; F: female; M:
male; QUIT Registry: Registro Español de Pacientes que Reciben Quimioterapia Intratecal; SCT: stem cell transplantation;
TIT: triple intrathecal therapy (including methotrexate, cytarabine and hydrocortisone); WBC: white blood cells.
the use of hydrocortisone instead of the
more common dexamethasone, prednisone or prednisolone described in other
studies3,17. This was due to the fact that
in Spain the protocols for adult ALL patients were developed from ongoing pediatric trials in which hydrocortisone was
the steroid drug used in TIT11,14,16. On the
other hand, the use of combined intrathecal therapy instead of monotherapy
with intrathecal methotrexate or intrathecal
cytarabine reported in other studies is of
note2,18. Despite these two differences, the
frequency of CNS relapse in Spain using
TIT as CNS prophylaxis1 was not different
from that reported in other studies.
Another remarkable point in this study is
the scarce use reported of intrathecal
prophylaxis in the conditioning regimen
for SCT. The reason could be that this is
not an uniformly admitted practice in SCT
units. Thus, a recent survey carried out
among EBMT (European Group for Bone
Marrow Transplantation) centers showed
that 47% of them never used pre-transplant intrathecal prophylaxis as part of
the conditioning regimen for allogeneic
SCT, whereas only 32% gave prophylactic intrathecal therapy after SCT19.
In this study, the low frequency of cranial
or craniospinal irradiation as CNS
prophylaxis or treatment schedules in
both ALL and AML is of note. In fact, recent studies performed in childhood
ALL20-23 have described low rates of CNS
relapse in patients in which CNS prophylaxis consisted of intrathecal therapy and
systemic chemotherapy with drugs able
to pass the blood-brain barrier, without
concomitant radiotherapy. In these studies radiotherapy was eliminated to avoid
its long-term effects on cognitive and endocrine function. Several studies have
demonstrated similar results in adults. In
a previous study from the PETHEMA
group1, the frequency of CNS recurrence
was only 5.8%, similar to that described
in other studies in which CNS radiotherapy was omitted, provided that intrathecal therapy was used together with highdose systemic therapy2,18,24. In addition,
in the present study radiotherapy was not
used as CNS therapy in cases of initial involvement or CNS relapse in both ALL
and AML (except in one patient), in spite
of the poor prognosis associated with these events. This was probably because intrathecal and high-dose systemic therapy
can adequately control CNS disease, and
the cause of this poor prognosis is in fact
systemic relapse, often present at the
time of CNS relapse. In this situation, the
best approach is systemic and CNS-directed therapy followed by SCT25-27.
The compassionate use of new formulations of intrathecal drugs such as depot
liposomal cytarabine is of note in this
study, provided that there is no accepted
indication by the regulatory agencies outside of neoplastic28-30 and lymphomatous31 meningeosis. Intrathecal depot liposomal cytarabine is a sustained-released
formulation of cytarabine that maintains
cytotoxic concentrations of the drug in
the CSF during more than 2 weeks, thereby allowing fewer intrathecal administrations32,33. Despite the demonstrated efficacy in CNS involvement from solid
tumors and lymphomas, there is scarce
information on its use in AL, mostly reported as individual cases or small series34-36. The largest reports are focused
on its use in meningeosis from ALL37,38
and describe response rates of about
80%. In a previous report from our
group36, 3 out of 4 patients with CNS involvement in AL treated with intrathecal
depot liposomal cytarabine (in 2 cases as
the only drug and in the remaining as adjuvant therapy to other CNS-directed therapies) achieved blast cell clearance in
CSF, whereas the remaining patient showed partial response. In an update of a
European collaborative study with 19 patients recruited, the response rate was
83% in ALL patients and 43% in patients
with Burkitt’s lymphoma or B-ALL (N.
Gökbuget, personnel communication).
Reports on the effectiveness of intrathecal depot liposomal cytarabine in AML
are extremely infrequent, but in another
study by our group39, 5 out of 6 AML patients receiving this drug alone achieved
cytologic response, although all responders also received systemic therapy with
high-dose cytarabine. Regarding the use
of intrathecal depot liposomal cytarabine
as CNS prophylaxis, there are 2 studies
in which the feasibility of the administration of this drug has been demonstrated40,41. In this sense, the recently published study by Jabbour et al41 points out
that 5 out of 31 patients (16%) developed neurotoxicity, almost always related
to the concomitant administration of systemic high-dose methotrexate and cytarabine (in this study high-dose cytarabine
was 3 g/m2 administered every 12 h for 2
days). These adverse events have not
been described in other series. The promising results with intrathecal depot liposomal cytarabine justify the development
of clinical trials to establish the role of this
new formulation in the therapy and the
prophylaxis of leukemic meningeosis.
The lack of the systematic inclusion of all
the cases in which CNS-directed therapy
was administered in Spain constitutes the
main limitation of the present study. However, this is probably a representative
sample since the results of the present
study are very similar to those obtained
from the analysis of the frequency and
patterns of CNS relapse in patients with
ALL in the PETHEMA studies1. There are
no similar published studies in AML, and
consequently the magnitude of the possible biases of the present study cannot be
demonstrated. A report on the use of
CNS-directed therapy in cases of AML
with CNS involvement carried out in Italy42
showed the preferential use of intrathecal
therapy, although the combination of intrathecal therapy, CNS irradiation and
high-dose systemic therapy yielded promising results.
The results of the QUIT Registry demonstrated the preferential use of intrathecal
therapy by lumbar route for prophylaxis
and therapy of AL meningeosis in Spain,
with the main reason for use being in the
setting of protocols for therapy of AML
and ALL. The lack of use of cranial irradiation is in concordance with modern
protocols in which irradiation tends to be
omitted due to excess toxicity when combined with chemotherapy. Finally, the anticipated phenomenon of compassionate
use of new formulations of drugs (such
as depot liposomal cytarabine) for which
a formal indication is still not established
has to be emphasized.
Acknowledgements
The following institutions and clinicians participated in the study: Hospital Universitari Germans Trias i Pujol, Badalona (J.M. Ribera, J.M.
Med Clin (Barc). 2008;131(11):401-5
403
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SANCHO JM ET AL. PRACTICE OF CENTRAL NERVOUS SYSTEM PROPHYLAXIS AND TREATMENT IN ACUTE LEUKEMIAS IN SPAIN.
PROSPECTIVE REGISTRY STUDY
Sancho, M. Morgades); Hospital Universitario
de la Princesa, Madrid (R. Arranz); Hospital
General Universitario de Alicante, Alicante (P.
Fernández-Abellán); Hospital Juan Canalejo, A
Coruña (G. Deben); Complejo Hospitalario Universitario de Santiago, Santiago de Compostela
(N. Alonso); Hospital Universitario La Fe, Valencia (M. Blanes); Hospital Universitario de
Canarias, Santa Cruz de Tenerife (M.J. Rodríguez); Hospital Universitario Central de Asturias, Oviedo (C. Nicolás); Hospital Vall d’Hebron, Barcelona (E. Sánchez); Hospital Duran i
Reynals, L’Hospitalet de Llobregat (A. Fernández de Sevilla); Hospital Marqués de Valdecilla,
Santander (E. Conde); Hospital Josep Trueta,
Girona (M. Hermosilla); Hospital Xeral, Lugo (J.
Arias); Hospital Universitario de Getafe, Madrid
(J.A. García); Hospital Universitario Virgen de la
Arrixaca, Murcia (P. Rosique); Hospital del
Mar, Barcelona (E. Abella); Hospital de Basurto, Bilbao (J.A. Márquez); Hospital Universitario
Príncipe de Asturias, Madrid (J. García); Hospital Universitario de Salamanca, Salamanca (L.
Vázquez); Hospital Universitario Miguel Servet,
Zaragoza (A. Rubio); Complexo Hospitalario
Universitario de Vigo, Pontevedra (C. Albo);
Hospital Clínico de Zaragoza, Zaragoza (L. Palomera); Hospital Virgen del Camino, Pamplona
(M.C. Mateos); Hospital General Universitario
Gregorio Marañón, Madrid (M. Mayayo); Hospital Universitario La Paz, Madrid (M.A. Canales);
Hospital de Fuenlabrada, Madrid (J.A. Hernández); Complejo Hospitalario de Jaén, Jaén (J.A.
López); Hospital Clínico Universitario de Valladolid, Valladolid (F.J. Fernández); Hospital de
Móstoles, Madrid (M.A. Andreu); Hospital Universitario Central de Asturias, Asturias (P. Chamorro); Hospital 12 de Octubre, Madrid (R.
Toscano); Hospital de Sant Pau, Barcelona (S.
Brunet).
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CRÍTICA DE LIBROS
Manual básico de cirugía bariátrica
para internistas clínicas médicas
de Norteamérica
Editado por Nilesh A. Patel, Lisa S. Koche.
Barcelona: Elsevier; 2007. 215 páginas.
Los primeros tres capítulos del libro son básicos para un internista: «Conocer el impacto
económico de la obesidad», «La evaluación
preoperatoria o la asistencia perioperatoria del
paciente intervenido» y el manual básico para
el internista de las distintas técnicas en cirugía
bariátrica. Sólo con este conocimiento, podrá
colaborar con cualquier unidad dedicada a
esta enfermedad.
El cuarto capítulo es interesante, pues se
adentra en el paciente que ya ha sufrido infinidad de tratamientos médicos y sus fracasos y
exige ser intervenido. Los autores también encuadran su proyecto en la mujer fértil intervenida de su obesidad, que puede presentar
problemas en el seguimiento a largo plazo,
bien sea por la hipoabsorción de anticonceptivos, bien por carencias de vitamina B (para
ella o el feto) o de ácido fólico, con posibles lesiones neuronales.
¿Y por qué no conocer los aspectos metabólicos que tan bien conocen hoy día los cirujanos
que se dedican a este tema? ¿Quién iba a decir que el mejor tratamiento de la diabetes del
adulto es la cirugía metabólica o que la hipoglucemia hiperinsulinémica endógena, es decir la neuroglucopenia, es una consecuencia
de una hipersecreción de GLP-1? Una revuelta
a la normalidad en un metabolismo mal encaminado en el obeso.
El impacto de la cirugía en el paciente obeso
con trastorno cardiovascular es tremendo. En
este siglo, un cardiólogo debe conocer qué
son las adipocinas (leptina y adiponectina) si
no quiere perder el concepto de la nueva fisiopatología cardiovascular de sus pacientes.
La obesidad, además de un problema de
peso, es una enfermedad de inflamación sistémica. El obeso presenta cambios moleculares
y anatómicos con sus consecuencias: asma,
apnea obstructiva del sueño, síndrome de hipoventilación e hipertensión pulmonar. Esta es
la ganancia final pero, para que toda vaya
bien, hay que reconocer que el obeso es un
enfermo que precisa una evaluación cuidadosa, multidisciplinaria, antes y después de la cirugía bariátrica. La conclusión final es simple y
cal complications associated with intrathecal liposomal cytarabine given prophylactically in
combination with high dose methotrexate and
cytarabine to patients with acute lymphocytic
leukemia. Blood. 2007;109:3214-8.
42. Castagnola C, Nozza A, Corso A, Bernasconi C.
The value of combination therapy in adult acute
myeloid leukemia with central nervous system involvement. Haematologica. 1997;82:577-80.
demoledora: la cirugía para perder peso parece ser inestimable en el tratamiento de la disfunción pulmonar relacionada con la obesidad.
Al médico de atención primaria le acudirán
pacientes intervenidos en quienes las consecuencias de la técnica y el diseño le incomodarán. La esteatohepatitis no alcohólica, la incidencia de litiasis postoperatorias, reflujo
gatroesofágico si el paciente lleva una banda
gástrica, son ejemplos de lo que se avecina.
Muchos trastornos nuevos como la oclusión, la
hernia interna o la invaginación, los aporta la
propia técnica y por el sólo hecho de haber
sido intervenidos.
Es necesario e imprescindible el papel de un
psicólogo en la valoración preoperatoria y todavía lo es más en el control postoperatorio de
algunos pacientes. Las consecuencias de la
intervención son impredecibles y particulares
y, por consiguiente, es necesario tener la posibilidad de dirigir a quien lo precise, y pueden
ser muchos, a un profesional que conozca el
tema. La experiencia de los autores de este
capítulo, en la que expresan su valoración de
2.500 pacientes candidatos a este tipo de cirugía, merece ser leída y tenida en cuenta.
Muchas de las complicaciones de las 250.000
intervenciones que posiblemente se realizarán
en Estados Unidos en el próximo año presentarán complicaciones. El médico que ha derivado a un determinado paciente a un centro
de excelencia en este tipo de técnicas deberá
cargar luego con el control ambulatorio de ese
paciente. Ése va a ser el pacto. La incidencia,
la presentación clínica y el tratamiento de las
complicaciones frecuentes deberán ser tenidas en cuenta y, sobre todo, conocidas por los
médicos responsables. ¿Cómo resolverá un
médico de asistencia primaria una ictericia
obstructiva si al paciente no se le puede realizar una colangiografia retrógrada endoscópica? ¿Cómo tratará una esofagitis por candidas
o una discinesia biliar? Y, sobre todo, ¿qué
hará cuando el paciente presente una gastroenteritis grave en un intestino corto o, simplemente, como suele pasar, recupere parte del
peso perdido con el tiempo y le pregunte por
qué?
En cuanto al capítulo de las complicaciones de
la banda gástrica, aunque el autor lo defina
como un tratamiento nuevo y prometedor, lo
cierto es que ya se conocen sus efectos y su
consecuencias, no muy buenas. Ajuste y reversibilidad son dos premisas que venden el
proceso, pero lo cierto es que es mejor remitirlos de nuevo a su cirujano, pues un médico de
asistencia primaria sólo puede hacer eso. Su
cirujano, si se ha complicado el proceso, debe
retirar la banda. Otra cosa es si en el año 2008
hay alguna indicación para colocar una banda
gástrica.
La obesidad es una forma de desnutrición. La
desnutrición es una consecuencia en muchos
pacientes de las técnicas hipoabsortivas, cada
vez más agresivas, que se realizan. Vitaminas
y minerales de por vida. En este penúltimo capítulo del libro, los autores a quienes corresponde esta tarea se adentran en reconocer la
desnutrición provocada y por ello es importante un estricto seguimiento por el equipo multidiciplinario y dietético, pues todos sabemos
que más del 50% de los pacientes presentarán algún grado de mala nutrición. Y saben
una cosa: muchos pacientes dejan de acudir
al seguimiento programado.
Y finalmente, el último capítulo, donde los autores afirman que existe una incidencia relativamente baja de complicaciones relacionadas
con el embarazo en pacientes que han sido intervenidas. Macrosomía, hipertensión inducida
por el embarazo, preeclampsia y diabetes gestacional, frecuentes en una madre obesa, son
inferiores si el peso se normaliza y similares a
las mujeres no obesas de la población general.
Aun así, se recomienda retrasar cualquier embarazo 2 años, aunque puede ser difícil pues
no existe consenso en cómo conseguirlo. Naturalmente, otro efecto beneficioso se verifica en
las pacientes con ovarios poliquísticos o con
esterilidad. Ambas afecciones mejoran con una
normalización del peso. Aunque estas beneficiosas consecuencias no deben ser consideradas como una indicación de la cirugía, sí que
pueden valorarse como ganancia secundaria
significativa para pacientes prospectivas.
En fin, hay que ver lo que están dando de sí la
obesidad y la cirugía. Los internistas, a quienes va dirigido este libro, deben leerlo con
atención, pues muchos de los pacientes intervenidos serán los suyos.
Solamente una última observación. Aconsejaría a los autores añadir junto al concepto de
bariátrica, la denominación de metabólica.
Antoni Alastrué Vidal
Unidad Hepatobiliopancreática, Metabólica-Obesidad,
Endocrino. Hospital Germans Trias i Pujol.
Badalona. Barcelona. España.
Med Clin (Barc). 2008;131(11):401-5
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