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J Neurooncol (2011) 104:545551

DOI 10.1007/s11060-010-0512-2

Ventriculoperitoneal shunt for hydrocephalus caused by central

nervous system metastasis
Seung Hoon Lee Doo Sik Kong Ho Joon Seol Do-Hyun Nam Jung-Il Lee

Received: 1 September 2010/Accepted: 20 December 2010/Published online: 28 January 2011

Springer Science+Business Media, LLC. 2011 adequate cancer treatment after VPS may provide the best
means of improving survival.
Keywords Ventriculoperitoneal shunt CNS
Abstract The development of better diagnostic tools and
metastasis Risk factor Survival
therapeutic modalities has increased the incidence of central
nervous system (CNS) metastasis in malignant tumor
patients. Hydrocephalus can result from CNS metastasis and
frustrate cancer treatment. The authors sought to investigate
the outcomes and the roles of ventriculoperitoneal shunts
Approximately 2535% of cancer patients will develop
(VPS) in patients with CNS metastasis. The medical records
brain metastasis [1]. The incidence of metastasis to the CNS
of 50 consecutive patients who underwent VPS for
is likely to increase due to introduction of better diagnostic
hydrocephalus related to CNS metastasis were analyzed
tools, which enable earlier detection, and to the development
retrospectively. Data included features of primary
of more efficient therapeutic modalities, which enable
malignancies, CNS involvement, clinical course and
longer systemic control and longer survival. Furthermore,
surgical outcome. Median patient age was 55.0 years (range
regardless of brain parenchymal metastasis, LMS (also
2577), and 30 female and 20 male patients were included
known as meningeal carcinomatosis, neoplastic meningitis,
in the study. At the time of VPS, 10 patients had
and carcinomatous meningitis) is in itself a devastating
parenchymal metastases only and 40 patients had
complication of cancer that affects 58% of patients with
leptomeningeal seeding (LMS). Symptom improvement
solid tumors [25].
was observed postoperatively in 40 patients (80%), mean
Of the various clinical manifestations of secondary CNS
Karnofsky performance status (KPS) scale change was from
malignancies, hydrocephalus may result from the
37.8 to 46.0, and median survival from VPS was 3.0 months
obstruction of a CSF pathway by a large mass or from the
(2 days to 54 months). A ventricular opening pressure of[30
dissemination of metastatic cells in the subarachnoid space
cmH2O (HR 6.44, 95% CI 1.2632.9,P= 0.02) andfurther
inducing CSF malabsorption. Symptoms of hydrocephalus,
cancer treatmentafter VPS (HR 0.17, 95% CI 0.070.42,
such as headache, nausea, vomiting, gait disturbance,
P\0.0001) were found to be independent risk factors of
urinary incontinence, cranial nerve palsy, and even mental
poorer and better survival, respectively. Hydrocephalus in
change, are disabling enough to prevent systemic cancer
CNS metastasis requiring VPS is commonly associated with
treatments [3]. In this paper, we present the clinical features
LMS. VPS is an effective palliative measure and an
and outcomes of our patients with advanced stage
Materials and methods
S. H. Lee D. S. Kong H. J. Seol D.-H. Nam
In this retrospective study, we enrolled 50 consecutive
J.-I. Lee (&)
Department of Neurosurgery, Samsung Medical Center, patients with a diagnosis of CNS metastasis who underwent
Sungkyunkwan University School of Medicine, VPS between March 2003 and March 2010. Patients with a
Seoul, Republic of Korea e-mail: primary brain tumor were excluded. All patient records were
reviewed for presenting symptoms, type of primary
CNS metastasis and hydrocephalus after VPS. malignancy, onset of CNS involvement, presence of LMS,

546 J Neurooncol (2011) 104:545551
type of hydrocephalus, ventricular opening We placed VPSs in a routine manner and used a pressure
pressure, symptom improvement after VPS, adjustable programmable valve (The CODMAN HAKIM
Karnofsky performance status (KPS) scale Programmable Valve System or The MIETHKE proGAV
change, procedure-related complications, cancer Shunt System) or a fixed-pressure valve (The CODMAN
treatments before and after VPS, systemic HAKIM Precision Fixed Pressure valve). High pressure
disease status at time of death, and post-VPS and valves were used in all cases (Fig. 1).
overall survival. We measured the height of CSF in the catheter from
CNS metastasis was diagnosed based on external auditory canal when we inserted the proximal
magnetic resonance image (MRI) findings, catheter into the ventricle. We defined this height as the
pathologic findings, or both. The presence of opening pressure. In our institution, endotracheal general
LMS at the time of VPS was diagnosed by MRI, anesthesia was maintained with neck position enabling good
by the presence of malignant cells in CSF, or venous drainage, no positive end expiratory pressure
both. Our definition of positive MRI finding is (PEEP), end tidal CO2 around 3035 mmHg, using
contrastenhancement of diffuse or localized osmotherapy (e.g., mannitol), and using propofol instead of
areas such as meninges, ependyma, tentorium, gas anesthetics as much as possible.
basal cistern and sulci. Since CSF cytology test The outcomes of VPS were analyzed with respect to the
for malignant cells has a 4050% falsenegative following risk factors; age ([55 versus B55 years), sex, type
rate, three serial spinal taps were performed to of primary malignancy (lung cancer versus breast cancer
reduce such a high rate. After cytospin versus others), onset of CNS involvement (synchronous
preparations, cells were evaluated, and if versus metachronous), systemic disease status (progressive
malignant cells were confirmed in CSF, we could versus non-progressive), hydrocephalus type
define cytologically positive LMS. (communicating versus obstructive), ventricular opening
Hydrocephalus was classified as obstructive pressure ([30 versus 1530 versus B15 cmH2O), and
hydrocephalus with a large parenchymal or additional cancer treatment after VPS. Univariate analysis
intraventricular mass obstructing the CSF was used to identify potential risk factors associated with
pathway or as communicating hydrocephalus post-VPS survival, and the KaplanMeier method was used
with leptomeningeal enhancement by MRI or to evaluate survival rates for different risk factors. The Log
positive CSF cytology (Fig. 1). We also rank test was used to compare group survival curves, and
documented the time intervals between initial multivariate analysis was performed using the Cox
primary tumor diagnosis, CNS involvement, and proportional hazards model to identify independent risk
VPS. In cases positive for LMS, the time factors.
intervals between brain parenchymal metastasis,
Fig. 1 Image findings of a breast
cancer patient with CNS
involvement. Left axial CT scan
shows ventriculomegaly,
periventricular low density, and
bilateral sulci obliteration. Post-
VPS CT scan (right) shows
much relieved
ventriculomegaly, loss of
periventricular low density, and
reappearance of bilateral sulci

LMS, and VPS were included. The indications of Results

VPS were (1) an uncontrollable increase in
intracranial pressure (ICP) despite aggressive The median age of the 50 adult patients (male:female =
ICP management, or (2) progressive 20:30) was 55.0 years (range 2577). The most common
ventriculomegaly with neurological deficits. presenting symptom was a headache (70%) followed by

J Neurooncol (2011) 104:545551 547
mental change (24%), gait disturbance (14%), consciousness. Cognitive function and urinary incontinence
cognitive dysfunction (e.g., memory did not respond as well to VPS (only 2 of 5 patients
impairment) (10%), urinary incontinence (10%), improved) (Table 1). Most of the patients were relieved from
seizure (4%), and cranial nerve palsy (2%). symptoms within 12 days after the operation. Complication
CNS metastasis was from a hematologic rate was 10%. Four patients experienced a valve pressure
malignancy (diffuse large B-cell lymphoma) in 1 adaptation failure, increased ICP, an overdrain, or
patient and from solid tumors in 49. Regarding uncontrolled hydrocephalus and underwent revision to
the solid tumors, the primary diagnosis was lung change the valve type. One death was attributed to
cancer in 32 patients (non-small cell lung cancer intracerebral hematoma probably provoked by multiple
in 29, small cell lung cancer in 2, and mixed in 1 ventricular puncture because of an inadequate initial
patient), breast cancer (invasive ductal trajectory. There were no coagulation disorders, abnormal
carcinoma) in 8, colorectal cancer in 3, renal cell vascular structures, or tumor which was blocking the
carcinoma in 2, and other cancers (gastric cancer, catheter trajectory for this patient. And no other shunt-
cervix cancer, ovarian cancer, and cancer of related complication, such as infection, valve malfunction,
unknown origin) in 5. or peritoneal carcinomatosis, was observed during the study
Thirty-seven patients were found to have CNS period.
involvement of metachronous onset and the After VPS, further systemic chemotherapy, WBRT,
remaining 13 patients synchronous onset. At the radiosurgery, and tumor resection performed in 11, 6, 4, and
time of hydrocephalus diagnosis and VPS, 10 1 patients, respectively. Intrathecal chemotherapy after VPS
patients had parenchymal metastases only and 40 was not considered because an onoff valve was not
patients had coexistent LMS. In these 40 LMS available and we did not believe it would work at that stage
positive patients, 18 patients had parenchymal of disease with an extremely high ICP and a blockage of
metastases prior to LMS and 22 patients were CSF flow. Five patients remained alive at the end of this
found to have brain parenchymal involvement study in May 2010. At the time of death, we found that
and LMS simultaneously. Primary diseases of systemic malignant tumor status had progressed in 27, but
LMS positive patients were 25 non-small cell no definitive progression was observed in 23. Deaths were
lung cancer, 8 breast cancer, 2 colorectal cancer, attributed to an increased ICP due to CNS lesion progression
and 5 other cancers. (gastric cancer, cervix in 10 patients, and to an aggravated general condition or an
cancer, ovarian cancer, and cancer of unknown organ failure in 35.
origin) And among them, synchronous Median time from initial primary malignancy diagnosis
development of LMS and intraparenchymal to CNS involvement was 10.5 months (range 0106), and
metastases was from 14 non-small cell lung from CNS involvement to VPS was 3.5 months (023). In
cancer, 1 small cell lung cancer, 3 breast cancer, 40 patients with LMS, median time from brain parenchymal
and other cancers. (1 gastric cancer, 1 colon metastasis to LMS was 0 months (023), and from LMS to
cancer, 1 diffuse large B-cell lymphoma, and 1 VPS was 1.0 month (2 days to 13 months). There were 2
unknown origin) In terms of hydrocephalus type, patients who had developed hydrocephalus and underwent
37 were of the communicating type and 13 were VPS before LMS appeared, 1 and 2 months
of the obstructive type, and of these 13, 6 were
blocked by a supratentorial and 7 by an
infratentorial lesion.
Before VPS, patients had been treated for
CNS lesions using various modalities; 23 by
whole-brain radiotherapy (WBRT), 24 by
radiosurgery, 23 by intrathecal chemotherapy,
and 5 by tumor resection. During surgery,
ventricular opening pressure was B15 cmH2O in
5 patients, 1530 cmH2O in 22, and [30 cmH2O
in 23. After VPS, symptoms improved in 40
patients, and most of these improvements
involved relief from headache, nausea, and/ or
vomiting, and an improved level of

548 J Neurooncol (2011) 104:545551

Table 1 Presenting symptom and improvement after VPS

Presenting symptom No. of Clinical improvement
patients (%) after VPS (%)

Headache 35 (70) 30 (86)

Mental change 12 (24) 10 (83)

Gait disturbance 7 (14) 5 (71)
Cognitive dysfunction 5 (10) 2 (40)
Urinary incontinence 5 (10) 2 (40)
Seizure 2 (4) 2 (100)

Fig. 2 Overall survival after VPS in patients with CNS metastasis.

Actuarial survivals were 52% at 3 months and 10% at 1 year after VPS
ahead respectively. Median overall survival after primary did so positively (HR 0.17, 95% CI 0.070.42, P\0.0001) for
malignancy diagnosis was 21.0 months (1113). Median better survival (Table 4; Fig. 4).
survivals after the diagnosis of CNS involvement, LMS, and
VPS (Fig. 2) were 7.5 months (155), 3.5 months (028),
and 3.0 months (2 days to 54 months), respectively (Table Discussion
Univariate analysis revealed that further treatment after Disseminated cancer cells result in multi-organ failure
VPS, including systemic chemotherapy, WBRT, finally experienced by end-stage cancer patients. CNS
radiosurgery, or tumor resection, conferred a survival involvement including LMS with an uncontrollable
advantage (P= 0.0002), whereas age, sex, type of primary increased ICP is considered a feature of the final stage. The
malignancy, onset of CNS involvement (synchronous or diagnosis of LMS, however, is sometimes equivocal in MRI
metachronous), type of hydrocephalus, ventricular opening or false-negative result by cytology [6], and few treatment
pressure, and systemic disease status were not found to be choices are available. Furthermore, treatment response rate
significant prognostic factors (Table 3; Fig. 3). Multivariate is very low when LMS is present: one study found that 52%
analysis showed that a ventricular opening pressure of [30 failed to respond. Omuro et al. pointed out the importance
cmH2O influenced survival negatively (HR 6.44, 95% CI of suspicion of intracranial hypertension in patients with
1.2632.9, P= 0.02) and further cancer treatment after VPS LMS, and our study confirms the frequent
No. of patients (%)

Age (years) 55.0 (range, 2577)

Sex: female/male 30 (60)/20 (40)

J Neurooncol (2011) 104:545551 549
Table 2 Characteristics of the patients Primary malignancy
Lung cancer [NSCLC/SCLC/Mixed] 32 (64) [29 (58)/2 (4)/1 (2)]
Breast cancer 8 (16)

Colorectal cancer 3 (6)

Renal cell carcinoma 2 (8)

Others 5 (10)

Onset of CNS involvement

37 (74)/13 (26)
Presence of LMS at the time of VPS
Yes/No 40 (80)/10(20)
Type of hydrocephalus
37 (74)/13 (26)
Ventricular opening pressure: B15 cmH2O/1530 cmH2O/[30 cmH2O 5 (10)/22 (44)/23 (46)

Treatment before/after VPS

WBRT 23 (46)/6 (12)
Systemic chemotherapy 43 (86)/11 (22)

Radiosurgery 24 (48)/4 (8)

Intrathecal chemotherapy 23 (46)/0 (0)

Craniotomy and tumor resection 5 (10)/1 (2)

Systemic disease status at the time of death

NSCLC non-small cell lung cancer, Progressive/Non-progressive 27 (54)/23 (46)
SCLC small cell lung cancer, DLBL Cause of death
diffuse large B-cell lymphoma, LMS
Uncontrolled ICP
leptomeningeal seeding, VP 10 (20)
ventriculoperitoneal, WBRT whole-
Aggravated general condition 35 (70)
brain radiotherapy, ICP intracranial
pressure, Dx diagnosis Median time interval between
Table 3 Univariate analysis of Initial primary malignancy Dx and CNS involve 10.5 months (0106)
prognostic factors for survival after
VP shunt insertion CNS involve and VPS 3.5 months (023)

Brain parenchymal metastasis and LMS 0 month (023)

LMS and VPS 1.0 month (013)

P value

Age[55 versus B55 years 0.59

LCA lung cancer, BCA breast
Sex: M versus F 0.79
Primary malignancy: LCA versus BCA versus others 0.93
Onset of CNS involvement: synchronous versus metachronous 0.40
Systemic disease status: progressive versus non-progressive 0.39
Type of hydrocephalus: communicating versus obstructive 0.60
Ventricular opening pressure: [30 versus 1530 versus B15 cmH2O 0.12
Further treatment after VPS: yes versus no 0.0002

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Fig. 3 Post-VPS survival in patients who received additional cancer Fig. 4 Post-VPS survival in patients according to ventricular opening
treatment versus those who received conservative management only. pressure. After VPS, the hazard ratio for patients with a ventricular
After VPS, the hazard ratio for death of patients who received further opening pressure[30 cmH2O versus those with a pressure B15 cmH2O
cancer treatment versus those who received supportive care alone was was 6.44 (95% CI 1.2632.9, P = 0.02)
0.17 (95% CI 0.070.42, P\0.0001)
associations between LMS and hydrocephalus or anesthesia and of various shunt-related complications [9
intracranial hypertension. In the present study, 80% of 11], and improves survival and favorably affects quality of
hydrocephalus patients who underwent VPS were found to life
have coexistent LMS. The dominant type of hydrocephalus [4].
was the communicating type associated with LMS, and the A median survival time of 1.85.8 months after a
median time interval between the diagnosis of LMS and diagnosis of LMS [2, 4, 5, 1214] and of 2.0 months
VPS was only 2.2 months. Accordingly, we recommend a
thorough investigation for LMS be undertaken when a
cancer patient develops neurological symptoms and signs of
hydrocephalus and/or images of ventriculomegaly. If LMS
is confirmed, its treatment should be actively pursued
without delay before VPS. The early diagnosis of LMS is
important because the opportunity to administer intrathecal
chemotherapy might be missed after VPS for
hydrocephalus. Furthermore, if hydrocephalus persists,
intrathecal chemotherapy cannot provide a viable treatment
option because CSF flow is inhibited, that is, CSF
compartmentalization and prohibits intrathecal
chemoagents being delivered effectively [2, 5, 7, 8].
In the present study, 80% of patients experienced
immediate post-operative symptom relief. A headache was
the most common symptom, and was resolved by surgery in
85.7% of cases. On the other hand, cognitive function and
urinary incontinence were improved in less than a half of
cases by VPS (40%). Unlike cancer treatment itself, the
treatment of intracranial hypertension is not optional
because of its debilitating consequences. When relief of the
symptoms and signs of increased ICP are of major concern,
VPS helps enormously despite the risks of general

J Neurooncol (2011) 104:545551 551
Table 4 Results of multivariate Cox Hazard ratio (95% CI) P value
regression analysis

Age: [55 versus B55 years 0.88 (0.411.88) 0.73

Sex: M versus F 1.27 (0.552.94) 0.57

Primary malignancy
LCA versus others
0.65 (0.172.48) 0.94
BCA versus others 0.45 (0.102.05) 0.48

Onset of CNS involvement: synchronous versus metachronous 0.73 (0.281.88) 0.51

Systemic disease status: progressive versus non-progressive 0.78 (0.391.55) 0.47

Type of hydrocephalus: cCommunicating versus obstructive 1.24 (0.413.74) 0.70

Ventricular opening pressure: [30 versus B15 cmH2O 6.44 (1.2632.9) 0.02

Further treatment after VPS: yes versus no 0.17 (0.070.42) \0.0001

(2 days to 3.6 years) after VPS [3] have been reported, which pressure, which reflects an increased ICP, probably
concur with our findings (3.5 months of median survival indicates severe distortion of CSF dynamics due to a long-
after a diagnosis of LMS and 3.0 months after VPS). standing, heavy tumor burden in the CNS when it is from a
Approximately 2434% of CNS metastasis patients communicating hydrocephalus, and although VPS can
succumb to LMS alone, 2225% to LMS and progressive effectively relieve an elevated ICP, a poor prognosis is
systemic cancer, 1944% to systemic progressive disease, expected due to the progression of the underlying disease.
and up to 10% to other causes [1518]. In the present study, When the hydrocephalus is obstructive, the lesion is usually
the majority of patients succumbed to aggravated systemic deep-seated around the third or fourth ventricle. Surgical
disease progression (70%), which included systemic cancer resection could be incomplete and even impossible, and this
progression and an aggravated general condition mainly due affects the survival unfavorably.
to an infection, like pneumonia. In a previous study, it was found that primary tumor
Furthermore, overall outcome was in line with that found histology has a significant impact on survival after a
previously, although it is noteworthy that five patients diagnosis of LMS. The longest median survival was
(10%) survived after VPS for more than 1 year and one observed in breast cancer (3.1 months), and the shortest in
patient on continuing systemic cancer treatment survived 54 lung cancer (0.8 months) [5]. However, we failed to find any
months. These patients who achieved long-term survival significant relationship between primary malignancy type
after VPS support the notion that LMS development and and survival after VPS; for example, median survival times
VPS do not necessarily mean the end of the further cancer after VPS in lung cancer, breast cancer, and other primary
treatment. Aggressive treatments in patients with CNS malignancies were 3.0, 2.0, and 2.5 months, respectively
metastasis have been reported to substantially increase (P= 0.93). Our findings could be explained by the fact that
survival [2, 46, 1315, 1921]. We also found that further CNS involvement with LMS represents the most advanced
aggressive cancer treatment after VPS was a prognostic stage of cancer irrespective of the nature of the primary
factor of better survival time by univariate and multivariate malignancy, and that short life expectancies do not allow
analysis. The most reasonable explanation for this result is survival differences to be attributed to different histologies.
that we selected patients with a better performance status To improve survival, further research should be focused
and a lower tumor burden, which increased the likelihood of on improving diagnostic and therapeutic tools. More
eligibility for further systemic or local cancer treatment. sensitive diagnostic tools are needed to overcome the high
Furthermore, this finding strengthens the hypothesis that the falsenegative rates of imaging and cytology findings.
bloodbrain barrier is made more permeable by infiltrative Furthermore, personalized and tumor-specific therapeutic
tumor cells and that systemic chemotherapy agents can regimens should be established. At present, systemic or
penetrate into the CSF space more easily, which may intrathecal chemotherapies based on methotrexate,
favorably affect survival after VPS. Multivariate analysis cytarabine, liposomal cytarabine, or thiotepa and on several
also identified an independent risk factor that negatively emerging drugs, such as mafosfamide, diaziquone,
affected survival after VPS, namely a ventricular opening topotecan, gemcitabine, and temozolomide, are being
pressure of [30 cmH2O. An elevated ventricular opening investigated to identify regimens best suited for particular

552 J Neurooncol (2011) 104:545551
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