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Bone Metastasis in Gastric Cancer Patients
Jae Bong Ahn, Tae Kyung Ha, and Sung Joon Kwon
Department of Surgery, Hanyang University College of Medicine, Seoul, Korea
Purpose: Bone metastasis from stomach cancer occurs only rarely and it is known to have a very poor prognosis. This study examined
the clinical characteristics and prognosis of patients who were diagnosed with stomach cancer and bone metastasis.
Materials and Methods: The subjects were 19 patients who were diagnosed with stomach cancer at Hanyang University Medical Center
from June 1992 to August 2010 and they also had bone metastasis. The survival rate according to many clinicopathologic factors was
retrospectively analyzed.
Results: 11 patients out of 18 patients (61%) who received an operation were in stage IV and the most common bone metastasis loca-
tion was the spine. Bone scintigraphy was mostly used for diagnosing bone metastasis and PET-CT and magnetic resonance imaging
were used singly or together. The serum alkaline phosphatase at the time of diagnosis had increased in 12 cases and there were clinical
symptoms (bone pain) in 16 cases. Treatment was given to 14 cases and it was mostly radiotherapy. There were 2 cases of discovering
bone metastasis at the time of diagnosing stomach cancer. The interval after operation to the time of diagnosing bone metastasis for the
18 cases that received a stomach cancer operation was on average 14.9±17.3 months and the period until death after the diagnosis
of bone metastasis was on average 3.8±2.6 months. As a result of univariate survival rate analysis, the group that was treated for bone
metastasis had a significantly better survival period when the bone metastasis was singular rather than multiple, as compared to the
non-treatment group, yet both factors were not independent prognosis factors on multivariate survival analysis.
Conclusions: An examination to confirm the status of bone metastasis when conducting a radio-tracer test after the initial diagnosis
and also after an operation is needed for stomach cancer patients, and bone scintigraphy is the most helpfully modality. Making the
diagnosis at the early stage and suitable treatments are expected to enhance the survival rate and improve the quality of life even for the
patients with bone metastasis.
Key Words: Stomach neoplasms, Bone metastasis, Diagnosis, Prognosis
Original Article
J Gastric Cancer 2011;11(1):38-45 y DOI:10.5230/jgc.2011.11.1.38
Correspondence to: Sung Joon Kwon
Department of Surgery, Hanyang University College of Medicine, 17,
Haengdang-dong, Seongdong-gu, Seoul 133-792, Korea
Tel: +82-2-2290-8453, Fax: +82-2-2281-0224
E-mail: sjkwon@hanyang.ac.kr
Received September 30, 2010
Accepted November 30, 2010
Introduction
The proportion of gastric cancer patients among the annually
registered cancer patients in Korea is as high as approximately 20%.(1)
It is very important to assess the presence or absence of metastasis
to establish the treatment plans for gastric cancer, which occurs at
such a high rate, and to predict the prognosis. Gastric cancer gen-
erally metastasizes to the peritoneal membrane, liver, lymph nodes,
etc., and it may metastasize to the spleen, adrenalin, ovary, lung,
brain and skin.
Bone metastasis generally occurs in patients with prostate can-
cer, breast cancer and lung cancer, and bone metastasis in gastric
cancer patients has been shown to be very rare.(2-4) Bone metas-
tasis is usually associated with disseminated vascular coagulation,
hemolytic anemia and other hematological complications, and the
prognosis is very poor.(5) The diverse incidence and prognosis of
bone metastasis from gastric cancer have been reported in numer-
ous studies, but this has not been sufficiently established in Korea.
Therefore, we conducted this study to examine the clinical charac-
teristics of the patients diagnosed with gastric cancer by gastroscopy
as well as histological tests, and these patients had bone metastasis
detected simultaneously or later, and we also wanted to assess their
prognosis.
Copyright © 2011 by The Korean Gastric Cancer Association
www
.jgc-online.org
Stomach Cancer with Bone Metastasis
39
Materials and Methods
1. The subjects
The study was conducted on 19 patients who were diagnosed as
having gastric caner with bone metastasis by histological tests from
June 1992 to August 2010 in the Department of Surgery, Hanyang
University Hospital.
2. Methods
Bone scintigraphy (Fig. 1), PET-CT (Fig. 2), and magnetic
resonance imaging (MRI) were used as the methods of diagnos-
ing bone metastasis. All the patients with bone metastasis were
classified according to Borrmann’s morphology as assessed by the
gastroscopic findings, the location of the gastric cancer and the
histological types, and their correlations with bone metastasis were
analyzed. In addition, the preferential site of bone metastasis, and
the association with lung metastasis and brain metastasis were ex-
amined. In addition, by measuring the serum alkaline phosphatase
(ALP) value, the changes of the ALP value in patients with bone
metastasis was examined (Table 1), and the difference of the mor-
tality rate according to with or without treatments for bone me-
tastasis was analyzed, as well as the treatment methods SPSS 13.0
(statistical Package for Social Science version 13.0, SPSS Inc., Chi-
cago, IL, USA) was used for the data analysis, the survival rate was
obtained by the Kaplan-Meier method and the significance of the
Table 1. Clinicopathological characteristics
Factor Subfactor No.
Sex Male/Female 13/6
Age (yr*) Mean 55.4±9.7
Median 57.0
Range 40~74
Type of surgery Subtotal gatrectomy 7
Total gastrectomy 10
Gastrojejunostomy 1
No surgery 1
TNM stage Ib 1
II 3
IIIa 2
IIIb 1
IV 12
Histology WEL 1
MOD 4
POR 8
SIG 5
MUC 1
Borrmann type 1 0
2 4
312
4 3
Site of primary tumor Lower 1/3 7
Middle 1/3 8
Upper 1/3 2
Whole stomach 2
No. of metastatic Mean 17.2±14.5
lymph node Median 17.0
Range 0~43
No. of dissected Mean 34.4±15.6
lymph node Median 35.0
Range 0~60
No. = number; yr = year; TNM = tumor node metastasis; WEL = well
differentiated adeno carcinoma; MOD = moderated differentiated
adenocarcinoma; POR = poorly di erentiated adenocarcinoma; SIG =
signet ring cell carcinoma; MUC = mucinous carcinoma.
Fig. 1. Bone scintigraphy shows increased uptake in multifocal area.
Fig. 2. PET-CT shows increased uptake in the vertebra, paravertebral
muscle .
Ahn JB, et al.
40
difference of the survival rate was validated by the log-rank test.
Cox’s proportional hazard model was used for multivariate analysis
of the survival rate and P-values less than 0.05 were considered to
be statistically significant.
Results
1. Clinicopathological characteristics of the gastric
cancer
Eighteen among the 19 subjects received surgery. Total gastrec-
tomy was performed on 10 patients, subtotal gastrectomy was per-
formed on 7 patients and gastrojejunostomy was performed on 1
patient. In regard to the disease stage of gastric cancer according to
the AJCC 6th edition, Ib was 1 case (5%), II was 3 cases (15%), IIIa
was 2 cases (10%), IIIb was 1 case (5%), and IV was 12 cases (63%).
Stage IV was the most prevalent. The patients were divided into
early gastric cancer and advanced gastric cancer according to the
macroscopic morphology observed on gastroscopy, and advanced
gastric cancer was defined as cases from Borrmann’s type 1 to type
4. In the 19 patients, there were 4 cases of Borrmann’
s type 2 (21%),
12 case of Borrmann’s type 3 (63%) and 3 cases of Borrmann’s
type 4 (16%). Concerning the histological types, there was 1 case
of highly differentiated cancer, 4 cases of moderately differentiated
cancer, 8 cases of poorly differentiated cancer, 5 cases of signet
ring cell carcinoma and 1 case of mucinous adenocarcinoma. The
undifferentiated type (14/19, 73%) was more abundant than the
differentiated types (5/19, 27%) (Table 1).
2. Clinicopathological characteristics of bone metastasis
The area of bone metastasis was in the order of the vertebrae
(17 cases, 89%), the costa (12 cases, 63%), the lower extremities (2
cases, 10 %), the scapula (2 cases, 10%) and the upper extremities
(1 case, 5%). In regard to the diagnosis of bone metastasis lesions,
there were 9 patients diagnosed by bone scintigraphy alone, 3 pa-
tients were diagnosed by using only positron emission tomography-
computed tomography and 1 patient was diagnosed by magnetic
resonance imaging alone. In the remaining 6 cases, together with
bone scintigraphy, positron emission tomography-computed to-
mography and magnetic resonance imaging were used simultane-
ously. In other words, bone scintigraphy was used most frequently
for the diagnosis. There were 5 patients (26%) with a solitary lesion
at the time of diagnosis and there were 14 patients (74%) with
multiple lesions at the time of diagnosis. Concerning the serum
ALP level at the time of the diagnosis of bone metastasis, it was
higher than the normal values (30~110 U/L) in 12 cases (66%),
the median value was 190 U/L and the average value was 484.4±
785.6 U/L. Backache, bone pain and other symptoms pertinent to
bone metastasis were noted in 16 cases (88%). Nine patients (47%),
were diagnosed bone metastasis only without distant metastasis,
there was 1 case of bone metastasis together with brain metastasis,
one case was associated with metastasis in the skin and periaortic
lymph node metastasis, there were 2 cases associated with liver
metastasis and periaortic lymph node metastasis, there was 1 case
associated with liver metastasis and peritoneal dissemination, there
was 1 case associated with peritoneal dissemination only, there
were 2 cases associated with lung metastasis and one case was as-
sociated with Virchow’s node metastasis. Excluding the 5 cases
whose general condition deteriorated due to the progression of gas-
tric cancer and so they could not be treated, 14 cases (73%) were
treated. Twelve cases were treated with radiation therapy alone,
1 case was treated with systemic injection of chemotherapeutics
and 1 case was treated with the combination treatment of systemic
injection of chemotherapeutic agents and radiation therapy. All 13
patients treated with radiation therapy presented with bone pain
caused by bone metastasis. After irradiation with 3,000~3,500 rad,
9 patients (69.2%) showed the amelioration of symptoms. One pa-
tient who was administered systemic chemotherapeutic agents did
not have symptoms associated with bone metastasis. In 2 cases,
bone metastasis was detected at the time of the diagnosis of gastric
cancer. In 18 cases, the interval from surgery to the diagnosis of
bone metastasis was on average 14.9±17.3 months (median value:
9 months, range: 0 ~73 months). The period from the diagnosis of
bone metastasis to death was on average 3.8±2.6 months (median
value: 3 months, range: 1~9 months (Table 2).
3. The survival period of the gastric cancer patients with
bone metastasis
In regard to the average survival period according to gender,
that for the males was 3.4±0.7 months, that for the females was
4.7±1.1 months and there was no significant difference (P=0.401).
Based on the age of 60 years, the survival rate of the 5 patients
older than 60 years and the 14 patients older than 60 years was 4.6
±0.8 months and 3.5±0.7 months, respectively, and a significant
difference was not shown (P=0.620) (Table 1). For the univari-
ate analysis of the survival rate according to the number of bone
metastasis lesions, the average survival period was 6.2±1.2 months
and 2.9±0.5 months for patients with solitary and multiple lesions,
respectively, and the survival period of the patients with a solitary
Stomach Cancer with Bone Metastasis
41
Table 2. Clinicopathological characteristics of bone metastasis
Factor Subfactor No.
Site of recurrence Bone 9
Bone+branin 1
Bone+local 1
Bone+skin+lymph node 1
Bone+liver+lymph node 2
Bone+peritoneum 1
Bone+lung 2
Bone+Virchow’s node 1
Bone+liver+peritoneum 1
Site of bone metastasis Numerous 8
Vertebra 5
Vertebra+rib 2
Vertebra+rib+scapula 1
Vertebra+femur 1
Rib+knee 1
Scapula+humerus 1
Diagnostic modality Bone scan 9
PET-CT 3
Bone scan+PET-CT 3
MRI 1
Bone scan+MRI 3
Bone pain Present 16
Absent 3
Alkaline phosphatase Mean 482.4±785.6
serum level (U/L) Median 190.0
Range 34~3,300
Treatment of bone Radiotherapy 12
metastasis Chemotherapy 1
Chemo-radiotherapy 1
None 5
Time to recurrence Mean 14.9±17.3
a er operation (mo) Median 9.0
Range 0~73
Time to death Mean 3.8±2.6
a er recurrence (mo) Median 3.0
Range 0~9
No. = number; MRI = magnetic resonance imaging; mo = month.
lesion was significantly longer than that of the patients with mul-
ticentric lesions (P=0.031). Nonetheless, the results of multivariate
analysis showed that the number of metastatic lesions was not an
independent prognostic factor. The survival period of the 16 cases
of Borrmann’s types 2 and 3 was compared with that of the 3 cases
of Borrmann’s type 4. The survival period was 3.9±0.7 months
and 3.0±1.2 months, respectively, and a statistically significant dif-
ference was not shown (P=0.502). On the analysis of the survival
period according to the disease stage, the survival period of the
three groups (4 cases of stages 1 and 2, 3 cases of stage 3 and 12
cases of stage 4) after the diagnosis of bone metastasis was 2.5±
0.9 months, 3.0±1.0 months and 4.4±0.8 months, respectively,
and a statistically significant difference was not shown (P=0.224).
When the survival period according to the histological types was
compared, that for the differentiated type was 2.8±0.8 months, that
for the undifferentiated type was 4.1±0.7 months and a statisti-
cally significant difference was not shown (P=0.228). The survival
period for the 9 cases with metastatic lesions in the bone only was
compared with that of the 10 cases with metastasis in other organs
in addition to the bone was compared, and it was 4.6±0.8 months
and 3.3±0.9 months, respectively, and the difference between the
two groups was not significant (P=0.375). The survival period of
the 14 patients treated for bone metastasis was compared with the 5
patients who were not treated and it was 4.4±0.7 months and 2.0
±0.4 months, respectively. The survival period of the treated group
Table 3. Univariate survival analysis of gastric cancer patient with
bone metastasis
Factor Subfactor No.
Duration
of survival
(mean±SD)
P
Sex Male 13 3.4±0.7 0.401
Female 6 4.7±1.1
Age (yr) <60 14 3.5±0.7 0.620
≥60 5 4.6±0.8
Histology Di erentiated 5 2.8±0.8 0.228
Undi erendiated 14 4.1±0.7
Borrmann type 1~3 16 3.9±0.7 0.502
4 3 3.0±1.2
Stage Ib+II 4 2.5±0.9 0.224
IIIa+IIIb 3 3.0±1.0
IV 12 4.4±0.8
Site of recurrence Bone only 9 4.6±0.8 0.375
Bone and other site 10 3.3±0.9
Treatment of Performed 14 4.4±0.7 0.019
bone metastasis Not performed 5 2.0±0.4
Number of Single 5 6.2±1.2 0.031
bone metastasis Multiple 14 2.9±0.5
No. = number; SD = standard deviation; yr = year.
Ahn JB, et al.
42
was significantly higher (P=0.019). Nonetheless, on the multivariate
analysis of the survival period, it was not an independent prognostic
factor (Table 3, 4).
Discussion
Bone metastasis frequently occurs in patients with breast cancer,
lung cancer, renal cancer, prostate cancer, bladder cancer and other
primary cancers. In comparison, it has been shown that bone me-
tastasis that originates from malignant tumors of the gastrointestinal
tract is rare.(2-4) In 1983, Yoshikawa and Kitaoka(6) reported that
the incidence of bone metastasis is 1~20%. In 1987, Nishidoi and
Koga(7) have reported that in 246 gastric cancer patients, bone me-
tastasis was associated in 33 patients (13.4%). In our study, among
the 2,150 patients diagnosed with gastric cancer from June 1992
to August 2010, bone metastasis was associated in 19 patients for
a frequency of 0.9%. In other words, depending on the research
institutions and investigators, the incidence of bone metastasis var-
ies greatly. Seto et al.(8) have reported that bone scintigraphy was
performed on 60 patients, and bone metastasis was suspected in
25% of these patients. Bone metastasis may occur more frequently
in cases with primary cancer in the body of stomach, poorly dif-
ferentiated adenocarcinoma and in cases with abundant lymph
node metastasis in the vicinity. In our study, like as shown in the
study reported by Seto et al., the undifferentiated histological types
(14/19, 73%) were more abundant than the differentiated types
(5/19, 27%). However, the survival period of the two groups was
not significantly different. Thus, the survival period was not dif-
ferent according to the histological types. In 1995, Choi et al.(9)
performed bone scintigraphy on 234 gastric cancer patients, and
based on the presence or absence of hot uptake lesions, the fre-
quency and pattern of bone metastasis were inferred and reported.
According to this, there were 106 patients who showed hot uptake
lesions, the estimated incidence of bone metastasis was 45.3% and
an elevated serum ALP value was associated with bone metastasis.
In our study, similarly, among the 19 patients, the serum ALP value
was elevated in 12 patients at the time of diagnosis. Similarly, in
2006, Kusumoto et al.(10) reported on the clinical characteristics
of 9 patients with bone metastasis from gastric cancer, and it was
observed that the serum ALP level was elevated in all 9 patient, and
the serum ALP value was an important factor for making the diag-
nosis of bone metastasis. Therefore, it is thought that in patients di-
agnosed with gastric cancer, if the ALP value is atypically elevated,
then evaluation of bone metastasis is required.
In our study, bone scintigraphy was applied most frequently for
the diagnosis of bone metastasis (15/19, 78%). In addition, pos i-
tron emission tomography-computed tomography and MRI were
used alone or in combination. On account of the use of a gamma
camera and the development of test agents such as Tc-99m MDP,
the sensitivity of bone scintigraphy is particularly high, and thus it
is known to be the most useful screening test. Bone scintigraphy
could detect the change of abnormal blood flow within the bone
that developed metastasis, and so it could detect bone metastasis at
the time approximately 3 months earlier than that with using plain
X-rays.(11,12) Nevertheless, hot uptake lesions may be detected
in Paget’s disease and other metabolic bone diseases, degenerative
arthritis, fractures, infectious bone diseases and other benign bone
diseases or primary bone tumors, and so it has limitations of low
specificity. In our study, among the 19 patients, there were only 5
patients with a solitary lesion. Several studies have examined the
rate of detecting bone metastasis with a solitary lesion as detected
by bone scintigraphy, and only approximately 50~55% of the cases
were diagnosed as having bone metastasis.(13-16) In other words,
bone scintigraphy has shortcomings that it is difficult to diagnose
bone metastasis from malignant tumors in the cases with a hot up-
take lesion. Therefore, it is considered that for cases with a solitary
hot uptake lesion detected by bone scintigraphy, together with ac-
curate history taking for fracture and other past medical problems,
the rate of a false diagnosis of bone metastasis from gastric cancer
could be decreased by making an accurate differential diagnosis
from infectious bone diseases, metabolic bone diseases and other
benign diseases. In our study, for the cases that a solitary lesion
Table 4. Survival rate of gastric cancer patient a er bone metastasis (multivariate analysis)
Factor Signi cance B 95% con dence interval
Treatment of bone metastasis Yes
No 0.143 0.386 0.108~1.381
Number of bone metastasis Single
Multiple 0.359 0.359 0.096~1.347
Stomach Cancer with Bone Metastasis
43
was detected by bone scintigraphy, efforts were made to increase
the accuracy of the diagnosis by additionally performing positron
emission tomography-computed tomography or magnetic reso-
nance imaging. The accuracy of the diagnosis may be increased
more by performing additional bone marrow tapping or bone mar-
row histological tests in parallel. Choi et al.(9) have reported that
the area where bone metastasis was frequently diagnosed by bone
scintigraphy was in the order of the vertebrae (66%), the costa (59%),
the pelvic bone (43%), the femur (30%) and the scapula and clav icle
(17%). In our study, among the 19 patients, metastasis in the ver-
tebrae was detected in 17 cases (89%), and so similar results were
obtained. Other metastases associated with bone metastasis were
also examined, and particularly, 3 of the 19 patients (15%) were as-
sociated with liver cancer. In general, for gastric cancer and includ-
ing early gastric cancer, the most frequently metastasized area by
hematogenous metastasis is the liver.(10) In our gastric cancer pa-
tients, the rate of liver metastasis was lower than the general rate of
liver metastasis. This could be explained by the difference of me-
tastasis routes. In the cases with well differentiated tumors, metas-
tasis is developed through the portal vein. On the other hand, in the
cases with poorly differentiated cancer, bone metastasis primarily
occurs through the vertebral vein system.(8,17) Several studies have
reported that the vertebrae are the site where bone metastasis oc-
curs most frequently, which supports that the vertebral vein system
is the major route of bone metastasis.(9,12,18) Kusumoto et al.(10)
have reported that in patients with gastric cancer, bone metastasis is
more prevalent in the young age groups, but in our study, age was
not found to be correlated with bone metastasis. In bone metasta-
sis from gastric cancer, the cancer cells diffusely proliferate in the
bone marrow and this can cause disseminated carcinomatosis; they
also proliferate rapidly and thus induce bone destruction as well as
hematological complications. Yet the developmental mechanism of
bone destruction has not yet been elucidated. More studies on this
are required.(10)
Yoshikawa and Kitaoka(6) and Nishidoi and Koga(7) have re-
ported that bone metastasis from gastric cancer is associated with
Borrmann’s types 3 and 4, which arereferred to as scirrhous carci-
noma. In our study, similarly, Borrmann’s types 3 and type 4 were
found in 17 cases of the entire 19 cases (89%), and these results are
similar to those of the above studies. In regard to the association
with the disease stage of primary gastric cancer, the 11 patients
who underwent surgery (61%) were stage IV. In other words, in the
Borrmann type 3 and 4 patients, bone metastasis occurs frequently
in the cases with primary cancer of a high disease stage. Nonethe-
less, the macroscopic type and disease stage were not significantly
correlated with the survival period after the diagnosis of bone
metastasis. Yet the number of cases in each disease stage was too
small, and a comparative analysis of the survival period of each
disease stage could not be performed. Analysis of a larger num-
ber of cases is required for a clearer interpretation of the results of
the analysis of our study(that the survival period according to the
disease stages was not different. Among the 19 patients diagnosed
with bone metastasis, 5 cases could not be treated because of the
deterioration of their general condition due to the progression of
gastric cancer, and the remaining 14 patients were treated. On the
univariate analysis of the survival period of the treatment group
and the non-treatment group, the survival period of the treatment
group was 4.4±0.7 months and it was significantly longer than the
2.0±0.4 survival period of the untreated group. The most common
clinical symptoms and complications of bone metastasis are bone
pain, pathologic fracture and spinal cord compression. In our study,
similarly, in the 19 subject patients, the majority or 16 patients (84%)
were positive for bone pain. Clinically, the cause of the worst suf-
fering of patients with bone metastasis is bone pain. Therefore,
pain management for patients with bone pain is very important.
In regard to radiation therapy for such bone pain, Murai et al.(19)
have reported that 68 patients with bone metastasis were classi-
fied according to the type of primary tumors, and radiation therapy
was effective in 73% of the lung cancer patients, 100% of the breast
cancer patients and 75% of the gastric cancer patients. In addition,
Yoshikawa and Kitaoka(20) have reported that in 23 gastric cancer
patients associated with bone metastasis, radiation therapy was ef-
fective for the amelioration of bone pain, yet chemotherapy was
not effective for this. McQuay et al.(21) have reported that in regard
to the effectiveness of radiation therapy for the amelioration of
bone pain, 1 month after the treatment, the bone pain was resolved
completely in 1/4 of the patients, and at least 50% pain amelioration
could be obtained in 1/3 of the patients. The survival period of was
recently improved by treatment with MTX+5FU, S1+paclitaxel,
S1+cisplatin and other chemotherapy,(22,23) and in addition it was
effective on the amelioration of pain.(24) Bisphosphonate(25) has
recently been used for the treatment of clinical symptoms caused
by bone metastasis and the complications. It suppressed the pro-
duction of proliferative factors by bones through the suppression of
the reabsorption of bone, and thus it suppressed the proliferation of
cancer cells.(26,27) Therefore, in patients with bone metastasis, it
reduces pain and it also suppresses or delays complications caused
by bone metastasis. Nonetheless, large scale studies on bone me-
Ahn JB, et al.
44
tastasis patients have not been conducted, and studies are needed
on the indications for the use of Bisphosphonate and to prove its
treatment effectiveness. Chung et al.(28) reported on 4 patient s
with bone metastasis caused by gastric cancer, and all 4 patients
died within 4 months after the diagnosis of bone metastasis. In our
study, similarly, the period from the diagnosis of bone metastasis
to death was on average 3.8±2.6 months, and it was found that the
prognosis was very poor.
In conclusion, the prognosis of bone metastasis caused by gastric
cancer is very poor and the prognosis of patients may be worsened
due to a delayed diagnosis. Hence, tests to assess for bone metas-
tasis are required for gastric cancer patients at the time of the initial
diagnosis and the postsurgical follow-up observation, and bone
scintigraphy with its high sensitivity appears to be most useful. In
such a manner, it is anticipated that the survival period as well as
the quality of life may be improved with making a rapid diagnosis
and by administering radiation therapy and other appropriate treat-
ments. Studies with a large number of larger subjects are required
to assess the effect ofimproving the survival period according to
different treatment methods.
References
1. Suh CI, Suh KA, Park SH, Chang HJ, Ko JW, Ahn DH. Annu-
al report of the central cancer registry in Korea - 1998 (Based
on Registered Data from 124 Hospitals). J Korean Cancer As-
soc 2000;32:827-834.
2. Crivellari D, Carbone A, Sigon R, Buonadonna A, Cannizzaro
R, Sorio R, et al. Gastric cancer with bone marrow invasion at
presentation: case-report and review of the literature. Tumori
1995;81:74-76.
3. Noda N, Sano T, Shirao K, Ono H, Katai H, Sasako M, et al.
A case of bone marrow recurrence from gastric carcinoma
after a nine-year disease-free interval. Jpn J Clin Oncol
1996;26:472-475.
4. Abrams HL, Spiro R, Goldstein N. Metastases in carcinoma;
analysis of 1000 autopsied cases. Cancer 1950;3:74-85.
5. Pasquini E, Gianni L, Aitini E, Nicolini M, Fattori PP,
Cavazzini G, et al. Acute disseminated intravascular coagula-
tion syndrome in cancer patients. Oncology 1995;52:505-508.
6. Yoshikawa K, Kitaoka H. Bone metastasis of gastric cancer.
Jpn J Surg 1983;13:173-176.
7. Nishidoi H, Koga S. Clinicopathological study of gastric can-
cer with bone metastasis. Gan To Kagaku Ryoho 1987;14(5 Pt
2):1717-1722.
8. Seto M, Tonami N, Koizumi K, Sui O, Hisada K. Bone metas-
tasis in gastric cancer--clinical evaluation of bone scintigrams.
Kaku Igaku 1983;20:795-801.
9. Choi CW, Lee DS, Chung JK, Lee MC, Kim NK, Choi KW, et
al. Evaluation of bone metastases by Tc-99m MDP imaging
in patients with stomach cancer. Clin Nucl Med 1995;20:310-
314.
10. Kusumoto H, Haraguchi M, Nozuka Y, Oda Y, Tsuneyoshi M,
Iguchi H. Characteristic features of disseminated carcinoma-
tosis of the bone marrow due to gastric cancer: the pathogen-
esis of bone destruction. Oncol Rep 2006;16:735-740.
11. Wilner D. Cancer metastasis to bone. In: Wilner D, ed. Radi-
ology of Bone Tumors and Allied Disorders. Vol 1. Philadel-
phia: WB Saunders, 1982:3641-3908.
12. Gold RI, Seeger LL, Bassett LW, Steckel RJ. An integrated ap-
proach to the evaluation of metastatic bone disease. Radiol
Clin North Am 1990;28:471-483.
13. Corcoran RJ, rall JH, Kyle RW, Kaminski R, Johnson MC.
Solitary abnormalities in bone scans of patients with extraos-
seous malignancies. Radiology 1976;121:663-667.
14. Shirazi PH, Rayudu GV, Fordham EW. Review of solitary 18F
bone scan lesions. Radiology 1974;112:369-372.
15. Brown ML. Significance of the solitary lesion in pediat-
ric bone scanning: concise communication. J Nucl Med
1983;24:114-115.
16. Rappaport AH, Ho er PB, Genant HK. Unifocal bone nd-
ings by scintigraphy. Clinical significance in patients with
known primary cancer. West J Med 1978;129:188-192.
17. Diel IJ, Kaufman M, Bastert G. Metastatic bone disease: fun-
damental and clinical aspects. 1st ed. Santa Clara: Springer-
Verlag Telos, 1994:22-23.
18. McNeil BJ. Value of bone scanning in neoplastic disease.
Semin Nucl Med 1984;14:277-286.
19. Murai N, Koga K, Nagamachi S, Nishikawa K, Matsuki K,
Kusumoto S, et al. Radiotherapy in bone metastases--with
special reference to its e ect on relieving pain. Gan No Rinsho
1989;35:1149-1152.
20. Yoshikawa K, Kitaoka H. Bone metastasis of gastric cancer.
Jpn J Surg 1983;13:173-176.
21. McQuay HJ, Collins SL, Carroll D, Moore RA. Radiotherapy
for the palliation of painful bone metastases. Cochrane Data-
base Syst Rev 2000;(2):CD001793.
22. Yasuda K, Kimura T, Seita M, Takahata T, Akazai Y. A case
Stomach Cancer with Bone Metastasis
45
of gastric cancer accompanied by disseminated carcino-
matosis of bone marrow with DIC recovered by sequential
therapy consisting of MTX and 5-FU. Gan To Kagaku Ryoho
2008;35:1941-1943.
23. Migita K, Watanabe A, Sakamoto C, Nakamura T, Ohyama
T, Ishikawa H, et al. A case of multiple bone metastases from
gastric cancer treated with combination chemotherapy of S-1
and CDDP. Gan To Kagaku Ryoho 2007;34:929-931.
24. Fujishima Y, Yoneda R, Iwai M, Fukunaga H, Miura M, Koide
M, et al. A case of advanced gastric cancer with disseminated
carcinomatosis of bone marrow treated by S-1 and CDDP.
Gan To Kagaku Ryoho 2009;36:2653-2655.
25. Berenson JR, Rosen LS, Howell A, Porter L, Coleman RE,
Morley W, et al. Zoledronic acid reduces skeletal-related
events in patients with osteolytic metastases. Cancer 2001;91:
1191-1200.
26. Carano A, Teitelbaum SL, Konsek JD, Schlesinger PH, Blair
HC. Bisphosphonates directly inhibit the bone resorption
activity of isolated avian osteoclasts in vitro. J Clin Invest
1990;85:456-461.
27. Hughes DE, Wright KR, Uy HL, Sasaki A, Yoneda T, Rood-
man GD, et al. Bisphosphonates promote apoptosis in
murine osteoclasts in vitro and in vivo. J Bone Miner Res
1995;10:1478-1487.
28. Chung YS, Choi TY, Ha CY, Kim HM, Lee KJ, Park CH, et al.
An unusual case of osteoblastic metastasis from gastric carci-
noma. Yonsei Med J 2002;43:377-380.
