A case of disseminated carcinomatosis of the bone marrow originating from gastric cancer 3 years after intraperitoneal chemotherapy against peritoneal carcinomatosis
© Okuno et al. 2016
Received: 10 June 2015
Accepted: 24 March 2016
Published: 14 April 2016
Clinical studies of intraperitoneal chemotherapy with paclitaxel in patients of gastric cancer with peritoneal carcinomatosis is well tolerated and effective, and rare cases of metastasis and recurrence have experienced during the treatment. Disseminated carcinomatosis of the bone marrow is highly rare in gastric cancer and associated with a poor prognosis.
A 59-year-old woman of gastric cancer with peritoneal carcinomatosis received five courses of chemotherapy with intraperitoneal administration of paclitaxel, and laparoscopy showed disappearance of the peritoneal carcinomatosis. She subsequently underwent total gastrectomy, and the histopathological findings showed a complete response to the chemotherapy. Postoperatively, chemotherapy with intraperitoneal administration of paclitaxel was continued for 30 months, without apparent recurrence. However, the gastric cancer recurred as disseminated carcinomatosis of the bone marrow with disseminated intravascular coagulation, and we hence changed the chemotherapy regimen to weekly irinotecan. Remission was achieved, and she did not experience any major symptoms; however, she died 6 months after the diagnosis of disseminated carcinomatosis of the bone marrow.
Since intraperitoneal paclitaxel administration can strongly suppress peritoneal carcinomatosis of gastric cancer, careful attention should be paid not only to peritoneal recurrence but also for rare site metastases, such as bone marrow metastases.
KeywordsGastric cancer Disseminated carcinomatosis of the bone marrow Intraperitoneal chemotherapy
Peritoneal carcinomatosis is the most frequent mode of metastasis and recurrence in patients with gastric cancer. Clinical studies investigating the effects of intraperitoneal chemotherapy with paclitaxel (PTX) performed by our group on such patients have shown that the treatment is well tolerated and effective [1–3]. Moreover, we have experienced rare cases of metastasis and recurrence recently, such as leptomeningeal carcinomatosis  after long-term control of peritoneal metastasis. Particularly, bone marrow metastasis is highly rare in gastric cancer , and disseminated carcinomatosis of the bone marrow (DCBM) is known to be closely associated with disseminated intravascular coagulation (DIC) and a poor prognosis [5, 6]. Herein, we present a rare case of DCBM originating from gastric cancer and developing 3 years after intraperitoneal chemotherapy with PTX against peritoneal carcinomatosis.
Two years and 6 months after the surgery, she experienced lumbago, with increases in the carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, and CA125 levels observed. Computed tomography showed bone metastases at the thoracic to lumbar vertebrae. A decreased platelet count was noted, indicating DIC, and the patient was hence readmitted to our hospital.
In the present case, gastric cancer metastasized to the bone marrow and caused DCBM associated with DIC 3 years after intraperitoneal chemotherapy against peritoneal carcinomatosis of gastric cancer. DCBM is uncommon in patients with gastric cancer; Kim et al. reported that only 2.4 % of metastatic, unresectable, or recurrent gastric cancers had confirmed bone marrow metastasis . And DCBM from solid tumors was closely associated with DIC . Jarcho et al. reported an association between multiple bone metastases and DIC in diffusely infiltrative gastric cancer as early as 1936 , and Brain et al. reported a close association between mucin-forming cancer and DIC and/or microangiopathic hemolytic anemia . Later, Pasquini et al. examined bone metastases from solid tumors with hematological disorders, and the prognosis is very poor . This condition is called DCBM [5, 6].
In patients with DCBM and DIC from solid tumors, gastric cancer accounts for the majority of cases . DCBM is associated with various symptoms, including bone pain, bleeding tendencies, anemia, general weakness, and elevated levels of serum alkaline phosphatase [5, 6, 10]. Macroscopic Borrmann types III and IV, histologically poorly differentiated adenocarcinoma, younger age, highly advanced tumors, and primary tumors in the upper part of the stomach are risk factors for gastric cancer resulting in DCBM [5, 6, 10]. Of note, many cases (66.7 %) recur over 5 years following the initial surgery, with recurrence at the bone marrow more than 10 years as reported in some case [11, 12], indicating the presence of “tumor dormancy,” a long latent phase of tumor progression . The present case matched most of these risk factors and presented all major symptoms described in the literature in the 2 months after presenting with lumbago.
DCBM is associated with a poor prognosis, with some patients dying within a few weeks as a result of bleeding or organ insufficiency caused by DIC [5, 6, 10]. Park et al. examined 203 cases of bone marrow metastasis originating from gastric cancer. They found that the median survival time was 103 days, with complicated DIC being associated with a significantly poorer prognosis, while patients receiving chemotherapy had a better prognosis (175 days). On the other hand, the median survival time of the patients who did not receive chemotherapy was only 43 days , indicating that aggressive chemotherapy is effective for DCBM [10–12]. In this case, we changed the regimen to weekly CPT-11 because the patient had already received other key drugs for gastric cancer, including S-1, cisplatin, and PTX. The patient overcame DIC once and survived for 6 months after the diagnosis of DCBM.
In our previous clinical studies, we treated peritoneal carcinomatosis of gastric cancer using intraperitoneal chemotherapy with PTX. In this intraperitoneal chemotherapy, PTX is repeatedly administered into the intraperitoneal space via a subcutaneously placed intraperitoneal access port. This combination chemotherapy is effective for peritoneal metastases and appears to produce a marked elongation of survival in these patients [1–3]. Moreover, peritoneal carcinomatosis often disappears macroscopically during the course of intraperitoneal chemotherapy. From August 2005 to April 2012, 158 cases of gastric cancer with peritoneal carcinomatosis underwent intraperitoneal chemotherapy with PTX in our department. Recurrence in the bone was found in 15 cases (9.5 %), with multiple bones implicated in 4 cases (2.5 %); of these, 3 cases (1.8 %) were clinically suspected as DCBM with DIC. Two of these three cases (with the exception of the present case) were treated with best supportive care and died within 1 month. The higher rate of DCBM experienced in our department compared with that in previous reports may be due to the strong suppression of peritoneal carcinomatosis by intraperitoneal administration of PTX.
We here experienced a patient of gastric cancer with peritoneal carcinomatosis who developed DCBM 3 years after initiation of intraperitoneal chemotherapy with PTX. Since intraperitoneal PTX administration can strongly suppress peritoneal carcinomatosis of gastric cancer, careful attention should be paid not only to peritoneal recurrence but also for rare site metastases, such as bone marrow metastases, during the course of intraperitoneal chemotherapy.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
disseminated carcinomatosis of the bone marrow
disseminated intravascular coagulation
This study was conducted without funding.
Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
- Ishigami H, Kitayama J, Otani K, Kamei T, Soma D, Miyato H, et al. Phase I pharmacokinetic study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer. Oncology. 2009;76:311–4.View ArticlePubMedGoogle Scholar
- Ishigami H, Kitayama J, Kaisaki S, Hidemura A, Kato M, Otani K, et al. Phase II study of weekly intravenous and intraperitoneal paclitaxel combined with S-1 for advanced gastric cancer with peritoneal metastasis. Ann Oncol. 2010;21:67–70.View ArticlePubMedGoogle Scholar
- Yamaguchi H, Kitayama J, Ishigami H, Emoto S, Yamashita H, Watanabe T. A phase 2 trial of intravenous and intraperitoneal paclitaxel combined with S-1 for treatment of gastric cancer with macroscopic peritoneal metastasis. Cancer. 2013;119:3354–8.View ArticlePubMedGoogle Scholar
- Emoto S, Ishigami H, Yamaguchi H, Yamashita H, Kaisaki S, Kitayama J. Frequent development of leptomeningeal carcinomatosis in patients with peritoneal dissemination of gastric cancer. Gastric Cancer. 2011;14:390–5.View ArticlePubMedGoogle Scholar
- Kim HS, Yi SY, Jun HJ, Lee J, Park JO, Park YS, et al. Clinical outcome of gastric cancer patients with bone marrow metastases. Oncology. 2007;73:192–7.View ArticlePubMedGoogle Scholar
- Kusumoto H, Haraguchi M, Nozuka Y, Oda Y, Tsuneyoshi M, Iguchi H. Characteristic features of disseminated carcinomatosis of the bone marrow due to gastric cancer: the pathogenesis of bone destruction. Oncol Rep. 2006;16:735–40.PubMedGoogle Scholar
- Jarcho S. Diffusely infiltrative carcinoma: a hitherto undescribed correlation of several varieties of tumor metastasis. Arch Pathol. 1936;22:674–96.Google Scholar
- Brain MC, Azzopardi JG, Baker LR, Pineo GF, Roberts PD, Dacie JV. Microangiopathic haemolytic anaemia and mucin-forming adenocarcinoma. Br J Haematol. 1970;18:183–93.View ArticlePubMedGoogle Scholar
- Pasquini E, Gianni L, Aitini E, Nicolini M, Fattori PP, Cavazzini G, et al. Acute disseminated intravascular coagulation syndrome in cancer patients. Oncology. 1995;52:505–8.View ArticlePubMedGoogle Scholar
- Kwon JY, Yun J, Kim HJ, Kim KH, Kim SH, Lee SC, et al. Clinical outcome of gastric cancer patients with bone marrow metastases. Cancer Res Treat. 2011;43:244–9.View ArticlePubMedPubMed CentralGoogle Scholar
- 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;26:472–5.View ArticlePubMedGoogle Scholar
- Kammori M, Seto Y, Haniuda N, Kawahara M, Takubo K, Endo H, et al. A case of bone metastasis from gastric carcinoma after a nine-year disease-free interval. Jpn J Clin Oncol. 2001;31:407–9.View ArticlePubMedGoogle Scholar
- Holmgren L, O’Reilly MS, Folkman J. Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med. 1995;1:149–53.View ArticlePubMedGoogle Scholar
- Park HS, Rha SY, Kim HS, Hyung WJ, Park JS, Chung HC, et al. A prognostic model to predict clinical outcome in gastric cancer patients with bone metastasis. Oncology. 2011;80:142–50.View ArticlePubMedGoogle Scholar