Clinical commentary
Cholangiocarcinoma with spinal metastasis: Single center survival analysis

https://doi.org/10.1016/j.jocn.2016.12.048Get rights and content

Highlights

  • Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from various locations within the biliary tree.

  • CCA with spinal metastases had a poor median survival.

  • A single level of affected spine and a Frankel scale of C or better demonstrated significantly longer median survival.

  • A moderate to high Kanofsky score, and radiation therapy showed significant longer median survival.

  • CCA resection and spinal surgery, combine with adjuvant treatments, may play an important role in prolonging survival.

Abstract

The aim of this study was to perform a survival analysis of Cholangiocarcinoma (CCA) with spinal metastases. 55 cases of CCA with spinal metastases were retrospectively reviewed. We recorded age, sex, Kanofsky performance score, Frankel scale, number and region of affected vertebrae, presence of appendicular bone metastases, treatment received, and survival time; then performed a survival analysis. Overall median survival was 4 months (95%CI, 2.89–5.11). Frankel A had the poorest survival (2 months—95%CI, 1.15–2.85) compared to Frankel C and D (P = 0.004 and <0.001, respectively). One-level spinal metastasis had the longest survival (8 months—95%CI, 5.98–10.02) compared to two-level and more than two-level involvement (P = 0.036 and 0.001, respectively). The higher Kanofsky score had the longer survival (11 months—95%CI, 9.61–12.39) compared with the low and moderate score groups (P < 0.001 and 0.012, respectively). Radiation therapy had a survival of 6 months (95%CI, 3.41–8.59), significantly longer than the 3 months for palliative spine surgery and 2 months for palliative treatment alone. CCA resection and palliative spine surgery—when performed together and/or combined with other adjuvant treatment(s)—had a survival time of longer than 9 months. In conclusion, CCA with spinal metastases had a poor median survival. A single level of affected spine, a Frankel scale of C or better, a moderate to high Kanofsky score, and radiation therapy were associated with significantly longer median survival. CCA resection and spinal surgery may play an important role in prolonging survival when used in conjunction with other adjuvant treatment modalities.

Introduction

Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from various locations within the biliary tree, presenting the marker for cholangiocyte differentiation [1]. CCA tends to progress locally and regionally by spreading through the lymphatic system with metastases through the venous and lymphatic systems [2], [3], [4], [5]. The incidence of CCA varies worldwide and the highest incidence is in Khon Kaen province, Thailand, where the incidence is 44.3 and 17.6 per 100,000 males and females, respectively [6]. A definite diagnosis of CCA is based on pathological examination; however, in general practice, diagnosis of CCA is usually based on clinical signs and symptoms with corroborative radiographic imaging (CT and MRI) [6].

The spine is the most commonly affected musculoskeletal metastasis [2], [7], [8], while the most commonly identified primary sites of metastases are the lungs, breasts, prostate, kidneys, and the hematopoietic system [2], [3], [9]. We recently reported that CCA was the second most common primary site metastasizing to the spine [2].

In a recent review of CCA with spinal metastases, Goodwin et al. [2] identified 16 CCA patients with spinal metastases. Most of the patients had multiple levels of spinal metastases at diagnosis. The median survival time was very poor (1.5 months after diagnosis) of the primary and/or spinal metastases. This is poorer than the median survival time of 4 months for primary CCA regardless of any treatment interventions [2], [10], [11], [12].

Our institute—Khon Kaen University Hospital—is a tertiary hospital and referral center centrally located in northeastern Thailand. This region is endemic for CCA. For example, our hospital had 661 new CCA patients diagnosed between 2008 and 2009 [6], [13]. Notwithstanding, survival analysis of CCA patients with spinal metastases is not well understood due to the relatively small number of patients.

The aim of this study was (a) to investigate median survival time of CCA patients with spinal metastases and (b) to compare survival outcomes between the various treatment modalities employed at Srinagarind Hospital for spinal metastasis.

Section snippets

Study design

Single center, retrospective study.

Selection of patients and grouping

We retrospectively reviewed 176 patients with a diagnosis of spinal metastases of CCA who received treatment in the Department of Orthopaedics between January 1993 and December 2013. The inclusion criteria were: (a) a diagnosis of CCA by clinical and imaging study with or without tissue diagnosis either from (i) an incisional or excisional biopsy at the primary tumor site or (ii) biopsy from the metastases site; (b) clear metastatic spinal lesions diagnosed by

Results

The demographic data are presented in Table 1. CCA with spinal metastases occurred predominately in males (61.8%). Most had incomplete cord lesions and more than two-thirds had two or more than two levels spinal metastases. The most commonly affected region was the thoracic spine followed by the lumbar spine. The mean Kanofsky functional score was intermediate (50.18 ± 22.65). One-third (29.1%) presented with associated appendicular bone metastases. Only 4 patients received CCA resection surgery

Discussion

CCA is an aggressive carcinoma arising in the biliary system with a generally poor prognosis because of late presentation and metastases. CCA is endemic in Khon Kaen province, Thailand [13], [16], [17]. Luvira et al. [6] reported 163 newly diagnosed cases of CCA within the 3 months of their survey, mostly diagnosed by CT or MRI/MRCP, with only 8.6% confirmed by a pathology report. Until recently, the prevalence of CCA with spinal metastases has been limited. A systematic review performed by

Conclusion

CCA is an aggressive and rare non-hepatocellular carcinoma, originating from the biliary system. Khon Kaen, Thailand is an endemic area for the disease. CCA with spinal metastases has a poor median survival time (4 months). Significantly longer median survival time was associated with: one affected spinal level; no appendicular skeletal metastasis; Frankel scale of C or better; a moderate to high Kanofsky score; and, radiation therapy. Further studies are needed on prognostic factors in CCA with

Conflict of interest

None of the authors have any conflict of interest to declare. All are medical practitioners, lecturers and researchers at the Department of Orthopedics, Faculty of Medicine, Khon Kaen University.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by our university ethical committee board. The ethical reference number is HE571095.

Acknowledgements

This study was granted by Faculty of medicine, Khon Kaen University, Thailand. The authors thank (a) the Hospital Records Division for their assistance and (b) Mr. Bryan Roderick Hamman for assistance with the English-language presentation of manuscript through the Publication Clinic, Research Affairs, Faculty of Medicine, Khon Kaen University.

References (17)

There are more references available in the full text version of this article.

Cited by (14)

  • Solitary 18F-fluorodeoxyglucose avid spinous process cholangiocarcinoma metastasis proven on CT guided percutaneous needle bone biopsy.

    2021, Radiology Case Reports
    Citation Excerpt :

    Metastatic spread of disease typically occurs first via the lymphatics to regional lymph nodes, then consequently via haematogenous spread to liver, lungs and peritoneum [1]. Bone metastases have been reported in the literature, however, these are often found in later stages of disease, at multiple vertebral levels and concurrently with other sites of metastases [5–7]. Bony metastases from cholangiocarcinoma typically show a mixed osteolytic/osteoblastic pattern on CT and predominantly involve the anterior spinal elements [8].

  • Imaging features of bone metastases from cholangiocarcinoma

    2020, European Journal of Radiology
    Citation Excerpt :

    The common distribution of vertebral metastases occurred in lumbar, upper thoracic, and lower thoracic and less frequently involved the cervical and sacral regions. Related to the other study, which analyzed 55 CCA patients with spinal metastasis and reported that more than two-third had two or more of spinal metastases with the predominance in thoracic followed by lumbar and cervical spine [7]. For non-vertebral metastasis, ribs were the most common place, followed by pelvis, femur, scapula, and humerus.

  • Prognostic and risk factors in patients with metastatic bone disease of an upper extremity

    2018, Journal of Bone Oncology
    Citation Excerpt :

    CCA is a cancer of the biliary system with a poor prognosis, and CCA metastasizing to bone is rare [17]. The incidence of CCA varies worldwide and the highest incidence is in Khon Kaen province Thailand where our institute is located [18,19]. Bone metastases of unknown origin occur in between 10% and 15% of patients with bone lesions.

  • Factors Associated with Bone Scintigraphy Positivity in Cholangiocarcinoma

    2023, Journal of Health Science and Medical Research
View all citing articles on Scopus
1

Pawalee Dowsiriroj and Permsak Paholpak are co-first authors and they contributed equally to this paper.

View full text