In this study, 46% of patients who underwent major hepatectomy with EBDR for perihilar cholangiocarcinoma had sarcopenia preoperatively; among the studied patients SMI decreased in 52% in the early postoperative period and also in 52% in the late postoperative period. Preoperative sarcopenia was not associated with a shorter OS or RFS. However, decreased SMI in the early postoperative period was independently associated with both shorter OS and RFS. Moreover, compared to elevated serum CA 19 − 9 level, decreased SMI in the early postoperative period was associated more strongly with recurrence and poor survival. On the other hand, decreased SMI in the late postoperative period was independently associated with a shorter OS but not with a shorter RFS.
Tran et al. found that elevated preoperative serum CA 19 − 9 level, lymph node metastasis, and R1 resection were associated with poorer 5-year survival among 194 patients who underwent perihilar cholangiocarcinoma resection.3 Zhang et al. systematically reviewed 38 cohort studies and found that lymph node metastasis, positive resection margin, intraoperative transfusion, pathological stage T3/4, and moderately or poorly differentiated adenocarcinoma were associated with poor prognosis in patients with perihilar cholangiocarcinoma.9 It should be noted that all variables evaluated in those studies were determined preoperatively or from pathological findings, whereas the present study evaluated variables determined pre-, intra-, and post-operatively.
One study evaluated the associations of the perioperative percent change in SMV with postoperative outcomes in patients who underwent major hepatectomy with EBDR for perihilar cholangiocarcinoma at a high-volume center in Japan.18 The authors measured the total psoas muscle area at the third lumbar vertebra on CT both preoperatively and 1 week postoperatively and showed that total psoas muscle area was significantly lower postoperatively than preoperatively, with a median percent change of − 2.2%. Furthermore, in that study, patients in whom total psoas muscle area decreased postoperatively had a significantly higher incidence of major postoperative complications and surgery-related mortality than those in whom total psoas muscle area did not decrease postoperatively. The authors described that skeletal muscle degradation 1 week postoperatively was due to the release of inflammatory cytokines, such as plasma interleukin (IL)-6 or tumor necrosis factor-α (TNF-α), triggered by surgery or postoperative complications.
Several studies evaluated the mechanism for the poor prognosis of patients in whom SMV decreased in the clinical course of malignant disease.19–20 Lutz et al. showed that IL-15, a myokine released by muscle, affects the development and survival of natural killer cells and negatively regulates adipose tissue to release inflammatory cytokines such as IL-6 and TNF-α, which inhibit the survival and activities of natural killer cells.20 Accordingly, they described that a decrease in SMV consequently reduces the number and functions of natural killer cells and attenuates antitumor responses, resulting in poor prognosis for patients with malignant diseases.
Serum CA 19 − 9 is usually measured during follow-up after surgery for perihilar cholangiocarcinoma10; its elevation is reported to be a risk factor for early recurrence and poor survival.21 In the present study, elevated serum CA 19 − 9 level in the late postoperative period, instead of the early postoperative period, was significantly associated with a shorter OS and RFS. In contrast, decreased SMI in the early postoperative period was significantly associated with a shorter OS and RFS.
These results collectively suggest that decreased SMI is a more useful predictor for early recurrence and poor survival than elevated serum CA 19 − 9 level. Thus, measurement of SMI was considered to be useful for monitoring patients after surgery, and a decrease in SMI might be an early sign of tumor progression that precedes the elevation of tumor markers and appearance of tumor on CT. Accordingly, detecting recurrence before lesions on radiological examination enables clinicians to plan closer follow-up or additional examinations, or start secondary treatment. Moreover, the initiation of systemic chemotherapy at an earlier disease stage might improve survival.
One limitation of this study was its retrospective design, which introduces a risk of selection bias mainly due to the exclusion of patients who were not surgical candidates. Second, although this study included a small sample size, surgery for patients with perihilar cholangiocarcinoma is rare owing to its incidence, difficulty in diagnosis, and invasiveness and risks in surgery. Third, secondary treatments after recurrence were not considered in survival analysis. However, patients who were receiving pre- or postoperative adjuvant therapy as part of a clinical trial were excluded because the presence of adjuvant therapy might affect survival outcomes, regardless of the change of SMI. Clinical variables that were associated especially with early recurrence in condition with no other anti-cancer therapy than surgery were sought in this study.