Sinusoidal Obstruction Syndrome and Postoperative Complications Resulting from Preoperative Chemotherapy for Colorectal Cancer Liver Metastasis

Abstract

Background/Aim: The aim of this study was to investigate the effects of preoperative chemotherapy on the healthy, metastasis-free part of the liver in colorectal cancer patients with liver metastasis, and the relationship between chemotherapy and postoperative complications. Patients and Methods: Our study included 90 cases of colorectal cancer liver metastasis resected after preoperative chemotherapy. The patients were divided into three groups according to the received chemotherapy regimen: 20 cases received mFOLFOX6, 54 cases a combination of mFOLFOX6 with bevacizumab, and 16 cases a combination of mFOLFOX6 and cetuximab or panitumumab. Results: The mean numbers of sinusoidal injuries for each chemotherapy type were compared. The group treated with the combination of mFOLFOX6 and bevacizumab showed a lower extent of sinusoidal injury relative to other groups; this intergroup difference became increasingly remarkable as the number of chemotherapy cycles increased. Complications of various extents were found in all three groups, but no significant differences were observed between the three groups. Conclusion: In cases where preoperative chemotherapy was extended over a long period, combined use of bevacizumab was thought to be effective because of stabilization of disturbed liver hemodynamics resulting from sinusoidal injury suppression effects, allowing effective distribution of anti-cancer agents to tumors. Colorectal cancer is one of the most frequently occurring malignant tumors worldwide (1). Approximately 60% of colon cancer patients have been reported to have complications of liver metastasis during the course of their disease (2). Surgical treatment presents the only possibility of curative treatment for colorectal cancer liver metastasis and has a strong impact on prognosis. A variety of efforts in recent years including preoperative liver function evaluation, preoperative chemotherapy, surgical procedures, preoperative management, and so on, have been reported to improve prognosis and liver resectability. Still, the major factor is the burden of chemotherapy itself (3-7). It has been reported (8) that, in cases where radical resection is possible, colorectal cancer liver metastasis shows approximately 60% recurrence, 80% of which are unresectable. Thus, chemotherapy will certainly play an increasingly important role in the future. Preoperative chemotherapy for colorectal cancer liver metastasis plays an important role in a regimen of multidisciplinary treatment. Chemotherapy also involves tissue adverse effects, and there are apprehensions regarding the effects on remnant liver when hepatectomy is performed following systemic chemotherapy (9). Veno-occlusive disease (VOD) (10), also known as sinusoidal obstruction syndrome (SOS), is a pathology that causes injury to sinusoidal and venule endothelial cells and is reported to be caused by radiotherapy, chemotherapy, and so on. Numerous reports have stated that SOS incidence is high in chemotherapy for colorectal cancer liver metastasis, especially in re...

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“…OXA-induced hepatic sinusoidal obstruction syndrome (HSOS) has been demonstrated in up to 77% of colorectal cancer patients with liver metastasis following OXA-based chemotherapy ( 33 ). Studies have reported that preoperative OXA was associated with HSOS and that this increased postoperative morbidity after partial hepatectomy with colorectal cancer liver metastasisn ( 34 , 35 ). OXA-induced HSOS frequently presents with ascites, jaundice, right upper quadrant pain, splenomegaly with subsequent thrombocytopenia, and portal hypertension.…”

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“…39 The rationale of precluding the induction treatment has often been a fear of causing parenchymal toxic effects, which could have perioperative and postoperative implications. [40][41][42][43] Previous reports have emphasized the need for randomized prospective trials to determine the best order of treatment for stage IV colorectal cancer with colorectal liver metastases. In contrast, the clinical and biological heterogeneity of this disease indicates that there is no one best treatment for all.…”

“…39 The rationale of precluding the induction treatment has often been a fear of causing parenchymal toxic effects, which could have perioperative and postoperative implications. 40–43…”