Serum CCL7 Is a Novel Prognostic Biomarker of Metastatic Colorectal Cancer.

BACKGROUND/AIM: Colorectal cancer is the third most common cancer globally, and the poor prognosis of patients with metastatic colorectal cancer (mCRC) warrants urgent attention. We previously obtained 10 candidate serum biomarkers for mCRC. Our aim with this study was to determine the prognostic performance of the pre-treatment serum C-C motif chemokine ligand 7 (CCL7) concentration in patients with mCRC. PATIENTS AND METHODS: Protein concentrations of CCL7 were examined using ELISA and immunohistochemistry for serum (n=110) and surgical specimens (n=85), respectively, of patients with mCRC. The relationship between protein concentration and prognosis was examined using Cox regression analysis, receiver operator characteristic curve analysis and the Kaplan-Meier method. RESULTS: The overall survival (OS) of patients with high concentrations of serum CCL7 was significantly poorer than that of patients with low concentrations. Patients with a high CCL7 concentration in the stroma had significantly poorer outcomes than those with a low concentration. The concentrations of carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 were significantly higher in the high-CCL7 group, compared to those in the low-CCL7 group. Univariate and multivariate analysis revealed that serum CCL7 concentration was a significant prognostic factor for mCRC. The combination of serum CCL and CEA concentrations was also useful in this regard (area under the curve=0.71). CONCLUSION: The combined pre-treatment serum levels of CCL7 and CEA are useful prognostic biomarkers for mCRC.

Serum LOX-1 is a novel prognostic biomarker of colorectal cancer.

BACKGROUND: Colorectal cancer is the third most common cancer worldwide. If biomarkers can be identified in liquid biopsy, diagnosis and treatment can be optimized even when cancerous tissues are not available. The purpose of this study was to identify proteins from liquid biopsy that would be useful as markers of poor prognosis. METHODS: First, we comprehensively analyzed serum proteins to identify potential biomarkers and focused on serum lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1). The relationship between LOX-1 and the prognosis of patients with colorectal cancer has not been reported. Next, we validated this marker using serum samples from 238 patients with colorectal cancer by ELISA and 100 tissue samples by immunohistochemical staining. RESULTS: The optimal cut-off value of serum LOX-1 was 538.7 pg/mL according to time-dependent receiver operating characteristics curve analysis. The overall survival of patients with high levels of serum LOX-1 was significantly poorer than that of individuals with low levels of LOX-1 in the training and test datasets. In multivariate analysis for overall survival, serum LOX-1 was an independent prognostic factor identified in liquid biopsy (hazard ratio = 1.729, p = 0.027). The prognosis of patients with high LOX-1 expression in tumor tissues was significantly poorer than that of individuals with low expression (p =0.047 ). Additionally, inflammatory factors such as white blood cell count, C-reactive protein level, neutrophil/lymphocyte ratio, and monocyte/lymphocyte ratio were significantly higher in the group with high serum LOX-1 levels. CONCLUSIONS: Serum LOX-1 might be a useful biomarker of poor prognosis in colorectal cancer.

Optimal use of antiplatelet agents, especially aspirin, in the perioperative management of colorectal cancer patients undergoing laparoscopic colorectal resection.

BACKGROUND: Laparoscopic abdominal surgery is considered superior to open surgery. However, efficacy and safety outcomes of laparoscopic surgery in colorectal cancer (CRC) are unclear, particularly in patients undergoing antiplatelet therapy (APT). The aim of this study was to evaluate safety of antiplatelet agents, especially aspirin, in peri-operative management of patients undergoing laparoscopic colorectal resection for CRC. METHODS: A total of 578 radical laparoscopic colorectal surgeries in CRC patients performed between January 2005 and December 2015 at the Kokura Memorial Hospital were retrospectively reviewed. Patients were divided into three groups based on the risk for thromboembolism: a high-risk group receiving APT (APT-HR), a low-risk group receiving APT (APT-LR), and a low-risk group not receiving APT (non-APT). Bleeding complications (BC) and thromboembolic complications (TC) were assessed. Perioperative and outcome variables in groups receiving APT were compared with those in the non-APT group. RESULTS: APT-HR, APT-LR, and non-APT groups included 54 (9.3%), 114 (19.7%), and 410 (70.9%) patients, respectively. Blood loss during operation (p = 0.304), operative time (p = 0.956), hospitalisation after surgery (p = 0.307), and Clavien-Dindo classification of surgery-related complications (p = 0.467) were not significantly different in the three groups. Occurrence of intra-operative BC (blood loss ≥ 200 ml) (p = 0.864), post-operative BC (p = 0.630), and TC (p = 0.287) were also not significantly different in the three groups. Results of our analysis indicated that APT and non-interrupted APT were not associated with BC or TC. CONCLUSIONS: Analysis of laparoscopic colorectal resection in CRC showed that APT was not a major factor for fatal BC or TC. In patients with high thromboembolic risk, continuing aspirin may inhibit the increase in TC without increasing BC in the peri-operative period.

[A case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of extensive dissemination in advanced colon cancer, and the primary lesion could be resected].

Here, we report a case wherein bevacizumab/XELOX combination therapy was remarkably effective for the treatment of a patient with unresectable advanced cecum cancer and carcinomatous peritonitis. A 52-year-old man was diagnosed with cecum cancer with extensive carcinomatous dissemination. He underwent open laparotomy, and the findings indicated a unresectable cecal tumor attached to the retroperitoneum; therefore, ileo-transverse colostomy was performed. After 6 courses of bevacizumab and XELOX therapy, the primary tumor as well as ascites and carcinomatous dissemination had disappeared, and a marked decrease in the serum carcinoembryonic antigen(CEA)level was noted. However, subsequently, positive emission tomography/computed tomography(PET/CT)indicated a recurrence of the primary tumor. Therefore, ileocecalectomy and D2 lymph node dissection were performed. Thus, we believe that bevacizumab/XELOX therapy may be useful as neoadjuvant chemotherapy for the treatment of advanced colon cancer with peritonitis carcinomatosa.

[A case of advanced esophageal cancer revealed a pathological complete response and survived more than 8 years, treated by radiation therapy combined with nedaplatin and 5-FU chemotherapy].

We report here the long-term survival case of advanced esophageal cancer treated with definitive chemoradiotherapy (CRT). A 61-year-old woman visited our hospital because of a disturbance in her swallowing in September, 2003. She was diagnosed with a middle esophageal type 3 tumor, which was 9 cm in length by endoscopy. Squamous cell carcinoma was diagnosed by pre-operative endoscopic biopsy. CT revealed the tumor with direct invasion to the aorta, and multiple metastases of the lymph nodes(T4, N1, M0: Stage IVa). CRT(combination of 5-FU and nedaplatin with 40 Gy of radiation)was administered. After the completion of CRT, the tumor size was remarkably reduced, but stenosis of the lumen of the esophagus remained partially. Therefore, we performed sub-total esophagectomy in February, 2004. A pathological complete response was diagnosed with no carcinoma cells evident in the resected specimen. Pathological therapeutic evaluation of the esophageal cancer was grade 3. The patient had received no adjuvant chemotherapy, but she is alive and healthy now with no relapse of carcinoma for more than 8 years after operation.

[Solitary ectopic thymoma at ligamentum arteriosum; report of a case].

We report a case of solitary ectopic thymoma at the ligamentum arteriosum, which was resected with thoracoscopic surgery. A 62-year-old male patient received chemoradiation therapy for laryngeal cancer approximately 1 year before. The present computed tomography scan indicated a mass (diameter, 2 cm) at the ligamentum arteriosum. Furthermore, positron emission tomography showed an abnormal accumulation on the mass. Malignant lymphoma and laryngeal cancer with lymph node metastasis were suspected, and thoracoscopic surgery was performed. The tumor had a clear margin;therefore, it could be extirpated easily. The results of the postoperative pathological examination indicated that the tumor was an ectopic thymoma. The patient was discharged 3 days after the surgery because he showed good clinical course and was kept under careful observation.

[A case report of a patient with overlap syndrome systemic lupus erythematosus( SLE) and polymyositis( PM)whose condition improved following treatment for coexisting descending colon cancer].

Here, we report a case of a patient with overlap syndrome (systemic lupus erythematosus[SLE]and polymyositis[PM]) whose condition improved following treatment for coexisting descending colon cancer. A 75-year-old man experienced Raynaud symptoms and arthralgia. He was diagnosed as having overlap syndrome (SLE/PM) and was treated with steroids. However, the symptoms did not improve. Descending colon cancer was diagnosed by colonoscopy. After surgery, overlap syndrome improved immediately. Overlap syndrome was considered as a paraneoplastic event caused by the coexisting descending colon cancer.

[A patient with intestinal gastrointestinal stromal tumor refractory to molecular targeted but whose quality of life improved after palliative surgery].

We herein report the case of a patient with intestinal gastrointestinal stromal tumor(GIST) who was refractory to molecular targeted therapy but showed improvement in quality of life(QOL) after palliative surgery. A 60-year-old man with a high-risk diagnosis underwent an incomplete resection for multiple abdominal tumors. He was treated with molecular targeted therapy after the operation, but he acquired secondary resistance to imatinib and intolerance to sunitinib. Although the patient was treated with imatinib again, he experienced vomiting, abdominal pain, and leg edema because of tumor regrowth 7 months after the re-treatment. His general condition deteriorated, and his Eastern Cooperative Oncology Group (ECOG) performance status(PS) was 3. After 35 months of the first treatment, palliative resection of tumors was performed to control the symptoms. After the operation, the general condition of the patient improved, and his ECOG PS was maintained as 1 for at least 4 months. Palliative resection may improve QOL.