Stratification of Stage II Colon Cancer Using Recurrence Prediction Value: A Multi-institutional International Retrospective Study.

OBJECTIVE: To create a recurrence prediction value (RPV) of high-risk factor and identify the patients with high risk of cancer recurrence. SUMMARY BACKGROUND DATA: There are several high-risk factors known to lead to poor outcomes. Weighting each high-risk factor based on their association with increased risk of cancer recurrence can provide a more precise understanding of risk of recurrence. METHODS: We performed a multi-institutional international retrospective analysis of patients with Stage II colon cancer patients who underwent surgery from 2010 to 2020. Patient data from a multi-institutional database were used as the Training data, and data from a completely separate international database from two countries were used as the Validation data. The primary endpoint was recurrence-free survival (RFS). RESULTS: A total of 739 patients were included from Training data. To validate the feasibility of RPV, 467 patients were included from Validation data. Training data patients were divided into RPV low (n = 564) and RPV high (n = 175). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (Hazard ratio (HR) 2.628; 95% confidence interval (CI) 1.887-3.660; P < 0.001). Validation data patients were divided into two groups (RPV low, n = 420) and RPV high (n = 47). Multivariate analysis revealed that risk of recurrence was significantly higher in the RPV high than the RPV low (HR 3.053; 95% CI 1.962-4.750; P < 0.001). CONCLUSIONS: RPV can identify Stage II colon cancer patients with high risk of cancer recurrence world-wide.

Total endoscopic thyroidectomy after open neck biopsy of the follicular lymphoma of the thyroid gland.

Remote-access total endoscopic thyroidectomy (TET) is a recently established approach that can avoid producing scars in the neck. There are no clear surgical indications for TET for benign nodules or for malignant tumors at present. We report a successful TET in a 50-year-old Japanese woman with follicular lymphoma of the thyroid gland after an open neck biopsy. She had been referred to us with a neck tumor noted 2 months earlier. Because of adhesion, we performed a combined resection of the thyroid and partial right sternohyoid muscle. To the best of our knowledge, there is no other report of a TET performed after open neck surgery. Our patient's case demonstrates that (a) the cosmetic outcome of TET is clearly superior to that of conventional open neck surgery, and (b) a TET can be suitable even for reoperation if carefully selected.

Therapeutic potential of transgenic mesenchymal stem cells engineered to mediate anti-high mobility group box 1 activity: targeting of colon cancer.

BACKGROUND: Mesenchymal stem cells (MSCs) are being developed as a new clinically relevant stem cell type to be recruited into and to repair injured tissue. A number of studies have focused on the therapeutic potential of MSCs by virtue of their immunomodulatory properties. Systemically administered MSCs can also migrate to sites of malignancies. Because of this latter phenomenon, we transfected human MSCs to secrete anti-high mobility group box (HMGB) 1 proteins. They were then injected into mice bearing human colon cancer to evaluate their efficacy as an antineoplastic agent. MATERIALS AND METHODS: The ABOX gene was used in this model, which encodes part of the HMGB1 protein and acts as an HMGB1 antagonist. It was cotransduced by electroporation with a FLAG-tag to visualize the secreted ABOX protein, levels of which in supernatants from cultured transfected MSCs were quantified by immunofluorescence imaging using an anti-FLAG antibody. Antiangiogenic effects were evaluated in vitro using a novel optical assay device for the quantitative measurement of cellular chemotaxis assessing the velocity and direction of endothelial cell movement stimulated by supernatant from tumor cells. We found that ABOX proteins released from transfected MSCs suppressed migration in this assay. Finally, MSCs were injected subcutaneously into Nonobese diabetic/severe combined immunodeficiency mice bearing human colon cancer from a cell line, which secreted large amounts of HMGB1. Ten days after MSC injection, mice were sacrificed and tumors evaluated by immunohistochemistry. RESULTS: From 12 ho through 7 d after gene transfection, ABOX proteins secreted from MSCs could be detected by immunofluorescence and enzyme-linked immunosorbent assay. Quantitative measurement of cellular chemotaxis demonstrated that ABOX proteins secreted from transfected MSCs decreased the velocity and interfered with the direction of movement of vascular endothelial cells. Moreover, in an in vivo human colon cancer xenograft model, injection of anti-HMGB1-transfected MSCs resulted in a decreased tumor volume due to the antiangiogenic properties of the secreted ABOX proteins. CONCLUSIONS: MSC modified to secrete HMGB1 antagonist proteins have therapeutic antineoplastic potential. These findings may contribute to future novel targeting strategies using autologous bone marrow-derived cells as gene delivery vectors.

[FOLFIRI with bevacizumab chemotherapy for a patient with recurrence of rectal cancer under haemodialysis for chronic renal failure].

As pharmacokinetics in patients undergoing haemodialysis is different from patients with normal renal function, it remains unclear whether chemotherapy can be performed safely for patients with haemodialysis as well as those who have normal renal function. Here, we report a case with recurrence of rectal cancer who received FOLFIRI with bevacizumab chemotherapy under haemodialysis, and obtained good tumor control. A 47-year-old woman had undergone haemodialysis for 10 years due to chronic renal failure. At 45 years of age, she received abdominoperineal resection due to rectal cancer (pStage II). Four months after the surgery, liver metastasis was found, for which partial resection of the liver and adjuvant chemotherapy [UFT (400 mg/body)/UZEL (75 mg/body)] were performed. Eighteen months after the liver resection, multiple lung metastases were found. Therefore, intensive chemotherapy using FOLFIRI (CPT-11: 90 mg/m2) with bevacizumab (2.5 mg/m2) was performed. Severe neutropenia (grade 3, 4), but not non-hematologic adverse events such as diarrhea and bevacizumab-specific adverse events, was observed. As she did not recover easily from neutropenia in spite of treatment with G-CSF, a dose reduction of the FOLFIRI regimen was gradually performed. Although chemotherapy was conducted approximately monthly, the tumor response reflected a stable disease 8 months after 8 courses of chemotherapy. We suggest that it is important to investigate the pharmacokinetics of toxic agents such as CPT-11, (SN38) for dose modification, and for the safe and continuous chemotherapy of patients receiving haemodialysis.

Nucleic acids of Enterococcus faecalis strain EC-12 are potent Toll-like receptor 7 and 9 ligands inducing interleukin-12 production from murine splenocytes and murine macrophage cell line J774.1.

In experiment 1 of this study, the interleukin-12 (IL-12)-inducing ability of six Enterococcus strains was evaluated in comparison with that of five Lactobacillus strains using murine splenocytes. At the same time, the involvement of Toll-like receptor (TLR) ligands in IL-12-inducing ability was assessed using splenocytes from TLR2-, TLR4- and MyD88-deficient mice. Most Enterococcus strains, especially Enterococcus faecalis strain EC-12, exerted higher IL-12-inducing ability compared with the Lactobacillus strains evaluated. Almost the same amount of IL-12 protein was produced by all lactic acid bacteria strains in splenocytes from TLR2- and TLR4-deficient mice, whereas splenocytes from MyD88-deficient mice showed no IL-12 production against all bacteria evaluated. In experiment 2, the role of TLR7, 8 and 9 ligands of E. faecalis strain EC-12 in the induction of IL-12 production was evaluated using murine macrophage cell line J774.1. A drastic decrease in IL-12-inducing ability was observed when heat-killed E. faecalis strain EC-12 was treated with nuclease, particularly RNase. In addition, less than one-tenth of IL-12 was produced by heat-killed E. faecalis strain EC-12 when both TLR7 and 9 were antagonized. These facts indicate that the nucleic acids of E. faecalis strain EC-12, particularly its RNA, are the potent TLR7 and 9 ligands that induce IL-12 production from antigen-presenting cells.

[Analysis of four patients with advanced gastric cancer undergoing gastrectomy after pre-operative combination chemotherapy using docetaxel, cisplatin and S-1].

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.