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.

BAF57 Is a Potential Determinant of Colorectal Cancer Malignancy.

BACKGROUND/AIM: The role of brahma-related gene 1 (BRG1)-associated factor 57 (BAF57), a transcription factor, has been determined in prostate, breast, and ovarian cancer. However, the relationship between BAF57 and colorectal cancer (CRC) is obscure. Thus, we examined the functional correlation between BAF57 expression and oncological malignancy in CRC in vitro. MATERIALS AND METHODS: BAF57 expression in WiDr and HT29 CRC cell lines and clinical specimens from CRC patients was analysed by western blotting and/or RT-PCR. BAF57 expression was down-regulated in WiDr cells through siRNA transfection. An invasion assay was also performed to assess malignancy. RESULTS: BAF57 was expressed in both human CRC cell lines. Overall survival and recurrence-free survival rates were significantly reduced in high BAF57-expressing specimens. BAF57 expression was an independent predictive factor for long-term survival. CONCLUSION: BAF57 correlates with oncological malignancy and may be a novel therapeutic target in CRC.

Inhibition of Heat-shock Protein 27 Reduces 5-Fluorouracil-acquired Resistance in Human Colon Cancer Cells.

BACKGROUND/AIM: In previous work we showed that expression of heat-shock protein 27 (HSP27; encoded by HSPB1) was associated with inherent resistance to 5-fluorouracil (5-FU). However, the relationship between HSP27 and acquired resistance remains unknown. MATERIALS AND METHODS: We generated an acquired resistance model (WiDr-R) of a colon cancer cell line by exposing WiDr cells to 5-FU. Cell viability assays under treatment with 5-FU, as well as down-regulation of HSP27 using small interfering HSP27 RNA, were performed. HSP27 mRNA and protein expression was analyzed using real-time polymerase chain reaction and western blotting. RESULTS: 5-FU-acquired resistance induced overexpression of HSP27 mRNA and protein levels in WiDr-R cells. Furthermore, siRNA knockdown of HSP27 in WiDr-R cells reduced 5-FU-acquired resistance. CONCLUSION: These findings demonstrate that HSP27 is associated with 5-FU resistance in human colon cancer cell cells and suggest that HSP27 regulation represents a novel approach to overcoming chemoresistance in colorectal cancer.

[A Case of Duodenal Perforation during Bevacizumab Combination Chemotherapy in a Patient with Multiple Lung Metastasis after a Sigmoidectomy].

A 73-year-old man underwent laparoscopic sigmoidectomy for sigmoid colon cancer. Two years after the operation, multiple lung metastasis was diagnosed and chemotherapy with bevacizumab, irinotecan, and TS-1®was started in the patient. However, epigastric pain developed 73 days after the initial course of chemotherapy. Abdominal CT revealed duodenal perforation and generalized peritonitis. Emergency operation with omental patch closure was immediately performed. The patient was discharged 15 days after the emergency operation without any complication. This is an extremely rare case of bevacizu- mab-related duodenal perforation.

The impact of the mesorectal apparent diffusion coefficient value on surgical difficulty in laparoscopic anterior resection for rectal cancer.

PURPOSE: We aimed to clarify the impact of the apparent diffusion coefficient (ADC) value of the mesorectum from preoperative magnetic resonance imaging (MRI) on surgical difficulty in laparoscopic anterior resection (Lap-AR) for rectal cancer. METHODS: In total, 67 patients who had undergone curative Lap-AR for rectal cancer in our hospital from January 2008 to March 2015 and had preoperative MRI findings available were included. We randomly calculated the average ADC in three regions of the mesorectum at the level of the upper edge of the superior border of the femur. Univariate and multivariate analyses were performed to evaluate the correlation between the patients' clinicopathological characteristics, including the ADC value and short-term surgical outcomes. RESULTS: The univariate analysis revealed that a lower ADC value was associated with a significantly increased operative blood loss (p = 0.008) and prolonged operative time (p < 0.001). The multivariate analysis adjusted for the body mass index, anal verge, tumor location, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for a prolonged operative time (R2 = 0.6003, p < 0.001). Furthermore, the multivariate analysis adjusted for the body mass index, anal verge, covering stoma, clinical T factor and conversion revealed that the ADC value was an independent risk factor for an increased blood loss (R2 = 0.4345, p = 0.008). CONCLUSION: A lower ADC value of the mesorectum might be a predictor of surgical difficulty in Lap-AR for rectal cancer.

Heat shock protein 27 knockdown using nucleotide­based therapies enhances sensitivity to 5-FU chemotherapy in SW480 human colon cancer cells.

Heat shock protein 27 (Hsp27) is a chaperone protein of low molecular weight that is produced in response to various stresses and has a cytoprotective function. In the present study we found that there is a strong correlation between sensitivity to 5-fluorouracil (5-FU) and the expression of Hsp27 in colorectal cancer. Apatorsen is an antisense oligonucleotide that targets Hsp27 and has various antitumor effects in some types of cancer, such as bladder and prostate. Although several clinical studies are currently studying apatorsen in many malignancies, to date no promising results have been reported for colorectal cancer. In the present study, we examined the impact of Hsp27 downregulation (via apatorsen) on 5-FU sensitivity in colon cancer both in vitro and in vivo. In vitro, apatorsen significantly decreased the levels of Hsp27 in a dose-dependent manner in human colon cancer SW480 cells. A cell proliferation assay revealed that although apatorsen did not inhibit tumor growth, it resulted in greater 5-FU sensitivity in comparison with treatment with OGX-411 (control). In vivo, intraperitoneal injection of apatorsen decreased the levels of Hsp27 in subcutaneous tumors in a xenograft mouse model using SW480 cells and enhanced 5-FU sensitivity, compared to controls. Although further research is warranted, the present study confirmed that concurrent treatment with Hsp27 knockdown using apatorsen and 5-FU could be a promising therapy for colon cancer.

Pelvic inlet shape measured by three-dimensional pelvimetry is a predictor of the operative time in the anterior resection of rectal cancer.

PURPOSE: We evaluated pelvic shape as a predictor of the surgical outcome of anterior resection in patients with rectal cancer. METHODS: In total, 228 patients who had undergone anterior resection (R0 resection and double-stapling anastomosis) for rectal cancer from 2005 to 2014 were included in this study. The anteroposterior (AP) and transverse (T) diameters of the pelvic inlet and outlet and pelvic depth were analyzed on three-dimensional volume-rendered images, and the AP/T ratio was calculated. Univariate and multivariate analyses were performed to determine the predictive significance of the operative time and intraoperative blood loss as surgical outcomes. RESULTS: No difference was observed between the inlet AP/T and patient sex ratios, but the other pelvic dimensions were significantly shorter in males than in females. The univariate analysis revealed that the operative time was significantly correlated with the inlet T diameter and that it tended to be correlated with the outlet T diameter and the inlet AP/T ratio. A multivariate analysis adjusted for operation-related factors revealed that the inlet AP/T ratio was the only independent risk factor for an extended operative time (p = 0.036). None of the pelvic dimensions were independent risk factors for increased blood loss. CONCLUSION: The shape of the pelvic inlet may be useful for predicting the operative time.

Pleomorphic carcinoma showing rapid growth, multiple metastases, and intestinal perforation.

Pleomorphic carcinoma is a rare and very aggressive subtype of lung cancer that tends to grow rapidly and invade adjacent structures. Here we report a case of pleomorphic carcinoma with rapid growth, multiple metastases, and intestinal perforation. A 46-year-old man was admitted to our hospital because of lung abscess. Several antibiotics were administered for 2 weeks, but his condition did not improve. F18-fluorodeoxyglucose positron emission tomography revealed high uptake in the right lung, stomach, and pancreas. CT-fluoroscopic lung biopsy was performed, and a diagnosis of pleomorphic carcinoma was made. His performance status worsened each day, and the lung tumor grew within 1 month. In addition, sudden severe abdominal pain and tenderness developed 10 days after lung biopsy. He was diagnosed with gastrointestinal perforation, and he underwent surgery. However, he died 2 weeks after the surgery. Autopsy revealed the presence of an enormous tumor in the right lung and multiple metastases in the stomach, duodenum, intestine, bilateral kidneys, pancreas, gallbladder, right adrenal gland and thyroid.