Cost-effective screening using a two-antibody panel for detecting mismatch repair deficiency in sporadic colorectal cancer.

BACKGROUND: The microsatellite instability (MSI) test and immunohistochemistry (IHC) are widely used to screen DNA mismatch repair (MMR) deficiency in sporadic colorectal cancer (CRC). For IHC, a two-antibody panel of MLH1 and MSH2 or four-antibody panel of MLH1, MSH2, PMS2, and MSH6 are used. In general, MSI is known as a more accurate screening test than IHC. AIM: To compare two- and four-antibody panels of IHC in terms of accuracy and cost benefit on the basis of MSI testing for detecting MMR deficiency. METHODS: We retrospectively analyzed patients with CRC who underwent curative surgery between 2015 and 2017 at a tertiary referral center. Both IHC with four antibodies and MSI tests were routinely performed. The sensitivity and specificity of a four- and two types of two-antibody panels (PMS2/MSH6 and MLH1/MSH2) were compared on the basis of MSI testing for detecting MMR deficiency. RESULTS: High-frequency MSI was found in 5.5% (n = 193) of the patients (n = 3486). The sensitivities of the four- and two types of two-antibody panels were 97.4%, 92.2%, and 87.6%, respectively. The specificities of the three types of panels did not differ significantly (99.6% for the four-antibody and PMS2/MSH6 panels, 99.7% for the MLH1/MSH2 panel). Based on Cohen's kappa statistic (κ), four- and two-antibody panels were in almost perfect agreement with the MSI test (κ > 0.9). The costs of the MSI test and the four- and two-antibody panels of IHC were approximately $200, $160, and $80, respectively. CONCLUSION: Considering the cost of the four-antibody panel IHC compared to that of the two-antibody panel IHC, a two-antibody panel of PMS2/MSH6 might be the best choice in terms of balancing cost-effectiveness and accuracy.

Improvement in the Assessment of Response to Preoperative Chemoradiotherapy for Rectal Cancer Using Magnetic Resonance Imaging and a Multigene Biomarker.

The response to preoperative chemoradiotherapy (PCRT) is correlated with oncologic outcomes in patients with locally advanced rectal cancer. Accurate prediction of PCRT response before surgery can provide crucial information to aid clinicians in further treatment planning. This study aimed to develop an evaluation tool incorporating a genetic biomarker and magnetic resonance imaging (MRI) to improve the assessment of response in post-CRT patients with locally advanced rectal cancer. A total of 198 patients who underwent PCRT followed by surgical resection for locally advanced rectal cancer between 2010 and 2016 were included in this study. Each patient's response prediction index (RPI) score, a multigene biomarker developed in our previous study, and magnetic resonance tumor regression grade (mrTRG) score were added to create a new predictive value for pathologic response after PCRT, called the combined radiation prediction value (cRPV). Based on the new value, 121 and 77 patients were predicted to be good and poor responders, respectively, showing significantly different cRPV values (p = 0.001). With an overall predictive accuracy of 84.8%, cRPV was superior to mrTRG and RPI for the prediction of pathologic chemoradiotherapy response (mrTRG, 69.2%; RPI, 77.3%). In multivariate analysis, cRPV was found to be the sole predictor of tumor response (odds ratio, 32.211; 95% confidence interval, 14.408-72.011; p = 0.001). With its good predictive value for final pathologic regression, cRPV may be a valuable tool for assessing the response to PCRT before surgery.

How to Combine Diffusion-Weighted and T2-Weighted Imaging for MRI Assessment of Pathologic Complete Response to Neoadjuvant Chemoradiotherapy in Patients with Rectal Cancer?

OBJECTIVE: Adequate methods of combining T2-weighted imaging (T2WI) and diffusion-weighted imaging (DWI) to assess complete response (CR) to chemoradiotherapy (CRT) for rectal cancer are obscure. We aimed to determine an algorithm for combining T2WI and DWI to optimally suggest CR on MRI using visual assessment. MATERIALS AND METHODS: We included 376 patients (male:female, 256:120; mean age ± standard deviation, 59.7 ± 11.1 years) who had undergone long-course CRT for rectal cancer and both pre- and post-CRT high-resolution rectal MRI during 2017-2018. Two experienced radiologists independently evaluated whether a tumor signal was absent, representing CR, on both post-CRT T2WI and DWI, and whether the pre-treatment DWI showed homogeneous hyperintensity throughout the lesion. Algorithms for combining T2WI and DWI were as follows: 'AND,' if both showed CR; 'OR,' if any one showed CR; and 'conditional OR,' if T2WI showed CR or DWI showed CR after the pre-treatment DWI showed homogeneous hyperintensity. Their efficacies for diagnosing pathologic CR (pCR) were determined in comparison with T2WI alone. RESULTS: Sixty-nine patients (18.4%) had pCR. AND had a lower sensitivity without statistical significance (vs. 62.3% [43/69]; 59.4% [41/69], p = 0.500) and a significantly higher specificity (vs. 87.0% [267/307]; 90.2% [277/307], p = 0.002) than those of T2WI. Both OR and conditional OR combinations resulted in a large increase in sensitivity (vs. 62.3% [43/69]; 81.2% [56/69], p < 0.001; and 73.9% [51/69], p = 0.008, respectively) and a large decrease in specificity (vs. 87.0% [267/307]; 57.0% [175/307], p < 0.001; and 69.1% [212/307], p < 0.001, respectively) as compared with T2WI, ultimately creating additional false interpretations of CR more frequently than additional identification of patients with pCR. CONCLUSION: AND combination of T2WI and DWI is an appropriate strategy for suggesting CR using visual assessment of MRI after CRT for rectal cancer.

Intraoperative perfusion assessment of the proximal colon by a visual grading system for safe anastomosis after resection in left-sided colorectal cancer patients.

We aimed to evaluate the clinical feasibility of a new visual grading system. We included 50 patients who underwent resection of primary colorectal cancer. Before anastomosis, the marginal vessel was cut and the perfusion status was assessed by a visual grading system. The visual grading system is comprised of five grades according to the bleeding from the marginal vessel and is categorized into 4 groups: good (grade A and B), moderate (grade C), poor (grade D) and none (grade E). Colorectal anastomosis was performed only in the good and moderate groups. We compared postoperative outcomes between the good and moderate groups and analysed the factors affecting the perfusion grade. Among the patients, 48% were grade A, 12% were grade B, and 40% were grade C. There was no anastomotic leakage. Only one patient with grade C showed ischemic colitis and needed reoperation. Age was the only factor correlated with perfusion grade in multivariate analysis (OR 1.080, 95% CI 1.006-1.159, p = 0.034). The perfusion grades were significantly different between > 65 and < 65 year-old patients (> 65, A 29.2% B 12.5% C 58.3% vs. < 65, A 65.4% B 11.5% C 23.1%, p = 0.006). Our intraoperative perfusion assessment that uses a cutting method and a visual grading system is simple and useful for performing a safe anastomosis after colorectal resection. If the perfusion grade is better than grade C, an anastomosis can be performed safely. Age was found to be an important factor affecting the perfusion grade.

Clinical assessment and identification of immuno-oncology markers concerning the 19-gene based risk classifier in stage IV colorectal cancer.

BACKGROUND: Genomic profiling of tumors has contributed to the understanding of colorectal cancer (CRC), facilitating diagnosis, prognosis and selection of treatments, including targeted regimens. A report suggested that a 19-gene-based risk classifier (TCA19) was a prognostic tool for patients with stage III CRC. The survival outcomes in patients with stage IV CRC are still poor and appropriate selection of targeted therapies and immunotherapies is challenging. AIM: To assess clinical implication of TCA19 in patients with stage IV CRC, and to identify TCA19 with involvement in immune-oncology. METHODS: A retrospective review of the medical records of 60 patients with stage IV CRC was conducted, assessing clinicopathological variables and progression-free survival (PFS). TCA19 gene expression was determined by quantitative polymerase chain reaction (qPCR) in matched normal and tumor tissues taken from the study cohort. Expression of potential immune-oncology regulatory proteins and targets was examined by immunohistochemistry (IHC), western blot, immunofluorescence staining in tissues from a validation cohort of 10 patients, and in CRC cell lines co-cultured with monocyte in vitro. RESULTS: In the patients with TCA19 score higher than the median, the PFS rates of eight patients who received the targeted regimens were significantly higher than the PFS rates of four patients who received 5-fluorouracil-based regimen (P = 0.041). In multivariate analysis, expression of signaling lymphocytic activation molecule family, member 7 (SLAMF7) and triggering receptor expressed on myeloid cells 1 (TREM1) was associated with PFS in the 60-patient cohort. After checking another 10 validate set, the expression of the IHC, the level of real-time qPCR, and the level of western blot were lower for SLAMF7 and higher for TREM7 in primary and metastatic tumors than in normal tissues. In CRC cells expressing SLAMF7 that were co-cultured with a monocytic cell line, levels of CD 68 and CD 73 were significantly lower at day 5 of co-culture than at day 0. CONCLUSION: The TCA19 score might be prognostic for target-regimen-specific PFS in stage IV CRC. Down-regulation of SLAMF7 and up-regulation of TREM1 occur in primary and metastatic tumor tissues.

Assessment of the Applicability of Integrative Tumor Response Assays in Advanced Epithelial Ovarian Cancer.

AIM: To prospectively correlate clinical responses to second-line chemotherapy for recurrent epithelial ovarian cancer (EOC) with in vitro integrative tumor-response assay (ITRA) results. PATIENTS AND METHODS: Forty-four patients with advanced EOC were enrolled from 2015-2017 at the Asan Medical Center, Seoul, Korea. ITRA comprised of two sequential histoculture drug response assays (HDRAs) of the tumor tissues. The first stage was HDRA with paclitaxel-carboplatin, paclitaxel, and carboplatin chemotherapy. The second stage was performed with surviving tumor cells from the first stage using topotecan, belotecan, gemcitabine, doxorubicin, ifosfamide, vinorelbine, and etoposide. RESULTS: The median follow-up period was 23.35 (range=4-35.35) months. Eighteen patients (40.9%) completed the second-line chemotherapy, based on the ITRA results. The objective response rate was 38.9%. The clinical response rate was 50%; two patients (11.1%) had stable disease. The sensitivity of ITRA for predicting response was 85.7% (specificity=18.2%; accuracy=44.44%). CONCLUSION: ITRAs had acceptable applicability and may help choose second-line chemotherapy for patients with advanced EOC.

Assessment by Using a Water-Soluble Contrast Enema Study of Radiologic Leakage in Lower Rectal Cancer Patients With Sphincter-Saving Surgery.

PURPOSE: This study evaluated the efficacy of a water-soluble contrast enema (WCE) in predicting anastomotic healing after a low anterior resection (LAR). METHODS: Between January 2000 and March 2012, 682 consecutive patients underwent a LAR or an ultra-low anterior resection (uLAR) and were followed up for leakage. Clinical leakage was established by using physical and laboratory findings. Radiologic leakage was identified by using retrograde WCE imaging. Abnormal radiologic features on WCE were categorized into four types based on morphology: namely, dendritic, horny, saccular, and serpentine. RESULTS: Of the 126 patients who received a concurrent diverting stoma, only two (1.6%) suffered clinical leakage due to pelvic abscess. However, 37 patients (6.7%) in the other group suffered clinical leakage following fecal diversion (P = 0.027). Among the 163 patients who received a fecal diversion, 20 showed radiologic leakage on the first WCE (eight with and 12 without a concurrent diversion); 16 had abnormal features continuously until the final WCE while four patients healed spontaneously. Eleven of the 16 patients (69%), by their surgeon's decision, underwent a stoma restoration based on clinical findings (2/3 dendritic, 3/4 horny, 5/7 saccular, 1/2 serpentine). After stoma reversal, only 2 of the 11 (19%) complained of complications related to the rectal anastomosis. CONCLUSION: WCE is helpful for detecting radiologic leakage before stoma restoration, especially in patients suffering clinical leakage after an uLAR. However, surgeons appear to opt for stoma restoration despite the persistent existence of radiologic leakage in cases with particular features on the WCE.

Quality of life in colorectal cancer patients with colectomy and the validation of the Functional Assessment of Cancer Therapy-Colorectal (FACT-C), Version 4.

The purpose of this study was to determine whether the Functional Assessment of Cancer Therapy-Colorectal (the FACT-C), a disease-specific tool for the assessment of colorectal cancer patients' QOL, is a valid assessment tool for measuring QOL changes. Ninety-eight colorectal cancer patients performed the assessment at baseline and 52 of these patients completed the instrument at one month and six months after colectomy. In addition to the FACT-C, the shortened forms of the Profile of Mood States, the Eastern Cooperative Oncology Group Performance Status Rating, Neuroticism Scale in the Eysenck Personality Questionnaire, and Functional Living Index-Cancer were completed. We found convergent and divergent validity and good reliability of the FACT-C. Patients' overall QOL was lower at one month after colectomy and recovered to the pre-surgery level at six months after colectomy.