Predictors and clinical impact of postoperative diarrhea after colorectal cancer surgery: a prospective, multicenter, observational study (SHISA-1602).

PURPOSE: Postoperative diarrhea, including high-output stoma (HOS), frequently occurs after colorectal surgery; its risk factors and clinical implications on subsequent complications remain unknown. This study aimed to evaluate the risk factors and clinical implications of postoperative diarrhea after primary colorectal cancer (CRC) surgery. METHODS: This prospective observational study included patients with CRC who underwent radical surgery at six hospitals between June 2016 and December 2017. The patients were categorized into three groups (non-stoma, colostoma, and ileostoma groups). RESULTS: A total of 178 patients participated in the study. In the non-stoma group, the incidence of postoperative diarrhea was 18.4% (27/147). The incidence of HOS was 28.6% (4/14) in the ileostoma group, and 0% in the colostoma group. Multivariable analyses of the incidence of diarrhea in the non-stoma group indicated that habitual smoking and hypertension were significantly associated with postoperative diarrhea (P = 0.012 and P = 0.0274, respectively). Postoperative diarrhea was more likely to occur in patients with rectal cancer than in those with colon cancer (P = 0.0501). In the non-stoma and ileostoma groups, the probability of the occurrence of other complications with Clavien-Dindo (C-D) grades II or higher was significantly higher in patients with C-D grade I diarrhea, including HOS, than in patients without diarrhea (39.3% vs. 14.6%, P = 0.0061). CONCLUSIONS: Smoking and hypertension are the independent predictors of postoperative diarrhea after an elective CRC surgery. Rectal cancer surgery seems to be associated with postoperative diarrhea more than colon cancer surgery does. Mild postoperative diarrhea may lead to more severe complications.

A Prospective Multicenter Observational Study of Venous Thromboembolism after Gastric Cancer Surgery (SHISA-1601).

INTRODUCTION: This study aimed to clarify the frequency and risk factors of intercurrent venous thromboembolism (VTE) in patients undergoing major curative gastric cancer surgery. METHODS: This prospective, multicenter, observational study included patients with gastric cancer who underwent radical gastrectomy at 5 hospitals between June 2016 and May 2018. Patients who were preoperatively administered anticoagulants were excluded. RESULTS: A total of 126 patients were eligible to participate. VTE occurred within 9 days postoperatively in 5 cases (4.0%; 2 symptomatic and 3 asymptomatic). Postoperative day (POD) 1 plasma D-dimer and soluble fibrin (SF) levels were significantly higher in the VTE group than in the non-VTE group. Receiver-operating characteristic curve (ROC) analysis indicated a statistically significant ability of POD 1 D-dimer and SF levels to predict postoperative VTE development after gastrectomy; this finding was reflected by an area under the curve (AUC) of 0.97 (95% CI 0.92-1.0) and 0.87 (95% CI 0.74-1.0), respectively. Cutoff values of D-dimer (24.6 µg/mL) and SF (64.1 µg/mL) were determined. Intraoperative blood transfusion (odds ratio [OR] 7.86), POD 1 D-dimer ≥24.6 µg/mL (OR 17.35), and POD 1 SF ≥64.1 µg/mL (OR 19.5) were independent predictive factors for postoperative VTE (p < 0.05). CONCLUSION: VTE occurred in 4.0% patients (1.6% symptomatic and 2.4% asymptomatic) after gastric cancer surgery; however, with an early diagnosis and anticoagulant therapy, no patients experienced progression. Careful observation of patients with a high risk for VTE, including intraoperative blood transfusion and high POD 1 D-dimer or SF levels, would contribute to the early detection of VTE.

Myeloid cells positive for CD10 at invasion front can predict poor outcome in stage II colorectal cancer.

BACKGROUND: Prediction of poor patient outcome as a effect of adjuvant therapy in stage II colorectal cancer (CRC) remains a matter of controversy. Tumor expression of CD10 and CD15 is reportedly related to poor outcome in CRC. In this study, we investigated whether the expression of CD10 and CD15 is a predictor of outcome and the effect of adjuvant therapy in stage II CRC. MATERIALS AND METHODS: Immunohistochemical analyses for CD10 and CD15 and some additional markers (CD11b, CD14, CD163, CD3, and CD20) were performed using paraffin sections of CRC specimens from 57 patients who had undergone curative surgical treatments between 1998 and 2004. Forty of these patients received postoperative adjuvant therapy. We distinguished between expression in tumor cells (tCD10 and tCD15), in stromal cells (sCD10), and infiltrating immune cells (iCD10 and iCD15). RESULTS: Expression of iCD10 was observed in 21.1% (12/57) of the specimens examined. Of all expression patterns, only iCD10 expression at the cancer invasion front was a useful predictor of a disease-free period and overall survival in stage II CRC. Adjuvant therapy improved the outcome of iCD10(+) patients. CD10(+) immune cells were heterogeneous in origin and partially overlapped the cells positive for myeloid lineage markers, including CD11b and CD15. CONCLUSIONS: iCD10 expression at the tumor invasion front is a useful marker for predicting a high risk of recurrence and mortality in stage II CRCs. CD10(+) immune cells appear to be of myeloid origin.

Novel statistical framework to identify differentially expressed genes allowing transcriptomic background differences.

MOTIVATION: Tests of differentially expressed genes (DEGs) from microarray experiments are based on the null hypothesis that genes that are irrelevant to the phenotype/stimulus are expressed equally in the target and control samples. However, this strict hypothesis is not always true, as there can be several transcriptomic background differences between target and control samples, including different cell/tissue types, different cell cycle stages and different biological donors. These differences lead to increased false positives, which have little biological/medical significance. RESULT: In this article, we propose a statistical framework to identify DEGs between target and control samples from expression microarray data allowing transcriptomic background differences between these samples by introducing a modified null hypothesis that the gene expression background difference is normally distributed. We use an iterative procedure to perform robust estimation of the null hypothesis and identify DEGs as outliers. We evaluated our method using our own triplicate microarray experiment, followed by validations with reverse transcription-polymerase chain reaction (RT-PCR) and on the MicroArray Quality Control dataset. The evaluations suggest that our technique (i) results in less false positive and false negative results, as measured by the degree of agreement with RT-PCR of the same samples, (ii) can be applied to different microarray platforms and results in better reproducibility as measured by the degree of DEG identification concordance both intra- and inter-platforms and (iii) can be applied efficiently with only a few microarray replicates. Based on these evaluations, we propose that this method not only identifies more reliable and biologically/medically significant DEG, but also reduces the power-cost tradeoff problem in the microarray field. AVAILABILITY: Source code and binaries freely available for download at http://comonca.org.cn/fdca/resources/softwares/deg.zip.

Real-time magnetic resonance-guided microwave coagulation therapy for pelvic recurrence of rectal cancer: initial clinical experience using a 0.5 T open magnetic resonance system.

PURPOSE: This study aims to evaluate consecutive cases of recurrent rectal cancer in the pelvic cavity treated with microwave coagulation therapy using real-time navigation by an open magnetic resonance system. METHODS: Nine recurrent pelvic lesions in 8 patients after curative resection of rectal cancer were treated with real-time magnetic resonance-guided microwave coagulation therapy as a palliative local therapy to reduce tumor volume and/or local pain. Clinical and pathological data were collected retrospectively by reviewing medical records and clinical imaging results. RESULTS: Seven patients received other treatments before real-time magnetic resonance-guided microwave coagulation. Six patients had distant synchronous metastases. Three patients underwent surgery under lumbar anesthesia. Microwave coagulation was performed percutaneously in 5 lesions and under laparotomy in 4 lesions. Although adverse events related to microwave coagulation (skin necrosis and nerve injury) were observed, no fatal complications occurred. Local re-recurrence was observed in 2 of 9 ablated lesions. Except for 1 patient who died of chronic renal failure, the remaining 7 patients died of cancer. Median overall survival after microwave coagulation for all patients was 10 months (range, 4-37 mo). Median overall survival after discovery of pelvic recurrence in all patients was 22 months (range, 9-42 mo). CONCLUSIONS: The benefits of using an open magnetic resonance system in the pelvic cavity include the abilities to treat tumors that cannot be visualized by other modalities, to demonstrate internal architectural changes during treatment, to differentiate treated vs untreated areas, and to allow adjustments to the treatment plan during the procedure. Additional studies are required to clarify the efficacy of tumor coagulation for local control.

Optimization of comparative expressed sequence hybridization for genome-wide expression profiling at chromosome level.

Comparative expressed sequence hybridization (CESH) has recently been developed for global expression profiling at chromosome level. To improve its specificity and sensitivity, we examined the effects of cDNA amplification and labeling methods on CESH profiles, using a gastric cancer cell line, Kato III, and compared the CESH profiles to cDNA microarray and reverse transcriptase-polymerase chain reaction (RT-PCR) data. CESH results were scarcely affected by the amplification process, either at the RNA level with T7 polymerase or at the cDNA level with degenerate oligonucleotide-primed PCR (DOP-PCR). The labeling method, however, did remarkably affect the CESH results; false positive shifts of the test/reference ratio (T/R) were not detected in self-matched CESH with pre-cDNA labeling and random priming labeling of cDNA but were consistently seen with DOP-PCR labeling in 11 chromosomes. The use of cDNA deriving from mRNA either with pre-cDNA or random priming labeling gave results of higher detection sensitivity for regions of up- or downregulated expression and higher concordance with the microarray and RT-PCR data in the corresponding regions than with conventional CESH. This modification of CESH with random priming labeling was found feasible by its application to Kato III cells with and without 5-aza-2'-deoxycytidine treatment; the regions identified as epigenetically silenced included genes that were reportedly methylated in Kato III.

Clinical predictive value of in vitro anticancer drug sensitivity test for the therapeutic effect of adjuvant chemotherapy in patients with stage II-III colorectal cancer.

Clinically useful predictors of the efficacy of adjuvant chemotherapy following curative colorectal surgery remain to be determined. In the present study, we investigated the clinical utility of the collagen gel droplet-embedded culture drug sensitivity test (CD-DST) as a predictor of the therapeutic response to 5-fluorouracil (5-FU)-based adjuvant chemo-therapy in patients with stage II-III colorectal cancer. CD-DST was conducted using tumor samples surgically obtained from 189 patients. The therapeutic effect of 5-FU-based regimens between high (high-group) and low (low-group) sensitivity groups and a group that did not receive chemotherapy [CTx(-) group] was compared. CD-DST was successfully performed in 151 out of the 189 patients (79.9%), 87 of whom received 5-FU-based adjuvant chemotherapy after surgery. Twenty-seven of these 87 patients (31.0%) were classified as the high-group and the remaining 60 (69.0%) as the low-group. The 5-year recurrence-free survival (RFS) in the high-group was significantly higher compared to that in the low- and the CTx(-) groups. No differences in the 5-year RFS were observed between the low- and CTx(-) groups. In conclusion, CD-DST appears to be useful for predicting the therapeutic response to 5-FU-based adjuvant chemotherapy in patients with stage II-III colorectal cancer.

Expression of Cdx2 in early GRCL of Barrett's esophagus induced in rats by duodenal reflux.

The intestine-specific caudal-related homeobox transcription factor Cdx2 is widely accepted to play a key role in intestinal development and differentiation in mammals. We studied the role of Cdx2 in the development of Barrett's esophagus (BE). In previous studies, we have shown a sequence of morphological changes of squamous epithelium leading to BE, found a peculiar metaplastic change common to other parts of gut, and proposed the concept of a "gut regenerative cell lineage" (GRCL). The GRCL is characterized by pyloric-foveolar metaplasia with goblet cell metaplasia, which occurs in the regenerative process in response to chronic inflammation. BE very likely develops through the GRCL, and we studied the expression of Cdx2 in various lesions of rat esophageal mucosa induced by duodenal reflux, using reverse transciptase-polymerase chain reaction and immunohistochemistry against Cdx2. We found that Cdx2 was expressed not only in specialized columnar epithelium (SCE) of BE, but also in several pyloric gland and foveolar metaplastic cells which developed in the basal layer of the squamous epithelium at an earlier stage of SCE development. These findings indicate that Cdx2 plays a crucial role in directing intestinal-type differentiation of the GRCL.

A faithful method for PCR-mediated global mRNA amplification and its integration into microarray analysis on laser-captured cells.

Quantitative and qualitative analyses of mRNAs from a small number of cells are extremely important for studies on gene expression in various physiological and pathological conditions in multicellular organisms. We present here an effective method for high-fidelity global mRNA amplification for in vivo gene expression profiling of as few as 100 cells obtained by laser-captured microdissection (LCM). This method, called TALPAT, is based on T7 RNA polymerase-mediated transcription, adaptor ligation, and PCR amplification followed by T7-transcription. More than 80% of genes were commonly identified as a more than 3-fold changed gene among three gastric cancer cell lines using cRNA amplified by both TALPAT and the ordinary in vitro T7-transcription. The reproducibility of TALPAT was validated by microarray analysis on 100 breast cancer cells obtained by LCM. For the application of the LCM-TALPAT method, we successfully obtained expression profiles of gastric cancer cells and the mesenchymal cells, enabling us to understand in vivo cell-to-cell cross-talk in the microenvironment.