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NSAIDs are commonly used as opioid-sparing analgesics in colorectal surgery. Many efforts are made to elucidate the risk of NSAID-associated anastomotic leakage after colorectal surgery. However, these results still remain controversial. In this study, we applied large-scale retrospective analysis using propensity score matching to fully clarify the association between risk of anastomotic leakage and use of NSAID after colorectal surgery.All colorectal cancer patients receiving operation during February 2008 to August 2018 in our multi-institution medical organization research database were enrolled. It is worthy to mention that only patients requiring re-operation within 21 days after colorectal surgery due to anastomotic leakage were counted as anastomosis leakage. Furthermore, a propensity score TriMatch analysis was performed to prevent from interference of confounding factors.A total of 10,584 patients were included in this study and divided into three groups, no NSAIDs group, non-selective NSAIDs group, and selective COX-2 inhibitors group, respectively. Before tri-matching analysis, significant differences in anastomotic leakage rate were observed. After propensity score matching analysis, the ratio of anastomotic leakage requiring re-operation occurred in 2.0%, 3.6%, and 2.0% in no NSAIDs, non-selective NSAIDs, and selective COX-2 inhibitors group, respectively. No significant difference was observed in these three groups.These results suggest that NSAIDs are not associated with incidence of anastomosis leakage following colorectal surgery. To our knowledge, it is the first study demonstrating that NSAIDs is not associated with incidence of anastomosis leakage following colorectal surgery using propensity score matching at a larger-scale retrospective study.

The red blood cell distribution width (RDW) is a simple and widely available parameter obtained from a complete blood cell count test and is usually used in the analysis of anemia. Recently, studies have discovered the association between RDW and the host inflammatory response of cancer patients. We aimed to determine the prognostic value of RDW in colorectal cancer (CRC) patients. 5315 total patients with stage I-II CRC from the Chang Gung Memorial Hospital between 2001 and 2018 were enrolled. The study cohort was divided into two groups using RDW = 13.8 as the cutoff value as determined by receiver operating curve. High RDW had worse overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS), and was also independently related to older age, more advanced tumor stage, lower albumin level, lower hemoglobin level, and more co-morbidities including diabetes, hypertension, and chronic kidney disease. We performed a propensity-score matched analysis to balance the heterogeneity between the two groups and to reduce the influence of confounding factors that may have compromised the prognosis. High RDW remained a negative predictor of OS (HR = 1.49, 95% CI: 1.25–1.78), as well as DFS and CSS. In conclusion, this is the first report using propensity matching to demonstrate the relationship between RDW and the prognosis of early-stage CRC patients.

(1) Background: To investigate the prognostic value of cancer-inflammation prognostic index (CIPI) in patients with metastatic colorectal cancer (mCRC) on regorafenib treatment, (2) Methods: Patients with mCRC who were given regorafenib as later-line treatment at Kaohsiung and Linkou Chang-Gung Memorial Hospital between November 2014 and January 2021 were consecutively enrolled. All relevant clinicopathologic, laboratory data and survival status were recorded. Independent prognostic factors were determined by the multivariate Cox regression method, (3) Results: In total, 106 patients in the training cohort and 250 in the validation cohort were enrolled. The median OS for patients with CIPI ≥ 300 and &lt, 300 in the training cohort was 3.8 and 9.0 months, respectively (hazard ratio (HR) 2.78, 95% confidence interval (CI) 1.82–4.23, p &lt, 0.0001). Time to regorafenib, liver metastasis and CIPI were independent factors by multivariate Cox regression analyses. A new scoring model demonstrated a good discriminatory ability to risk stratification of a patient’s survival, (4) Conclusions: We identified CIPI as a novel serum marker highly associated with overall survival in patients with mCRC receiving regorafenib treatment. Further confirmatory studies are warranted.

// Wei-Chien Huang 1, 2, 3, 4 , Chao-Ming Hung 5, 6 , Ching-Ting Wei 5, 6, * , Tsung-Ming Chen 7, * , Pei-Hsuan Chien 8 , Hsiao-Lin Pan 5 , Yueh-Ming Lin 9 , Yun-Ju Chen 5, 8, 10 1 The Ph.D. program for Cancer Biology and Drug Discovery, China Medical University and Academia Sinica, Taichung 404, Taiwan 2 Graduate Institute of Cancer Biology, China Medical University, Taichung 404, Taiwan 3 Center for Molecular Medicine, China Medical University and Hospital, Taichung 404, Taiwan 4 Department of Biotechnology, Asia University, Taichung 413, Taiwan 5 School of Medicine for International Students, I-Shou University, Kaohsiung 824, Taiwan 6 Department of General Surgery, E-Da Hospital, Kaohsiung 824, Taiwan 7 Department and Graduate Institute of Aquaculture, National Kaohsiung Marine University, Kaohsiung 811, Taiwan 8 Department of Medical Research, E-Da Hospital, Kaohsiung 824, Taiwan 9 Division of Colorectal Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 833, Taiwan 10 Department of Biological Science & Technology, I-Shou University, Kaohsiung 824, Taiwan * These authors have contributed equally to this work Correspondence to: Yun-Ju Chen, email: yjchen0326@isu.edu.tw Keywords: lapatinib, interleukin-6, HER2, resistance, breast cancer Received: February 10, 2016 Accepted: August 09, 2016 Published: August 22, 2016 ABSTRACT Lapatinib is an inhibitor of human epidermal growth factor receptor 2 (HER2), which is overexpressed in 20-25% of breast cancers. Clinically, lapatinib has shown promising benefits for HER2-positive breast cancer patients; however, patients eventually acquire resistance, limiting its long-term use. In a previous study, we found that interleukin-6 (IL-6) production was increased in acquired lapatinib-resistant HER2-positive breast cancer cells. In the present study, we confirmed that lapatinib-resistant cells had elevated IL-6 expression and also maintained both stemness population and property. The increase in IL-6 was required for stemness property maintenance, which was mediated primarily through the activation of signal transducer and activator of transcription 3 (STAT3). Blocking IL-6 activity reduced spheroid formation, cell viability and subsequently overcame lapatinib resistance, whereas stimulation of IL-6 rendered parental cells more resistant to lapatinib-induced cytotoxicity. These results point to a novel mechanism underlying lapatinib resistance and provide a potential strategy to overcome resistance via IL-6 inhibition.

Cyclooxygenase-2 (COX-2) is frequently overexpressed and enhances colorectal cancer (CRC) tumorigenesis, including cancer stem cell (CSC) regulation. Accordingly, nonsteroidal anti-inflammatory drugs (NSAIDs), inhibiting COX-1/2 activity, are viewed as potential drugs for CRC treatment. Accumulated evidence indicates that celecoxib has the most potency for antitumor growth among NSAIDs and the underlying mechanism is only partly dependent on COX-2 inhibition. However, the potency of these NSAIDs on CSC inhibition is still not known. In this study, we found that among these NSAIDs, celecoxib has the most potency for CSC inhibition of CRC cells, largely correlating to inhibition of c-Met, not COX-2. Further analysis reveals that c-Met activity was required for basal CSC property. Silence of c-Met blocked whereas overexpression of c-Met enhanced the celecoxib-inhibited CSC property. Collectively, these results not only first elucidate the mechanism underlying celecoxib-inhibited CSC but also indicate c-Met as a critical factor for the CSC property of CRC cells.

Summary Background/Objectives Septic postoperative complications are debated in patients with complicated acute appendicitis treated with laparoscopic appendectomy (LA). The aim of this study was to investigate the results of LA in both complicated and uncomplicated cases of acute appendicitis. Methods From January to December 2009, 94 patients with acute appendicitis underwent LA by the same surgeon using the three-port technique. Data were accumulated and compared between complicated and uncomplicated acute appendicitis. Results Of the 94 patients (45 women and 49 men), 19 had complicated and 75 uncomplicated acute appendicitis. The group with complicated acute appendicitis, as compared to the uncomplicated group, was significantly older (55.7 ± 20.5 years vs. 41.0 ± 18.0 years), and had a significantly increased operation time (117.6 ± 45.5 minutes vs. 78.2 ± 39.4 minutes), longer length of hospital stay (9.0 ± 3.3 days vs. 5.2 ± 6.0 days) and higher conversion rate (21.1% vs. 2.7%). No increase in surgical complications was noted in patients with complicated acute appendicitis, as compared to those with uncomplicated acute appendicitis. Conclusion This study demonstrated no increase in surgical complications after LA in patients with complicated acute appendicitis when compared with those who had uncomplicated disease. Therefore, LA may be considered the first-choice treatment option for both uncomplicated and complicated acute appendicitis.

Single-incision laparoscopic colectomy (SILC) is one of several promising operation choices. Our previous study demonstrated that SILC with a self-made glove-port system both improves the feasibility of SILC and decreases the cost expense of surgery. Because the incision site for SILC could be made at either the umbilicus or McBurney's point, we are interested in whether the incision site affects the outcomes of patients, which is a less explored topic. The purpose of this study is not only to show the results of SILC with a self-made glove-port system for supporting its feasibility, but also to compare the short-term surgical outcomes between SILC with the incision made at the umbilicus and at McBurney's point.We collected and reviewed the medical records of patients who received SILC with a self-made glove-port system for tumors in the left side of the colon from August 2009 to March 2011. All operations were performed by a single surgeon. Comparisons of the demographic characteristics, perioperative data, and clinical outcomes between umbilical and McBurney's SILCs were performed. Postoperative pain was assessed by a visual analog scale and opiate demand.In total, 61 patients were enrolled in this retrospective study. Five of 48 (10.4%) tumors in the umbilical SILC group and 5 of 13 (38.5%) tumors in the McBurney's SILC group were located below the peritoneal reflection. The tumor location was significantly different between these two groups (P=.015). Patients in the umbilical SILC group had significantly higher frequency of opiate demand than those in the McBurney's SILC group (0.4±0.7 versus 1.4±1.8, respectively; P=.002).This study further provides evidence for supporting the safety and feasibility of SILC in treating colorectal diseases. More important is that McBurney's SILC not only alleviates the patient response to wound pain, but also provides the same site for a diverting enterostomy to avoid creating an additional wound.

The instrument crowding derived from commercially available access devices in single-incision laparoscopic surgery (SILS) is a challenge to overcome. This study was designed to evaluate the short-term surgical outcomes of SILS by applying a self-made device in patients with benign colon diseases.We collected and reviewed the medical records of patients who received SILC by using a self-made glove-port system from March 2007 to July 2012. All operations were performed by a single surgeon. Sixty-four patients (36 males and 28 females) were enrolled for this study. Among them, 15 patients received right-side colon resection, 31 patients received left-side colon resection, and 18 patients received total colectomy.In the analysis of medical records from these groups of patients, we found that there was no significant difference of gender, body mass index, tumor size, incision length, and blood loss among these three groups. Furthermore, no significant difference of the pain scores, average length of hospital stay, and average duration of bowel return was observed among these three groups. However, it was notable that younger age, longer duration of operation, and longer bowel resection were indeed significantly found in the patients undergoing total colectomy. On the other hand, curved instruments were used in 5 (16.1%) of 31 patients with left-side colon resection.A simple self-made glove-port device was proven as a practical method of SILS for colorectal diseases. These findings suggested that single-incision laparoscopic total colectomy provides compatible clinical outcome in the patients with benign colon diseases compared with the other two surgical procedures used in this study.

The multikinase inhibitor, sorafenib (Nexavar®, BAY43-9006), which inhibits both the Raf/MEK/ERK pathway and several receptor tyrosine kinases (RTKs), has shown significantly therapeutic benefits in advanced hepatocellular carcinoma (HCC). However, not all HCC patients respond to sorafenib well and new therapeutic strategies to optimize the efficacy of sorafenib are urgently required. Overexpression of breast cancer resistance protein (BCRP/ABCG2) mediates the drug-efflux of several tyrosine kinase inhibitors (TKIs) to attenuate their efficacy. This study aimed to investigate the role of BCRP/ABCG2 in the sensitivity of HCC to sorafenib. Our data showed that BCRP/ABCG2 mediated the efflux of sorafenib. Co-treatment with a BCRP/ABCG2 inhibitor greatly augmented the cytotoxicity of sorafenib in HCC cells. Similar results were also achieved by the competitive inhibitor of BCRP/ABCG2, gefitinib, in combination with sorafenib. These results suggest not only that BCRP/ABCG2 is a potential predictor for the sorafenib sensitivity in HCC, but also that blockage of BCRP/ABCG2 may be a potential strategy to increase the response of HCC cells to sorafenib.