Inferior mesenteric artery arteriovenous malformation, a rare cause of ischemic colitis: A case report.

RATIONALE: An arteriovenous malformation (AVM) is an abnormal tangle of blood vessels that connects the arteries and the veins. Because normal capillary bed is partially or completely absented in the AVM, the blood passes quickly from the arteries to the veins, which disrupts normal blood flow and oxygen supply to the surrounding tissues. This is called "steal phenomenon," and in the inferior mesenteric artery (IMA) territory, this may lead to abdominal pain, gastrointestinal bleeding, portal hypertension, and even ischemic colitis. PATIENT CONCERNS: A 67-year-old man presented to our emergency department because of left side abdominal pain. DIAGNOSES: The abdominal computed tomography with contrast enhancement revealed a cluster of abnormal vascular lesions abutting the IMA with early opacification of the left colonic marginal vein. In addition, poor enhancement of segmental colonic wall was found from proximal descending colon to middle rectum. The diagnosis of AVM of the IMA and ischemic colitis was made. INTERVENTIONS: The patient underwent left hemicolectomy as well as the AVM resection. OUTCOMES: He was discharged uneventfully after the surgery without complications. LESSONS: IMA AVM carries the risk of ischemic colitis. computed tomography scan is helpful not only to the diagnosis of AVMs but also to exclude other lesions as well. Treatment options include endovascular embolization, surgical intervention, and a combination of both. Due to the complexity of this disease, treatment requires a case-specific multidisciplinary approach and a coordination of medical, radiological, and surgical staffs.

Risk of NSAID-associated anastomosis leakage after colorectal surgery: a large-scale retrospective study using propensity score matching.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

High Red Cell Distribution Width Is Associated with Worse Prognosis in Early Colorectal Cancer after Curative Resection: A Propensity-Matched Analysis.

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.

Development and Validation of a Novel Serum Prognostic Marker for Patients with Metastatic Colorectal Cancer on Regorafenib Treatment.

(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 < 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 < 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.

Pim1 Kinase Inhibitors Exert Anti-Cancer Activity Against HER2-Positive Breast Cancer Cells Through Downregulation of HER2.

The proviral integration site for moloney murine leukemia virus 1 (Pim1) is a serine/threonine kinase and able to promote cell proliferation, survival and drug resistance. Overexpression of Pim1 has been observed in many cancer types and is associated with the poor prognosis of breast cancer. However, it remains unclear whether Pim1 kinase is a potential therapeutic target for breast cancer patients. In this study, we found that Pim1 expression was strongly associated with HER2 expression and that HER2-overexpressing breast cancer cells were more sensitive to Pim1 inhibitor-induced inhibitions of cell viability and metastatic ability. Mechanistically, Pim1 inhibitor suppressed the expression of HER2 at least in part through transcriptional level. More importantly, Pim1 inhibitor overcame the resistance of breast cancer cells to HER2 tyrosine kinase inhibitor lapatinib. In summary, downregulation of HER2 by targeting Pim1 may be a promising and effective therapeutic approach not only for anti-cancer growth but also for circumventing lapatinib resistance in HER2-positive breast cancer patients.

c-Met inhibition is required for the celecoxib-attenuated stemness property of human colorectal cancer cells.

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.

Chrysin Attenuates Cell Viability of Human Colorectal Cancer Cells through Autophagy Induction Unlike 5-Fluorouracil/Oxaliplatin.

Chemotherapeutic 5-fluorouracil (5-FU) combined with oxaliplatin is often used as the standard treatment for colorectal cancer (CRC). The disturbing side effects and drug resistance commonly observed in chemotherapy motivate us to develop alternative optimal therapeutic options for CRC treatment. Chrysin, a natural and biologically active flavonoid abundant in propolis, is reported to have antitumor effects on a few CRCs. However, whether and how chrysin achieves similar effectiveness to the 5-FU combination is not clear. In this study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), western blotting, fluorescence microscopy, and reactive oxygen species (ROS) production were assayed. We found that chrysin exhibited similar inhibition of cell viability as the 5-FU combination in a panel of human CRC cells. Furthermore, the results showed that chrysin significantly increased the levels of LC3-II, an autophagy-related marker, in CRC cells, which was not observed with the 5-FU combination. More importantly, blockage of autophagy induction restored chrysin-attenuated CRC cell viability. Further mechanistic analysis revealed that chrysin, not the 5-FU combination, induced ROS generation, and in turn, inhibited the phosphorylation of protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Collectively, these results imply that chrysin may be a potential replacement for the 5-FU and oxaliplatin combination to achieve antitumor activity through autophagy for CRC treatment in the future.

Interleukin-6 expression contributes to lapatinib resistance through maintenance of stemness property in HER2-positive breast cancer cells.

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.

Association study between novel CYP26 polymorphisms and the risk of betel quid-related malignant oral disorders.

BQ chewing may produce significant amounts of reactive oxygen species (ROS), resulting in oral mucosa damage, and ROS may be metabolized by CYP26 families. Because the CYP26 polymorphisms associated with malignant oral disorders are not well known, we conducted an association study on the associations between the single nucleotide polymorphisms (SNP) of CYP26 families and the risks of malignant oral disorders. BQ chewers with the CYP26A1 rs4411227 C/C+C/G genotype and C allele showed an increased risk of oral and pharyngeal cancer (adjusted odds ratio (aOR) = 2.30 and 1.93, respectively). The CYP26B1 rs3768647 G allele may be associated with oral and pharyngeal cancer (aOR = 3.12) and OPMDs (aOR = 2.23). Subjects with the rs9309462 CT genotype and C allele had an increased risk of oral and pharyngeal cancer (aOR = 9.24 and 8.86, respectively) and OPMDs (aOR = 8.17 and 7.87, respectively). The analysis of joint effects between the CYP26A1 rs4411227 and CYP26B1 rs3768647/rs9309462 polymorphisms revealed statistical significance (aOR = 29.91 and 10.03, respectively). Additionally, we observed a significant mRNA expression of CY26A1 and CYP26B1 in cancerous tissues compared with adjacent noncancerous tissues. Our findings suggest that novel CYP26 polymorphisms are associated with an increased risk of malignant oral disorders, particularly among BQ chewers.

The application of McBurney's single-incision laparoscopic colectomy alleviates the response of patients to postoperative wound pain.

BACKGROUND: 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. SUBJECTS AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Single-incision laparoscopic colectomy using self-made glove port for benign colon diseases.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Resection of an intra-operative ruptured hepatocellular carcinoma with continuous pringle maneuver and in situ hypothermic perfusion through the inferior mesenteric vein: a case report.

Intra-operative tumor rupture is a serious complication during resection of large hepatocellular carcinoma (HCC) leading to more blood loss. We report our experience in applying continuous Pringle maneuver with in situ hypothermic perfusion via inferior mesenteric vein catheterization to the portal vein of the remnant liver for resection during an extended left lobectomy of a large HCC which ruptured intraoperatively. Using this method, we successfully managed the patient without any further morbidity. This technique provides easier accessibility of in situ perfusion, decreases operative blood loss and prevents warm ischemic injury to the remnant liver during parenchymal transection. This method could be effective for the resection of large ruptured HCC.

BCRP/ABCG2 inhibition sensitizes hepatocellular carcinoma cells to sorafenib.

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.

Laparoscopic appendectomy for complicated acute appendicitis does not result in increased surgical complications.

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.