E-Cadherin and Angiopoietin-2 as Potential Biomarkers for Colorectal Cancer With Peritoneal Carcinomatosis.

BACKGROUND/AIM: E-Cadherin has been implicated in cell-cell adhesion, and soluble E-cadherin is involved in angiogenesis and resistance to anti-angiogenic therapy in several cancer types. This study aimed to investigate the expression and clinical significance of soluble E-cadherin and other angiogenesis-related factors in plasma and malignant ascites of colorectal cancer (CRC) in patients with peritoneal carcinomatosis (PC). MATERIALS AND METHODS: Multiplex enzyme-linked immunosorbent assay was performed on 95 body fluid samples (57 plasma and 38 malignant ascites) from patients with CRC. The status of E-cadherin and angiopoietin-2 (AGNPT2) was retrospectively evaluated by immunohistochemistry in primary CRC and paired metastatic peritoneal tissues or cell blocks of malignant ascites of 30 patients with peritoneal metastases of CRC. RESULTS: The expression levels of soluble E-cadherin and ANGPT2 in plasma samples were significantly increased in patients with PC compared with those without. E-Cadherin concentration was significantly lower and ANGPT2 concentration was significantly higher in malignant ascites than plasma samples. Expression of E-cadherin was strongly positive, whilst that of ANGPT2 was negative in primary colorectal tissues, metastatic peritoneal tissues, and cell blocks of malignant ascites by immunohistochemistry. High levels of soluble E-cadherin or ANGPT2 in ascites were negatively associated with overall survival in patients with CRC with malignant ascites. CONCLUSION: Our findings suggest that soluble E-cadherin and ANGPT2 may be surrogate biomarkers for clinical outcome in patients with PC from CRC.

The Prognostic Ability of RAS Pathway-Related Gene Mutations in Patients with Myeloid Neoplasms Treated with Hypomethylating Agents.

INTRODUCTION: This study aimed to identify genetic predictors of treatment response and survival in patients with myeloid neoplasms treated with hypomethylating agents (HMAs). METHODS: We performed next-generation sequencing on bone marrow aspiration samples of 59 patients diagnosed with acute myeloid leukemia (AML), myelodysplastic syndrome with excess blasts-2, or chronic myelomonocytic leukemia and treated with decitabine or azacitidine as a frontline therapy. RESULTS: A single gene with the most common mutations was TP53 (14 of 59 patients), and mutations in RAS pathway-related genes including KRAS, NRAS, FLT3, PTPN11, CBL, and KIT were found in 28.8% of patients. The overall response rate to HMAs was 33.9%. Predictive factors for a poor response were an age >75 years (p = 0.007), 3 or more gene mutations (p = 0.004), mutations in RAS pathway-related genes (p = 0.033), and a mutated NRAS gene (p = 0.042). An age >75 years (hazard ratio 2.946), diagnosis of AML (hazard ratio 2.915), and mutations in NRAS (hazard ratio 4.440) were identified as poor prognostic factors for survival. CONCLUSION: In conclusion, mutations in RAS pathway-related genes were predictors of a poor response to HMAs. Particularly, mutated NRAS was associated with inferior survival rates.

Pseudoprogression presenting as intestinal perforation in non-small cell lung cancer treated with anti-PD-1: A case report.

Pseudoprogression is not frequently observed in patients with non-small cell lung cancer (NSCLC) who are treated with immune checkpoint inhibitors. We report on a case of pseudoprogression, which was presented as intestinal perforation after pembrolizumab immunotherapy for NSCLC. A-54-year-old man with stage IV NSCLC received pembrolizumab therapy. The patient was admitted to our hospital because of acute abdominal pain and the computed tomography scan revealed diffuse wall thickening of the small bowel with free intraperitoneal air. Intestinal perforation was suspected and surgical resection was performed. Histological evaluation of the resected specimen showed infiltrated lymphocytes positive for CD3, CD8 with necrotic tumor cells, suggestive of an immune reaction. Although intestinal perforation after treatment with immune checkpoint inhibitors is rare, it can be an unusual presentation of pseudoprogression and clinicians should be aware of this possibility.

EGFR Mutation Status in Lung Adenocarcinoma-Associated Malignant Pleural Effusion and Efficacy of EGFR Tyrosine Kinase Inhibitors.

PURPOSE: Malignant pleural effusions (MPEs) are often observed in lung cancer, particularly adenocarcinoma. The aim of this study was to investigate epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma-associated MPEs (LA-MPEs) and its correlation with efficacy of EGFR tyrosine kinase inhibitor (TKI) therapy. MATERIALS AND METHODS: Samples comprised 40 cell blocks of pathologically-confirmed LA-MPEs collected before the start of EGFR TKI therapy. EGFR mutation status was re-evaluated by peptide nucleic acid clamping and the clinical outcomes of EGFR TKI‒treated patients were analyzed retrospectively. RESULTS: EGFR mutations were detected in 72.5% of LA-MPE cell blocks (29/40). The median progression-free survival for patients with EGFR mutations in LA-MPEs was better than that for patients with wild-type EGFR (7.33 months vs. 2.07 months; hazard ratio, 0.486; 95% confidence interval, 0.206 to 1.144; p=0.032). The objective response rate (ORR) of 26 patients with EGFR mutations in LA-MPEs among the 36 patients with measurable lesions was 80.8%, while the ORR of the 10 patients with wild-type EGFR in LA-MPEs was 10% (p < 0.001). Among the 26 patients with EGFR mutations in LA-MPEs, the ORR of target lesions and LA-MPEs were 88.5% and 61.5%, respectively (p=0.026). CONCLUSION: EGFR mutation status in cell blocks of LA-MPEs confirmed by pathologic diagnosis is highly predictive of EGFR TKI efficacy. For patients with EGFR mutations in LA-MPEs, the response to EGFR TKIs seems to be worse for pleural effusions than for solid tumors.

Prevalence of and factors associated with anxiety and depression in Korean patients with newly diagnosed advanced gastrointestinal cancer.

BACKGROUND/AIMS: The purpose of the present study was to assess the prevalence of and factors associated with anxiety and depression in Korean patients with advanced gastrointestinal cancer. METHODS: One hundred and twenty consecutive patients with newly diagnosed, advanced gastrointestinal cancer who were scheduled to receive palliative chemotherapy between July 2012 and June 2014 were enrolled in this observational prospective study. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale (HADS) and Patient Health Questionnaire-9 (PHQ-9). RESULTS: Thirty-seven patients (30.8%) had anxiety or depression with clinical significance according to HADS or PHQ-9. Multivariate analysis identified lower performance status (odds ratio [OR], 4.19; 95% confidence interval [CI], 1.22 to 14.35; p = 0.023), gastric cancer (OR, 5.39; 95% CI, 0.37 to 78.23; p = 0.018), and knowledge of advanced cancer (OR, 15.07; 95% CI, 1.80 to 125.90; p = 0.012) as significantly associated with anxiety or depression. Twenty-one patients with anxiety or depression visited the psycho-oncologic clinic. In these patients, PHQ-9 score (p = 0.008), global health status (p = 0.023), fatigue (p = 0.047), and appetite loss (p = 0.006) improved from baseline to 3 months after study enrollment. CONCLUSIONS: Approximately 30% of Korean patients with advanced gastrointestinal cancer had anxiety or depression. The prevalence of anxiety or depression was higher in patients with poor performance status, gastric cancer, or knowledge of advanced cancer. Psychiatric interventions may be effective in reducing depression and improving quality of life in cancer patients with anxiety or depression.

A Pilot Study Evaluating Steroid-Induced Diabetes after Antiemetic Dexamethasone Therapy in Chemotherapy-Treated Cancer Patients.

PURPOSE: Dexamethasone is a mainstay antiemetic regimen for the prevention of chemotherapy-induced nausea and vomiting. The aim of this pilot study was to assess the incidence of and factors associated with steroid-induced diabetes in cancer patients receiving chemotherapy with dexamethasone as an antiemetic. MATERIALS AND METHODS: Non-diabetic patients with newly diagnosed gastrointestinal cancer who received at least three cycles of highly or moderately emetogenic chemotherapy with dexamethasone as an antiemetic were enrolled. Fasting plasma glucose levels, 2-hour postprandial glucose levels, and hemoglobin A1C tests for the diagnosis of diabetes were performed before chemotherapy and at 3 and 6 months after the start of chemotherapy. The homeostasis model assessment of insulin resistance (HOMA-IR) was used as an index for measurement of insulin resistance, defined as a HOMA-IR ≥ 2.5. RESULTS: Between January 2012 and November 2013, 101 patients with no history of diabetes underwent laboratory tests for assessment of eligibility; 77 of these patients were included in the analysis. Forty-five patients (58.4%) were insulin resistant and 17 (22.1%) developed steroid-induced diabetes at 3 or 6 months after the first chemotherapy, which included dexamethasone as an antiemetic. Multivariate analysis showed significant association of the incidence of steroid-induced diabetes with the cumulative dose of dexamethasone (p=0.049). CONCLUSION: We suggest that development of steroid-induced diabetes after antiemetic dexamethasone therapy occurs in approximately 20% of non-diabetic cancer patients; this is particularly significant for patients receiving high doses of dexamethasone.

Abdominal compartment syndrome in severe acute pancreatitis treated with percutaneous catheter drainage.

Acute pancreatitis is one of the main causes of intra-abdominal hypertension (IAH). IAH contributes to multiple physiologic alterations and leads to the development of abdominal compartment syndrome (ACS) that induces multiorgan failure. We report a case of ACS in a patient with severe acute pancreatitis. A 44-year-old man who was admitted in a drunk state was found to have severe acute pancreatitis. During management with fluid resuscitation in an intensive care unit, drowsy mentality, respiratory acidosis, shock requiring inotropes, and oliguria developed in the patient, with his abdomen tensely distended. With a presumptive diagnosis of ACS, abdominal decompression through percutaneous catheter drainage was performed immediately. The intraperitoneal pressure measured with a drainage catheter was 31 mm Hg. After abdominal decompression, the multiorgan failure was reversed. We present a case of ACS managed with percutaneous catheter decompression.

Identification of suitable reference genes for the relative quantification of microRNAs in pleural effusion.

Circulating cell-free microRNAs (miRNAs) are potential biomarkers of cancer. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is widely used in miRNA expression studies. The aim of this study was to identify suitable reference genes for RT-qPCR analyses of miRNA expression levels in pleural effusion. The expression levels of candidate reference miRNAs were investigated in 10 benign pleural effusion (BPE) and 10 lung adenocarcinoma-associated malignant pleural effusion (LA-MPE) samples using miRNA microarrays. The expression levels of candidate reference miRNAs, together with those of U6 small nuclear RNA (snRNA), RNU6B, RNU44 and RNU48 small RNAs, in 46 BPE and 45 LA-MPE samples were validated by RT-qPCR, and were analyzed using the NormFinder and BestKeeper algorithms. The impact of different normalization approaches on the detection of differential expression levels of miR-198 in BPE and LA-MPE samples was also assessed. As determined by the miRNA microarray data, five candidate reference miRNAs were identified. Following RT-qPCR validation, U6 snRNA, miR-192, miR-20a, miR-221, miR-222 and miR-16 were evaluated using the NormFinder and BestKeeper software programs. U6 snRNA and miR-192 were identified as single reference genes and the combination of these genes was preferred for the relative quantification of miRNA expression levels in pleural effusion. Normalization of miR-98 expression levels to those of U6 snRNA, miR-192 or a combination of these genes enabled the detection of a significant difference between BPE and LA-MPE samples. Therefore, U6 snRNA and miR-192 are recommended as reference genes for the relative quantification of miRNA expression levels in pleural effusion.

Impact of hyperglycemia on survival and infection-related adverse events in patients with metastatic colorectal cancer who were receiving palliative chemotherapy.

PURPOSE: Non-metastatic colorectal cancer patients with diabetes have poor overall survival than those without diabetes. However, the effect of hyperglycemia on survival after diagnosis of metastatic colorectal cancer (CRC) has not been assessed. Therefore, we assessed the impact of hyperglycemia on the survival and infection-related adverse events (AEs) in patients with metastatic CRC. MATERIALS AND METHODS: We reviewed the records of 206 patients with newly diagnosed metastatic CRC who were treated with palliative chemotherapy from March 2000 to December 2012 at Chungbuk National University Hospital. The mean glucose level of each patient was calculated using all available glucose results. RESULTS: The mean glucose levels ranged between 76.8 and 303.5 mg/dL, and patients were categorized into quartiles in accordance to their mean glucose level: group 1 (< 106.7 mg/dL), group 2 (106.7-117.2 mg/dL), group 3 (117.3-142.6 mg/dL), and group 4 (> 142.6 mg/dL). The median overall survival for patients in groups 1, 2, 3, and 4 were 22.6, 20.1, 18.9, and 17.9 months, respectively; however, this difference was not statistically significant (p=0.643). Compared with patients in group 1, those in groups 2, 3, and 4 were at a higher risk of infection-related AEs, according to a multivariate analysis (p=0.002). CONCLUSION: Hyperglycemia was not associated with shorter survival; however, it was associated with infection-related AEs in patients with newly diagnosed metastatic CRC receiving palliative chemotherapy.

Fate of dyspeptic or colonic symptoms after laparoscopic cholecystectomy.

BACKGROUND/AIMS: Gallbladder diseases can give rise to dyspeptic or colonic symptoms in addition to biliary pain. Although most biliary pain shows improvement after cholecystectomy, the fates of dyspeptic or colonic symptoms still remain controversial. This study as-sessed whether nonspecific gastrointestinal symptoms improved after laparoscopic cholecystectomy (LC) and identified the char-acteristics of patients who experienced continuing or exacerbated symptoms following surgery. METHODS: Sixty-five patients who underwent LC for uncomplicated gallbladder stones or gallbladder polyps were enrolled. The patients were surveyed on their dyspeptic or colonic symptoms before surgery and again at 3 and 6 months after surgery. Patients' mental sanity was also assessed using a psychological symptom score with the Symptom Checklist-90-Revised questionnaire. RESULTS: Forty-four (67.7%) patients showed one or more dyspeptic or colonic symptoms before surgery. Among these, 31 (47.7%) and 36 (55.4%) patients showed improvement at 3 and 6 months after surgery, respectively. However, 18.5% of patients showed continuing or exacerbated symptoms at 6 months after surgery. These patients did not differ with respect to gallstone or gall-bladder polyps, but differed in frequency of gastritis. These patients reported lower postoperative satisfaction. Patients with ab-dominal symptoms showed higher psychological symptom scores than others. However, poor mental sanity was not related to the symptom exacerbation. CONCLUSIONS: Elective LC improves dyspeptic or colonic symptoms. Approximately 19% of patients reported continuing or exacerbated symp-toms following LC. Detailed history-taking regarding gastritis before surgery can be helpful in predicting patients' outcome after LC.

Gallbladder Metastasis of Non-small Cell Lung Cancer Presenting as Acute Cholecystitis.

Although non-small cell lung cancer (NSCLC) can metastasize to almost any organ, metastasis to the gallbladder with significant clinical manifestation is relatively rare. Here, we report a case of gallbladder metastasis of NSCLC presenting as acute cholecystitis. A 79-year-old man presented with pain in the right upper quadrant and fever. A computed tomography (CT) scan of the chest and abdomen showed a cavitary mass in the right lower lobe of the lung and irregular wall thickening of the gallbladder. Open cholecystectomy and needle biopsy of the lung mass were performed. Histological examination of the gallbladder revealed a moderately-differentiated squamous cell carcinoma displaying the same morphology as the lung mass assessed by needle biopsy. Subsequent immunohistochemical examination of the gallbladder and lung tissue showed that the tumor cells were positive for P63 but negative for cytokeratin 7, cytokeratin 20 and thyroid transcription factor-1. A second primary tumor of the gallbladder was excluded by immunohistochemical methods, and the final pathological diagnosis was gallbladder metastasis of NSCLC. Although the incidence is extremely rare, acute cholecystitis can occur in association with lung cancer metastasis to the gallbladder.