The use of multiple molecular markers as predictors of the clinical prognosis of patients with colorectal cancer

AbstractSerum carcinoembryonic antigen (CEA) is most commonly used as a prognostic biomarker for evaluating curatively resected colorectal cancer (CRC) patients, but it has a low sensitivity and specificity. The aim of this study was to evaluate potential genetic markers in CRC patients using membrane array. Fifty CRC patients were enrolled and mRNA expression in their tissues were analyzed using membrane array analysis. Seven genes were analyzed in this study, including ATP2A2, GLUT1, MMP13, MAGE-A2, MAGE-A7, MAGE-A8, and MAGE-A12. Correlations between the results of the membrane array and the clinicopathological features of these CRC patients were then evaluated. The results show that the overexpression of any three or four of these seven genes is correlated with tumor invasion depth, lymphatic invasion, advanced stage, and postoperative recurrence (all p < 0.005). Furthermore, the expression of any four genes was more significantly correlated with clinicopathological characteristics than the expression of only two or three genes. The combination of multiple molecular markers and the membrane array method might be useful for predicting postoperative relapse in CRC patients

Efficacy of concurrent radiotherapy in patients with locally advanced rectal cancer and synchronous metastasis receiving systemic therapy

BackgroundNeoadjuvant chemoradiotherapy followed by total mesorectal excision is the standard treatment for patients with nonmetastatic locally advanced rectal cancer (LARC). However, for patients with LARC and synchronous metastasis, the optimal treatment strategy and sequence remain inconclusive. In the present study, we evaluated the efficacy and safety of concurrent radiotherapy in patients with de novo metastatic rectal cancer who received chemotherapy and targeted therapy.MethodsWe retrospectively reviewed the data of 63 patients with LARC and synchronous metastasis who received intensive therapy at the study hospital between April 2015 and November 2018. The included patients were divided into two groups: RT-CT, those who received systemic chemotherapy with targeted therapy and concurrent radiotherapy (for primary rectal cancer), and CT, those who received only systemic chemotherapy with targeted therapy.ResultsTreatment response was better in the RT-CT group than in the CT group. The rate of primary tumor resection (PTR) was higher in the RT-CT group than in the CT group (71.4% and 42.9%, respectively; P = .0286). The RT-CT group exhibited considerably longer local recurrence-free survival (P = .0453) and progression-free survival (PFS; from 13.3 to 22.5 months) than did the CT group (P = .0091); however, the groups did not differ in terms of overall survival (OS; P = .49). Adverse events were almost similar between the groups, except frequent diarrhea, the prevalence of which was higher in the RT-CT group than in the CT group (59.5% and 23.8%, respectively; P = .0075).ConclusionsIn the era of biologics, radiotherapy may increase the resectability of primary rectal tumors, reducing the risk of locoregional failure and prolonging PFS. Concurrent pelvic radiotherapy may not substantially improve OS, which is indicated by metastasis. Hence, the resection of the distant metastases may be essential for improving long-term OS. To further determine the efficacy of concurrent radiotherapy, additional prospective, randomized studies must combine preoperative pelvic radiotherapy with PTR and metastectomy to treat patients with stage IV LARC

Functional Effects of let-7g Expression in Colon Cancer Metastasis.

MicroRNA regulation is crucial for gene expression and cell functions. It has been linked to tumorigenesis, development and metastasis in colorectal cancer (CRC). Recently, the let-7 family has been identified as a tumor suppressor in different types of cancers. However, the function of the let-7 family in CRC metastasis has not been fully investigated. Here, we focused on analyzing the role of let-7g in CRC. The Cancer Genome Atlas (TCGA) genomic datasets of CRC and detailed data from a Taiwanese CRC cohort were applied to study the expression pattern of let-7g. In addition, in vitro as well as in vivo studies have been performed to uncover the effects of let-7g on CRC. We found that the expression of let-7g was significantly lower in CRC specimens. Our results further supported the inhibitory effects of let-7g on CRC cell migration, invasion and extracellular calcium influx through store-operated calcium channels. We report a critical role for let-7g in the pathogenesis of CRC and suggest let-7g as a potential therapeutic target for CRC treatment

Pleural Effusion after Percutaneous Radiofrequency Ablation for Hepatic Malignancies

AbstractBackground and AimsRadiofrequency ablation (RFA) can play an important role in the treatment of primary or metastatic liver tumors. Currently, percutaneous RFA is generally regarded as a safe, effective, and minimally invasive procedure. This study aimed to evaluate the presence and course of pleural effusion after monopolar RFA.MethodsFrom October 2008 to July 2013, a total of 54 patients (28 male and 26 female, mean age 65.2) treated with monopolar RFA were included in our study. 47 patients were diagnosed with hepatocellular carcinoma, 4 patients with hepatic metastasis, and 3 patients had other diagnoses. There were a total of 115 sessions of treatment and 199 liver tumors to be treated (1.73 ± 1.02 tumors treated per session). The tumor size ranged from 0.8 cm to 5.0 cm (mean 2.31 cm, standard deviation 1.04 cm). Thereafter, a follow-up ultrasound was performed within 24 hours subsequent to ablation to evaluate the presence of pleural effusion. The degree of pleural effusion was assessed by chest X-ray.ResultsFifteen (13.0%) treatment sessions in 14 patients showed right-sided pleural effusion after ablations. One patient had a large amount of effusion, while other patients manifested a minimal to small amount of effusion. There were 5 patients that experienced delayed resolution of pleural effusion; one patient (0.87%) had a minimal amount of pleural effusion even after one month. Overall, there was no pneumothorax, or periprocedural morality. Age, gender, tumor numbers, tumor sizes, and complete ablation of target tumors were similar among groups presenting with or without pleural effusion. Tumor locations associated with S78 segments abutting the diaphragm or right lobe of the liver were not associated with development of pleural effusion. Only the duration of ablation time had a marginal trend toward significance (p = 0.051).ConclusionsThe transient appearance of right-sided pleural effusion after percutaneous RFA for hepatic malignancies was not infrequent. However, refractory pleural effusion was rare

Endoscopic Submucosal Dissection for Gastric Epithelial Tumors: A Multicenter Study in Taiwan

Background/PurposeEndoscopic submucosal dissection (ESD) is an advanced endoscopic procedure to resect early gastric cancer (EGC). The purpose of this study was to determine the effectiveness and complications of ESD for gastric epithelial tumors in Taiwan.MethodsWe retrospectively analyzed the efficacy and outcome of ESD in patients who received ESD for gastric epithelial tumors between June 2004 and August 2007.ResultsA total of 70 patients with gastric epithelial tumors were treated by ESD. The mean age was 66.5 ±12.9 years (range, 35–84 years). The mean size of the gastric epithelial tumors was 1.85 ± 0.81 cm. The mean size of resected specimens was 3.26 ± 1.39 cm. The one-piece resection rate was 91.4% (64/70). The median operation time was 92.4 minutes. The complicating bleeding and perforation rates were 5.7% (4/70) and 4.3% (3/70), respectively. Emergency surgery was performed for three patients with perforations. The local recurrence rate of gastric cancer was 2.8%. Except for one patient who died of congestive heart failure and another who died of stroke, the remaining 68 patients (97.1%) survived.ConclusionESD is a promising local curative treatment option for EGC in Taiwan but it still carries risks of perforation and bleeding. The education and learning curve of endoscopists will improve the outcome of this procedure

safety and effectiveness of regorafenib in patients with metastatic colorectal cancer in routine clinical practice in the prospective observational correlate study

Abstract Background Regorafenib prolonged overall survival (OS) versus placebo in patients with treatment-refractory metastatic colorectal cancer (mCRC) in phase III trials. We conducted an observational study of regorafenib for patients with mCRC in real-world clinical practice. Methods The international, prospective, CORRELATE study recruited patients with mCRC previously treated with approved therapies, for whom the decision to treat with regorafenib was made by the treating physician according to the local health authority approved label. The primary objective was safety, assessed by treatment-emergent adverse events (TEAEs; National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03). Results A total of 1037 patients were treated. The median age was 65 years (range: 24–93); 87% of patients had Eastern Cooperative Oncology Group performance status 0–1, 56% of patients had KRAS, 7% had NRAS and 4% had BRAF mutations. The initial regorafenib dose was 160 mg/day in 57% of patients. The most common grade III or IV drug-related TEAEs were fatigue (9%), hand–foot skin reaction (7%) and hypertension (6%). Drug-related grade V (fatal) TEAEs occurred in 1% of patients. Dose reductions for drug-related TEAEs occurred in 24% of patients. Median OS was 7.7 months (95% confidence interval [CI]: 7.2–8.3), and median progression-free survival (PFS) was 2.9 months (95% CI: 2.8–3.0). Conclusions In this real-world, observational study of patients with mCRC, the regorafenib toxicity profile was similar to that reported in phase III trials. The starting dose for almost half of patients was less than the approved 160-mg dose, and the median OS and PFS were in the range observed in phase III trials. Trial registration: NCT02042144

Characterization of membranous and cytoplasmic EGFR expression in human normal renal cortex and renal cell carcinoma

Metastatic renal cell carcinoma (RCC) is highly resistant to conventional systemic treatments, including chemotherapy, radiotherapy and hormonal therapies. Previous studies have shown over-expression of EGFR is associated with high grade tumors and a worse prognosis. Recent studies suggest anticancer therapies targeting the EGFR pathway have shown promising results in clinical trials of RCC patients. Therefore, characterization of the level and localization of EGFR expression in RCC is important for target-dependent therapy. In this study, we investigated the clinical significance of cellular localization of EGFR in human normal renal cortex and RCC. RCC and adjacent normal kidney tissues of 63 patients were obtained for characterization of EGFR expression. EGFR protein expression was assessed by immunohistochemistry on a scale from 0 to 300 (percentage of positive cells × staining intensity) and Western blotting. EGFR membranous staining was significantly stronger in RCC tumors than in normal tissues (P < 0.001). In contrast, EGFR cytoplasmic staining was significantly higher in normal than in tumor tissues (P < 0.001). The levels of membranous or cytoplasmic EGFR expression in RCC tissues were not correlated with sex, tumor grade, TNM stage or overall survival (P > 0.05). These results showed abundant expression of membranous EGFR in RCC, and abundant expression of cytoplasmic EGFR in normal tissues. EGFR expression in RCC was mostly located in the cell membrane, whereas the EGFR expression in normal renal tissues was chiefly seen in cytoplasm. Our results suggest different locations of EGFR expression may be associated with human renal tumorigenesis

Activation of EDTA-resistant gelatinases in malignant human tumors

Among the many proteases associated with human cancer, seprase or fibroblast activation protein alpha, a type II transmembrane glycoprotein, has two types of EDTA-resistant protease activities: dipeptidyl peptidase and a 170-kDa gelatinase activity. To test if activation of gelatinases associated with seprase could be involved in malignant tumors, we used a mammalian expression system to generate a soluble recombinant seprase (r-seprase). In the presence of putative EDTA-sensitive activators, r-seprase was converted into 70- to 50-kDa shortened forms of seprase (s-seprase), which exhibited a 7-fold increase in gelatinase activity, whereas levels of dipeptidyl peptidase activity remained unchanged. In malignant human tumors, seprase is expressed predominantly in tumor cells as shown by in situ hybridization and immunohistochemistry. Proteins purified from experimental xenografts and malignant tumors using antibody- or lectin-affinity columns in the presence of 5 mmol/L EDTA were assayed for seprase activation in vivo. Seprase expression and activation occur most prevalently in ovarian carcinoma but were also detected in four other malignant tumor types, including adenocarcinoma of the colon and stomach, invasive ductal carcinoma of the breast, and malignant melanoma. Together, these data show that, in malignant tumors, seprase is proteolytically activated to confer its substrate specificity in collagen proteolysis and tumor invasion

Preoperative serum carcinoembryonic antigen, albumin and age are supplementary to UICC staging systems in predicting survival for colorectal cancer patients undergoing surgical treatment

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine influence of prognostic factors in addition to UICC staging systems, on cancer-specific and overall survival rates for patients with colorectal cancer (CRC) undergoing surgical treatment.</p> <p>Methods</p> <p>Between January 1996 and December 2006, a total of 1367 CRC patients who underwent surgical treatment in Kaohsiung Medical University Hospital were analyzed. We retrospectively investigated clinicopathologic features of these patients. All patients were followed up intensively, and their outcomes were investigated completely.</p> <p>Results</p> <p>Of 1367 CRC patients, there were seven hundred and fifty-seven males (55.4%) and 610 (44.6%) females. The median follow-up period was 60 months (range, 3–132 months). A multivariate analysis identified that low serum albumin level (<it>P </it>= 0.011), advanced UICC stage (<it>P </it>< 0.001), and high carcinoembryonic antigen (CEA) level (<it>P </it>< 0.001) were independent prognostic factors of cancer-specific survival. Meanwhile, a multivariate analysis showed age over 65 years (<it>P </it>< 0.001), advanced UICC stage (<it>P </it>< 0.001), and high CEA level (<it>P </it>< 0.001) were independent prognostic factors of overall survival. Furthermore, combination of UICC stage, serum CEA and albumin levels as predictors of cancer-specific survival showed that the poorer the prognostic factors involved, the poorer the cancer-specific survival rate. Likewise, combination of UICC stage, age and serum CEA level as predictors of overall survival showed that the poorer the prognostic factors involved, the poorer the overall survival rate. Of these prognostic factors, preoperative serum CEA level was the only significant prognostic factor for patients with stage II and III CRCs in both cancer-specific and overall survival categories.</p> <p>Conclusion</p> <p>Preoperative serum albumin level, CEA level and age could prominently affect postoperative outcome of CRC patients undergoing surgical treatment. In addition to conventional UICC staging system, it might be imperative to take these additional characteristics of factors into account in CRC patients prior to surgical treatment.</p