Circulating tumor cells detected using fluid-assisted separation technique in esophageal squamous cell carcinoma.

BACKGROUND AND AIM: Esophageal squamous cell carcinoma (ESCC) is one of the aggressive gastrointestinal tract cancers. Detection of circulating tumor cells (CTCs) in peripheral blood from patients with various malignancies has been reported to have diagnostic, prognostic, and therapeutic implications. We aimed to evaluate CTCs in patients with ESCC and assess the clinical significance of CTCs in the early diagnosis of ESCC. METHODS: Peripheral blood samples for CTCs analyses were prospectively obtained from 73 patients with ESCC prior to treatment between March 2015 and June 2018. CTCs were detected using a centrifugal microfluidic system with a new fluid-assisted separation technique. Blood samples from 31 healthy volunteers were used as controls. RESULTS: After creating a receiver operating characteristic curve to determine the optimal CTC threshold to differentiate patients with ESCC from healthy controls, sensitivity and specificity were most optimized at a CTC threshold of two per 7.5 mL of blood. Among 66 subjects with ≥ 2 CTCs per 7.5 mL of blood, 63 (95.5%) had ESCC. Among 38 subjects with < 2 CTCs per 7.5 mL of blood, 28 (73.7%) were healthy controls. When using this threshold, the sensitivity and specificity for differentiating patients with ESCC from healthy controls were 86.3% and 90.3%, respectively. CTC count was associated with tumor-node-metastasis stage, especially lymph node metastasis, but there was no correlation with any other relevant clinicopathologic variable. CONCLUSIONS: Our results suggest that CTCs detected using fluid-assisted separation technique could be helpful for early diagnosis of ESCC. Further large-scale prospective studies are warranted to validate our findings.

Functionalized vertical GaN micro pillar arrays with high signal-to-background ratio for detection and analysis of proteins secreted from breast tumor cells.

The detection of cancer biomarkers has recently attracted significant attention as a means of determining the correct course of treatment with targeted therapeutics. However, because the concentration of these biomarkers in blood is usually relatively low, highly sensitive biosensors for fluorescence imaging and precise detection are needed. In this study, we have successfully developed vertical GaN micropillar (MP) based biosensors for fluorescence sensing and quantitative measurement of CA15-3 antigens. The highly ordered vertical GaN MP arrays result in the successful immobilization of CA15-3 antigens on each feature of the arrays, thereby allowing the detection of an individual fluorescence signal from the top surface of the arrays owing to the high regularity of fluorophore-tagged MP spots and relatively low background signal. Therefore, our fluorescence-labeled and CA15-3 functionalized vertical GaN-MP-based biosensor is suitable for the selective quantitative analysis of secreted CA15-3 antigens from MCF-7 cell lines, and helps in the early diagnosis and prognosis of serious diseases as well as the monitoring of the therapeutic response of breast cancer patients.

Effect of graphene oxide ratio on the cell adhesion and growth behavior on a graphene oxide-coated silicon substrate.

Control of living cells on biocompatible materials or on modified substrates is important for the development of bio-applications, including biosensors and implant biomaterials. The topography and hydrophobicity of substrates highly affect cell adhesion, growth, and cell growth kinetics, which is of great importance in bio-applications. Herein, we investigate the adhesion, growth, and morphology of cultured breast cancer cells on a silicon substrate, on which graphene oxides (GO) was partially formed. By minimizing the size and amount of the GO-containing solution and the further annealing process, GO-coated Si samples were prepared which partially covered the Si substrates. The coverage of GO on Si samples decreases upon annealing. The behaviors of cells cultured on two samples have been observed, i.e. partially GO-coated Si (P-GO) and annealed partially GO-coated Si (Annealed p-GO), with a different coverage of GO. Indeed, the spreading area covered by the cells and the number of cells for a given culture period in the incubator were highly dependent on the hydrophobicity and the presence of oxygenated groups on GO and Si substrates, suggesting hydrophobicity-driven cell growth. Thus, the presented method can be used to control the cell growth via an appropriate surface modification.

Hypopituitarism Presenting as Adrenal Insufficiency and Hypothyroidism in a Patient with Wilson's Disease: a Case Report.

Wilson's disease typically presents symptoms associated with liver damage or neuropsychiatric disturbances, while endocrinologic abnormalities are rare. We report an unprecedented case of hypopituitarism in a patient with Wilson's disease. A 40-year-old woman presented with depression, general weakness and anorexia. Laboratory tests and imaging studies were compatible with liver cirrhosis due to Wilson's disease. Basal hormone levels and pituitary function tests indicated secondary hypothyroidism and adrenal insufficiency due to hypopituitarism. Brain MRI showed T2 hyperintense signals in both basal ganglia and midbrain but the pituitary imaging was normal. She is currently receiving chelation therapy along with thyroid hormone and steroid replacement. There may be a relationship between Wilson's disease and hypopituitarism. Copper deposition or secondary neuronal damage in the pituitary may be a possible explanation for this theory.

Enhancement of Capture Sensitivity for Circulating Tumor Cells in a Breast Cancer Patient's Blood by Silicon Nanowire Platform.

The separation of circulating tumor cells (CTCs) from the blood of cancer patients with high sensitivity is an essential technique for selecting chemotherapeutic agents at a patient-by-patient level. Recently, various research groups have reported a nanostructure-based platform for rare cell capture due to its high surface area and 3D nanotopographic features. However, evaluation of capture sensitivity based on chemical modification of the nanostructure surface has not yet been performed. Here, we evaluated the capture sensitivity for CTCs from the blood of three patients diagnosed with stage IV metastatic breast cancer by using the following three platforms: streptavidin-conjugated silicon nanowire (STR-SiNW), poly-l-lysine-coated silicon nanowire (PLL-SiNW), and poly-l-lysine-coated glass (PLL-glass). The number of evaluated CTCs on STR-SiNW, PLL-SiNW, and PLL-glass were 16.2 ± 5.5 cells, 7.3 ± 2.9 cells, and 4.7 ± 1.5 cells, respectively, per 0.5 ml. Therefore, we suggest that the STR-SiNW platform is highly adaptable for the quantitative evaluation of CTCs from the blood of cancer patients in the clinical setting.

Drug response of captured BT20 cells and evaluation of circulating tumor cells on a silicon nanowire platform.

Research on specific drug responses of circulating tumor cells (CTCs) provides very important information for treatment of cancer patients at a patient-specific level. For this reason, platforms for high capture efficiency of CTCs are essential for clinical evaluation of patient-specific drug responses of CTCs. Recently, nanostructure based platforms have been developed with a high capture efficiency of more than 93% due to high-affinity binding and the 3D nanotopographic features of the nanostructure substrate. In this study, the breast carcinoma cell-line (BT20) cells with an ultra-low abundance range were captured by streptavidin (STR)-functionalized silicon nanowire (SiNW) platforms for evaluation of capture efficiency. A capture efficiency of more than 90% was achieved. Specific drug responses of BT20 cells captured on STR-SiNW platforms were analyzed using tamoxifen or docetaxel as a function of incubation time and dose, and compared with a 96-well plate platform. The drug responses of CTCs on STR-SiNW platforms were more sensitive than a 96-well plate platform. In addition, CTCs were successfully captured and evaluated their size distribution from the blood of breast cancer patients using fluorescence imaging. In conclusion, we suggest that the SiNW platform is adaptable for clinical use in evaluation of CTCs and drug response tests.

Clinicopathologic factors influencing the accuracy of EUS for superficial esophageal carcinoma.

AIM: To identify clinicopathologic factors influencing the accuracy of a high-frequency catheter probe endoscopic ultrasonography (EUS) for superficial esophageal carcinomas (SECs). METHODS: A total of 126 patients with endoscopically suspected SEC, who underwent EUS and curative treatment at Pusan National University Hospital during 2005-2013, were enrolled. We reviewed the medical records of the 126 patients and compared EUS findings with histopathologic results according to clinicopathologic factors. RESULTS: A total of 114 lesions in 113 patients were included in the final analysis. The EUS assessment of tumor invasion depth was accurate in 78.9% (90/114) patients. Accuracy did not differ according to histologic type, tumor differentiation, tumor location, or macroscopic shape. However, accuracy significantly decreased for tumors ≥ 3 cm in size (P = 0.002). Overestimation and underestimation of the invasion depth occurred for 11 (9.6%) and 13 lesions (11.4%), respectively. In multivariate analyses, tumor size ≥ 3 cm was the only factor significantly associated with EUS accuracy (P = 0.031), and was specifically associated with the underestimation of invasion depth. CONCLUSION: EUS using a high-frequency catheter probe generally provides highly accurate assessments of SEC invasion depth, but its accuracy decreases for tumors ≥ 3 cm.

Long-term outcomes of endoscopic submucosal dissection for early gastric cancer: a single-center experience.

BACKGROUND: In Korea, endoscopic submucosal dissection (ESD) has been widely accepted for the treatment of early gastric cancers (EGCs). However, the understanding of the long-term clinical outcome of ESD for EGC remains insufficient. Therefore, the aim of the present study was to assess the long-term clinical outcome and efficacy of ESD for the treatment of EGCs, including the clinical application of the expanded criteria for ESD. METHODS: From January 2006 to December 2010, a total of 515 patients with 522 EGCs were treated by ESD in our hospital; study enrollment was based on the expanded criteria. Comparisons of resectability (en bloc or piecemeal resection), curability (curative or non-curative), and complications (bleeding and perforation) between the standard and expanded groups were assessed. Thereafter, 336 patients with 342 EGCs were finally included in a long-term analysis of local tumor recurrence, development of synchronous and metachronous cancers, and overall and disease-specific survival rates. RESULTS: En bloc and curative resection rates of 96.7 % and 88.3 %, respectively, were achieved. The curative resection rate was significantly lower in the expanded group than in the standard group (82.1 % vs. 91.5 %, p = 0.001). During a median follow-up of 24 months, the local tumor recurrence rate was also higher in the expanded group than in the standard group (7.0 % vs. 1.8 %, p = 0.025). Local recurrence was more frequent in lesions with non-curative resection than in those with curative resection (20.0 % vs. 1.3 %, p < 0.001). The 5-year overall and disease-specific survival rates were 88 % and 100 %, respectively; the difference between the standard and expanded groups was not significant (p = 0.834). CONCLUSIONS: ESD appears to be a feasible and effective method for treating EGCs, based on the standard and expanded criteria. Close follow-up surveillance, after ESD, should be standard for all patients.

Clinical predictors for response to proton pump inhibitor treatment in patients with globus.

BACKGROUND/AIMS: Globus is a persistent or intermittent non-painful sensation of a lump or foreign body in the throat. Given the benign nature of the condition and the association of gastroesophageal reflux disease, empirical therapy with proton pump inhibitor seems reasonable for patients with typical globus. The aim of this study was to investigate the clinical predictors for symptom response to short-term proton pump inhibitor treatment in patients with globus symptom. METHODS: Fifty-four patients with globus symptom were enrolled prospectively. All patients were treated with pantoprazole 40 mg daily for 4 weeks. Treatment response was defined as a > 50% reduction in symptom scores between symptom assessments. Univariate and multivariate logistic regression analysis between responders and non-responders was performed to identify variables predicting response to pantoprazole treatment. RESULTS: Of the 54 consecutive patients considered, 13 were excluded on the basis of exclusion criteria and/or refusal to participate in the study. Finally, 41 patients were included in this study. After 4-week pantoprazole treatment, 22 patients (53.7%) were classified as responders. On multivariate analysis, the presence of reflux symptom was associated with a higher response rate to 4-week pantoprazole treatment (OR, 68.56; P = 0.043), and long symptom duration (≥ 3 months) were associated with a lower response rate to pantoprazole treatment (OR, 0.03; P = 0.034). CONCLUSIONS: Presence of reflux symptom and short symptom duration were independent predictors of responsiveness to 4-week pantoprazole treatment in patients with globus.

Primary squamous cell carcinoma of the liver initially presenting with pseudoachalasia.

Pseudoachalasia secondary to primary squamous cell carcinoma (SCC) of the liver is extremely rare and has not been reported until now. Here, we report a unique case of primary SCC of the liver initially presenting with progressive dysphagia along with short periods of significant weight loss. A 58-year-old man initially presented with progressive dysphagia along with significant weight loss over brief periods of time. The radiographic and manometric findings were consistent with achalasia. Subsequent esophagogastroduodenoscopy revealed a moderately dilated esophagus without evidence of neoplasm or organic obstruction. However, firm resistance was encountered while traversing the esophagogastric junction (EGJ), although no mucosal lesion was identified. Due to the clinical suspicion of the presence of a malignant tumor, endoscopic ultrasonography (EUS) and computed tomography scans of the chest and abdomen were obtained. A huge hepatic mass with irregular margins extending to the EGJ was found. EUS-guided fine-needle aspiration was performed, and the mass was diagnosed as a primary SCC of the liver by immunohistochemical staining.

[Diagnosis and treatment of gastric MALT lymphoma].

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma represents approximately 40% of gastric lymphomas, and its incidence is increasing. An early diagnosis for gastric MALT lymphoma is important, but not easy due to non-specific symptoms and endoscopic findings. Diagnosis is based on the histopathologic evaluation of multiple, deep and repeated biopsies taken from normal and any abnormal appearing sites of the stomach. In addition, the presence of Helicobacter pylori (H. pylori) infection must be determined to determine therapeutic approach. Endoscopic ultrasonography (EUS) is essential for the evaluation of regional lymph nodes and the depth of tumor invasion in the gastric wall, for predicting response to H. pylori eradication, and for monitoring tumor regression or recurrence. The eradication of H. pylori is recommended as an initial treatment for low-grade gastric MALT lymphoma with H. pylori infection. Both radiation therapy and chemotherapy are suitable alternative options for H. pylori-negative, refractory, or high-grade gastric MALT lymphoma. But, the role of surgery is diminishing. After treatment, strict endoscopic regular follow-up including EUS is recommended with multiple biopsies. However, controversy remains regarding the best diagnosis, treatment and follow-up strategy for this disease.

Predictive value of post-transplant bone marrow plasma cell percent in multiple myeloma patients undergone autologous transplantation.

BACKGROUND/AIMS: Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment. METHODS: We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (≥ 2 vs. < 2%), international scoring system (ISS) stage (II vs. III), response after 3 cycles of VAD therapy (complete response [CR] vs. non-CR), deletion of chromosome 13q (del[13q]) (presence of the abnormality vs. absence), and BMPCp at diagnosis (≥ 50 vs. < 50%) on progression-free survival (PFS) and overall survival (OS). RESULTS: During the median follow-up of 28.0 months, the median PFS and OS were 29.1 and 42.1 months, respectively. By univariate analysis, ISS stage III at diagnosis, BMPCp ≥ 50% at diagnosis, CR after 3 cycles of VAD therapy, del (13q) by fluorescence in situ hybridization, and BMPCp ≥ 2% at post-transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp ≥ 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters. CONCLUSIONS: Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.

[A case of duodenal perforation caused by biliary plastic stent treated with approximation using endoclip and detachable snare].

Endoscopic retrograde biliary drainage (ERBD) is useful for the palliative decompression of biliary obstruction. However, the complications of ERBD include cholangitis, hemorrhage, acute pancreatitis, obstruction of the stent, and duodenal perforation. Pressure necrosis on the duodenal mucosa by the stent may contribute to perforation. Although duodenal perforation following ERBD is very rare compared to other complications, it can result in a fatal outcome. Recent reports describe nonsurgical treatment for small gastrointestinal perforation with localized peritonitis and suggest that endoclipping may be appropriate in the management of a well selected group of patients with iatrogenic perforation. We describe a case of duodenal perforation secondary to ERBD that was successfully treated with approximating using endoclip and detachable snare.

Toxic epidermal necrolysis associated with sorafenib and tosufloxacin in a patient with hepatocellular carcinoma.

This is the first case report to describe a 44-year-old woman with a history of advanced hepatocellular carcinoma who developed toxic epidermal necrolysis (TEN) clinically after taking 400 mg sorafenib (Nexavar®, BAY 43-9006) and tosufloxacin orally once per day. Both sorafenib and tosufloxacin were eventually discontinued, and the TEN resolved with corticosteroids and supportive treatment. Clinical physicians should be aware of this possible complication so that early interventions can be made.