Wuping Wang

Clinicopathologic features and prognostic implications of Gankyrin protein expression in non-small cell lung cancer

PURPOSE The expression of Gankyrin, a liver cancer-related oncoprotein, has been observed in several human malignancies including non-small cell lung cancer (NSCLC). However, the clinic relevance of Gankyrin expression in NSCLC remains unclear. METHODS Gankyrin expression was assessed using immunohistochemical (IHC) methods in 166 paired paraffin-embedded NSCLC specimens and adjacent normal tissues. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were employed to measure the expression of Gankyrin in 24 paired fresh NSCLC specimens and the corresponding normal tissues. The association of Gankyrin expression with clinicopathological parameters was also evaluated. Kaplan-Meier survival analysis and Cox proportional hazards models were used to estimate the effect of Gankyrin expression on survival. RESULTS Data showed that Gankyrin was expressed in 78.3% (130/166) and 28.9% (48/166) of cancer lesions and corresponding adjacent normal tissue, respectively. And the Gankyrin overexpression in tumor tissue occurred in 53.6% (89/166) of patients, while overexpression of Gankyrin in normal tissue occurred only in 4.8% (8/166) of patients (P<0.001). Semi-quantitative RT-PCR and Western blotting showed that NSCLC specimens had increased Gankyrin mRNA and protein expression compared to the corresponding normal tissues. Out of all the clinicopathological factors analyzed, Gankyrin overexpression was significantly correlated with lymphatic metastasis (P<0.001) and p-TNM stage (P<0.001). Gankyrin-overexpressed NSCLC patients had a significantly shorter survival time (P<0.001, Log-rank test), and the prognostic significance of Gankyrin overexpression was apparent in both squamous cell carcinoma patients (P=0.028) and adenocarcinoma patients (P<0.001). Multivariate analysis indicated that Gankyrin overexpression may be an independent prognostic factor in NSCLC (hazard ratio [HR], 1.51; P=0.041). CONCLUSION Our results indicate that Gankyrin overexpression is of clinical significance and can serve as a prognostic biomarker in NSCLC.

Isolated Crohn’s disease of the esophagus with esophago-mediastinal fistula formation

Isolated Crohn’s disease of the esophagus is rare, and accurate diagnosis and treatment in its early course are difficult. Most cases are often found very late, when severe strictures or other complications have occurred. We report the case of a male 60-year-old patient with complaints of progressive dysphagia for more than two months and the sudden appearance of heartburn for seven consecutive days. Clinical examination revealed severe esophageal stricture with a suspected fistula and mediastinitis. The patient received a successful esophagectomy. The resected specimen and pathological results confirmed a deep linear ulcer, chronic and noncaseating granulomatous inflammation, as well as a circular stricture of the esophagus with fistula into the mediastinum due to isolated esophageal Crohn’s disease.

Apoptosis-related protein-1 acts as a tumor suppressor in cholangiocarcinoma cells by inducing cell cycle arrest via downregulation of cyclin-dependent kinase subunits

Cholangiocarcinoma, a malignancy arising from the biliary tract, is associated with high mortality due to the late diagnosis and lack of effective therapeutic approaches. Our knowledge of the molecular alterations during the carcinogenesis of cholangiocarcinoma is limited. Previous study suggests that apoptosis-related protein-1 (Apr-1) is involved in cancer cell proliferation and survival. In the present study, we first detected the expression pattern of Apr-1 in human cholangiocarcinoma tissues and the effects of forced Apr-1 expression on cell proliferation and cell cycle progression. Cell cycle gene array analysis was used to identify downstream molecules that were regulated by Apr-1, and their expression levels were further evaluated in human cholangiocarcinoma tissues. We showed that Apr-1 expression was downregulated in human cholangiocarcinoma tissues. Forced expression of Apr-1 inhibited cell proliferation of cholangiocarcinoma cell line QBC939 and induced G2/M phase arrest. Downregulation of cell cycle-related genes cyclin-dependent kinase (Cdk) 2, and cyclin-dependent kinase subunits (Cks) 1 and 2 was involved in Apr-1-induced cell cycle arrest. Furthermore, we found that Cdk2 and Cks1/2 expression levels were elevated in human cholangiocarcinoma tissues. Taken together, our data showed that Apr-1 plays a crucial role in cell proliferation by controlling cell cycle progression, implying a tumor-suppressor function of Apr-1 in cholangiocarcinoma carcinogenesis. Thus, the present study provides a rationale to further study the underlying mechanisms of Apr-1 downregulation in cholangiocarcinoma for exploring potential diagnostic and therapeutic targets.

A case report of para-esophageal bronchogenic cyst with esophageal communication.

Paraesophageal bronchogenic cyst was one of common mediastinal congenital cystic lesions of foregut origin. Because of an intimate embryologic relationship with the esophagus, they were usually found intramural (intramural esophageal bronchogenic cysts) with the local esophageal mucosa being intact and the paraesophageal bronchogenic cysts were rarely communicated with esophageal lumen. We report a case of para-esophageal bronchogenic cyst communicating to the esophageal lumen thorough a pedicle of canal, which looked liked a diverticulum on X-ray. During the operation, a communication of paraesophageal bronchogenic cyst with esophageal was found and the pathology diagnosis were made then. The symptoms of chest pain and dysphagia were relieved immediately after operation. The follow-up was well 2 years after the surgery.

Gankyrin promotes epithelial-mesenchymal transition and metastasis in NSCLC through forming a closed circle with IL-6/ STAT3 and TGF-β/SMAD3 signaling pathway.

Our previous research showed that Gankyrin was overexpressed in NSCLC and significantly associated with clinicopathologic features and poor prognosis. In this study, we will explore potential effect of Gankyrin on EMT and metastasis in NSCLC. The ectopic higher expression of Gankyrin markedly increased the migration and invasion in NSCLC cells. In contrast, silencing Gankyrin inhibit this aggressive behavior in NSCLC cells. Further study demonstrated that overexpression of Gankyrin could decrease E-cadherin expression and increase expression of Vimentin and Twist1 at mRNA and protein levels. These data indicated that Gankyrin could facilitate occurrence and development of EMT. Also IHC analysis showed that Gankyrin expression was negatively correlated with E-cadherin expression, while positively correlated with Vimentin and Twist1 expression in NSCLC tissues. The mechanism study finally suggested that the Gankyrin-driven EMT was partially due to IL-6/p-STAT3 and TGF-β/p-SMAD3 pathways activation. Taken together, our data provided a novel mechanism of Gankyrin promoting EMT and metastasis in NSCLC through forming a closed circle with IL-6/p-STAT3 and TGF-β/p-SMAD3 signaling pathway.

Spontaneous rupture of a giant intrapericardial bronchogenic cyst.

Bronchogenic cysts arise from an abnormal budding of the ventral diverticulum of the foregut or the tracheobronchial tree during embryogenesis. They are rarely found intrapericardially. Herein, we report the case of a 43-year-old man who presented with a ruptured intrapericardial bronchogenic cyst (IBC), with aggravating symptoms of chest tightness and shortness of breath. The cyst was completely resected, and the patients postoperative recovery was uneventful. This is the first report with radiologic evidence of an IBC that ruptured, rapidly releasing cystic liquid into the pericardium and exacerbating the patients symptoms. These results argue for the complete surgical excision of an IBC at the time of diagnosis, even if the patient is asymptomatic.

An unusual cause of dysphagia: thoracic aorta aneurysm

The vascular structure related compression of esophagus is rather rare. Aberrant right subclavicular artery accounts for the majority of the rare entity, while the thoracic aorta aneurysm is a more dangerous type, called as dysphagia aortica. Delay in diagnosis and treatment of the dysphagia aortica predisposes to rupture and death. Herein, we reported a female patient with thoracic aorta aneurysm. A quick diagnosis by using chest contrast computed tomography (CT) scan and angiography of heart was made, and followed by emergent surgery. In the process, there was no delay on the diagnosis and treatment. The patient is going on well in the follow up.

Benign esophago-pulmonary fistula complicating achalasia: case report and literature review

The achalasia, a common benign disease of esophagus, plays an important role in esophago-respiratory fistula, which has not yet been well recognized. In present study, a case is reported of a patient with benign esophago-pulmonary fistula secondary to a longstanding achalasia. To our knowledge, this is the fifth patient of English literature presenting benign esophago-pulmonary fistula associated with achalasia, we performed Hellers myotomy as well as fundoplication through trans-abdominal route and colon replacement of the esophagus through retro-sternal procedure, but with the thoracic esophageal fistula as well as the right lung left being intact. The patient is going on well in the follow up.

Bronchiolitis obliterans complicating a pneumothorax after Stevens-Johnson syndrome induced by lamotrigine

Bronchiolitis obliterans (BO) was defined as a nonreversible obstructive lung disease in which the bronchioles are always compressed and narrowed by fibrosis or inflammation. In the severe event of lung collapse after BO, surgical intervention is often recommended, and conservative therapy is thought to be ineffective. Here, we report the case of a 9-year old girl clinically diagnosed as having bronchiolitis obliterans with abrupt occlusion of the right B4b bronchus. After a lamotrigine-induced Stevens-Johnson syndrome (SJS) occurred, she presented with total collapse of the right lung on admission, which was subsequently complicated by a pneumothorax during conservative treatment, but with the re-expansion of the right upper lobe after intervention. The case indicates the possibility of reversing pulmonary atelectasis in BO. Thus, surgery may not be necessary.

Effects of Lipid Emulsions in Parenteral Nutrition of Esophageal Cancer Surgical Patients Receiving Enteral Nutrition: A Comparative Analysis

Background: Olive oil-based lipid emulsion (LE) and medium chain triglyceride/long chain triglyceride (MCT/LCT) emulsion are both LEs with low ω-6 polyunsaturated fat acids (PUFAs) content. However, which one of these LEs is associated with a lower infection risk in patients receiving parenteral nutrition (PN) remains unclear. The aim of the study was to compare the effects of the two LEs in PN in esophageal cancer patients undergoing surgery. Methods: Patients with resectable esophageal carcinoma were recruited and allocated randomly to two groups. The test group was given enteral nutrition (EN) with PN containing olive oil-based LE after tumor resection for ≥7 days, and the patients in the control group were supported by EN with MCT/LCT emulsion-based PN after surgery for the same time period. Immunological markers and inflammatory indicators were tested and perioperative clinical outcomes were determined. The trial was registered in the Chinese Clinical Trial Register, number ChiCTR-TRC-13003562. 94 Patients were recruited, and grouped (olive oil-based LE, n = 46 and MCT/LCT, n = 48), matched for sex, age, body mass index, histological type, TNM stage, and nutrition risk screening (NRS) 2002 score. Results: There were no differences in perioperative fever (>38 °C), infectious complications, length of hospital stay (>14 days), length of critical care stay (>2 days), time for oral food intake, and in-hospital mortality between the two groups. The test group showed a higher increase in IgG level compared with the MCT/LCT group (p = 0.028). There was no difference in other immunological markers and inflammatory indicators between the two groups. Conclusion: PN containing olive oil-based or MCT/LCT LEs had similar effects on perioperative outcome, cell-mediated immune function and inflammatory response in esophageal cancer patients who had undergone surgery and were receiving EN.