Status quo of p53 in the treatment of tumors.

The p53 gene is pivotal for oncogenesis in a combination of mutations in oncogenes and antioncogenes. The ubiquitous loss of the p53 pathway in human cancers has generated considerable interest in developing p53-targeted cancer therapies, but current ideas and approaches targeting p53 are conflicting. Current researches focus on cancer-selective drugs with therapeutic strategies that both activate and inhibit p53. As p53 is ubiquitously lost in human cancers, the strategy of exogenous p53 addition is reasonable. However, p53 acts not equally in all cell types; thus, individualized p53 therapy is the direction of future research. To clarify the controversies on p53 for improvement of future antitumor studies, the review focuses on the available technological protocols, including their advantages and limitations in terms of future therapeutic use of p53 in the management of tumors.

Clinical application of partial splenic embolization.

Partial splenic embolization (PSE) is one of the intra-arterial therapeutic approaches of diseases. With the development of interventional radiology, the applications of PSE in clinical practice are greatly extended, while various materials are developed for embolization use. Common indications of PSE include hypersplenism with portal hypertension, hereditary spherocytosis, thalassemia, autoimmune hemolytic anemia, splenic trauma, idiopathic thrombocytopenic purpura, splenic hemangioma, and liver cancer. It is also performed to exclude splenic artery aneurysms from the parent vessel lumen and prevent aneurysm rupture, to treat splenic artery steal syndrome and improve liver perfusion in liver transplant recipients, and to administer targeted treatment to areas of neoplastic disease in the splenic parenchyma. Indicators of the therapeutic effect evaluation of PSE comprise blood routine test, changes in hemodynamics and in splenic volume. Major complications of PSE include the pulmonary complications, severe infection, damages of renal and liver function, and portal vein thrombosis. The limitations of PSE exist mainly in the difficulties in selecting the arteries to embolize and in evaluating the embolized volume.

Role of antiviral therapy in the management of hepatocellular carcinoma.

Globally, hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infection leads to liver fibrosis and cirrhosis, which in turn causes resultant hepatocellular carcinoma (HCC). Frequently, HCC recurs very soon even after a potentially curative treatment such as surgical interference or locoregional ablative therapies. Chronic HBV/HCV infection is often responsible for this recurrence, through secondary carcinogenesis. Antiviral therapy after a curative treatment of HCC plays an important role in preventing or delaying recurrence and improves survival in patients with HBV/HCV infection-related HCC. This article reviews the worldwide epidemiology of HBV/HCV infection, the association of viral infection with HCC, the mechanism of hepatitis virus-related hepatocarcinogenesis, and the paramount importance of antiviral therapy in the management of HCC.

Primary central nervous system burkitt lymphoma with non-immunoglobulin heavy chain translocation in right ventricle: case report.

Primary central nervous system Burkitt lymphoma (PCNSBL) is rare. Few cases of primary central nervous system involvement with sporadic Burkitt lymphoma have been reported and its treatment is now controversial. Here, the authors report a case of a 14-year-old boy suffering from non-immunoglobulin heavy chain (IgH) translocation PCNSBL. To the authors' knowledge, this is the second case report describing primary Burkitt lymphoma involving cerebral ventricles. After receiving combination treatment with surgery, stereotactic radiosurgery, and a chemotherapy regimen including high-dose methotrexate, the patient had a disease-free survival of 18 months.

Correlation between tumor perfusion and lipiodol deposition in hepatocellular carcinoma after transarterial chemoembolization.

PURPOSE: To study the correlation of tumor perfusion with lipiodol deposition in hepatocellular carcinoma (HCC) after transarterial chemoembolization with multidetector computed tomography (MDCT) perfusion imaging. MATERIALS AND METHODS: MDCT perfusion imaging was performed in 24 patients with HCC 1 to 7 days before chemoembolization. The computed tomography (CT) perfusion parameters, such as hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP), total liver perfusion (TLP), and hepatic arterial perfusion index (HAPI), were calculated with the slope method. The follow-up CT scans (noncontrast) were performed 4 weeks after chemoembolization to analyze lipiodol deposition. The lipiodol deposition in the tumor was classified into three grades and compared with CT perfusion parameters before chemoembolization. RESULTS: The HAP and TLP of tumors before chemoembolization were correlated with the grades of lipiodol deposition in tumors after chemoembolization (r = 0.768, P < .0001 and r = 0.616, P = .001, respectively). However, the HPP and HAPI of the tumors were not related to the grades of iodized oil deposition (r = 0.227, P = .286 and r = 0.111, P = .607, respectively). Higher HAP was correlated with better lipiodol deposition, and lower HAP was correlated with poorer lipiodol deposition. CONCLUSIONS: MDCT perfusion imaging has the potential to help select more appropriate patients with HCC for chemoembolization.

Development of novel 5-fluorouracil carrier erythrocyte with pharmacokinetics and potent antitumor activity in mice bearing malignant ascites.

BACKGROUND: To investigate pharmacokinetics and potency of antitumor activity of a novel 5-fluorouracil carrier erythrocyte (RBC-FU) in mice bearing malignant ascites. METHODS: RBC-FU was synthesized with a hyperosmotic technique. The entrapment efficiency of targeted carrier erythrocytes was determined by reverse dialysis method with high-performance liquid chromatography (HPLC) for analyzing the quantity of 5-fluorouracil (5-FU). After a H22 hepatocarcinoma malignant ascites model was established in Kunming mice, 5-FU encapsulated by carrier erythrocytes (for Group A) and 5-FU solution (for Group B) at 20 mg per kg were injected into the peritoneal cavity of the mice, respectively. Blood and ascites samples were collected at different times to detect 5-FU quantity by HPLC. Body weight and survival time of mice were recorded in Group A, B and the Control Group in which mice were injected with normal saline only. RESULTS: 5-FU was effectively encapsulated into erythrocytes, with an encapsulating effect as 55 +/- 0.50%. In Group A, the maximum concentration (Cmax) and the area under curve (AUC) in peritoneal exudates were significantly higher than those of Group B (P < 0.05). On the other hand, 5-FU level in serum was significantly lower than that in peritoneal exudates of Group A and B (P < 0.05). High drug levels in the abdominal cavity in Group A were maintained longer than those in Group B. Compared with that in Group B and the control, the quantity of malignant ascites in Group A had significant regression and the survival time was prolonged. CONCLUSION: The hyperosmotic method described here could be suitable for producing this novel RBC-FU as a liposomal drug of potential value for treating malignant ascites by intraperitoneal administration.

Anastomotic leakage with abscess after laparoscopic sleeve gastrectomy for obesity: report of a series and review of literature.

Anastomotic leakage with abscess is a rare but severe complication of bariatric surgery. However, there is currently a lack of attention regarding this complication. This study aimed to investigate the risk factors for this complication and relevant treatment strategies to call attention to this severe complication. We retrospectively reviewed the patients who were rehospitalized for anastomotic leakage with abscess after bariatric surgeries in West China Hospital of Sichuan University from November 2017 to November 2018. The clinical profiles analyzed included body mass index, body weight before and after surgery, postoperative hospital stay, diet prescriptions, treatment strategies, and outcomes. A total of six patients (two men and four women) were included. The mean baseline body mass index was 37.52 (29.84-43.37), and the mean weight was 104.95 kg (74.5-127.5). The chief complaints leading to rehospitalization were fever and dull abdominal pain. The average postoperative hospital stay was 3.3 (3-4) days, and the onset time ranged from 7 to 15 days. Finally, revision surgeries were performed in two of the six patients (33%), and they were all cured by percutaneous drainage-based treatments. The postoperative fever and abdominal pain were the signs of leakage and abscess. Similar patients should be followed up once a week for 3 weeks after bariatric surgery to facilitate the early recognition of this complication. A longer hospital stay and sufficient parenteral nutrition plus a later implementation of diet should be helpful to minimize this severe complication. Percutaneous drainage played a significant role in the treatment of these patients.

Expression of HIF-1alpha and VEGF in colorectal cancer: association with clinical outcomes and prognostic implications.

BACKGROUND: Hypoxia-inducible factor 1 alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) are frequently overexpressed in numerous types of cancers and are known to be important regulators of angiogenesis. Until now, few studies have been carried out to investigate the prognostic role of these factors in solid tumors, especially in colorectal cancer (CRC). The purpose of this study was to evaluate the expression of HIF-1alpha and VEGF in CRC tissues, and to analyze the association of these two factors with several clinical and pathological characteristics, and patients' survival. METHODS: Paraffin-embedded tissue samples were retrospectively collected from 71 CRC patients, who received surgical resection between 2001 and 2002, with a median follow-up of 5 years. We examined the patterns of expression of HIF-1alpha and VEGF by immunohistochemistry method. Statistical analysis was performed with univariate tests and multivariate Cox proportional hazards model to evaluate the differences. RESULTS: Expression of HIF-1alpha and VEGF was positively observed in 54.93% and 56.34% among the patients, respectively. HIF-1alpha and VEGF status were significantly associated with tumor stage, lymph nodes and liver metastases (P < 0.05). Expression of both HIF-1alpha and VEGF remained significantly associated with overall survival (OS) (P < 0.01), and HIF-1alpha was positively correlative to VEGF in CRC (r = 0.72, P < 0.001). CONCLUSIONS: HIF-1alpha and VEGF could be used as biomarkers indicating tumors in advanced stage and independently implied poor prognosis in patients with CRC. Treatment that inhibits HIF-1alpha might be a promising targeted approach in CRC to exhibit its potential to improve outcomes in future perspective, just as VEGF targeting has proved to be.

Anastomotic leakage with abscess: Neglected severe complication of bariatric surgery for obesity: A case report.

INTRODUCTION: Presently, bariatric surgery is a widespread treatment for obesity and its co-morbidities. Comprehensive evidence from outcomes of bariatric surgery supported that the surgery is safe and effective. However, we should be aware of the multiple risks of bariatric surgery, especially the severe infection at the operation site. CASE PRESENTATION: A 30-year-old woman was hospitalized for anastomotic leakage with abscess after laparoscopic sleeve gastrectomy. After 53 days of percutaneous drainage, absolute diet fasting, parenteral nutrition and culture based antibiotics etc., she was discharged for recovery. DISCUSSION: Theoretically, malabsorption and early diet will increase the risk of anastomotic leakage, but this problem is seldom to be mentioned in related articles. Moreover, it seems to be common that people received bariatric surgery had a relatively short post-operative stay. CONCLUSION: Essential nutritional support, longer post-operative hospital stay and strict follow-up are necessary to minimize this complication.

Arterial chemotherapy and conformal radiation abolish malignant biliary obstruction.

Malignant biliary obstruction has been a challenge to clinical practitioners, especially when it is serious and complete. Chemotherapy or radiation alone is often unsuccessful. In this study, the authors report a 59-year-old patient with complete common bile duct obstruction caused by cholangiocarcinoma who was treated with arterial chemotherapy followed by 3-dimensional conformal radiation, which resulted in a good clinical outcome.

Colonography by CT, MRI and PET/CT combined with conventional colonoscopy in colorectal cancer screening and staging.

Colorectal cancer (CRC) remains a leading cancer killer worldwide. But the disease is both curable and preventable at an early stage. Regular CRC cancer screening has been shown to reduce the risk of dying from CRC. However, the importance of large-scale screening is only now starting to be appreciated. This article reviews a variety of imaging procedures available for detecting ulcerative colitis (UC) and Crohn's disease (CD), polyps and CRC in their early stage and also presents details on various screening options. Detecting, staging and re-staging of patients with CRC also require multimodality, multistep imaging approaches. Staging and re-staging with conventional colonoscopy (CC), computer tomography colonography (CTC), magnetic resonance colonography (MRC) and positron emission tomography/computer tomography colonography (PET/CTC) are of paramount importance in determining the most appropriate therapeutic method and in predicting the risk of tumor recurrence and overall prognosis. The advantages and limitations of these modalities are also discussed.

Highly metabolic thrombus of the portal vein: 18F fluorodeoxyglucose positron emission tomography/computer tomography demonstration and clinical significance in hepatocellular carcinoma.

AIM: To assess the ability of (18)F-fluorodeoxyglucose positron emission tomography/computer tomography ((18)F-FDG PET/CT) to differentiate between benign and malignant portal vein thrombosis in hepatocellular carcinoma (HCC) patients. METHODS: Five consecutive patients who had HBV cirrhosis, biopsy-proven HCC, and thrombosis of the main portal vein and/or left/right portal vein on ultrasound (US), computer tomography (CT) or magnetic resonance imaging (MRI) were studied with (18)F-FDG PET/CT. The presence or absence of a highly metabolic thrombus on (18)F-FDG PET/CT was considered diagnostic for malignant or benign portal vein thrombosis, respectively. All patients were followed-up monthly with US, CT or MRI. Shrinkage of the thrombus or recanalization of the vessels on US, CT or MRI during follow-up was considered to be definitive evidence of the benign nature of the thrombosis, whereas enlargement of the thrombus, disruption of the vessel wall, and parenchymal infiltration over follow-up were considered to be consistent with malignancy. (18)F-FDG PET/CT, and US, CT or MRI results were compared. RESULTS: Follow-up (1 to 10 mo) showed signs of malignant thrombosis in 4 of the 5 patients. US, CT or MRI produced a true-positive result for malignancy in 4 of the patients, and a false-positive result in 1. (18)F-FDG PET/CT showed a highly metabolic thrombus in 4 of the 5 patients. (18)F-FDG PET/CT achieved a true-positive result in all 4 of these patients, and a true-negative result in the other patient. No false-positive result was observed using (18)F-FDG PET/CT. CONCLUSION: (18)F-FDG PET/CT may be helpful in discriminating between benign and malignant portal vein thrombi. Patients may benefit from (18)F-FDG PET/CT when portal vein thrombi can not be diagnosed exactly by US, CT or MRI.

Clinical role of 18F-fluorodeoxyglucose positron emission tomography/computed tomography in post-operative follow up of gastric cancer: initial results.

AIM: To evaluate the clinical role of (18)F-fluorodeoxyglucose positron emission and computed tomography ((18)F-FDG PET/CT) in detection of gastric cancer recurrence after initial surgical resection. METHODS: In the period from January 2007 to May 2008, 23 patients who had previous surgical resection of histopathologically diagnosed gastric cancer underwent a total of 25 (18)F-FDG PET/CT scans as follow-up visits in our center. The standard of reference for tumor recurrence consisted of histopathologic confirmation or clinical follow-up information for at least 5 mo after PET/CT examinations. RESULTS: PET/CT was positive in 14 patients (61%) and negative in 9 (39%). When correlated with final diagnosis, which was confirmed by histopathologic evidence of tumor recurrence in 8 of the 23 patients (35%) and by clinical follow-up in 15 (65%), PET/CT was true positive in 12 patients, false positive in 2, true negative in 8 and false negative in 2. Overall, the accuracy of PET/CT was 82.6%, the negative predictive value (NPV) was 77.7%, and the positive predictive value (PPV) was 85.7%. The 2 false positive PET/CT findings were actually chronic inflammatory tissue lesions. For the two patients with false negative PET/CT, the final diagnosis was recurrence of mucinous adenocarcinoma in the anastomosis in one patient and abdominal wall metastasis in the other. Importantly, PET/CT revealed true-positive findings in 11 (47.8%) patients who had negative or no definite findings by CT. PET/CT revealed extra-abdominal metastases in 7 patients and additional esophageal carcinoma in one patient. Clinical treatment decisions were changed in 7 (30.4%) patients after introducing PET/CT into their conventional post-operative follow-up program. CONCLUSION: Whole body (18)F-FDG PET/CT was highly effective in discriminating true recurrence in post-operative patients with gastric cancer and had important impacts on clinical decisions in a considerable portion of patients.

Achievable complete remission of advanced non-small-cell lung cancer: Case report and review of the literature.

Surgery is the first choice of treatment for patients with non-small-cell lung cancer (NSCLC), but few patients can be treated surgically because of either advanced disease or poor pulmonary function. Other therapies include radiotherapy and chemotherapy, as well as complementary and alternative therapies, usually with disappointing results. Bronchial artery infusion (BAI) is a manageable and effective method for treating advanced NSCLC. Outcome is good by BAI due to its repeatability and low toxicity. Icotinib hydrochloride is a newly developed and highly specific epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor and has been safely and efficiently used to treat advanced NSCLC. We herein report a 73-year-old patient with chronic cough, who was diagnosed with advanced NSCLC with the EGFR mutation of L858R substitution in exon 21, and treated with the combination of oral icotinib and BAI chemotherapy as the first-line therapy, which resulted in a satisfactory clinical outcome. Complete remission of advanced NSCLC can be achieved using the combination of oral icotinib and BAI chemotherapy.

Positron emission tomography/computer tomography: challenge to conventional imaging modalities in evaluating primary and metastatic liver malignancies.

Computer tomography (CT) and magnetic resonance imaging (MRI), as conventional imaging modalities, are the preferred methodology for tumor, nodal and systemic metastasis (TNM) staging. However, all the noninvasive techniques in current use are not sufficiently able to identify primary tumors and even unable to define the extent of metastatic spread. In addition, relying exclusively on macromorphological characteristics to make a conclusion runs the risk of misdiagnosis due mainly to the intrinsic limitations of the imaging modalities themselves. Solely based on the macromorphological characteristics of cancer, one cannot give an appropriate assessment of the biological characteristics of tumors. Currently, positron emission tomography/computer tomography (PET/CT) are more and more widely available and their application with (18)F-fluorodeoxyglucose ((18)F-FDG) in oncology has become one of the standard imaging modalities in diagnosing and staging of tumors, and monitoring the therapeutic efficacy in hepatic malignancies. Recently, investigators have measured glucose utilization in liver tumors using (18)F-FDG, PET and PET/CT in order to establish diagnosis of tumors, assess their biologic characteristics and predict therapeutic effects on hepatic malignancies. PET/CT with (18)F-FDG as a radiotracer may further enhance the hepatic malignancy diagnostic algorithm by accurate diagnosis, staging, restaging and evaluating its biological characteristics, which can benefit the patients suffering from hepatic metastases, hepatocellular carcinoma and cholangiocarcinoma.

A rare case of pregnancy complicated by mesenteric mass: what does chylous ascites tell us?

Mesenteric fibromatosis is a rare benign nonmetastatic neoplasm that appears as a sporadic lesion or occurs in patients with familial polyposis, while chylous ascites associated with aggressive mesenteric fibromatosis during pregnancy has never been reported thus far. Here we present the case of a 28-year old pregnant woman, in whom an aggressive mesenteric fibromatosis with chylous ascites was detected, involving the jejunum, superior mesenteric artery (SMA) and superior mesenteric vein (SMV) and pancreas. One year after a successful surgical excision, the patient had no signs of recurrence. The authors report the case for its rarity and emphasize on combining clinicopathological, radiological and immunohistochemistry analysis for management of the disease.

p53 gene in treatment of hepatic carcinoma: status quo.

Hepatocellular carcinoma (HCC) is one of the 10 most common cancers worldwide. There is no ideal treatment for HCC yet and many researchers are trying to improve the effects of treatment by changing therapeutic strategies. As the majority of human cancers seem to exhibit either abnormal p53 gene or disrupted p53 gene activation pathways, intervention to restore wild-type p53 (wt-p53) activities is an attractive anti-cancer therapy including HCC. Abnormalities of p53 are also considered a predisposition factor for hepatocarcinogenesis. p53 is frequently mutated in HCC. Most HCCs have defects in the p53-mediated apoptotic pathway although they carry wt-p53. High expression of p53 in vivo may exert therapeutic effects on HCC in two aspects: (1) High expression of exogenous p53 protein induces apoptosis of tumor cells by inhibiting proliferation of cells through several biologic pathways and (2) Exogenous p53 renders HCC more sensitive to some chemotherapeutic agents. Several approaches have been designed for the treatment of HCC via the p53 pathway by restoring the tumor suppression function from inactivation, rescuing the mutated p53 gene from instability, or delivering therapeutic exogenous p53. Products with p53 status as the target have been studied extensively in vitro and in vivo. This review elaborates some therapeutic mechanisms and advances in using recombinant human adenovirus p53 and oncolytic virus products for the treatment of HCC.

Positron emission tomography/computed tomography with (18)F-fluorodeoxyglucose identifies tumor growth or thrombosis in the portal vein with hepatocellular carcinoma.

Patients suffering from hepatocellular carcinoma (HCC) with tumor thrombus in the portal vein generally have a poor prognosis. Portal vein tumor thrombus must be distinguished from portal vein blood thrombus, and this identification plays a very important role in management of HCC. Conventional imaging modalities have limitations in discrimination of portal vein tumor thrombus. The application of positron emission tomography (PET) with (18)F-fluorodeoxyglucose ((18)F-FDG) for discrimination between tumor extension and blood thrombus has been reported in few cases of HCC, while portal tumor thrombosis and portal vein clot identified by (18)F-FDG PET/CT in HCC patients has not been reported so far. We present two HCC cases, one with portal vein tumor thrombus and one thrombosis who were identified with (18)F-FDG PET/CT. This report illustrates the complimentary value of combining the morphological and functional imaging in achieving a correct diagnosis in such clinical situations.

Epidermal growth factor receptor antibody plus recombinant human endostatin in treatment of hepatic metastases after remnant gastric cancer resection.

We report a 55-year-old male who developed advanced hepatic metastasis and peritoneal carcinomatosis after resection of remnant gastric cancer resection 3 mo ago. The patient only received epidermal growth factor (EGF) receptor antibody (Cetuximab) plus recombinant human endostatin (Endostar). Anti-tumor activity was assessed by (18)F-fluorodeoxyglucose ((18)F-FDG) positron emission tomography/computer tomography (PET/CT) at baseline and then every 4 wk. The case illustrates that (18)FDG-PET/CT could make an early prediction of the response to Cetuximab plus Endostar in such clinical situations. (18)FDG-PET/CT is a useful molecular imaging modality to evaluate the biological response advanced hepatic metastasis and peritoneal carcinomatosis to Cetuximab plus Endostar in patients after remnant gastric cancer resection.

Positron emission tomography/computer tomography in guidance of extrahepatic hepatocellular carcinoma metastasis management.

Hepatocellular carcinoma (HCC) is one of the most common primary cancers in the world. Surgery is the gold standard for treatment of patients with HCC. Recurrence and metastasis are the major obstacles to further improve the prognosis of HCC. Most recurrences are intrahepatic. However, 30% of the recurrences are extrahepatic. The role of resection in intrahepatic recurrences is widely accepted. The role of resection in extrahepatic HCC recurrence and metastasis is not well established. 18F fluorodeoxyglucose (18F-FDG) positron emission tomography/computer tomography (PET/CT) is useful in detecting distant metastasis from a variety of malignancies and shows superior accuracy to conventional imaging modalities in identification of intrahepatic and extrahepatic metastasis. We present one patient with one new isolated omental lymph node metastasis, who had a history of huge HCC resected six years ago. The metastatic focus was identified with 18 F-FDG PET/CT and resected. The follow-up revealed good prognosis with a long-term survival potential after resection of the omental lymphatic metastasis.