Prognostic value of pre-treatment F-18-FDG PET-CT in patients with hepatocellular carcinoma undergoing radioembolization

AIM To evaluate the value of pre-treatment 18F-FDG PET/CT in patients with HCC following liver radioembolization.METHODS We identified 34 patients with HCC who underwent an FDG PET/CT scan prior to hepatic radioembolization at our institution between 2009 and 2013. Patients wereseen in clinic one month after radioembolization and then at 2-3 mo intervals. We assessed the influence of FDG tumor uptake on outcomes including local liver control(LLC), distant liver control(DLC), time to distant metastases(DM), progression free survival(PFS) and overall survival(OS).RESULTS The majority of patients were males(n = 25, 74%), and had Child Pugh Class A(n = 31, 91%), with a median age of 68 years(46-84 years). FDG-avid disease was found in 19(56%) patients with SUVmax ranging from 3 to 20. Female patients were more likely to have an FDG-avid HCC(P = 0.02). Median follow up of patients following radioembolization was 12 months(1.2-62.8 mo). FDG-avid disease was associated with a decreased 1 year LLC, DLC, DM and PFS(P 0.05). Using multivariate analysis, FDG avidity predicted for LLC, DLC, and PFS(all P 0.05).CONCLUSION In this retrospective study, pre-treatment HCC FDGavidity was found to be associated with worse LLC, DLC, and PFS following radioembolization. Larger studies are needed to validate our initial findings to assess the role of F-18-FDG PET/CT scans as biomarker for patients with HCC following radioembolization.     

Toward early detection of <Emphasis Type="Italic">Helicobacter pylori</Emphasis>-associated gastric cancer

Background

Gastric cancer is typically diagnosed at a late stage, leading to poor prognoses. Helicobacter pylori is responsible for 70% of gastric cancers globally, and patients with this bacterial infection often present with early stages of the carcinogenic pathway such as inflammation or gastritis. Although many patients continue to progress to advanced-stage disease after antibacterial treatment, there are no follow-up screening protocols for patients with a history of H. pylori.

Methods

Several biomarkers (Lgr5, CD133, CD44) become upregulated during gastric carcinogenesis. A logistic regression model is developed using clinical data from 59 patients at different stages of the carcinogenic pathway to identify the likelihood of being at an advanced stage of disease for all combinations of age, sex, and marker positivity. Using these likelihood distributions and the observed rate of marker positivity increase, time to high likelihood (probability >0.8) of advanced disease for individual patients is predicted.

Results

A strong correlation between marker positivity and disease stage was found for all three markers. Disease stage was accurately classified by the respective regression models for more than 86% of retrospective patients. Highly patient-specific predictions of time to onset of dysplasia were made, allowing the classification of 17 patients initially diagnosed with intestinal metaplasia into high-, intermediate-, or low-risk categories.

Conclusions

We present an approach designed to integrate pathology, mathematics, and statistics for detection of the earliest precancerous, treatable lesion. Given the simplicity and robustness of the framework, such technique has the potential to guide personalized screening schedules to minimize the risk of undetected malignant transformation.

     

Pancreatic Adenocarcinoma, version 2.2012: featured updates to the NCCN Guidelines

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Pancreatic Adenocarcinoma discuss the workup and management of tumors of the exocrine pancreas. These NCCN Guidelines Insights provide a summary and explanation of major changes to the 2012 NCCN Guidelines for Pancreatic Adenocarcinoma. The panel made 3 significant updates to the guidelines: 1) more detail was added regarding multiphase CT techniques for diagnosis and staging of pancreatic cancer, and pancreas protocol MRI was added as an emerging alternative to CT; 2) the use of a fluoropyrimidine plus oxaliplatin (e.g., 5-FU/leucovorin/oxaliplatin or capecitabine/oxaliplatin) was added as an acceptable chemotherapy combination for patients with advanced or metastatic disease and good performance status as a category 2B recommendation; and 3) the panel developed new recommendations concerning surgical technique and pathologic analysis and reporting.     

Activation of the serine/threonine protein kinase AKT during the progression of colorectal neoplasia

BACKGROUND: AKT has been identified as a major regulator of cell proliferation, tumorigenesis, and apoptosis. In this study, we evaluated changes in the activity of AKT during colorectal cancer (CRC) progression. MATERIALS AND METHODS: We used stage-oriented human CRC tissue microarrays, including 99 invasive carcinomas, 28 tubular adenomas, and 18 samples of normal colonic mucosa. The tissue array slides were stained with a mouse monoclonal antiphospho-AKT antibody using the avidin-biotin complex method. RESULTS: Activation of AKT was detected mostly in the invasive carcinomas. Sixty-three percent of carcinomas demonstrated strong to moderate AKT activity. Seven percent of carcinomas were phospho-AKT (p-AKT) negative, and 30% (30 of 99) were p-AKT weakly positive. Conversely, 78% of normal colonic mucosas were p-AKT negative, and only 4 samples stained weakly for p-AKT. Eighty-two percent of adenomas were weakly positive for p-AKT, 1 was p-AKT negative, and none exhibited strong or moderate p-AKT stain. At a significance level of .05, we found that the distribution of p-AKT stain scores for cancer was shifted to the right of adenoma (P < .0001) and normal (P < .0001) and for adenoma was shifted to the right of normal (P < .0001). AKT activation did not correlate with tumor stage (P = .28), lymph node metastasis (P = .45), lymphatic invasion (P = .46), or distant metastasis (P = .34). CONCLUSION: This study shows increasing activation of AKT during CRC progression. This finding suggests a role of p-AKT in colorectal carcinogenesis and provides a rationale for using p-AKT inhibitor API-2/triciribine, which is currently under clinical investigation for the treatment of CRC.     

Vitamin E succinate suppresses prostate tumor growth by inducing apoptosis

Prostate cancer is a major cause of cancer death and morbidity in western countries. However, because of its intrinsic nature of chemoresistance, there is only limited systemic therapy available for the patients. Vitamin E (VE) has been under intensive study as a chemopreventive agent for various types of cancers. Preclinical studies suggest that vitamin E succinate (VES) is the most effective antitumor analogue of VE, yet there are scarce studies of VES in prostate cancer. In this study, we investigated the effects of VES on a panel of prostate cancer cells, and a xenograft model of prostate cancer. Our results indicate that VES significantly inhibited proliferation and induced apoptosis of prostate cancer cell lines in a dose and time dependent manner. The results of microarray analysis followed by real-time RT-PCR and inhibitor analyses indicated that the VES-induced apoptosis is mediated by caspase-4 in prostate tumor cells. In our animal model of prostate cancer in SCID mouse, daily injection of VES significantly suppressed tumor growth as well as lung metastases. These results suggest a potential therapeutic utility of VES for patients with prostate cancer.     

Periareolar injection for localization of sentinel nodes in breast cancer patients

The goal of this study was to evaluate the periareolar injection of technetium 99m sulfur colloid to identify axillary sentinel nodes and compare the number of sentinel lymph nodes identified with preoperative lymphoscintigraphy to intraoperative biopsy using a handheld gamma probe. A total of 104 consecutive patients diagnosed with invasive breast cancer participated in this prospective study, with 81 patients receiving an intradermal periareolar injection and 23 patients receiving an intradermal peritumoral injection of filtered technetium 99m sulfur colloid. Preoperative lymphoscintigraphy was performed for sentinel node mapping and localization. In addition to selective sentinel node biopsy, axillary dissection was performed on all patients to determine false-negative rates. Routine histologic staining was performed on all identified nodes, along with immunohistochemical staining of sentinel nodes negative on initial routine staining. With an intradermal periareolar injection, the sentinel node identification rate was 91.4% (74/81), axillary metastatic rate 35.1% (26/74), sentinel node positive only 61.5% (16/26), and false negative 3.8% (1/26). With an intradermal peritumoral injection, the sentinel node identification rate was 91.3% (21/23), axillary metastatic rate 42.9% (9/21), sentinel node positive only 88.9% (8/9), and false negative 0% (0/9). A total of 241 sentinel nodes were identified with biplanar lymphoscintigraphy and 173 sentinel nodes were harvested during surgery, yielding a 28.2% increase in sentinel nodes identified with lymphoscintigraphy. This study demonstrates that intradermal periareolar injection of filtered technetium 99m sulfur colloid is successful in identifying axillary sentinel nodes with a low false-negative rate. Preoperative lymphoscintigraphy aids in the identification and surgical planning of sentinel node biopsy and provides an objective measure of surgical performance.     

MnSOD expression is increased in metastatic gastric cancer

BACKGROUND: Manganese superoxide dismutase (MnSOD) catalyzes the scavenging of superoxide radicals in order to protect cells from the damage caused by reactive oxygen species. Previous studies implicate MnSOD in cancer progression, but its role in gastric cancer metastasis is poorly understood. MATERIALS AND METHODS: To determine whether MnSOD expression correlates with gastric cancer metastasis, we compared immunostaining for MnSOD in the primary tumors of gastric cancer patients with (n = 15) and without (n = 9) nodal metastases. These patients were matched for risk factors associated with gastric cancer metastasis, such as tumor site, depth, and grade. MnSOD expression was scored positive (increased) if MnSOD staining of tumor cells was more intense than MnSOD staining in corresponding normal gastric epithelial cells. Statistical analyses were via chi(2) test and Fisher's exact test. RESULTS: MnSOD expression was increased in 14 of the 15 (93%) metastatic tumors, compared to only 4 of the 9 (44%) nonmetastatic tumors (P = 0.015). There was no significant difference in staining when the two groups were compared based on tumor grade (P = 0.70) or depth of tumor cell invasion (T stage) (P = 0.22). CONCLUSIONS: MnSOD expression is upregulated in the primary tumors of gastric cancer patients with lymph node metastases. This finding supports an involvement of MnSOD and possibly the reactive oxygen status of the gastric tumor microenvironment in gastric cancer metastasis.