Non-cancer Lesions Research Articles

Computer-aided diagnostic system with automated deep learning method based on the AutoGluon framework improved the diagnostic accuracy of early esophageal cancer.

There have been studies on the application of computer-aided diagnosis (CAD) in the endoscopic diagnosis of early esophageal cancer (EEC), but there is still a significant gap from clinical application. We developed an endoscopic CAD system for EEC based on the AutoGluon framework, aiming to explore the feasibility of automatic deep learning (DL) in clinical application. The endoscopic pictures of normal esophagus, esophagitis, and EEC were collected from The First Affiliated Hospital of Soochow University (September 2015 to December 2021) and the Norwegian HyperKvasir database. All images of non-cancerous esophageal lesions and EEC in this study were pathologically examined. There were three tasks: task A was normal vs. lesion classification under non-magnifying endoscopy (n=932 vs. 1,092); task B was non-cancer lesion vs. EEC classification under non-magnifying endoscopy (n=594 vs. 429); and task C was non-cancer lesion vs. EEC classification under magnifying endoscopy (n=505 vs. 824). In all classification tasks, we took 100 pictures as the verification set, and the rest comprised as the training set. The CAD system was established based on the AutoGluon framework. Diagnostic performance of the model was compared with that of endoscopists grouped according to years of experience (senior >15 years; junior <5 years). Model evaluation indicators included accuracy, recall rate, precision, F1 value, interpretation time, and the area under the receiver operating characteristic (ROC) curve (AUC). In tasks A and B, the accuracies of medium-performance CAD and high-performance CAD were lower than those of junior doctors and senior doctors. In task C, the medium-performance and high-performance CAD accuracies were close to those of junior doctors and senior doctors. The high-performance CAD model outperformed the junior doctors in both task A (0.850 vs. 0.830) and task C (0.840 vs. 0.830) in sensitivity comparison, but there was still a large gap between high-performance CAD models and doctors in sensitivity comparison. In task A, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.880 to 0.915 and from 0.920 to 0.945, respectively); the time spent on film reading was significantly shortened (junior: from 11.3 to 8.7 s; senior: from 6.7 to 5.5 s). In task C, with the aid of CAD pre-interpretation, the accuracy of junior and senior physicians were significantly improved (from 0.850 to 0.865 and from 0.915 to 0.935, respectively); the reading time was significantly shortened (junior: from 9.5 to 7.7 s; senior: from 5.6 to 3.0 s). The CAD system based on the AutoGluon framework can assist doctors to improve the diagnostic accuracy and reading time of EEC under endoscopy. This study reveals that automatic DL methods are promising in clinical application.

Quantitative Analysis of Prostate MRI: Correlation between Contrast-Enhanced Magnetic Resonance Fingerprinting and Dynamic Contrast-Enhanced MRI Parameters.

This research aimed to assess the relationship between contrast-enhanced (CE) magnetic resonance fingerprinting (MRF) values and dynamic contrast-enhanced (DCE) MRI parameters including (Ktrans, Kep, Ve, and iAUC). To evaluate the correlation between the MRF-derived values (T1 and T2 values, CE T1 and T2 values, T1 and T2 change) and DCE-MRI parameters and the differences in the parameters between prostate cancer and noncancer lesions in 68 patients, two radiologists independently drew regions-of-interest (ROIs) at the focal prostate lesions. Prostate cancer was identified in 75% (51/68) of patients. The CE T2 value was significantly lower in prostate cancer than in noncancer lesions in the peripheral zone and transition zone. Ktrans, Kep, and iAUC were significantly higher in prostate cancer than noncancer lesions in the peripheral zone (p < 0.05), but not in the transition zone. The CE T1 value was significantly correlated with Ktrans, Ve, and iAUC in prostate cancer, and the CE T2 value was correlated to Ve in noncancer. Some CE MRF values are different between prostate cancer and noncancer tissues and correlate with DCE-MRI parameters. Prostate cancer and noncancer tissues may have different characteristics regarding contrast enhancement.

Evolutionary histories of breast cancer and related clones

Recent studies have documented frequent evolution of clones carrying common cancer mutations in apparently normal tissues, which are implicated in cancer development1–3. However, our knowledge is still missing with regard to what additional driver events take place in what order, before one or more of these clones in normal tissues ultimately evolve to cancer. Here, using phylogenetic analyses of multiple microdissected samples from both cancer and non-cancer lesions, we show unique evolutionary histories of breast cancers harbouring der(1;16), a common driver alteration found in roughly 20% of breast cancers. The approximate timing of early evolutionary events was estimated from the mutation rate measured in normal epithelial cells. In der(1;16)(+) cancers, the derivative chromosome was acquired from early puberty to late adolescence, followed by the emergence of a common ancestor by the patient’s early 30s, from which both cancer and non-cancer clones evolved. Replacing the pre-existing mammary epithelium in the following years, these clones occupied a large area within the premenopausal breast tissues by the time of cancer diagnosis. Evolution of multiple independent cancer founders from the non-cancer ancestors was common, contributing to intratumour heterogeneity. The number of driver events did not correlate with histology, suggesting the role of local microenvironments and/or epigenetic driver events. A similar evolutionary pattern was also observed in another case evolving from an AKT1-mutated founder. Taken together, our findings provide new insight into how breast cancer evolves.

Eosinophilic peritonitis with colon cancer: a case report

BackgroundEosinophilic gastrointestinal disorders (EGIDs) are a rare group of inflammatory disorders that can occur anywhere along the gastrointestinal tract, from the esophagus to the rectum. In particular, those with malignant or benign tumors are extremely rare.Case presentationA 62-year-old man was referred to our hospital with a chief complaint of abdominal fullness. The peripheral white blood cell count was 19,400/µL, and the eosinophil count was 13,300/µL. Abdominal computed tomography showed massive ascites. Cytology of the ascitic fluid showed a large amount of eosinophils and no malignancy. Upper and lower gastrointestinal endoscopies were performed on the suspicion of EGIDs, and colon cancer with no other abnormalities was found. The biopsies of the cancer lesions and non-cancer lesions also showed significant differences in eosinophil counts per high-power field (HPF) between the cancer and non-cancer lesions (median 77.5 [IQR 52–115] vs. 40.5 [35–56]/HPF, P < 0.05). Exploratory laparoscopy showed cloudy massive ascites and thickening of the mesentery. Pathological examination of the mesentery showed a large amount of eosinophils (median 177.5 [IQR 91–227]/HPF) and no malignancy. Based on these findings, it was suspected that the massive ascites due to eosinophilic peritonitis could be associated with colon cancer. Steroid administration resulted in immediate disappearance of the ascites, and laparoscopic left hemicolectomy was safely performed 6 weeks after steroid administration.ConclusionThis report presented a case of eosinophilic peritonitis that could be related to colon cancer. Exploratory laparoscopy was useful to detect the cause of ascites. The possibility that eosinophilic peritonitis was associated with colon cancer is discussed based on the histopathological findings.

Nuclear staining of claudin-18 is a new immunohistochemical marker for diagnosing intramucosal well-differentiated gastric adenocarcinoma.

Diagnosis of gastric adenocarcinoma using small biopsy samples is occasionally difficult. Various markers have been employed for improving the diagnostic accuracy, but there remains room for improvement. A total of 129 endoscopically biopsied samples were studied, consisting of 104 intramucosal tubular adenocarcinomas, 24 non-cancerous lesions and one cancer sample originally suspected of non-cancer but revised as cancer after immunostaining. We evaluated the association between histopathology and immunohistochemical expression of MUC1, HER2, p53, CEA, E-cadherin, β-catenin and claudin-18. Regarding β-catenin and claudin-18, not only membranous expression (β-catenin(M) and claudin-18(M)) but also nuclear expression (β-catenin(N) and claudin-18(N)) were analyzed. When subtyped with mucin core protein expression, the gastric-type cancers dominantly expressed claudin-18(M), while claudin-18(N) was significantly encountered in intestinal- and mixed-types. Expression of MUC1 (P = 0.0010), HER2 (P = 0.0173), p53 (P = 0.0002), CEA (P = 0.0019) and claudin-18(N) (P < 0.0001) revealed significant correlation with gastric cancers. Negative correlation of claudin-18(M) (P = 0.0125) was also noted. MUC1 and p53 were negative in non-cancer lesions. The non-cancer group exceptionally expressed HER2 and β-catenin(N). Membranous expression of E-cadherin was consistent in both groups. Logistic regression analysis showed that MUC1 (P = 0.0086), p53 (P = 0.0031), claudin-18(M) (P = 0.0158) and claudin-18(N) (P = 0.0190) were independently associated with gastric cancers. Nuclear expression of claudin-18 should be the novel diagnostic marker for gastric cancer.

Liver Cancer Detection Using Hybridized Fully Convolutional Neural Network Based on Deep Learning Framework

Liver cancer is one of the world’s largest causes of death to humans. It is a difficult task and time consuming to identify the cancer tissue manually in the present scenario. The segmentation of liver lesions in CT images can be used to assess the tumor load, plan treatments predict, and monitor the clinical response. In this paper, the Hybridized Fully Convolutional Neural Network (HFCNN) has been proposed for liver tumor segmentation, which has been modeled mathematically to resolve the current issue of liver cancer. For semantic segmentation, HFCNN has been used as a powerful tool for liver cancer analysis. Whereas the CT-based lesion-type definition defines the diagnosis and therapeutic strategy, the distinction between cancer and non-cancer lesions is crucial. It demands highly qualified experience, expertise, and resources. However, a deep end-to-end learning approach to help discrimination in abdominal CT images of the liver between liver metastases of colorectal cancer and benign cysts has been analyzed. Our method includes the successful extraction of features from Inception combined with residual and pre-trained weights. Feature maps have been consistent with the original image voxel features, and The importance of features seemed to represent the most relevant imaging criteria for every class. This deep learning system shows the concept of illumination portions of the decision-making process of a pre-trained deep neural network, through an analysis of inner layers and the description of features that lead to predictions.

Molecular Mechanism of Uptake of Cationic Photoantimicrobial Phthalocyanine across Bacterial Membranes Revealed by Molecular Dynamics Simulations.

Phthalocyanines are aromatic macrocyclic compounds, which are structurally related to porphyrins. In clinical practice, phthalocyanines are used in fluorescence imaging and photodynamic therapy of cancer and noncancer lesions. Certain forms of the substituted polycationic metallophthalocyanines have been previously shown to be active in photodynamic inactivation of both Gram-negative and Gram-positive bacteria; one of them is zinc octakis(cholinyl)phthalocyanine (ZnPcChol8+). However, the molecular details of how these compounds translocate across bacterial membranes still remain unclear. In the present work, we have developed a coarse-grained (CG) molecular model of ZnPcChol8+ within the framework of the popular MARTINI CG force field. The obtained model was used to probe the solvation behavior of phthalocyanine molecules, which agreed with experimental results. Subsequently, it was used to investigate the molecular details of interactions between phthalocyanines and membranes of various compositions. The results demonstrate that ZnPcChol8+ has high affinity to both the inner and the outer model membranes of Gram-negative bacteria, although this species does not show noticeable affinity to the 1-palmitoyl-2-oleoyl- sn-glycero-3-phosphatidylcholine membrane. Furthermore, we found out that the process of ZnPcChol8+ penetration toward the center of the outer bacterial membrane is energetically favorable and leads to its overall disturbance and formation of the aqueous pore. Such intramembrane localization of ZnPcChol8+ suggests their twofold cytotoxic effect on bacterial cells: (1) via induction of lipid peroxidation by enhanced production of reactive oxygen species (i.e., photodynamic toxicity); (2) via rendering the bacterial membrane more permeable for additional Pc molecules as well as other compounds. We also found that the kinetics of penetration depends on the presence of phospholipid defects in the lipopolysaccharide leaflet of the outer membrane and the type of counterions, which stabilize it. Thus, the results of our simulations provide a detailed molecular view of ZnPcChol8+ "self-promoted uptake", the pathway previously proposed for some small molecules crossing the outer bacterial membrane.

P-126 - Impact of TGF-b and CD-44 for the benefit of radical surgery in elderly patients with adenocarcinoma of gastric cardia

Introduction: Adenocarcinoma near the esophagogastric junction is one of the most lethal GI malignancies known. Surgical treatment of these cancers stay determinative factors of patient survival. Older persons often differ from the younger adult population in terms of biological and functional perspectives; as such, they may have particular needs which require an interdisciplinary approach and intervention, especially when faced with a cancer diagnosis. The aim of this study was to detected expression of TGF-ß and CD-44 in age specific subgroup. Methods: The expressions of TGF-ß and CD-44 were evaluated immunohistochemically in 23 patients with adenocarcinoma of gastric cardia who underwent curative surgery (R0) without any neo/adjuvant therapy. Additionally we analyzed control group of patients with non-cancer lesion or normal tissue of upper digestive tract (13 patients). We divided the patients into two groups. Group A consisted of 13 cancer patients and 7 control patients 65 years of age or older, while Group B consisted of 10 cancer and 6 control patients younger than 65 years of age. The two groups were comparable - there were no differences between the two groups regarding tumor stage. Results: Elderly patients have statistically significant better survival (median 20,2 month) compared with younger patients (median 15,4 month) (p = 0.045). The median survival rate of patients without TGF-ß and/or CD-44 expression was significantly lower (7m) than that of patients with positive expression (>15m) (p = 0.003). Regardless of patients age, CD-44 was significantly higher in the cancer tissue of elderly patients than in younger (p < 0,035). But no significant difference was observed in the TGF-ß expression between group A and group B cancers tissue (p = 0.005). Conclusion: The biology of tumors may be different in elderly patients, leading to a lower rate of tumor-related mortality.

Human papillomavirus vaccine efficacy in the prevention of anogenital warts: systematic review and meta-analysis.

To review evidence on the efficacy of HPV vaccines in the prevention of non-cancer lesions (anogenital warts [AGW], recurrent laryngeal papillomatosis and oral papillomatosis). We conducted a systematic review of randomized trials. We performed random effect models and effects were reported as relative risks (RR) and their confidence intervals (95%CI) following both intention to treat (ITT) and per protocol (PP) analyses. We included six studies (n=27 078). One study was rated as high risk of bias. One study could not be included in the meta-analysis because it provided combined results. We found that quadrivalent vaccine reduced the risk of AGW by 62% (RR: 0.38, 95%CI:0.32-0.45, I2:0%) in the ITT analysis and by 95% (RR: 0.05, 95%CI:0.01-0.25, I2:66%) in the PP analysis. Subgroup analyses of studies in women or with low-risk of bias provided similar results. HPV quadrivalent vaccine is efficacious in preventing AGW in men and women.

Efficacy of HPV Vaccines against Non-Cancer Lesions: Systematic Review and Meta-Analysis.

Efficacy of HPV Vaccines against Non-Cancer Lesions: Systematic Review and Meta-Analysis.

English

English

Association of positive fluid balance and cardiovascular complications after thoracotomy for noncancer lesions.

ObjectiveThe purpose of this study was to explore the influence of positive fluid balance on cardiovascular complications after thoracotomy for noncancer lesions.MethodsAfter approval from an institutional review board, a retrospective cohort study was conducted. All consecutive patients undergoing thoracotomy between January 1, 2005 and December 31, 2011 in a single medical center were recruited. The primary outcome of the study was the incidence of cardiovascular complications, which were defined as cardiac arrhythmia, cardiac arrest, heart failure, myocardial ischemia, and pulmonary embolism. Univariable and multivariable risk regression analyses were used to evaluate the association between positive fluid balance and cardiovascular complications.ResultsA total of 720 patients were included in this study. The incidence of cardiovascular complications after thoracotomy for noncancer lesions was 6.7% (48 of 720). Patients with positive fluid balance >2,000 mL had a significantly higher incidence of cardiovascular complications than those with positive fluid balance ≤2,000 mL (22.2% versus 7.0%, P=0.005). Cardiac arrhythmias were the most common complication. Univariable risk regression showed that positive fluid balance >2,000 mL was a significant risk factor (risk ratio =3.15, 95% confident interval [CI] =1.44–6.90, P-value =0.004). After adjustment for all potential confounding variables during multivariable risk regression analysis, positive fluid balance >2,000 mL remained a strong risk factor for cardiovascular complications (risk ratio =2.18, 95% CI =1.36–3.51, P-value =0.001). Causes of positive fluid balance >2,000 mL included excessive hemorrhage (48%), hypotension without excessive hemorrhage (29.6%), and liberal fluid administration (22.4%).ConclusionPositive fluid balance was a significant risk factor for cardiovascular complications. Strategies to minimize positive fluid balance during surgery for patients at high risk of cardiovascular complications include preparing adequate blood and blood products, considering appropriate hemoglobin level as a transfusion trigger, and adjusting the optimal dose of local anesthetic for intraoperative thoracic epidural analgesia.

Abstract 3550: Benefits of follow-up screening for Epstein Barr virus DNA in patients with localized nasopharyngial carcinoma .

Abstract Objective: In this study, we investigated whether detection of Epstein Barr virus (EBV)-DNA in plasma is a prognostic indicator of disease recurrence in patients who have been treated for localized nasopharyngeal carcinoma. Methods: Study subjects comprised 389 patients who had received treatment for localized nasopharyngeal carcinoma in our outpatient department. Copy numbers of EBV-DNA in plasma were assessed by real-time quantitative PCR. Patients in whom disease recurrence was suspected underwent positron emission tomography (PET) imaging studies. Results: Plasma EBV-DNA was detectable in 60 of 63 (95%) patients with metastatic disease and all had positive PET findings. In addition, of the 45 patients with localized recurrent disease, plasma EBV-DNA was detectable in 23 (51%) patients and positive PET scan results were obtained in 40 (89%) of the patients. Of the 284 patients who were disease free, plasma EBV-DNA was detected in 90 (32%) patients. Of the 19 patients in disease free group who were suspected disease recurrence with PET scanning, 7 positive PET images were found including 3 second primary malignancy and 4 non-cancer lesions. Two lymphoma cases with positive EBV-DNA value sequentially attacked before or after their NPC were diagnosed. Conclusions: EBV-DNA is a good marker of localized disease recurrence/metastasis after treatment for NPC but needs to be combined with imaging studies such as PET to monitor disease status. Citation Format: Cheng-Lung Hsu. Benefits of follow-up screening for Epstein Barr virus DNA in patients with localized nasopharyngial carcinoma . [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 3550. doi:10.1158/1538-7445.AM2013-3550

Expression of ERG protein, a prostate cancer specific marker, in high grade prostatic intraepithelial neoplasia (HGPIN): lack of utility to stratify cancer risks associated with HGPIN

What's known on the subject? and What does the study add? High grade prostatic intraepithelial neoplasia is a pre-malignant lesion to prostate cancer and is associated with 20%-25% risk of prostate cancer in subsequent repeat biopsies. ERG is a highly prostate-cancer-specific marker. Expression of ERG is rare in isolated high grade prostatic intraepithelial neoplasia diagnosed in prostate biopsy and is not associated with cancer risk in subsequent repeat biopsies. • To evaluate how often ERG, a highly prostate-cancer-specific marker, is expressed in isolated high grade prostatic intraepithelial neoplasia (HGPIN) by immunohistochemistry. • To study whether a positive ERG immunostain in HGPIN correlates with prostate cancer (PCa) detection in subsequent repeat biopsies. • Patients with initial HGPIN in biopsies and at least one follow-up prostate biopsy were included. • Biopsies with HGPIN were immunostained for ERG. • The ERG staining results were then correlated with the PCa risk in subsequent biopsies. • The mean age of 94 patients was 63 years (range 48-78). A mean of 1.8 (range 1-5) repeat biopsy sessions were carried out at a mean interval of 27.4 months (range 1.5-140). The repeat biopsies showed PCa and non-cancer lesions (benign, HGPIN, atypical glands suspicious for cancer) in 36 patients (38%) and 58 patients (62%) respectively. • ERG immunostain was positive in five (5.3%) biopsies with HGPIN, in which PCa was found in two (40%) subsequent biopsies. Of 89 biopsies with negative ERG staining, PCa was found in 34 (38%) repeat biopsies. The cancer detection rate was not different between ERG positive and negative cases (P= 0.299). • This is the first study to investigate the ERG protein expression in prostate biopsy containing HGPIN only and its use to stratify the cancer risk associated with HGPIN. We found that ERG expression is distinctly uncommon in isolated HGPIN (5.3%). • Positive ERG expression is not associated with increased cancer detection in subsequent repeat biopsies. The use of ERG immunostain in the evaluation and cancer risk stratification of HGPIN is of limited value.

T2-weighted hypointense lesions within prostate gland: Differential diagnosis using wash-in rate parameter on the basis of dynamic contrast-enhanced magnetic resonance imaging—Hystopatology correlations

Background and aimsDynamic contrast enhanced magnetic resonance improves prostate cancer detection. The aims of this paper are to verify whether wash-in-rate parameter (speed of contrast uptake in dynamic contrast enhanced magnetic resonance) can help to differentiate prostate cancer from non-neoplastic T2-weighted hypointense lesions within prostate gland and to assess a cut-off for prostate cancer diagnosis. MethodsProspective, monocentric, multi-departmental study. Thirty consecutive patients underwent T2-weighted and dynamic contrast enhanced magnetic resonance, and re-biopsy. T2-weighted hypointense lesions, >5mm in size, were noted. Lesions were assessed as cancerous (showing mass effect, or no defined margin within transitional zone) and non cancerous (no mass effect) and were compared with histopathology by 2×2 tables. Wash-in-rate of each lesion was calculated and was correlated with histopathology. Student's t-test was adopted to assess significant differences. Receiver operating characteristic (ROC) analysis was employed to identify the best cut-off for wash-in-rate in detecting prostate cancer. ResultsAt re-biopsy, cancer was proven in 43% of patients. On T2-weighted MRI, 111 hypointense lesions ≥5mm in size were found. Sensitivity, specificity and accuracy of T2-weighted MRI were 80% (±12.4 CI 95%), 74.6% (±10.1 CI 95%), and 76.5% (±7.9 CI 95%), respectively. Mean WR was 5.8±1.9/s for PCa zones and 2.96±1.44/s for non-PCa zones (p<0.00000001). At ROC analysis, the best area under curve (AUC) for wash-in-rate parameter was associated to 4.2/s threshold with 82.5% sensitivity (CI±7.07), 97.2% specificity (CI±4.99) and 91.2% accuracy (CI±5.27). Eighteen false positive lesions on T2-weighted MRI showed low wash-in-rate values suggesting non-cancer lesions, while in 5/8 false negative cases high wash-in-rate values correctly suggested prostate cancer. Nine lesions with surgically proven cancer were not included in the saturation biopsy scheme, in 2/9 cases the only site of cancer. ConclusionsWash-in-rate parameter allows to differentiate prostate cancer from non-neoplastic lesions, helping cancer detection in areas not included in the biopsy scheme.

P-0066 Impact of TGF-B and CD-44 for the Benefit of Radical Surgery in Elderly Patients with Gastroesophageal Cancer

IntroductionAdenocarcinoma near the esophagogastric junction is one of the most lethal GI malignancies known. Surgical treatment of these cancers stays determinative factors of patient survival. Older persons often differ from the younger adult population in terms of biological and functional perspectives; as such, they may have particular needs which require an interdisciplinary approach and intervention, especially when faced with a cancer diagnosis. The aim of this study was to detected expression of TGF-ß and CD-44 in age specific subgroup. MethodsThe expressions of TGF-ß and CD-44 were evaluated immunohistochemically in 23 patients with adenocarcinoma of gastric cardia who underwent curative surgery (R0) without any neo/adjuvant therapy. Additionally we analyzed control group of patients with non-cancer lesion or normal tissue of upper digestive tract (13 patients). We divided the patients into two groups. Group A consisted of 13 cancer patients and 7 control patients 65 years of age or older, while Group B consisted of 10 cancer and 6 control patients younger than 65 years of age. The two groups were comparable - there were no differences between the two groups regarding tumor stage. ResultsElderly patients have statistically significant better survival (median 20.2 month) compared with younger patients (median 15.4 month) (p=0.045). The median survival rate of patients without TGF-ß and/or CD-44 expression was significantly lower (7m) than that of patients with positive expression (>15m) (p=0.003). Regardless of patients age, CD-44 was significantly higher in the cancer tissue of elderly patients than in younger (p<0.035). But no significant difference was observed in the TGF-ß expression between group A and group B cancers tissue (p=0.005). ConclusionThe biology of tumors may be different in elderly patients, leading to a lower rate of tumor-related mortality.

Photodynamic therapy for gynecological diseases and breast cancer.

Photodynamic therapy (PDT) is a minimally invasive and promising new method in cancer treatment. Cytotoxic reactive oxygen species (ROS) are generated by the tissue-localized non-toxic sensitizer upon illumination and in the presence of oxygen. Thus, selective destruction of a targeted tumor may be achieved. Compared with traditional cancer treatment, PDI has advantages including higher selectivity and lower rate of toxicity. The high degree of selectivity of the proposed method was applied to cancer diagnosis using fluorescence. This article reviews previous studies done on PDT treatment and photodetection of cervical intraepithelial neoplasia, vulvar intraepithelial neoplasia, ovarian and breast cancer, and PDT application in treating non-cancer lesions. The article also highlights the clinical responses to PDT, and discusses the possibility of enhancing treatment efficacy by combination with immunotherapy and targeted therapy.

Abstract 3371: Expression levels of EMT-related genes in hepatocellular carcinoma

Abstract Epithelial-Mesenchymal Transition (EMT) has been recognized as a cellular process by which epithelial cells undergo mesenchymal phenotype leading to increased motility and invasion in cancer cells. We recently have reported that sorafenib exerts a potent inhibitory activity against the EMT by inhibiting MAPK signaling and SNAI1 expression in hepatocellular carcinoma (HCC). Large-scale clinical data on SNAI1 expression and the prognosis of patients with HCC was recently reported, and the overexpression of Snail and/or Twist was correlated with a worse prognosis. However, it remains largely unclear on clinico-pathological features of other EMT-related genes and whether these genes are overexpressed in HCC compared with paired non-cancer lesion of the liver. Here, we examined the mRNA expression levels of EMT-related genes including SNAI1/Snail, SNAI2/slug, ZEB1/TCF8, ZEB2/SIP1, TWIST, CDH1/E-cadherin, CDH2/N-cadherin, VIM/vimentin and FN1/fibronectin in HCC. RNA was extracted from frozen surgical HCC samples (n=48) and their paired liver samples (n=14). Real-time RT-PCR amplification was performed. Glyceraldehyde 3-phosphate dehydrogenase (GAPD) was used to normalize the expression levels in the subsequent quantitative analyses. E-cadherin was significantly downregulated in most of HCC (12/14) and those of 5 HCC were markedly downregulated below 25% of paired liver. Interestingly, we found that ZEB1 is tended to be upregulated in HCC, while ZEB2 was downregulated. Regarding EMT-inducible transcription factors, SNAI1, SNAI2, ZEB1, ZEB2 and TWIST, these expression levels were overexpressed in several HCC samples. In conclusion, our findings indicate that some HCC subpopulation actually undergo EMT via upregulation of SNAI1, SNAI2, ZEB1, ZEB2 and TWIST. Evaluation of clinico-pathological features on these expression and analysis of additional HCC samples up to 100 cases are now under way. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3371. doi:10.1158/1538-7445.AM2011-3371

Evaluation of double vital staining with lugol's iodine and methylene blue in diagnosing superficial esophageal lesions

Objective. To evaluate the accuracy of double vital staining with lugol's iodine and methylene blue in the diagnosis of superficial esophageal lesions. Methods. Doubtful superficial esophageal lesions identified with conventional endoscope were sprayed with 3% lugol's iodine and 0.5% methylene blue in order and observed in detail after each staining. Depending on the mucosal staining, biopsy specimen was obtained and underwent pathological examination. Results. Using conventional endoscope, we found 356 lesions in 297 patients, among which 179 were esophageal squamous cell carcinoma and precancerous lesions (CAPs) (including 71 early esophageal squamous cell carcinoma, 23 esophageal high-grade intraepithelial neoplasias, 85 esophageal low-grade intraepithelial neoplasias) and 177 were non-cancer non-precancerous lesions (NCNPs) (i.e. esophagitis and esophageal squamous cell hyperplasia). Most of CAPs were lightly stained or unstained, while NCNPs were hyperstained after lugol's iodine stained. The specificity, sensitivity, positive predictive value, negative predictive value and accuracy of lugol's lightly stained and unstained for identifying CAPs were 34.5%, 100%, 60.7%, 100% and 67.4%, respectively. Most of CAPs were lightly stained or hyperstained, while NCNPs were unstained after double vital staining. The specificity, sensitivity, positive predictive value, negative predictive value and accuracy of double vital staining lightly stained and hyperstained for identifying CAPs were 97.7%, 100%, 97.8%, 100% and 98.9%, respectively. The accuracy of double vital staining for identifying CAPs was higher than that of lugol's iodine stained (p = 0.000). Conclusion. The double staining with lugol's iodine and methylene blue significantly improves the detection and diagnosis of early esophageal squamous cell CAPs.

Lymphagenesis correlates with expression of vascular endothelial growth factor-C in colorectal cancer

Lymphagenesis in gastrointestinal tumors is not well described. To clarify its presence and regulation, we assessed the microlymphatic count (MLC) in colorectal cancer patients. Lymphatic vessels were evaluated by enzyme-histochemistry for 5'-nucleotidase (5'-NA). Since vascular endothelial growth factor (VEGF)-C is reportedly associated with lymphagenesis, the expression of VEGF-C protein was immunohistochemically assessed by the catalyzed signal amplification (CSA) method. MLC of peritumoral lesions was significantly higher than that of non-cancer and intratumoral lesions (p<0.01); it increased where VEGF-C was highly expressed (p<0.01) and increased with the depth of invasion in peritumoral lesions. These results indicate significant findings at peritumoral lesion: that lymphagenesis may be elicited by tumor spread; that VEGF-C expression is associated with lymphagenesis and is a potent factor stimulating lymphagenesis.