Flat Tumors Research Articles

Location-specific diagnostic efficiency of photodynamic diagnosis-guided biopsy in bladder mapping biopsies.

Photodynamic diagnosis (PDD)-assisted transurethral resection of bladder tumors (TURBT) has emerged as a promising complementary tool to white light (WL) cystoscopy, potentially improving cancer detection and replacing conventional mapping biopsies. This study aimed to investigate the diagnostic accuracy of PDD by anatomical locations in mapping biopsies through lesion-based analysis. PDD and WL findings were prospectively recorded in 102 patients undergoing mapping biopsies and PDD-assisted TURBT using oral 5-aminolevulinic acid. We evaluated 673 specimens collected from flat tumor or normal-looking lesions on WL cystoscopy, after excluding 98 specimens collected from papillary or nodular tumors. Among the 673 lesions, cancer was detected in 110 (16%) by lesion-based analysis. PDD demonstrated significantly higher sensitivity (65.5% vs. 46.4%, p < 0.001) and negative predictive value (92.5% vs. 89.5%, p < 0.001) compared to WL. The sensitivity of PDD findings varied by location: posterior (100%), right (78.6%), dome (73.3%), left (70.6%), trigone (58.8%), bladder neck (41.7%), anterior (40.0%), and prostatic urethra (25.0%). Incorporating targeted biopsies of specific locations (bladder neck, anterior, and prostatic urethra) into the PDD-guided biopsies, regardless of PDD findings, significantly increased the overall sensitivity from 65.5% to 82.7% (p = 0.001). This study first demonstrated the detection rate of location-specific mapping biopsies using PDD, revealing difficulties in accuracy assessment in areas susceptible to tangential fluorescence. While PDD-guided biopsy improves cancer detection compared to WL cystoscopy even for flat tumors or normal-looking lesions, more careful decisions, including mapping biopsies, may be beneficial for an assessment in these tangential areas.

Multiparameter interferometric polarization-enhanced imaging differentiates carcinoma in situ from inflammation of the bladder: an ex vivo study.

Successful differentiation of carcinoma in situ (CIS) from inflammation in the bladder is key to preventing unnecessary biopsies and enabling accurate therapeutic decisions. Current standard-of-care diagnostic imaging techniques lack the specificity needed to differentiate these states, leading to false positives. We introduce multiparameter interferometric polarization-enhanced (MultiPIPE) imaging as a promising technology to improve the specificity of detection for better biopsy guidance and clinical outcomes. In this ex vivo study, we extract tissue attenuation-coefficient-based and birefringence-based parameters from MultiPIPE imaging data, collected with a bench-top system, to develop a classifier for the differentiation of benign and CIS tissues. We also analyze morphological features from second harmonic generation imaging and histology slides and perform imaging-to-morphology correlation analysis. MultiPIPE enhances specificity to differentiate CIS from benign tissues by nearly 20% and reduces the false-positive rate by more than four-fold over clinical standards. We also show that the MultiPIPE measurements correlate well with changes in morphological features in histological assessments. The results of our study show the promise of MultiPIPE imaging to be used for better differentiation of bladder inflammation from flat tumors, leading to a fewer number of unnecessary procedures and shorter operating room (OR) time.

Novel urine-based DNA methylation biomarkers for urothelial bladder carcinoma detection in patients with hematuria

ABSTRACT Background Urothelial bladder carcinoma (UBC) is usually detected during work-up for hematuria. Cystoscopy and/or contrast-enhanced imaging are the gold standard tools for UBC diagnosis, despite limited by being invasive, expensive and low yield in small flat tumors. Objectives To assess the diagnostic performance of urine-based DNA methylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in patients with hematuria. Patients and methods Voided urine was collected from consecutive patients presented with hematuria for urine cytology and DNA methylation assay of the assigned genes using methylation-specific Polymerase Chain Reaction (PCR). Further assessment by office cystoscopy and imaging with subsequent inpatient cystoscopic biopsy for positive findings was done. The diagnostic characteristics of DNA methylation and urine cytology were assessed based on its capability to predict UBC. Results We included 246 patients in the study with identified macroscopic hematuria in 204 (82.9%) patients. Positive cytology was found in 78 (31.7%) patients. DNA methylation of GATA4, P16, P14, APC, CDH1 and CD99 genes was identified in 127 (51.6%), 52 (21.1%), 117 (47.6%), 106 (43.1%), 90 (36.6%) and 71 (28.9%) patients, respectively. The sensitivity of the assigned genes for UBC detection ranges from 35% (95%CI: 31–39) to 83% (95%CI: 79–87). Optimal specificity (SP) (100%) was noted for P16, APC and CDH1 genes. While for the other genes (GATA4, P14 and CD99), the SP was 95% (95%CI: 92–98), 96% (95%CI: 92–99) and 97% (95%CI: 93–99), respectively. On multivariate logistic regression analysis, all genes exclusively demonstrated independent prediction of UBC. On receiver operator characteristic (ROC) analysis, all tested genes methylation showed superior area under the curve (AUC) when compared to urine cytology. Conclusions We have developed a novel urine-based DNA methylation assay for detection of UBC in patients with hematuria with superior diagnostic performance and independent predictive capacity over urine cytology.

Radiological work‐up for proton beam therapy of uveal melanoma patients

AbstractPurposeIn ocular proton beam therapy (PBT), 2.5 mm tantalum clips are surgically sutured near the tumour border for clinical target volume marking. The clip‐tumour distances are assessed peroperative using transillumination, indentation and or fundoscopy. To support the clip localisation, target definition and 3D tumour modelling, a dedicated MRI‐protocol was developed and evaluated.Methods23 consecutive uveal melanoma (UM) patients, planned for PBT, were scanned on a 3T MRI. MRI based clip‐tumour distances were compared with the peroperative measurements. For clips with more than 1mm difference, the most likely origin of this discrepancy was discussed in a multidisciplinary setting.ResultsIn 39/87 (45%) of the clips, both measurements differed more than 1 mm. For the majority of these clips, the MRI showed a larger clip‐tumour distance (n = 30). Largest differences were observed in flat UM (n = 13) where an average absolute difference of 3.9 mm was found. Here, MRI was generally considered less reliable as the extend of flat tumours is difficult to determine on MRI. In 15% of the clips, the discrepancy was attributed to a complex tumour geometry. Here an average absolute difference of 3.2 mm was observed. In these cases 3D imaging provided valuable additional information for the treatment planning. In 10% of the clips, the anterior localized tumour casted a shadow, resulting in an overestimation of the tumour dimensions during surgery, leading to an average absolute difference of 3.7 mm. For these patients, MR‐imaging was considered more reliable as obtaining correct peroperative measurements was difficult.ConclusionsMRI and peroperative measurements were equal in 55% of the cases. For flat UM, MRI generally underestimates tumour dimensions. For complex and anterior UM, MRI‐based clip‐tumour measurements are more reliable, which could result in more accurate target definition, thereby possibly reducing toxicity and improving probability to retain vision.

Intravesical ichthyosis: a rare case report

BackgroundIchthyosis is a rare skin disorder, in which the shedding of squamous cells is altered. Intravesical ichthyosis is an extremely rare condition. There is evidence for an association with intravesical condylomata accuminata, caused by urogenital infections of the human papilloma virus. These lesions are generally benign but known to be of a carcinogenic potential and therefore should be treated immediately and followed-up closely.Case presentationWe present the case of a 39-year-old woman who presented with recurrent urinary tract infections. During cystoscopy diffuse black pigmented flat bladder tumours were visualized. After transurethral resection the pathological report diagnosed an ichthyosis vesicae.ConclusionWe recommend a complete resection with frequent clinical and cystoscopic follow-up. Furthermore, testing for the human papilloma virus should be performed and a vaccination should be offered to the patient. As ichthyosis vesicae is a rare phenomenon, there is an evident lack of clinical data regarding therapy, prognosis and follow-up. With our report, we want to emphasize the need for further research.

MR imaging characteristics of uveal melanoma with histopathological validation

PurposeTo evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology.MethodsMR images from 42 UM were compared with US and fundoscopy, and on 14 enucleated cases with histopathology.ResultsA significant relationship between the signal intensity on T1 and pigmentation on histopathology was found (p=0.024). T1 hyperintense UM were always moderately or strongly pigmented on histopathology, while T1-hypointense UM were either pigmented or non-pigmented. Mean apparent diffusion coefficient (ADC) of the UM was 1.16 ± 0.26 × 10−3 mm2/s. Two-thirds of the UM had a wash-out and the remaining a plateau perfusion time-intensity curve (TIC). MRI was limited in evaluating the basal diameter of flat tumors. US tends to show larger tumor prominence (0.5mm larger, p=0.008) and largest basal diameter (1.4mm larger, p<0.001). MRI was good in diagnosing ciliary body involvement, extrascleral extension, and optic nerve invasion, but limited on identifying scleral invasion. An increase of tumor prominence was associated with lower ADC values (p=0.030) and favored a wash-out TIC (p=0.028). An increase of tumor ADC correlated with a plateau TIC (p=0.011).ConclusionsThe anatomical and functional MRI characteristics of UM were comprehensively assessed. Knowing the MRI characteristics of UM is important in order to confirm the diagnosis and to differentiate UM from other intra-ocular lesions and because it has implications for treatment planning. MRI is a good technique to evaluate UM, being only limited in case of flat tumors or on identifying scleral invasion.

Comprehensive assessment of the effect of eye plaque tilt on tumor dosimetry

PURPOSE: Tilting of the posterior plaque margin during eye plaque brachytherapy can lead to tumor underdosing and increased risk of local recurrence. We performed a quantitative analysis of the dosimetric effects of plaque tilt as a function of tumor position, basal dimension, height and plaque type using 3D treatment planning software.MATERIALS AND METHODS: Posterior and anterior tumors with largest basal dimensions of 6, 12 and 18 mm and heights of 4, 7 and 10 mm were modeled. Both Eye Physics and COMS plaques were simulated and uniformly loaded. Plans were normalized to 85 Gy at the tumor apex. Posterior plaque tilts of 1, 2, 3 and 4 mm were simulated.RESULTS: Volumetric coverage is more sensitive to tilt than the area coverage. Wide, flat tumors are more susceptible to tilt. Apical dose changed significantly as a function of tumor height and diameter. No other parameter exhibited significant differences. Posterior tumors are slightly more susceptible to tilt due to the use of notched plaques. Plaque type does not significantly alter the effect of plaque tilt.CONCLUSIONS: Wide, flat tumors are the most susceptible to plaque tilt. Tumor location or plaque type does not have a significant effect on dosimetry changes from plaque tilt. Robust clinical procedures such as the use of mattress sutures, pre- and post-implant ultrasound and post-implant dosimetry can all mitigate the risk associated with plaque tilt.

Research Progress of Autofluorescence Imaging Technology in the Diagnosis of Early Gastrointestinal Tumors.

Early diagnosis and early treatment of gastrointestinal tumors are helpful to improve the prognosis of patients. Endoscopy is the best method for the diagnosis of early gastrointestinal tumors, but some early flat tumors may be missed under conventional white-light endoscopy. In order to improve the accuracy of endoscopic diagnosis of gastrointestinal tumors, especially early flat tumors, endoscopic autofluorescence imaging (AFI) as a new technique has been widely used in clinics in recent years. This article reviews the progress of the clinical application of AFI in the diagnosis of various gastrointestinal tumors.

Endoscopic submucosal dissection in the treatment of patients with early colorectal carcinoma and precancerous lesions.

Our study aims to explore the indications and clinical efficacy of endoscopic submucosal dissection (ESD) on the early colorectal carcinoma and precancerous lesions. The clinical data of 29 patients with early colorectal carcinoma and precancerous lesions who were treated with ESD at Nantong First People's Hospital between January 2018 and December 2019 were collected. Then the endoscopic morphology, postoperative pathological classification, tumor resection rate, postoperative complications, and follow-up outcomes were analyzed. Colorectal carcinoma lesions were distributed in the left colon, accounting for 89.6%. There were 14 cases (48.3%) with protuberant endoscopic tumors, accounting for the highest proportion, while 2 cases (6.9%) of the flat tumors, accounting for the lowest proportion. The average operation time for ESD was 123 minutes, and en-bloc resection was 100% while the curative resection rate was 89.6%. There were 3 cases (10.3%) with delayed hemorrhage after ESD, and 1 case with persistent hemorrhage during the operation was transferred to surgical treatment. No cases with infection or perforation after ESD. For postoperative pathological classification, villous-tubular adenoma with low-grade epithelioma accounted for 31%; tubular adenoma with high-grade epithelioma only accounted for 3.4%. There was no recurrence in the follow-up for 1-20 months. Control of surgical indications strictly, improvement of operation skills, attention to postoperative pathological feedback, and close follow-up are necessary guarantees to improve the clinical effectiveness of ESD.

Abstract A08: Application of Miltuximab®-IRDye800 for near-infrared fluorescence imaging of urothelial carcinoma in vivo

Abstract Introduction and Objectives: Up to 50% of patients with non-muscle invasive bladder cancer suffer from recurrence or progression into a muscle-invasive disease despite multiple resections and long-term chemo and immunotherapy. Possible reasons for that are incomplete resection and reimplantation of cancer cells, which could be prevented by early detection and improved resection of tumor margins. Fluorescence-guided surgery is beneficial in some patients with flat tumors; however, it is currently based on metabolic differences of cancer cells and lacks specificity in many cases. Molecular imaging could improve the specificity of fluorescence-guided surgery since it can target biomarkers expressed by individual tumors. We aimed to select a biomarker and develop a probe for molecular imaging of urothelial carcinoma (UC). Methods: One of the biomarkers present in UC is a heparan sulphate proteoglycan Glypican-1 (GPC-1). The anti-GPC-1 monoclonal antibody Miltuximab (Glytherix Ltd. Sydney, Australia) was used to analyze the expression of GPC-1 in UC cell lines T24 and UM-UC-6. Miltuximab was then labelled by a fluorescent dye IRDye800CW and tested in vivo. Luciferase-transfected UM-UC-6 cells were injected subcutaneously into the hind leg of ten nude mice. When the tumors reached 1000 mm3 in volume, the mice were intravenously injected with 5.7 mg/kg Miltuximab-IRDye800 or isotype IgG-IRDye800. They were then imaged daily for ten days and sacrificed for ex vivo imaging to study the distribution of Miltuximab within the body and its accumulation in the tumors. Results: Flow cytometry and Western blotting demonstrated high expression of GPC-1 in cells UM-UC-6 and T24. UM-UC-6 cells formed subcutaneous tumors that were histologically representative of tumors of human bladder in all animals. From one to ten days after the intravenous injection of the fluorescently labeled Miltuximab, we detected its high accumulation in the tumors by in vivo and ex vivo imaging. One day after the injection, tumors could be visualized in both groups with tumor-to-noise (T/N) ratio of 2. On the 5th day, this value went up to 6.7 for Miltuximab and 3.5 for the Isotype IgG group. By day 10, non-bound antibody molecules further cleared from the mice, resulting in T/N ratio of 14.1 in the mice injected with Miltuximab, while in the control group the value reached only 4.8. Conclusions: Overexpression of GPC-1 in UC shows its high potential as a target for molecular imaging. The animal model developed in this study demonstrated accumulation of the antibody in the tumor and its strong visualization, which could be helpful in tumor detection and resection. Another advantage of this platform is its high potential for clinical translation. IRDye800 can be visualized by existing equipment for indocyanine green imaging and has been proven to be safe in several clinical trials. The antibody Miltuximab has also been used in clinic and has an excellent safety profile. Citation Format: Dmitry Polikarpov, Douglas Campbell, Lucinda McRobb, Alexander Zaslavsky, Andrei Zvyagin, Bradley Walsh, Ganesh Palapattu, David Gillatt. Application of Miltuximab®-IRDye800 for near-infrared fluorescence imaging of urothelial carcinoma in vivo [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2019 May 18-21; Denver, CO. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(15_Suppl):Abstract nr A08.

Support System of Cystoscopic Diagnosis for Bladder Cancer Based on Artificial Intelligence.

Introduction: Nonmuscle-invasive bladder cancer has a relatively high postoperative recurrence rate despite the implementation of conventional treatment methods. Cystoscopy is essential for diagnosing and monitoring bladder cancer, but lesions are overlooked while using white-light imaging. Using cystoscopy, tumors with a small diameter; flat tumors, such as carcinoma in situ; and the extent of flat lesions associated with the elevated lesions are difficult to identify. In addition, the accuracy of diagnosis and treatment using cystoscopy varies according to the skill and experience of physicians. Therefore, to improve the quality of bladder cancer diagnosis, we aimed to support the cystoscopic diagnosis of bladder cancer using artificial intelligence (AI).Materials and Methods: A total of 2102 cystoscopic images, consisting of 1671 images of normal tissue and 431 images of tumor lesions, were used to create a dataset with an 8:2 ratio of training and test images. We constructed a tumor classifier based on a convolutional neural network (CNN). The performance of the trained classifier was evaluated using test data. True-positive rate and false-positive rate were plotted when the threshold was changed as the receiver operating characteristic (ROC) curve.Results: In the test data (tumor image: 87, normal image: 335), 78 images were true positive, 315 true negative, 20 false positive, and 9 false negative. The area under the ROC curve was 0.98, with a maximum Youden index of 0.837, sensitivity of 89.7%, and specificity of 94.0%.Conclusion: By objectively evaluating the cystoscopic image with CNN, it was possible to classify the image, including tumor lesions and normality. The objective evaluation of cystoscopic images using AI is expected to contribute to improvement in the accuracy of the diagnosis and treatment of bladder cancer.

The Histochemical Alterations of Mucin in Colorectal Carcinoma Quantified by Two Efficient Algorithms of Digital Image Analysis.

The practical use of knowledge on the diagnostic-prognostic role of polysaccharide components of mucins in colorectal cancer (CRC) has been difficult, due to the number of histochemical (HC) reaction types, as well as lack of standard methods of computer-assisted analysis of tissue expression of these molecules. Using two algorithms of digital image analysis (by application of Image-Pro Premier and our originally designed program Filter HSV), we evaluated the expression of polysaccharides in tissue samples of CRC patients (n = 33), and fragments of normal colorectal tissue from the same patients (control) using periodic acid Schiff reaction (PAS) (neutral mucins) and alcian blue staining (AB) (acidic mucins). Our results indicate lower expression of the PAS+ and AB+ mucins in CRC, as compared to the control samples. The higher expression of PAS+ polysaccharides was detected in flat tumors than in protruded CRC, while higher AB+ mucins expression was a feature of mucinous CRC subtypes. Positive correlation between mutual PAS+ and AB+ expression, as well as correlations with glucose concentration (PAS+ mucins), and hemoglobin level (AB+ mucins) were observed exclusively in unchanged colorectal samples (control). Both algorithms of digital image analysis (smart segmentation and Filter HSV) work properly and can be used interchangeably in daily practice of pathologists, as useful tools of quantitative evaluation of HC reaction in both normal and cancerous tissues.

Abstract A075: A protective role for group 3 innate lymphoid cells in colitis-associated colorectal cancer

Abstract Chronic inflammation is recognized as a causative factor in the development of cancer and recent paradigms suggest that microbe-driven chronic inflammation is causally associated with the development and progression of cancer in the colon. Further, recent studies in mice have implicated innate lymphoid cells (ILC) as a key cell population that regulates intestinal inflammation. Group 3 innate lymphoid cells (ILC3) are essential regulators of immunity, inflammation and tissue homeostasis in the intestine, yet their role in cancer remains poorly defined. Here, we identify that ILC3 are associated with both human and mouse colon tumors. Tumor-associated ILC3 are selectively localized within lymphoid aggregates and exhibit a unique phenotypic profile as compared with nonmalignant tissue. Critically, mice with a selective deletion of ILC3-specific MHCII exhibit a striking increased susceptibility to intestinal tissue damage and develop highly invasive and flat colorectal tumors. These data demonstrate a protective role for antigen-presenting ILC3 in the context of cancer development and progression in the intestine, and suggest that further interrogation may lead to the development of novel immunotherapeutic strategies in colon cancer. Citation Format: Jeremy Goc, Nick Bessman, Sheena Sahota, Flamar Anne Laure, Gregory Putzel, David Withers, Janelle Arthur, Manish Shah, Gregory Sonnenberg. A protective role for group 3 innate lymphoid cells in colitis-associated colorectal cancer [abstract]. In: Proceedings of the Fourth CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; Sept 30-Oct 3, 2018; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2019;7(2 Suppl):Abstract nr A075.

Efficacy of autofluorescence imaging for flat neoplasm detection: a multicenter randomized controlled trial (A-FLAT trial)

Colorectal flat (nonpolypoid) lesions can be overlooked during colonoscopy. This study evaluated the efficacy of updated autofluorescence imaging (AFI) for detecting colorectal flat neoplasms. This was a prospective, multicenter, randomized controlled trial in 9 Japanese tertiary institutions. Patients undergoing colonoscopy because of positive fecal immunochemical tests, surveillance after polypectomy, or investigation of minor symptoms were enrolled and randomly assigned to either the white-light imaging (WLI) or the AFI group. Primary outcome measurement was number of flat neoplasms per patient. From November 2015 to June 2017, 817 patients were enrolled. After excluding 15 patients, 802 were finally analyzed (404, WLI; 398, AFI). Patients' backgrounds (sex, age, indication of colonoscopy, experience of endoscopists) and quality of colonoscopy (bowel preparation, sedative use, cecal insertion rate, insertion and withdrawal time) were not different between groups. Number of flat neoplasms in each patient was significantly higher in the AFI than in the WLI group (.87 [95% confidence interval [CI], .78-.97] vs .53 [95% CI, .46-.61]), whereas overall and polypoid neoplasm detection was not significantly different betweenthe groups (1.33 [95% CI, 1.22-1.45] vs 1.14 [95% CI, 1.03-1.24], .46 [95% CI, .40-.53] vs .60 [95% CI, .53-.68]). Flat neoplasms were more frequently detected in the right-sided colon with AFI (.61 [95% CI, .54-.70] vs .30 [95% CI, .25-.36]) but not in the left-sided colon and rectum (.26 [95% CI, .21-.32] vs .23 [95% CI, .19-.28]). Updated AFI improves the detection of flat colorectal neoplasms in the right-sided colon compared with WLI. (Clinical trial registration number: UMIN000019355.).

Urine cytology is a feasible tool for assessing erythematous bladder lesions after bacille Calmette-Guérin (BCG) treatment.

To investigate the need to biopsy erythematous lesions of the bladder after bacille Calmette-Guérin (BCG) treatment as well as the diagnostic value of voided urine cytology in the detection of recurrence. Data on 206 consecutive patients with non-muscle-invasive bladder cancer treated with one or more BCG instillations in the period 2009-2015 at Satakunta Central Hospital and Turku University Hospital were reviewed. Biopsy histology was pooled according to lesion cystoscopy appearance regarding growth pattern and presence of erythema. Voided urine cytology grading before resection was reviewed. We correlated the cystoscopy findings with histology and calculated the sensitivity, specificity, and positive (PPV) and negative predictive value (NPV) for voided urine cytology. In total, 159 patients with a median follow-up of 35 months were included in the study. Altogether, 367 biopsies were analysed. In the case of papillary or flat tumours, 76% of biopsies showed malignant histology and the diagnostic value of cytology was very limited (sensitivity 33%, specificity 84%). Erythematous lesions constituted 57% of all biopsy targets, with the majority being either chronic non-specific inflammation or granulomatous inflammation; 10% of erythematous lesions were malignant at pathological examination. In contrast to papillary and flat tumours, cytology proved to be more accurate in the case of erythematous lesions with a sensitivity, specificity, PPV and NPV of 59%, 76%, 23% and 94%, respectively. Bladder lesions after BCG instillations pose a challenge during follow-up and the appropriate management strategy is not clear. Lesions should not be overlooked as being BCG-induced irritation because they may harbour significant malignancies. The presence of papillary or flat tumour always warrants a biopsy or resection. In the case of erythematous lesions, our results suggest that biopsy may be avoided if voided urine cytology is negative.

Water immersion-assisted endoscopic en bloc resection for colorectal sessile tumors

Objective To compare the feasibility and efficacy of attempted underwater endoscopic mucosal resection(EMR) with conventional EMR for colorectal sessile or flat tumors. Methods A total of 120 colorectal tumors of 5 to 30 mm in size were removed using underwater EMR or conventional EMR. En bloc resection rates of the two groups were retrospectively analyzed. Results Underwater EMR was performed on 53 colorectal sessile/flat tumors with the median size of 22 mm, and conventional EMR was performed on 67 tumors of the same median size. The overall en bloc resection rate of the underwater EMR group was higher than that of the conventional EMR group(81.1% VS 59.7%, P=0.012). The subgroup analysis showed en bloc resection rates of Paris 0-Ⅱa tumor (76.7% VS 50.0%, P=0.035) and those located at the inaccessible regions (100.0% VS 42.9%, P=0.004) were higher than that of conventional EMR. Neither postoperative bleeding nor perforation occurred in the two groups. Residual adenoma was found in 1 patient in underwater EMR group and 2 in the conventional EMR group, respectively(P=0.712). Conclusion Underwater EMR with prior submucosal injection appears superior to conventional EMR for the removal of colorectal sessile or flat Paris 0-Ⅰs/Ⅱa tumors of less than 3 cm in size in the rate of complete endoscopic resection and defect closure. Key words: Intestinal neoplasms; Endoscopes; Endoscopic mucosal resection; Water-immersion

Real-time photoacoustic and ultrasonic dual-modality imaging system for early gastric cancer: Phantom and ex vivo studies

Photoacoustic (PA) and ultrasonic (US) imaging are promising techniques for imaging biological tissue and diagnosing internal organs. This paper presents a real-time PA and US dual-modality imaging system for early gastric cancer (EGC) based on a clinical US transducer. It has the advantage that only the PA excitation is inside the body but the US imaging system is outside the body, which makes the system less invasive for EGC detection and will be a potential tool for clinical use. The first experiments produced real-time PA images of blood vessel phantoms. Cross-sectional 2D PA images and reconstructed 3D PA images of the blood vessel phantoms demonstrate the system can clearly identity tissue structure. The experiments show that the system has a high axial spatial resolution but a relatively low lateral spatial resolution. The second experiments combining US and PA imaging, an artificial slightly elevated tumor and three artificial superficial flat tumors embedded inside the pig stomach mucosa ex vivo, demonstrate that the system is able to detect EGC accurately.

Radiation-associated colon cancer: A case report.

Radiation-associated colon cancer is a rare clinical entity. We herein describe the case of a patient with radiation-associated colon cancer who had undergone low anterior resection for rectal cancer following preoperative radiotherapy. Certain characteristics of radiation-associated colon cancer are highlighted. The patient was a 48-year-old man who had undergone low anterior resection for rectal cancer following preoperative radiotherapy at a total dose of 50 Gy, at the age of 29 years. When the patient presented at the University of Tokyo Hospital, 19 years after the surgery, he complained of severe anal pain and frequent defecation. Colonoscopy revealed two flat tumors in the sigmoid colon, located 10 cm to the oral side of the anastomosis site, which were diagnosed as well-differentiated adenocarcinomas. In addition, colonoscopy identified five flat polyps near the tumors, which were resected endoscopically. Computed tomography and magnetic resonance imaging revealed a mass in the sigmoid colon and no evidence of distant metastasis. Laparoscopic-assisted intersphincteric resection of the rectum and sigmoid colon with diverting ileostomy was performed. There were no specific postoperative complications and the patient was discharged from the hospital on the 20th postoperative day. On pathological examination, the resected rectum and sigmoid colon contained two separate tumors and six flat polyps. The two tumors were diagnosed as well-differentiated adenocarcinomas with invasion of the subserosa and submucosa, respectively. A total of 17 regional lymph nodes without metastasis were resected. The six flat polyps were diagnosed as tubular adenomas. We herein present a case of a radiation-associated colon cancer in a patient who had undergone low anterior resection for rectal cancer following preoperative radiotherapy 19 years prior. Colonoscopic surveillance of radiation-associated colon cancer may be indicated for rectal cancer patients treated with preoperative radiotherapy, particularly for those with long-standing radiation-induced colitis.

Intraductal neoplasms of the bile duct. A new challenge to biliary tract tumor pathology.

Invasive biliary tract carcinomas are usually tubular adenocaricnomas with abundant desmoplastic reactions and frequent ductal and periductal invasion at the time of the diagnosis. Recently, several intraductal neoplasms of the bile duct, particularly at a pre-invasive stage, have been recognized. They include intraductal papillary neoplasm of the bile duct (IPNB), biliary intraepithelial neoplasm (BilIN), and others, such as intraductal tubulopapillary neoplasm (ITPN) of the bile duct. IPNBs are grossly visible predominantly intraductal-growing papillary neoplasms covered by well-differentiated neoplastic epithelium with fine fibrovascular cores in the dilated bile ducts. Regarding their similarities to intraductal papillary mucinous neoplasm of the pancreas (IPMN) of main pancreatic duct type, some IPNBs resemble IPMN ("pancreatic type"), while others are only somewhat similar or variably different from IPMN ("non-pancreatic type"). Some IPNBs develop via a common oncogenic signaling pathway, and others, particularly those of intestinal type, frequently show GNAS mutations, as in IPMN. BilINs are a microscopically recognizable flat or micropapillary pre-invasive neoplasm and are presumed to precede conventional nodular-sclerosing cholangiocarcinomas. ITPN of the bile duct is a rare neoplasm composed of densely packed tubular glands. These three types of neoplasms are not infrequently associated with invasive adenocarcinoma. Pre-invasive intraglandular neoplasms of the peribiliary glands, another epithelial system in the biliary tree, have been also reported. Further characterization of these intraductal and intraglandular neoplasms of the bile duct is needed to overcome devastating invasive biliary tract carcinoma.

New technologies for upper tract urothelial carcinoma management.

Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC. Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC. Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.