Predictors of treatment efficacy and liver stiffness changes following therapy with Sofosbuvir plus Ribavirin in patients infected with HCV genotype 2.

While the combination therapy of ribavirin (RBV) and sofosbuvir (SOF) is effective in genotype 2 HCV infection, the predictors of treatment efficacy and posttreatment changes in α-fetoprotein (AFP) and liver stiffness (markers of hepatocellular carcinoma), remain unclear. In this study, 302 patients with chronic HCV genotype 2 infection were treated with SOF (400 mg) plus RBV (400-1000 mg; based on body weight) for 12 weeks. We evaluated the efficacy and safety of treatment, as well as measured serum AFP, liver stiffness, and controlled attenuation parameter (CAP, a surrogate marker of steatosis) at baseline and within 48 weeks of treatment completion. The intention-to-treat analysis showed a sustained virological response (SVR) rate of 95.7%. None of the patients discontinued treatment due to side effects. Multivariate analysis identified pretreatment (no treatment with interferon), level of AFP (AFP; <10 µg/L), and RBV/body weight (BW) ratio (≥9.0 mg/kg) as independent predictors of SVR. The SVR rate in patients with two predictors of poor response (AFP ≥10 µg/L and RBV/BW ratio <9.0 mg/kg) was significantly lower than in other patients. In the SVR group, posttreatment AFP level and liver stiffness were significantly lower than at baseline. CAP tended to be higher after treatment than at baseline in all patients. SOF plus RBV combination therapy achieved a high SVR rate and was safe in HCV genotype 2 infected patients. Treatment reduced AFP levels and improved liver stiffness, but increased CAP.

Serial changes in liver stiffness and controlled attenuation parameter following direct-acting antiviral therapy against hepatitis C virus genotype 1b.

Little information is available on the impact of direct-acting antiviral (DAA) therapy on changes in liver fibrosis and steatosis. Liver stiffness (LS) and controlled attenuation parameter (CAP) values were evaluated using transient elastography. The study subjects were 214 elderly patients infected with HCV genotype 1b who received 24-week daclatasvir and asunaprevir dual therapy. All patients of this retrospective study had no hepatocellular carcinoma before and during DAA therapy. LS and CAP were assessed before treatment (baseline), at end of treatment (EOT), and at 24, 48, 72 weeks (W) after EOT. The rate of sustained viral response (SVR) by daclatasvir and asunaprevir therapy was 91%. LS values for the entire group correlated with Fib-4 index at baseline (r = 0.565, P < 0.001). LS in both chronic hepatitis group (Fib-4 index <3.25) and cirrhosis group (Fib-4 index ≥3.25) decreased significantly at each time point compared with baseline (P < 0.001). Especially, a larger decrease in LS from baseline to EOT was seen in the cirrhosis group than chronic hepatitis group (P < 0.001). LS was also significantly lower in the SVR group at EOT, 24W, 48W, 72W compared with baseline (P < 0.001). Even in the non-SVR group, LS tended to be lower at EOT (P = 0.039), 24W (P = 0.009), 48W (P = 0.475), 72W (P = 0.033) compared with baseline. CAP increased significantly following the treatment from baseline to 48W post-EOT (P = 0.018). Our results showed significant improvement in LS in response to daclatasvir and asunaprevir dual therapy. In the other hand, there was a tendency that CAP increased from baseline.

Direct-Acting Antivirals Decreased Tumor Recurrence After Initial Treatment of Hepatitis C Virus-Related Hepatocellular Carcinoma.

BACKGROUND: Suppressive activity of recurrence by interferon-free direct-acting antivirals (DAA) is not elucidated after curative treatment of hepatocellular carcinoma (HCC). PATIENTS AND METHODS: A total of 177 patients received DAA after curative manners of HCC: 89 patients underwent DAA therapy after initial HCC treatment, and the other 88 patients after repeated therapy of 2-10 times. Among a cohort of HCC patients with surgery and radiofrequency ablation, 89 patients were chosen adjusting age, gender, and Barcelona Clinic Liver Cancer (BCLC) staging with 89 patients with initial HCC therapy. RESULTS: HCC recurrence rates at the end of first and second year were 18.1 and 22.1% in patients with once of HCC therapy, 28.2 and 41.6% in those with 2-3 times of therapy, and 60.2 and 74.5% in those with 4 or more times of therapy, respectively (P < 0.0001). Recurrence rates were compared between 89 patients with DAA therapy after initial HCC therapy and 89 age-, gender-, and BCLC staging-matched patients without antiviral therapy after initial HCC therapy. HCC recurrence rates at first and second year were 18.1 and 25.0% in patients with DAA therapy and 21.8 and 46.5% in those without DAA therapy, respectively (P = 0.003). Multivariate analysis showed DAA therapy significantly decreased recurrence rate with a hazard ratio of 0.353 (confidence interval: 0.191-0.651) after adjustment with covariates of tumor multiplicity, alpha-fetoprotein value, and prothrombin time. CONCLUSIONS: DAA therapy significantly decreased recurrence rate when it was performed after initial HCC therapy.

A case of large cell neuroendocrine carcinoma of the stomach with multiple liver metastases.

A 79-year-old man was admitted to our hospital to determine the cause of his melena. He underwent esophagogastric endoscopy and computed tomography, revealing a submucosal tumor on the anterior wall of the gastric antrum with multiple liver metastases. Endoscopic biopsy revealed a large cell neuroendocrine cell carcinoma. A subtotal gastrostomy was performed to prevent pyloric stenosis and anemia caused by tumor hemorrhage. Previous studies on gastric neuroendocrine carcinoma reported poor prognosis. Large- and small-cell types of gastric neuroendocrine carcinomas were differentiated for the first time in the 14th edition of the Japanese Classification of Gastric Carcinoma. It is expected that the number of reports of gastric neuroendocrine carcinomas classified as either the large-cell or small-cell type will increase. It is necessary to collect information on more cases to improve prognosis and to establish appropriate treatment guidelines.

Defocus-aware Dirichlet particle filter for stable endoscopic video frame recognition.

BACKGROUND AND OBJECTIVE: A computer-aided system for colorectal endoscopy could provide endoscopists with important helpful diagnostic support during examinations. A straightforward means of providing an objective diagnosis in real time might be for using classifiers to identify individual parts of every endoscopic video frame, but the results could be highly unstable due to out-of-focus frames. To address this problem, we propose a defocus-aware Dirichlet particle filter (D-DPF) that combines a particle filter with a Dirichlet distribution and defocus information. METHODS: We develop a particle filter with a Dirichlet distribution that represents the state transition and likelihood of each video frame. We also incorporate additional defocus information by using isolated pixel ratios to sample from a Rayleigh distribution. RESULTS: We tested the performance of the proposed method using synthetic and real endoscopic videos with a frame-wise classifier trained on 1671 images of colorectal endoscopy. Two synthetic videos comprising 600 frames were used for comparisons with a Kalman filter and D-DPF without defocus information, and D-DPF was shown to be more robust against the instability of frame-wise classification results. Computation time was approximately 88ms/frame, which is sufficient for real-time applications. We applied our method to 33 endoscopic videos and showed that the proposed method can effectively smoothen highly unstable probability curves under actual defocus of the endoscopic videos. CONCLUSION: The proposed D-DPF is a useful tool for smoothing unstable results of frame-wise classification of endoscopic videos to support real-time diagnosis during endoscopic examinations.

Computer-aided diagnosis of colorectal polyp histology by using a real-time image recognition system and narrow-band imaging magnifying colonoscopy.

BACKGROUND AND AIMS: It is necessary to establish cost-effective examinations and treatments for diminutive colorectal tumors that consider the treatment risk and surveillance interval after treatment. The Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) committee of the American Society for Gastrointestinal Endoscopy published a statement recommending the establishment of endoscopic techniques that practice the resect and discard strategy. The aims of this study were to evaluate whether our newly developed real-time image recognition system can predict histologic diagnoses of colorectal lesions depicted on narrow-band imaging and to satisfy some problems with the PIVI recommendations. METHODS: We enrolled 41 patients who had undergone endoscopic resection of 118 colorectal lesions (45 nonneoplastic lesions and 73 neoplastic lesions). We compared the results of real-time image recognition system analysis with that of narrow-band imaging diagnosis and evaluated the correlation between image analysis and the pathological results. RESULTS: Concordance between the endoscopic diagnosis and diagnosis by a real-time image recognition system with a support vector machine output value was 97.5% (115/118). Accuracy between the histologic findings of diminutive colorectal lesions (polyps) and diagnosis by a real-time image recognition system with a support vector machine output value was 93.2% (sensitivity, 93.0%; specificity, 93.3%; positive predictive value (PPV), 93.0%; and negative predictive value, 93.3%). CONCLUSIONS: Although further investigation is necessary to establish our computer-aided diagnosis system, this real-time image recognition system may satisfy the PIVI recommendations and be useful for predicting the histology of colorectal tumors.

Evaluation of dual-wavelength excitation autofluorescence imaging of colorectal tumours with a high-sensitivity CMOS imager: a cross-sectional study.

BACKGROUND: It is important to devise efficient and easy methods of detecting colorectal tumours to reduce mortality from colorectal cancer. Dual-wavelength excitation autofluorescence intensity can be used to visualize colorectal tumours. Therefore, we evaluated dual-wavelength excitation autofluorescence images of colorectal tumours obtained with a newly developed, high-sensitivity complementary metal-oxide-semiconductor (CMOS) imager. METHODS: A total 107 colorectal tumours (44 adenomas, 43 adenocarcinomas with intramucosal invasion, and 20 sessile serrated adenoma/polyps [SSA/Ps]) in 98 patients who underwent endoscopic tumour resection were included. The specimens were irradiated with excitation light at 365 nm and 405 nm, and autofluorescence images measured with a 475 ± 25-nm band pass filter were obtained using a new, high-sensitivity CMOS imager. Ratio images (F365ex/F405ex) were created to evaluate the lesion brightness compared with that of normal mucosa, and specimens were categorized into a no signal or high signal group. RESULTS: Adenomas and adenocarcinomas were depicted in 87 ratio images, with 86.2% (n = 75) in the High signal group. SSA/P was depicted in 20 ratio images, with 70.0% (n = 14) in the High signal group. CONCLUSIONS: Dual-wavelength excitation autofluorescence images of colorectal tumours can be acquired using our high-sensitivity CMOS imager, and are useful in detecting colorectal tumours.

Transfer learning for Bag-of-Visual words approach to NBI endoscopic image classification.

We address a problem of endoscopic image classification taken by different (e.g., old and new) endoscopies. Our proposed method formulates the problem as a constraint optimization that estimates a linear transformation between feature vectors (or Bag-of-Visual words histograms) in a framework of transfer learning. Experimental results show that the proposed method works much better than the case without feature transformation.

Image segmentation of pyramid style identifier based on Support Vector Machine for colorectal endoscopic images.

With the increase of colorectal cancer patients in recent years, the needs of quantitative evaluation of colorectal cancer are increased, and the computer-aided diagnosis (CAD) system which supports doctor's diagnosis is essential. In this paper, a hardware design of type identification module in CAD system for colorectal endoscopic images with narrow band imaging (NBI) magnification is proposed for real-time processing of full high definition image (1920 × 1080 pixel). A pyramid style image segmentation with SVMs for multi-size scan windows, which can be implemented on an FPGA with small circuit area and achieve high accuracy, is proposed for actual complex colorectal endoscopic images.

A computer system to be used with laser-based endoscopy for quantitative diagnosis of early gastric cancer.

GOALS: To evaluate the usefulness of a newly devised computer system for use with laser-based endoscopy in differentiating between early gastric cancer, reddened lesions, and surrounding tissue. BACKGROUND: Narrow-band imaging based on laser light illumination has come into recent use. We devised a support vector machine (SVM)-based analysis system to be used with the newly devised endoscopy system to quantitatively identify gastric cancer on images obtained by magnifying endoscopy with blue-laser imaging (BLI). We evaluated the usefulness of the computer system in combination with the new endoscopy system. STUDY: We evaluated the system as applied to 100 consecutive early gastric cancers in 95 patients examined by BLI magnification at Hiroshima University Hospital. We produced a set of images from the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened lesions; and surrounding tissues, and we attempted to identify gastric cancer, reddened lesions, and surrounding tissue quantitatively. RESULTS: The average SVM output value was 0.846 ± 0.220 for cancerous lesions, 0.381 ± 0.349 for reddened lesions, and 0.219 ± 0.277 for surrounding tissue, with the SVM output value for cancerous lesions being significantly greater than that for reddened lesions or surrounding tissue. The average SVM output value for differentiated-type cancer was 0.840 ± 0.207 and for undifferentiated-type cancer was 0.865 ± 0.259. CONCLUSIONS: Although further development is needed, we conclude that our computer-based analysis system used with BLI will identify gastric cancers quantitatively.

SVM-MRF segmentation of colorectal NBI endoscopic images.

In this paper we investigate a method for segmentation of colorectal Narrow Band Imaging (NBI) endoscopic images with Support Vector Machine (SVM) and Markov Random Field (MRF). SVM classifiers recognize each square patch of an NBI image and output posterior probabilities that represent how likely the given patch falls into a certain label. To prevent the spatial inconsistency between adjacent patches and encourage segmented regions to have smoother shapes, MRF is introduced by using the posterior outputs of SVMs as a unary term of MRF energy function. Segmentation results of 1191 NBI images are evaluated in experiments in which SVMs were trained with 480 trimmed NBI images and the MRF energy was minimized by an α - ß swap Graph Cut.

Calibration of a 3D endoscopic system based on active stereo method for shape measurement of biological tissues and specimen.

For endoscopic medical treatment, measuring the size and shape of the lesion, such as a tumor, is important for the improvement of diagnostic accuracy. We are developing a system to measure the shapes and sizes of living tissue by active stereo method using a normal endoscope on which a micro pattern projector is attached. In order to perform 3D reconstruction, estimating the intrinsic and extrinsic parameters of the endoscopic camera and the pattern projector is required. Particularly, calibration of the pattern projector is difficult. In this paper, we propose a simultaneous estimation method of both intrinsic and extrinsic parameters of the pattern projector. This simplifies the calibration procedure required in practical scenes. Furthermore, we have developed an efficient user interface to intuitively operate the calibration and reconstruction procedures. Using the developed system, we measured the shape of an internal tissue of the soft palate of a human and a biological specimen.

Labeling colorectal NBI zoom-videoendoscope image sequences with MRF and SVM.

In this paper, we propose a sequence labeling method by using SVM posterior probabilities with a Markov Random Field (MRF) model for colorectal Narrow Band Imaging (NBI) zoom-videoendoscope. Classifying each frame of a video sequence by SVM classifiers independently leads to an output sequence which is unstable and hard to understand by endoscopists. To make it more stable and readable, we use an MRF model to label the sequence of posterior probabilities. In addition, we introduce class asymmetry for the NBI images in order to keep and enhance frames where there is a possibility that cancers might have been detected. Experimental results with NBI video sequences demonstrate that the proposed MRF model with class asymmetry performs much better than a model without asymmetry.

[A case of diversion colitis successfully treated with 5-aminosalicylic acid].

An 84-year-old man was admitted to our hospital because of blood in the stool. He had previously undergone a subtotal colectomy and ileostomy with a mucous fistula of the sigmoid colon because of a large bowel hemorrhage of unknown origin. Five years later, a minor hemorrhage developed in the remnant rectum. The clinical history, colonoscopic findings, and the histology of the diverted colon specimens were suggestive of diversion colitis. Treatment was initiated with short-chain fatty acid enema, but slight blood loss through the stool continued;thus, the patient was administered 5-aminosalicylic acid (5-ASA) enema. Subsequently, his symptoms and endoscopic findings improved. 5-ASA enema appears to be both safe and effective in the treatment of diversion colitis following intestinal tract surgery.

[A case of clonorchiasis complicated with the expansion of liver cyst].

A 61-year-old man was admitted to our hospital for examination of the cause of rapid growth of a liver cyst. We found a slight dilatation of bile duct in the vicinity of the liver cyst. Then, we underwent ERCP and found a communication between the bile duct and liver cyst. Bile cytodiagnosis revealed a large quantity of clonorchis eggs. The patient like to do eat raw freshwater fish and we suspected that the acute expansion of the cyst was due to clonorchiasis. Following administration of 40mg/kg praziquantel, the blood clonorchis antibody disappeared and the liver cyst also disappeared after 6 months. We encountered a case of clonorchiasis complicated with growth of a liver cyst. Medical interviews should be conducted carefully along with meticulous examinations.

Quantitative identification of mucosal gastric cancer under magnifying endoscopy with flexible spectral imaging color enhancement.

BACKGROUND AND AIM: Magnifying endoscopy with flexible spectral imaging color enhancement (FICE) is clinically useful in diagnosing gastric cancer and determining treatment options; however, there is a learning curve. Accurate FICE-based diagnosis requires training and experience. In addition, objectivity is necessary. Thus, a software program that can identify gastric cancer quantitatively was developed. METHODS: A bag-of-features framework with densely sampled scale-invariant feature transform descriptors to magnifying endoscopy images of 46 mucosal gastric cancers was applied. Computer-based findings were compared with histologic findings. The probability of gastric cancer was calculated by means of logistic regression, and sensitivity and specificity of the system were determined. RESULTS: The average probability was 0.78 ± 0.25 for the images of cancer and 0.31 ± 0.25 for the images of noncancer tissue, with a significant difference between the two groups. An optimal cut-off point of 0.59 was determined on the basis of the receiver operating characteristic curves. The computer-aided diagnosis system yielded a detection accuracy of 85.9% (79/92), sensitivity for a diagnosis of cancer of 84.8% (39/46), and specificity of 87.0% (40/46). CONCLUSION: Further development of this system will allow for quantitative evaluation of mucosal gastric cancers on magnifying gastrointestinal endoscopy images obtained with FICE.

[Classification of the bleeding pattern in colonic diverticulum is useful to predict the risk of bleeding or re-bleeding after endoscopic treatment].

We examined the re-bleeding rate after endoscopic hemostasis according to the bleeding pattern in patients with an acute lower gastrointestinal hemorrhage from colonic diverticula in 34 patients with active bleeding (Type 1) and 49 patients with exposed vessels and/or erosions in the base of diverticulum and no active bleeding (Type 2). Endoscopic hemostasis was performed by clipping the exposed vessel or erosions (direct method) or the entire diverticular orifice (reefing method). The incidence of re-bleeding was significantly higher in the Type 1 group than in the Type 2 group (p=0.002). All Type 1 cases were treated by the reefing method. In contrast, 14 of the 49 Type 2 cases were treated by the direct method, and no re-bleeding was observed in these cases. Of the other 35 Type 2 cases treated by reafing, rebleeding was seen in 5 cases. More effective endoscopic treatment is needed to prevent early re-bleeding, especially for Type 1 patients. The direct method may therefore reduce the rate of re-bleeding in Type 2 patients.

Endoscopic hemostasis for hemorrhage from an ileal diverticulum.

Hemorrhage from a non-Meckelian jejunoileal diverticulum is rare, and it is generally difficult to diagnose the source of the bleeding. Here, we report the case of a 59-year-old male with hemorrhage from an ileal diverticulum. Contrast computed tomography scans demonstrated the ileal diverticulum and extravasation of the contrast medium around it. The diagnosis was then made by computed tomography scans, and endoscopic mechanical hemostasis was performed under colonoscopy with three metal clips. The management of hemorrhage from jejunoileal diverticula is discussed.

Trans-differentiation of a duodenal phenotype on duodenal transplantation of different normal tissues in F344 rats.

The mechanisms regulating stem cell differentiation and self-renewal are largely unknown. Our ultimate goal is to be able to regulate somatic stem cell differentiation and proliferation. In the present study the ability of trans-differentiation was studied when different normal tissue types were transplanted into the duodenum in rats. Pieces of ear (skin), bladder, trachea, diaphragm, pyloric gland, and forestomach from 8-week old GFP-F344 rats were transplanted into the duodenum of F344 rats. Goblet cells with alcian-blue PAS positive mucin and brash border with alkaline phosphatase (ALP) activity appeared in tissues implanted into the duodenum. In addition, GFP-positive duodenal mucosa was observed in all cases by immunohistochemical staining. Moreover, the GFP-positive cells were found to carry the GFP transgene by PCR analysis, indicating that the bladder, trachea, ear (skin), diaphragm, pyloric gland, and forestomach tissues showed a multipotential ability for differentiation. These results indicated that stem cells within tissues have a multipotential ability, trans-differentiating into different organs when transplanted into different environments.