Contributions of endoscopic ultrasonography-guided tissue acquisition (EUS-TA) to the diagnostics of biliary stricture and gallbladder lesions.

Endoscopic ultrasonography (EUS) provides high spatial resolution and more detailed images than other diagnostic modalities. Furthermore, EUS-guided tissue acquisition (EUS-TA), such as EUS-guided fine needle aspiration or biopsy (EUS-FNA/FNB), is an indispensable tool in pancreaticobiliary disease diagnostics, supporting a conclusive pathological diagnosis. In this review, we evaluate the current status and the usefulness of EUS-TA for the diagnostics of the following biliary tract diseases: (A) biliary stricture diagnostics, (B) biliary tract cancer (BTC) itself, and (C) staging of advanced BTC. Previous reports have shown that EUS-FNA for biliary lesions is a safe procedure that is useful in differentiating biliary cancer from benign lesions and in the staging of BTC. On the other hand, the diagnostic performance of EUS-TA for bile duct lesions is reported to be similar to that of transpapillary biopsy. Overall, EUS-TA for biliary lesions may be a safe and effective method, but it should be performed with an understanding of the risk of serious adverse events such as bile leakage and peritoneal dissemination of cancer. It is recommended for distal biliary stricture lesions for which endoscopic retrograde cholangiopancreatography cannot confirm the diagnosis or gallbladder lesions if they do not require the needle to pass through the biliary lumen.

The role of contrast-enhanced endoscopic ultrasound for biliary diseases.

Contrast-enhanced endoscopic ultrasound (CE-EUS) has emerged as a promising diagnostic modality for assessing biliary diseases. CE-EUS is a noninvasive imaging technique that utilizes contrast agents to enhance the visualization of blood vessels and perfusion within target tissues. In the context of biliary diseases, CE-EUS allows for improved characterization of biliary lesions, aiding in differential diagnosis and treatment planning. This review highlights several key findings regarding the usefulness of CE-EUS in biliary disease assessment and therapeutic procedures.

Use of contrast-enhanced harmonic endoscopic ultrasonography for the diagnosis of pancreatic cystic lesions.

Endoscopic ultrasonography (EUS) provides high spatial and contrast resolution and is a useful tool for evaluating the pancreato-biliary regions. Recently, contrast-enhanced harmonic EUS (CH-EUS) has been used to evaluate lesion vascularity, especially for the diagnosis of pancreatic tumors. CH-EUS adds two major advantages when diagnosing pancreatic cystic lesions (PCL). First, it can differentiate between mural nodules and mucous clots, thereby improving the accurate classification of PCL. Second, it helps with evaluation of the malignant potential of PCL, especially of intraductal papillary mucinous neoplasms by revealing the vascularity in the mural nodules and solid components. This review discusses the use and limitations of CH-EUS for the diagnosis of PCL.

Current Status of the Diagnosis of Early-Stage Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) can be treated with surgery, chemotherapy, and radiotherapy. Despite medical progress in each field in recent years, it is still insufficient for managing PDAC, and at present, the only curative treatment is surgery. A typical pancreatic cancer is relatively easy to diagnose with imaging. However, it is often not recommended for surgical treatment at the time of diagnosis due to metastatic spread beyond the pancreas. Even if it is operable, it often recurs during postoperative follow-up. In the case of PDAC with a diameter of 10 mm or less, the 5-year survival rate is as good as 80% or more, and the best index for curative treatment is tumor size. The early detection of pancreatic cancer with a diameter of less than 10 mm or carcinoma in situ is critical. Here, we provide an overview of the current status of diagnostic imaging features and genetic tests for the accurate diagnosis of early-stage PDAC.

Changes in intestinal bacteria and imbalances of metabolites induced in the intestines of pancreatic ductal adenocarcinoma patients in a Japanese population: a preliminary result.

BACKGROUND: The relationship between pancreatic ductal adenocarcinoma (PDAC) and the intestinal environment is not fully understood. The purpose of this study was to elucidate the characteristics of the intestinal environment in PDAC. METHODS: We performed a case-control study of 5 Japanese patients with unresectable PDAC located in the body or tail (PDAC-bt). The number of patients analyzed was limited for this preliminary study. We included 68 healthy subjects, herein control, of pre-printed study in the preliminary study. 16S rRNA amplicon sequencing and metabolomic analysis were performed using fecal samples from the subjects. RESULTS: There was no difference in the Shannon index and Principal Coordinate Analysis between PDAC-bt and the control. However, a significant increase in oral-associated bacteria (Actinomyces, Streptococcus, Veillonella, Lactobacillus) was observed. A significant decrease of Anaerostipes was demonstrated in the feces of PDAC-bt compared with the control. The intestinal propionic acid and deoxycholic acid were significantly lower in PDAC-bt compared with the control. CONCLUSIONS: We showed that the intestinal environment of PDAC-bt is characterized by an increase in oral-associated bacteria and an imbalance of metabolites but without changes in alpha and beta diversity of the gut microbiota profiles.Clinical Trial Registration: www.umin.ac.jp, UMIN 000041974, 000023675, 000023970.

Endoscopic imaging in inflammatory bowel disease.

In inflammatory bowel disease, including Crohn's disease and ulcerative colitis, an excessive immune response due primarily to T-cell lymphocytes causes inflammation in the gastrointestinal tract. Lesions in Crohn's disease can occur anywhere in the gastrointestinal tract, i.e., from the oral cavity to the anus. Endoscopically, aphthoid lesions/ulcers believed to be initial lesions progress to discrete ulcers, which coalesce to form a longitudinal array and progress to longitudinal ulcers with a cobblestone appearance, which is a typical endoscopic finding. Before long, complications such as strictures, fistulas, and abscesses form. Lesions in ulcerative colitis generally extend continuously from the rectum and diffusely from a portion of the colon to the entire colon. Endoscopically, lack of vascular pattern, fine granular mucosa, erythema, aphthae, and small yellowish spots are seen in mild cases; coarse mucosa, erosions, small ulcers, bleeding (contact bleeding), and adhesion of mucous, bloody, and purulent discharge in moderate cases; and widespread ulcers and marked spontaneous bleeding in severe cases.

A rare case of inflammatory polyp in the common bile duct with cholangitis.

The diagnosis of bile duct tumors can be difficult at times. A transpapillary bile duct biopsy findings with endoscopic retrograde cholangiopancreatography sometimes contradict diagnostic imaging findings. In bile duct tumors, inflammatory polyps in the extrahepatic bile duct are relatively rare with extrahepatic cholangitis. The disease's clinical relevance, including its natural history and prognosis, is not always clear. We show here a rare case of an inflammatory polyp in the common bile duct. A 69-year-old woman with abdominal pain was diagnosed with cholangitis. The findings of contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested that she had extrahepatic cholangiocarcinoma. The examination and therapy of cholangitis were performed by endoscopic retrograde cholangiopancreatography. The cholangiography revealed a suspected tumor in the hilar bile duct with some common bile duct stones. Then, after endoscopic sphincterotomy to remove tiny common bile duct stones, further detailed examinations were performed at the same time using an oral cholangioscope revealed a papillary raised lesion with a somewhat white surface in the bile duct; a biopsy was conducted on the same spot, and epithelial cells with mild atypia appeared in the shape of a papilla. Since the malignant tumor or the intraductal papillary neoplasm of the bile duct could not be ruled out, extrahepatic bile duct resection was conducted with the patient's informed consent. Bile duct inflammatory polyp was the histopathological diagnosis.

Transabdominal ultrasonographic diagnosis of relatively rare pancreatic neoplasms.

There are various types of pancreatic neoplasms, and their prognosis and treatment methods are different. Therefore, accurate diagnosis is important to determine the best treatment strategy. Transabdominal ultrasonography is frequently used as a screening examination for diagnostic imaging of pancreatic neoplasms. In this review, we have focused on the characteristics of ultrasonic findings for relatively rare pancreatic neoplasms.

A rare case of pancreatic neuroendocrine neoplasm causing Cushing's syndrome.

Pancreatic neuroendocrine neoplasms (PNENs) are relatively rare with a reported incidence of 1-2/100,000 and generally thought to originate from the precursor of the neuroendocrine cells including the islet and the pancreatic duct cells. About 65% of PNENs are non-functional. While insulinomas and gastrinomas are the most common functional PNENs, ACTH-producing PNENs are extremely rare. We herein present an extremely rare case of a patient with Cushing's syndrome caused by PNEN. A 46-year-old woman with edema in bilateral lower extremities and moon face was admitted with a suspicious pancreatic tumor. Enhanced computed tomography and endoscopic ultrasonography revealed a pancreatic tumor. The final diagnosis of ACTH-producing PNEN with Cushing's syndrome was based on clinical and biochemical test results and endocrinological studies. The symptoms associated Cushing's syndrome improved after pancreaticoduodenectomy for PNEN.

Early Changes in Alpha-Fetoprotein Are a Useful Predictor of Efficacy of Atezolizumab plus Bevacizumab Treatment in Patients with Advanced Hepatocellular Carcinoma.

INTRODUCTION: The aim of this study was to investigate the early changes in alpha-fetoprotein (AFP) and des-γ-carboxy prothrombin (DCP) levels in patients with advanced hepatocellular carcinoma (HCC) treated with atezolizumab plus bevacizumab and to evaluate the relationship between changes in these tumor markers and treatment efficacy. METHODS: Of 58 consecutive patients who started atezolizumab plus bevacizumab at our institution, 50 patients with information on antitumor response obtained at 6 weeks after therapy were enrolled in this study and their treatment outcomes were retrospectively evaluated. RESULTS: According to the Response Evaluation Criteria in Solid Tumors at 6 weeks, the objective response (OR) rate was 22.0% and the disease control (DC) rate was 78.0%. In patients who achieved OR at 6 weeks, median AFP and DCP ratios at weeks 1, 2, 3, and 6 were significantly lower than those in patients who did not achieve OR. AFP ratios in patients who did not achieve DC at 6 weeks (Non-6W-DC group) were significantly higher than in those who achieved DC at week 6 (6W-DC group). Median overall survival in the Non-6W-DC group was significantly shorter than in the 6W-DC group (156 days vs. not reached, p = 0.0008). An AFP ratio of 1.4 or higher at 3 weeks had a specificity of 88.0% and a sensitivity of 88.9% for predicting Non-6W-DC. Median progression-free survival was significantly shorter in patients with an AFP ratio of 1.4 or higher at 3 weeks than in those with an AFP ratio of <1.4 (42 days vs. 210 days, p = 0.0003). CONCLUSION: Early changes in AFP might be useful for predicting the antitumor efficacy of atezolizumab plus bevacizumab in patients with advanced HCC. An AFP ratio of 1.4 or higher at 3 weeks might be an early predictor of refractoriness to atezolizumab plus bevacizumab therapy.

Current status of the diagnosis of chronic pancreatitis by ultrasonographic elastography.

Chronic pancreatitis (CP) is pathologically characterized by the loss of exocrine pancreatic parenchyma, irregular fibrosis, cellular infiltration, and ductal abnormalities. Diagnosing CP objectively is difficult because standard diagnostic criteria are insufficient. The change of parenchymal hardness is the key factor for the diagnosis and understanding of the severity of CP. The ultrasonography (US) or endoscopic ultrasonography (EUS) elastography have been used to diagnose pancreatic diseases. Both strain elastography (SE) and shear wave elastography are specific diagnostic techniques for measuring tissue hardness. Most previous studies were conducted with SE. There are three methods of interpreting SE; the method of recognizing the patterns in SE distribution images in the region of interest, the method of using strain ratio to compare the hardness of adipose tissue or connective tissue with that of the lesion, and the method of evaluating the hardness distribution of a target by histogram analysis. These former two methods have been used primarily for neoplastic diseases, and histograms analysis has been used to assess hardness distribution in the evaluation of CP. Since the hardness of the pancreas increases with aging, it is necessary to consider the age in the diagnosis of pancreatic disorders using US or EUS elastography.

The Role of Endoscopic Ultrasound in the Diagnosis of Gallbladder Lesions.

Gallbladder (GB) diseases represent various lesions including gallstones, cholesterol polyps, adenomyomatosis, and GB carcinoma. This review aims to summarize the role of endoscopic ultrasound (EUS) in the diagnosis of GB lesions. EUS provides high-resolution images that can improve the diagnosis of GB polypoid lesions, GB wall thickness, and GB carcinoma staging. Contrast-enhancing agents may be useful for the differential diagnosis of GB lesions, but the evidence of their effectiveness is still limited. Thus, further studies are required in this area to establish its usefulness. EUS combined with fine-needle aspiration has played an increasing role in providing a histological diagnosis of GB tumors in addition to GB wall thickness.

Transcatheter arterial infusion chemotherapy with cisplatin in combination with transcatheter arterial chemoembolization decreases intrahepatic distant recurrence of unresectable hepatocellular carcinoma.

BACKGROUND AND AIM: This study investigated the efficacy of transcatheter arterial infusion (TAI) chemotherapy with cisplatin combined with transcatheter arterial chemoembolization (TACE). The goal was to prevent intrahepatic distant recurrence (IDR) of hepatocellular carcinoma (HCC), compared with TACE alone, in patients with unresectable HCC. METHODS: We conducted a historical cohort study, which involved 68 unresectable HCC patients. The study was performed on 44 and 24 consecutive patients who underwent TAI using cisplatin combined with TACE using epirubicin and TACE using epirubicin alone, respectively. We performed a propensity score analysis to identify the independent risk factors associated with IDR, and constructed propensity score-adjusted survival curves. RESULTS: After propensity score-adjusting, the adjusted cumulative IDR rates at 1 and 3 years were 76.8 and 76.8% in TACE alone group, and 21.3 and 73.1% in TACE with TAI group, respectively. TACE alone group had a significantly higher IDR rate in comparison with TACE with TAI group (P = 0.0073). Combined with TAI was associated with preventing IDR after propensity score-adjusting (hazard ratio [HR] 0.40, 95% confidence intervals [CI] 0.17-0.91, P = 0.028). Combined with TAI (HR 0.26, 95% CI 0.10-0.68, P = 0.0056) and Stage ≥III (HR 2.98, 95% CI 1.25-7.12, P = 0.014) were independent IDR predictors after adjusting for significant risk factors with propensity score. CONCLUSIONS: We demonstrated that cisplatin TAI accompanied with TACE decreased IDR compared with TACE alone. Our findings suggest that cisplatin TAI might contribute to a longer progression-free period in unresectable HCC patients treated with TACE.

Probe-based confocal laser endomicroscopy for the diagnosis of pancreatic ductal structures.

BACKGROUND AND AIM: The image-based diagnosis of pancreatic diseases can be difficult and requires pathological evaluation. Probe-based confocal laser endomicroscopy (pCLE) enables real-time observation of the microscopic tissue pattern of lesion and may be a useful assistance for the diagnosis. This study aimed to evaluate the feasibility and utility of pCLE for the diagnosis of pancreatic diseases. METHODS: Thirty patients who underwent endoscopic retrograde cholangiopancreatography with pCLE for the evaluation of indeterminate pancreatic diseases from June 2015 to October 2018 were included in this study. The pCLE findings were interpreted according to the Miami Classification. RESULTS: Among a total of 30 patients, 12, 10, 4, and 4 patients received the definitive diagnoses of pancreatic ductal adenocarcinoma (PDAC), main duct intrapapillary mucinous neoplasm, autoimmune pancreatitis, and chronic pancreatitis, respectively. The diagnostic accuracy of pCLE for PDAC and pancreatitis (96.7% and 93.3%, respectively) was higher than that of cytology (76.7% and 63.3%, respectively) (P = 0.0227 and 0.0048, respectively). The sensitivity of pCLE for PDAC was significantly higher (91.7%) than that of cytology (41.7%) (P = 0.0094). Moreover, the specificity of pCLE for pancreatitis was significantly higher than that of cytology (90.9% vs 50%; P = 0.0029). However, the diagnostic accuracies of pCLE and cytology for main duct intrapapillary mucinous neoplasm did not differ significantly (96.7% and 86.7%, respectively). CONCLUSIONS: Probe-based confocal laser endomicroscopy may be effective for the diagnosis of pancreatic diseases as adjunct modality. It requires technical learning and further evaluation of its usefulness.

Initial Experience of Atezolizumab Plus Bevacizumab for Advanced Hepatocellular Carcinoma in Clinical Practice.

Background/Aim: The aim of this study was to investigate the outcomes of atezolizumab plus bevacizumab in patients with advanced hepatocellular carcinoma (HCC), including those with disease refractory to lenvatinib, in clinical practice. Patients and Methods: Of 34 patients treated with atezolizumab plus bevacizumab, a total of 23, including 16 with lenvatinib failure, were enrolled in this retrospective study. The adverse events, changes in liver function and antitumor responses at 6 weeks after starting therapy were evaluated. Results: The incidence of grade 3 adverse events was low, at 13.0%. Albumin-bilirubin scores did not worsen at 3 and 6 weeks compared to baseline. The objective response rate and disease control rate at 6 weeks were 17.4% and 78.3% according to Response Evaluation Criteria in Solid Tumors (RECIST), and 30.4% and 78.3% according to modified RECIST, respectively. Conclusion: Our results suggest that atezolizumab plus bevacizumab might have potential therapeutic safety and efficacy in patients with advanced HCC, including those with disease refractory to lenvatinib. Further studies are needed to confirm the outcomes of atezolizumab plus bevacizumab after lenvatinib failure.

Role of transabdominal ultrasonography in the diagnosis of pancreatic cystic lesions.

Pancreatic cystic lesions (PCLs) are incidental findings that are being increasingly identified because of recent advancements in abdominal imaging technologies. PCLs include different entities, with each of them having a peculiar biological behavior, and they range from benign to premalignant or malignant neoplasms. Therefore, accurate diagnosis is important to determine the best treatment strategy. As transabdominal ultrasonography (US) is noninvasive, inexpensive, and widely available, it is considered to be the most appropriate imaging modality for the initial evaluation of abdominal diseases, including PCLs, and for follow-up assessment. We present a review of the possibilities and limits of US in the diagnosis of PCLs, the technical development of US, and the ultrasonographic characteristics of PCLs.

Evaluation of a 12-mm diameter covered self-expandable end bare metal stent for malignant biliary obstruction.

Background and study aims Biliary metallic stents are used to drain unresectable malignant distal biliary obstructions. This study aimed to evaluate the efficacy of a novel 12-mm-diameter covered, self-expandable end bare metal stent (12-mm CSEEMS). Patients and methods We evaluated 99 patients with unresectable malignant distal biliary obstructions treated with covered biliary metallic stents. Of the 99 patients, 33 underwent 12-mm CSEEMS placement between June 2015 and April 2017 (12-mm-CSEEMS group) and 66 underwent 10-mm fully-covered self-expandable metal stent (FCSEMS) placement between January 2010 and July 2015 (10-mm-FCSEMS group). The overall survival (OS), the recurrent biliary obstruction (RBO), cause of RBO, time to RBO (TRBO) and adverse events in 12-mm-CSEEMS group and 10-mm-FCSEMS group were evaluated retrospectively. Results The OS tended to be longer in the 12-mm-CSEEMS group (log rank, P  = 0.081) and TRBO was significantly longer in the 12-mm-CSEEMS group (log rank, P  = 0.001) than in the 10-mm-FCSEMS group. Both univariate (HR, 0.449; 95 % CI, 0.27967 - 0.72215; P  = 0.001) and multivariate (HR, 0.458; 95 % CI, 0.28395 - 0.73744; P  = 0.001) Cox hazard analysis found that risk of RBO was significantly lower in 12-mm CSEEMS than in 10-mm FCSEMS. There were no significant differences between the 12-mm-CSEEMS group and 10-mm-FCSEMS group regarding the cause of RBO and adverse events. Conclusions The 12-mm CSEEMS showed a low risk of RBO compared with 10-mm FCSEMS and was considered to be effective and safe for draining unresectable malignant distal biliary obstruction.

Increase in Albumin by Daclatasvir/asunaprevir Therapy is Correlated with Decrease in Aspartate Transaminase.

OBJECTIVE: To elucidate the mechanism of an increase in the albumin levels by daclatasvir (DCV)/asunaprevir (ASV) therapy, we assessed the factors associated with an increase in the albumin levels. METHODS: We retrospectively analyzed 125 patients with chronic hepatitis C virus (HCV) infection, treated with DCV/ASV from November 2014 to January 2016. RESULTS: Albumin levels significantly increased from 4.0 ± 0.4 g/dL at baseline to 4.2 ± 0.4 g/dL at 24 weeks after the end of treatment (EOT) (P < 0.0001) in 108 patients with SVR. Patients with SVR were divided into three groups according to their baseline albumin levels: group A, ≥ 4 g/dL; group B, 3.6-3.9 g/dL; and group C, ≤ 3.5 g/dL. The increase in albumin levels from baseline to at 24 weeks after EOT was significantly larger in group C (0.5 ± 0.5 g/dL, P < 0.0001) and group B (0.2 ± 0.4 g/dL, P = 0.0059) than in group A (0.0 ± 0.3 g/dL). Multivariate analysis showed that aspartate transaminase (AST) levels was the only factor associated with ≥ 0.3 g/dL increase in albumin levels in groups B and C (P = 0.0305). An increase in albumin levels was significantly correlated with a decrease in AST levels (r = 0.4729, P = 0.0119). CONCLUSION: DCV/ASV therapy resulted in an increase in albumin levels in SVR patients, which was significantly correlated with a decrease in AST levels. It is probable that the reduction of inflammation, but not by reduction of fibrosis, mainly caused an increase in albumin levels.