Utility of contrast-enhanced harmonic endoscopic ultrasonography for T-staging of patients with extrahepatic bile duct cancer.

BACKGROUND: The value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for T-staging in patients with extrahepatic bile duct cancer was evaluated. METHODS: This single-center, retrospective study included consecutive patients with extrahepatic bile duct cancer who underwent surgical resection after preoperative EUS, CH-EUS, and contrast-enhanced CT (CE-CT) examinations between June 2014 and August 2017. The capacity of these modalities for T-staging of extrahepatic bile duct cancer was evaluated by assessing invasion beyond the biliary wall into the surrounding tissue, gallbladder, liver, pancreas, duodenum, portal vein system (portal vein and/or superior mesenteric vein), inferior vena cava, and hepatic arteries (proper hepatic artery, right. and/or left. hepatic artery). Blind reading of EUS, CH-EUS, and CE-CT images was performed by two expert reviewers each. RESULTS: 38 patients were eligible for analysis, of which eight had perihilar bile duct cancer and 30 had distal bile duct cancer. Postoperative T-staging was T1 in 6, T2 in 16, and T3 in 16 cases. CH-EUS was superior to CE-CT for diagnosing invasion beyond the biliary wall into surrounding tissue (92.1% vs. 45.9%, P = 0.0002); the ability to detect invasion to other organs did not differ significantly between the two modalities. The accuracy of CH-EUS for T-staging of tumors was better than that of CE-CT (73.7% vs. 39.5%, P = 0.0059). CH-EUS tended to have a better accuracy than EUS for the diagnosis of invasion beyond the biliary wall into the surrounding tissue (92.1% vs. 78.9%, P = 0.074) and T-staging (73.7% vs. 60.5%, P = 0.074). CONCLUSION: CH-EUS is useful for T-staging of extra hepatic bile duct cancer, especially in terms of invasion beyond the biliary wall into the surrounding tissue.

Performance of Idylla™ RAS-BRAF mutation test for formalin-fixed paraffin-embedded tissues of colorectal cancer.

BACKGROUND: The Biocartis Idylla™ platform is a fully automated, real-time PCR-based diagnostic system. The Idylla™ KRAS and NRAS-BRAF Mutation Tests have been developed for the qualitative detection of mutations in KRAS, NRAS and BRAF genes, facilitating the genomic profiling of patients with colorectal cancer. The aim of the present study was to evaluate clinical performances of these tests in Japan. METHODS: The RAS and BRAF mutation statuses of 253 formalin-fixed paraffin-embedded (FFPE) colorectal cancer tissues were analyzed using the Investigational Use Only Idylla™ KRAS Mutation Test and the Idylla™ NRAS-BRAF Mutation Test and an in vitro diagnostics (IVD) kit (MEBGEN RASKET™-B kit). RESULTS: The success rate for obtaining a valid mutational data without retest of the Idylla tests was 97.6% (247/253): 111 KRAS mutations (43.8%), 9 NRAS mutations (3.6%), and 36 BRAF V600E mutations (14.2%) were detected using the Idylla tests. Compared with the MEBGEN RASKET-B results, the positive concordance rate was 97.4%, the negative concordance rate was 95.7%, and the overall concordance rate was 95.3% (κ = 0.919, 95% CI 0.871-0.967). The average turnaround time to Idylla™ KRAS and NRAS-BRAF Mutation Test was 5.6 working days (range: 3-11 days). CONCLUSION: This result demonstrates a high concordance between the Idylla™ KRAS and NRAS-BRAF Mutation Tests and an existing IVD kit. In this manner, the Idylla™ mutation tests were validated for the detection of clinically significant KRAS, NRAS, and BRAF mutations in FFPE samples from colorectal cancer patients.

Improved detection of liver metastasis using Kupffer-phase imaging in contrast-enhanced harmonic EUS in patients with pancreatic cancer (with video).

BACKGROUND AND AIMS: Kupffer-phase imaging visualized by perfluorobutane (Sonazoid) distribution into normal liver tissues upon phagocytosis by Kupffer cells potentially aids in improving detection of liver metastasis compared with fundamental B-mode EUS (FB-EUS). However, the diagnostic performance of Kupffer-phase imaging in contrast-enhanced harmonic EUS (CH-EUS) remains unclear. Hence, this study aimed to evaluate the usefulness of CH-EUS-based Kupffer-phase imaging for diagnosing liver metastasis from pancreatic cancer. METHODS: We retrospectively analyzed consecutive patients with pancreatic cancer who underwent contrast-enhanced CT (CE-CT) and FB-EUS, followed by CH-EUS, from 2011 to 2017. The diagnostic ability of CH-EUS against that of CE-CT and FB-EUS for metastasis in the left liver lobe was compared. Subsequently, the influences of CH-EUS on the determination of clinical stage and patient management for pancreatic cancer were assessed. RESULTS: We enrolled 426 patients with pancreatic cancer. Metastasis in the left liver lobe was present in 27.2% of patients. The diagnostic accuracy of CE-CT, FB-EUS, and CH-EUS was 90.6%, 93.4%, and 98.4%, respectively. The sensitivity and diagnostic accuracy of CH-EUS for metastasis in the left liver lobe were significantly higher than those of FB-EUS or CE-CT. The sensitivity of CH-EUS for detecting small liver metastasis (<10 mm) was considerably higher than that of CE-CT or FB-EUS (P < .001). In 2.1% of patients, only CH-EUS could detect a single distant metastasis of the left liver lobe, thereby upgrading the tumor staging and altering the clinical management. CONCLUSIONS: CH-EUS-based Kupffer-phase imaging increased the detectability of metastasis in the left liver lobe. This technique could be a reliable pretreatment imaging modality for clinical decision-making in patients with pancreatic cancer.

Utility of contrast-enhanced harmonic endoscopic ultrasonography for predicting the prognosis of pancreatic neuroendocrine neoplasms.

BACKGROUND AND AIMS: Pancreatic neuroendocrine neoplasms (PanNENs), including Grade 1 (G1) or G2 tumors, can have a poor prognosis. This study investigated the value of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for predicting the prognosis of PanNENs. METHODS: This single-center, retrospective study included 47 consecutive patients who underwent CH-EUS and were diagnosed with PanNEN by surgical resection or EUS-guided fine needle aspiration between December 2011 and February 2016. Patients were divided into aggressive and non-aggressive groups according to the degree of clinical malignancy. CH-EUS was assessed regarding its capacity for diagnosing aggressive PanNEN, the correspondence between contrast patterns and pathological features, and its ability to predict the prognosis of PanNEN. RESULTS: There were 19 cases of aggressive PanNEN and 28 cases of non-aggressive PanNEN. The aggressive group included three G1, four G2, three G3 tumors, three mixed neuroendocrine non-neuroendocrine neoplasms, and six neuroendocrine carcinomas. CH-EUS was superior to contrast-enhanced computed tomography for the diagnosis of aggressive PanNEN (P < 0.001): hypo-enhancement on CH-EUS was an indicator of aggressive PanNEN, with sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 94.7%, 100%, 100%, 96.6%, and 97.9%, respectively. Among G1/G2 PanNENs, cases with hypo-enhancement on CH-EUS had a poorer prognosis than those with hyper/iso-enhancement (P = 0.0009). Assessment of 36 resected specimens showed that hypo-enhancement on CH-EUS was associated with smaller and fewer vessels and greater degree of fibrosis. CONCLUSION: Contrast-enhanced harmonic endoscopic ultrasonography may be useful for predicting the prognosis of PanNENs.

Soft Tissue Myoepithelioma of the Shoulder.

Soft tissue myoepitheliomas are often misdiagnosed due to their rarity. Herein, we describe a case of soft tissue myoepithelioma of the shoulder. A 72-year-old woman had a suspected sarcoma on her shoulder and under-went open biopsy. She was referred to our hospital, where the tumor was widely resected and the diagnosis of myoepithelioma was histologically confirmed. No recurrence has been observed in the 3 years since the sur-gery. Careful and prompt planning is necessary for the effective treatment of myoepithelioma.

A multicenter randomized trial comparing a 25-gauge EUS fine-needle aspiration device with a 20-gauge EUS fine-needle biopsy device.

BACKGROUND AND AIMS: Several studies have compared EUS-guided FNA with fine-needle biopsy (FNB), but none have proven superiority. We performed a multicenter randomized controlled trial to compare the performance of a commonly used 25-gauge FNA needle with a newly designed 20-gauge FNB needle. METHODS: Consecutive patients with a solid lesion were randomized in this international multicenter study between a 25-gauge FNA (EchoTip Ultra) or a 20-gauge FNB needle (ProCore). The primary endpoint was diagnostic accuracy for malignancy and the Bethesda classification (non-diagnostic, benign, atypical, malignant). Technical success, safety, and sample quality were also assessed. Multivariable and supplementary analyses were performed to adjust for confounders. RESULTS: A total of 608 patients were allocated to FNA (n = 306) or FNB (n = 302); 312 pancreatic lesions (51%), 147 lymph nodes (24%), and 149 other lesions (25%). Technical success rate was 100% for the 25-gauge FNA and 99% for the 20-gauge FNB needle (P = .043), with no differences in adverse events. The 20-gauge FNB needle outperformed 25-gauge FNA in terms of histologic yield (77% vs 44%, P < .001), accuracy for malignancy (87% vs 78%, P = .002) and Bethesda classification (82% vs 72%, P = .002). This was robust when corrected for indication, lesion size, number of passes, and presence of an on-site pathologist (odds ratio, 3.53; 95% confidence interval, 1.55-8.56; P = .004), and did not differ among centers (P = .836). CONCLUSION: The 20-gauge FNB needle outperformed the 25-gauge FNA needle in terms of histologic yield and diagnostic accuracy. This benefit was irrespective of the indication and was consistent among participating centers, supporting the general applicability of our findings. (Clinical trial registration number: NCT02167074.).

A fungal ball within a maxillary sinus with dental root canal filler and rare fungal propagules.

A fungal ball of a maxillary sinus sometimes includes dental treatment-related foreign material because the sinus is close to the root of the upper teeth. We present a case of right maxillary sinus fungal ball with a gutta-percha point, a dental root canal filler. X-ray analysis of the foreign material in the paraffin section of the fungal ball successfully detected zinc, sulfur, and barium, all of which were constituents of the gutta-percha point. The gutta-percha point might have facilitated the formation of the fungal ball through disruption of the sinus-clearing mechanism. Another interesting histological feature of the fungal ball was the finding of calcium oxalate crystals and non-hyphal fungal elements such as cleistothecia, Hülle cells, and conidial heads. This is the first report of such a combination being found in a specimen of human fungal disease. Although fungal culture was not available in the present case, molecular analysis of the formalin-fixed paraffin-embedded tissue of the fungal ball succeeded in revealing only DNA sequences of Aspergillus nidulans and some other environmental Aspergillus spp.

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432). CONCLUSION: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers.

Impact of avascular areas, as measured by contrast-enhanced harmonic EUS, on the accuracy of FNA for pancreatic adenocarcinoma.

BACKGROUND AND AIMS: EUS-guided FNA (EUS-FNA) is used for the diagnosis of pancreatic adenocarcinoma, but sometimes the method results in a false negative. Occasionally, an avascular area may be observed within the pancreatic adenocarcinoma tumor during contrast-enhanced harmonic EUS (CH-EUS). The aim of this study was to evaluate whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was affected by the presence of avascularity on CH-EUS. METHODS: Two hundred ninety-two patients with pancreatic adenocarcinoma who presented at Kindai University Hospital for EUS-FNA and CH-EUS between June 2009 and August 2013 were retrospectively evaluated. This was a single-center retrospective analysis of prospectively collected data held in a registry. The overall sensitivity of EUS-FNA for the diagnosis of pancreatic adenocarcinoma was calculated. The sensitivities of cytology, histology, and the combination of cytology and histology were also evaluated. These variables were individually evaluated according to the presence or absence of an avascular area on CH-EUS to assess whether the diagnostic sensitivity of EUS-FNA for pancreatic adenocarcinoma was related to the presence of an avascular area within the tumors. RESULTS: The overall sensitivity of EUS-FNA was 90.8% (265/292). The sensitivities of EUS-FNA for lesions with and without an avascular area were 72.9% (35/48) and 94.3% (230/244), respectively, with the difference being statistically significant (P < .001). CONCLUSIONS: EUS-FNA has lower sensitivity for pancreatic adenocarcinoma with avascular areas on CH-EUS.

Dual-energy computed tomography for non-invasive staging of liver fibrosis: Accuracy of iodine density measurements from contrast-enhanced data.

AIM: To investigate whether iodine density measurements from contrast-enhanced dual-energy computed tomography (CT) data can non-invasively stage liver fibrosis. METHODS: This single-center, prospective study was approved by our IRB with written informed consent. Forty-seven consecutive patients (26 men and 21 women; mean age, 63.1 years) with chronic liver disease underwent contrast-enhanced dual-energy CT of the liver (non-contrast, arterial, portal venous, and equilibrium phase images), followed by liver biopsy. Iodine density of liver and aorta were obtained by two independent observers. Iodine uptake of the liver (Δ Liver), representing the difference in iodine density between equilibrium phase and non-contrast images, was calculated and normalized by aorta (Δ Liver/Aorta). We accounted for contrast agent distribution volume by using hematocrit level. Accuracy of iodine density measurements for staging liver fibrosis was assessed by using receiver operating characteristic (ROC) curves. Multivariate linear regression analysis was used to assess the impact of independent variables (liver fibrosis stage and patient-related confounders) on iodine uptake. RESULTS: The Δ Liver/Aorta significantly increased and moderately correlated with METAVIR liver fibrosis stage (ρ = 0.645, P < 0.001). Areas under the ROC curve ranged from 0.795 to 0.855 for discriminating each liver fibrosis score (≥F1-F4). METAVIR fibrosis stage was the most significant independent factor associated with Δ Liver (P = 0.005) and Δ Liver/Aorta (P < 0.001). CONCLUSION: Hepatic extracellular volume fraction with contrast-enhanced dual-energy CT can non-invasively stage liver fibrosis in chronic liver diseases. This technique could prove useful for monitoring disease progression and treatment response, potentially reducing the need for liver biopsy.

Intracystic papillary carcinoma of the male breast: a case report.

BACKGROUND: Intracystic papillary carcinoma (IPC) is defined as cancer that develops from the wall of a cyst in the breast. As breast cancer in men accounts for only 1% of all breast cancers, male IPC is an extremely rare form of the disease. The present case report examines IPC in a man, along with an in-depth literature discussion. CASE PRESENTATION: A 64-year-old Japanese man noticed a mass in the right breast and sought medical attention. An elastic and soft neoplastic 3-cm lesion was palpated in the right papilla. As a 1-cm solid tumor with a gradual rise from the cyst wall was confirmed within the cyst, vacuum-assisted biopsy (VAB) was performed on that site. Pathological examination of the biopsy revealed heterotypic cells with an enlarged oval nucleus forming dense papillary structures mainly of vascular connective tissue component. Contrast-enhanced computed tomography (CT) confirmed thickening of the wall that protruded outside the cyst. The preoperative diagnosis was right breast cancer (male IPC) TisN0M0 stage 0 luminal B-like. Total mastectomy and sentinel lymph node biopsy were performed. In the excised specimen, a 4.0-cm unilocular cyst was found, along with a 1-cm solid tumor with a gradual rise from the cyst wall. Pathological diagnosis of the resected specimen shared similar characteristics with the solid tumor in the cyst: notably, an oval nucleus with histologically clear nucleolus and fine granular chromatin, cylindrically shaped heterotypic cells, and the presence of basophilic cells in the papillary growth with a thin stem of fibrovasculature as the axis. Some invasion of tumor cells into the interstitium was confirmed. As such, the final diagnosis was right breast cancer (male IPC) T2N0M0 stage IIA luminal B-like. The expression of hormone receptor (ER and PgR) was high, and endocrine therapy was initiated postoperatively (20 mg/day tamoxifen). At the present time (3 months postoperation), there has not been any evidence of metastasis. CONCLUSIONS: We reported a rare case of an IPC in the male breast, along with a literature review.

Contrast-enhanced harmonic endoscopic ultrasonography for differential diagnosis of localized gallbladder lesions.

BACKGROUND AND AIM: Differential diagnosis of localized gallbladder lesions is challenging. The aim of the present study was to evaluate the utility of contrast-enhanced harmonic endoscopic ultrasonography (CH-EUS) for diagnosis of localized gallbladder lesions. METHODS: One hundred and twenty-five patients with localized gallbladder lesions were evaluated by CH-EUS between March 2007 and February 2014. This was a single-center retrospective study. Utilities of fundamental B-mode EUS (FB-EUS) and CH-EUS in the differentiation of gallbladder lesions and sludge plug were initially compared. Thereafter, these two examinations were compared with respect to their accuracy in the diagnosis of malignant lesions. Five reviewers blinded to the clinicopathological results evaluated microcirculation patterns in the vascular and perfusion images. RESULTS: In the differentiation between gallbladder lesions and sludge plug, FB-EUS had a sensitivity, specificity, and accuracy of 82%, 100%, and 95%, respectively, whereas CH-EUS had a sensitivity, specificity, and accuracy of 100%, 99%, and 99%, respectively. FB-EUS-based diagnosis of carcinomas based on tumor size and/or shape had a sensitivity, specificity, and accuracy of 61-87%, 71-88%, and 74-86%, respectively. Additional information regarding irregular vessel patterns in the vascular image and/or heterogeneous enhancement in the perfusion image on CH-EUS increased the sensitivity, specificity, and accuracy for the diagnosis of carcinomas to 90%, 98%, and 96%, respectively. There was a significant difference between FB-EUS and CH-EUS in terms of carcinoma diagnosis. CONCLUSION: CH-EUS was useful for the evaluation of localized gallbladder lesions.

Value of additional endoscopic ultrasonography for surveillance after surgical removal of intraductal papillary mucinous neoplasms.

BACKGROUND AND AIM: This study evaluated the utility of endoscopic ultrasonography (EUS) combined with contrast-enhanced harmonic EUS (CH-EUS) for surveillance of the remnant pancreas after surgery for intraductal papillary mucinous neoplasm (IPMN). METHODS: This was a single-center, retrospective, descriptive study. A total of 134 consecutive patients who underwent surgical resection for IPMN between April 2009 and March 2015 were evaluated. Rates of recurrence and development of IPMN-concomitant pancreatic ductal adenocarcinoma (PDAC) during follow up were assessed. Clinical findings of patients with recurrence or development of PDAC were also evaluated. RESULTS: Of 134 resected IPMN 56 (41.8%) and 78 (58.2%) were classified as benign and malignant, respectively. Patients were followed up for a median of 29 months, 33 (24.6%) by both contrast-enhanced computed tomography (CE-CT) and EUS, and 101 (75.4%) by computed tomography (CT) alone. Thirteen patients (9.7%) showed tumor recurrence, five with intra-pancreatic recurrence and eight with extra-pancreatic metastases. An enhancing mural nodule within the dilated main pancreatic duct was successfully detected by EUS in one patient, but not by CE-CT. Two patients developed IPMN-concomitant PDAC during follow up. EUS combined with CH-EUS successfully detected small IPMN-concomitant PDAC in two patients, whereas these lesions were not detected by CT. CH-EUS was useful for better visualization of the margins of IPMN-concomitant PDAC in one of these two patients. CONCLUSION: Endoscopic ultrasonography combined with CH-EUS may improve follow up of patients with resected IPMN.

[A Case of Apocrine Carcinoma in the Breast That Was Difficult to Distinguish from Axillary Apocrine Adenocarcinoma].

An 86-year-old woman visited our hospital with a tumor on her right axilla. Ultrasonography(US)showed a 4 cm tumor between mammary gland and axilla with swelling of some lymph nodes. No distant metastatic lesions were found. The pathological findings revealed breast apocrine carcinoma; therefore, we performed total mastectomy and axillary lymph node dissection. The postoperative pathological findings revealed breast apocrine carcinoma with pT4N2M0, Stage Ⅲb(ER positive, PgR negative, HER2 positive, Ki-67 6%). We present a case of breast apocrine carcinoma confused with axially apocrine adenocarcinoma during the diagnosis and report the relevant literature.

[A Case of Breast Cancer with Infarcted Necrosis That Was Diagnosed Based on Axillary Lymph Node Metastasis].

A 61-year-old woman with a breast tumor detected by mammography examination was admitted to our hospital. Ultrasonography showed a 15.5×7.2mm sized irregular mass at the left BD area. Vacuum-assisted biopsy did not reveal any malignant cells. After 3 months, ultrasonography reexamination showed that the irregular mass had increased to 24.2×16.5mm in size, and it had spread to multiple axillary lymph nodes. The patient was diagnosed with breast cancer by core needle biopsy of the axillary lymph node. Total mastectomy with axillary lymph node dissection was performed. The pathological diagnosis was solid-tubular carcinoma with infarcted necrosis. The number of metastatic axillary lymph nodes was confirmed to be 23 in total. This case was considered very rare and important because there have been very few reports of breast cancer with infarcted necrosis.

[A Case of Advanced Esophageal Cancer Successfully Treated with Neoadjuvant Chemotherapy Containing 5-FU, Docetaxel. and Nedaplatin Combination Therapy].

A 71-year-old man with a history of hypertension, diabetes mellitus, and cerebral infarction was admitted to our hospital with dysphagia. Gastroduodenoscopy, thoracoabdominal CT, and PET-CT findings showed type 2 advanced esophageal cancer( squamous cell carcinoma)with upper mediastinal and cervical lymph node(LN)metastasis: cT3N2M1(LYM #104L), cStage Ⅳ. Two courses of neoadjuvant UDONchemotherapy containing 5-FU(640mg/m / 2, days 1-5), docetaxel(28mg/m2, days 1 and 15), and nedaplatin(72mg/m2, day 1)were administered every 4 weeks. UDONtherapy caused grade(Gr)3 febrile neutropenia, Gr 2 diarrhea, and Gr 1 thrombopenia; the tumor and LNs partially responded to the therapy. After 2 courses of UDONtherapy, esophagectomy with right thoracotomy, 3-field LNdissection, and reconstruction of the gastric tube were performed. The postoperative course was almost uneventful besides recurrent nerve palsy, aspiration, pneumonia, and delirium, and the patient was discharged 60 days after surgery. The pathological diagnosis was ypT0N0M0, ypStage 0, and the histological response of the primary tumor and LNs were evaluated as Gr 3. Neoadjuvant UDON therapy is feasible for elderly patients with advanced esophageal cancer and renal failure or comorbidities, for whom CDDP could not be administered. We are planning a clinical trial to assess the effectiveness of neoadjuvant UDONtherapy.

Imaging and clinicopathological features of nivolumab-related cholangitis in patients with non-small cell lung cancer.

Background Nivolumab demonstrates promising efficacy for the treatment of non-small cell lung cancer and other malignancies. The clinical benefit of nivolumab, however, may be hampered by specific immune-related adverse events (irAEs), and little is known regarding nivolumab-related cholangitis. Methods A computerized search of our clinical database identified 3 metastatic non-small cell lung cancer patients with nivolumab-related cholangitis. All patients were treated with intravenous nivolumab monotherapy (3.0 mg/kg) every 2 weeks until disease progression or irAEs occurred. Clinical data regarding the duration of nivolumab treatment, symptoms, laboratory abnormalities, pathological findings of liver parenchyma biopsy specimens, and management of nivolumab-related cholangitis were analyzed. Results Our analysis revealed that nivolumab-related cholangitis was characterized by (1) localized extrahepatic bile duct dilation without obstruction; (2) diffuse hypertrophy of the extrahepatic bile duct wall; (3) a dominant increase in the biliary tract enzymes alkaline phosphatase and gamma-glutamyl transpeptidase relative to the hepatic enzymes aspartate and alanine aminotransferase; (4) normal or reduced levels of the serum immunological markers antinuclear antibody, antimitochondrial antibody, smooth muscle antibody, and immunoglobulin G4; (5) the pathological finding of biliary tract cluster of differentiation 8-positive T cell infiltration from liver biopsy; and (6) a moderate to poor response to steroid therapy. Conclusions Nivolumab-related cholangitis is associated with distinct imaging and clinicopathological features that distinguish it from acute cholangitis of common etiologies and other immune-related cholangitis. Further studies are warranted to establish the optimal management of patients with this irAE.

Risk Factors for Postoperative Bleeding in Endoscopic Submucosal Dissection of Colorectal Tumors.

BACKGROUND: Colonoscopic removal of adenomatous polyps or early cancer prevents death from colorectal cancer. Endoscopic submucosal dissection (ESD), which enables endoscopists to perform en bloc resection of flat or depressed colorectal tumors >20 mm, has recently been introduced and become a standard procedure in Japan. Although postoperative bleeding (POB) is a major complication associated with ESD, risk factors for POB have not been fully identified. METHODS: A total of 451 patients (509 lesions) who underwent colorectal ESD were retrospectively analyzed to identify clinical parameters associated with POB. RESULTS: POB occurred in 14 patients, and 7 of them had received antithrombotic therapy before ESD. Uni- and multivariate analyses revealed that antithrombotic therapy and rectal tumor location were strongly associated with POB following colorectal ESD. The incidence of POB was higher in patients on heparin bridge therapy (HBT) for the replacement of antithrombotic therapy than in patients with no HBT. Four of 7 patients (57.1%) on antithrombotic therapy experienced POB from the rectal lesions. CONCLUSION: Antithrombotic therapy and rectal lesions result in a higher POB incidence after colorectal ESD.

Primary Hepatic Adenosquamous Carcinoma Associated with Primary Sclerosing Cholangitis.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disorder characterized by multiple fibrotic strictures of the bile duct. More than 40% of deaths in PSC patients are related to malignant tumors, including cholangiocarcinoma. Primary hepatic adenosquamous carcinoma (ASC) is a rare subtype of cholangiocarcinoma containing adenocarcinoma (AC) and squamous cell carcinoma (SCC) components, with a poorer prognosis than other cholangiocarcinomas. We report the first case of a hepatic ASC in a patient with PSC. CASE REPORT: A 28-year-old man was referred for diagnosis and treatment of a liver abscess suspected by contrast-enhanced computed tomography (CE-CT). He had a history of ulcerative colitis and PSC. Abdominal CE-CT revealed a 60-mm-diameter ring-shaped mass with central necrosis in the left lobe. Magnetic resonance imaging demonstrated a poorly circumscribed low-signal-intensity mass in T1-weighted imaging and a high-signal-intensity mass with a scattered low-signal-intensity area in T2-weighted imaging. Abdominal ultrasonography showed a hypoechoic component with a diffuse hyperechoic area in the tumor. Ultrasound-guided biopsy and histological examination showed tumor cells with both squamous and glandular differentiation. Left lobectomy was performed. Microscopic examination revealed 2 components, including moderately differentiated AC and well-differentiated SCC. The final diagnosis was hepatic ASC. CONCLUSION: This is the first reported case of hepatic ASC in a patient with PSC. Patients with PSC should be recognized as being at a risk of not only general cholangiocarcinoma, hepatocellular carcinoma, and metastatic liver tumor, but also ASC.

Detection of High-Grade Pancreatic Intraepithelial Neoplasia without Morphological Changes of the Main Pancreatic Duct over a Long Period: Importance for Close Follow-Up for Confirmation.

Pancreatic intraepithelial neoplasia (PanIN) is a microscopic papillary noninvasive lesion arising from the pancreatic ductal epithelium. However, the natural history and time to progression of high-grade PanIN remain unclear. Herein, we report 2 cases of high-grade PanIN without morphological changes of the main pancreatic duct (MPD) over relatively long periods. In the first case, a 63-year-old man was identified with MPD dilation. Magnetic resonance cholangiopancreatography showed localized stenosis in the pancreatic body with distal MPD dilation. Endoscopic retrograde pancreatography (ERP) was attempted because of possible high-grade PanIN but was unsuccessful. At 15-month follow-up, there was no change in the form of the MPD in various images. However, ERP was re-performed because of possible high-grade PanIN, and cytology showed adenocarcinoma. Postoperative pathology indicated diffuse lesions corresponding to high-grade PanINs in the MPD stenosis and surrounding branches. Final diagnosis was high-grade PanIN. In the second case, a 77-year-old man was identified with MPD dilation. Magnetic resonance cholangiography showed localized stenosis in the MPD of the pancreatic head with distal MPD dilation. He was diagnosed with MPD stenosis caused by chronic pancreatitis, and further examination was not recommended. At 25 months, the patient was referred to our hospital because of a mild change in MPD dilation. ERP showed localized irregular stenosis in the MPD, and cytology showed suspected adenocarcinoma. Postoperative pathology indicated a localized lesion with high-grade PanIN in the branch duct around the MPD stenosis. Final diagnosis was high-grade PanIN. In conclusion, we report 2 cases of high-grade PanIN without morphological changes of the MPD over relatively long periods. Even if a definite diagnosis is not obtained at initial examination, a strict follow-up observational study should be performed. Re-examination, including ERP, should also be considered in cases with risk factors of pancreatic cancer, even if there is no change in MPD form.