Publications by authors named "Michiyo Higashi"

98 Publications

A case of immunoglobulin G4-related sclerosing mesenteritis without other organ involvement.

Clin J Gastroenterol 2021 Jun 7. Epub 2021 Jun 7.

Department of Human and Environmental Sciences, Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.

A 64-year-old man presented to our hospital with abdominal pain and 4-5 episodes of watery diarrhea per day for 2 months. Abdominal ultrasound examination revealed a mass in the peritoneal cavity, and computed tomography showed a 13.4 cm mass in the mesentery and a 3 cm mass in the mesocolon. The patient underwent laparoscopic partial resection for diagnosis. Microscopically, abundant fibrosis and numerous immunoglobulin (Ig) G4-positive plasma cells were observed. The serum level of IgG4 was 665 mg/dl postoperatively. These findings suggested that the lesion was consistent with IgG4-related sclerosing mesenteritis. Oral steroids resulted in rapid disappearance of symptoms and a decrease in masses. Recently, sclerosing mesenteritis are reported as IgG4-related disease or mimicking IgG4-related disease but multiple lesions rarely occur in the same organ. We report a case of IgG4-related sclerosing mesenteritis with multiple lesions without involvement of other organs, such as the pancreas and salivary glands.
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http://dx.doi.org/10.1007/s12328-021-01451-1DOI Listing
June 2021

Pulmonary infarction caused by sarcoidosis vascular involvement: A case report.

Pathol Int 2021 Jul 26;71(7):480-484. Epub 2021 Apr 26.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Sarcoidosis is a systemic granulomatous disease. In pulmonary sarcoidosis, granulomatous vascular involvement is a common feature that occurs in all types of vessels, including large elastic arteries to venules, but sarcoidosis complicated with pulmonary infarction has not been reported. We report a case of a 60 years old female, who was operated on a clinical diagnosis of lung cancer, and histological examination revealed a pulmonary infarction and sarcoidosis. In the pulmonary elastic arteries, granulomas infiltrated the adventitia and media, and caused elastic fiber collapse and destruction. Arterial occlusion by granulomas was observed in the edge of the infarcted area. It was considered that the arterial sarcoidosis granuloma involvement was the cause of pulmonary infarction. Sarcoidosis is a significant risk factor for cardiovascular events. However, pulmonary infarction is an extremely rare complication of sarcoidosis. Our case suggests that sarcoidosis may cause vascular events in the lungs.
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http://dx.doi.org/10.1111/pin.13104DOI Listing
July 2021

Rare histological subtype of invasive micropapillary carcinoma in the ampulla of Vater: A case report.

World J Clin Cases 2021 Apr;9(11):2671-2678

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.

Background: Carcinoma of the ampulla of Vater is an uncommon ampullo-pancreatobiliary neoplasm, and the most common histological type is adenocarcinoma with a tubular growth pattern. Invasive micropapillary carcinoma (IMPC) is an aggressive variant of adenocarcinoma in several organs that is associated with lymph node metastasis and poor prognosis. IMPC was first described as a histological subtype of breast cancer; however, IMPC of the ampulla of Vater is extremely rare, with only three articles reported in the English literature.

Case Summary: We have reported a case of IMPC of the ampulla of Vater in an 80-year-old man. Microscopically, the surface area of the carcinoma was composed of tubulopapillary structures mimicking intra-ampullary papillary-tubular neoplasm, and the deep invasive front area exhibited a pattern of IMPC. The carcinoma showed lymphatic invasion and extensive lymph node metastasis. The immunohistochemical study revealed mixed intestinal and gastric/pan-creatobiliary phenotypes.

Conclusion: This rare subtype tumor in the ampulla of Vater showed a histologically mixed phenotype and exhibited aggressive behavior.
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http://dx.doi.org/10.12998/wjcc.v9.i11.2671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8040169PMC
April 2021

A deep learning model to detect pancreatic ductal adenocarcinoma on endoscopic ultrasound-guided fine-needle biopsy.

Sci Rep 2021 Apr 19;11(1):8454. Epub 2021 Apr 19.

Department of Pathology, Kurume University School of Medicine, Kurume, 830-0011, Japan.

Histopathological diagnosis of pancreatic ductal adenocarcinoma (PDAC) on endoscopic ultrasonography-guided fine-needle biopsy (EUS-FNB) specimens has become the mainstay of preoperative pathological diagnosis. However, on EUS-FNB specimens, accurate histopathological evaluation is difficult due to low specimen volume with isolated cancer cells and high contamination of blood, inflammatory and digestive tract cells. In this study, we performed annotations for training sets by expert pancreatic pathologists and trained a deep learning model to assess PDAC on EUS-FNB of the pancreas in histopathological whole-slide images. We obtained a high receiver operator curve area under the curve of 0.984, accuracy of 0.9417, sensitivity of 0.9302 and specificity of 0.9706. Our model was able to accurately detect difficult cases of isolated and low volume cancer cells. If adopted as a supportive system in routine diagnosis of pancreatic EUS-FNB specimens, our model has the potential to aid pathologists diagnose difficult cases.
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http://dx.doi.org/10.1038/s41598-021-87748-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8055968PMC
April 2021

Prognostic significance of extracellular volume fraction with equilibrium contrast-enhanced computed tomography for pancreatic neuroendocrine neoplasms.

Pancreatology 2021 Jun 3;21(4):779-786. Epub 2021 Mar 3.

Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima City, 890-8520, Japan.

Background: /Objectives: Identifying reliable pretreatment imaging biomarkers for pancreatic neuroendocrine neoplasm (PanNEN) is a key imperative. Extracellular volume (ECV) fraction quantified with equilibrium contrast-enhanced CT can be easily integrated into routine examinations. This study aimed to determine whether ECV fraction with equilibrium contrast-enhanced computed tomography (CECT) could predict long-term outcomes in patients with PanNEN.

Methods: This study was a retrospective observational study of 80 patients pathologically diagnosed with PanNEN at a single institution. ECV fraction of the primary lesion was calculated using region-of-interest measurement within PanNEN and the aorta on unenhanced and equilibrium CECT. The impact of clinical factors and tumor ECV fraction on progression-free survival (PFS) and overall survival (OS) was assessed with univariate and multivariate analyses using Cox proportional hazards models. The correlation between WHO classification and tumor ECV fraction was evaluated using Kendall rank correlation coefficients.

Results: PFS and OS rates were estimated as 93.4% and 94.6%, 78.7% and 86.2%, 78.7% and 77.0%, and 78.7% and 66.6% at 1, 3, 5, and 10 years, respectively. Multivariate analysis revealed that Union for International Cancer Control (UICC) stage (hazard ratio [HR] = 3.95, P = 0.003), WHO classification (HR = 12.27, P = 0.003), and tumor ECV fraction (HR = 11.93, P = 0.039) were independent predictors of PFS. Patient age (HR = 1.11, P < 0.001), UICC stage (HR = 3.14, P = 0.001), and tumor ECV fraction (HR = 5.27, P = 0.024) were independent significant variables for predicting OS. Tumor ECV fraction had a weak inverse relationship with WHO classification (P = 0.045, τ = -0.178).

Conclusions: ECV fraction determined by equilibrium CECT and UICC stage may predict survival in patients with PanNEN.
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http://dx.doi.org/10.1016/j.pan.2021.02.020DOI Listing
June 2021

Primary monophasic synovial sarcoma of the cervical esophagus confirmed by detection of the SS18-SSX2 fusion transcripts: case report and literature review.

Surg Case Rep 2020 Jul 20;6(1):176. Epub 2020 Jul 20.

Department of Digestive Surgery, Breast and Thyroid Surgery, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima-shi, Kagoshima, 890-8520, Japan.

Background: Synovial sarcoma (SS) of the esophagus is extremely rare. Because of the microscopic features of SS, the monophasic type can easily be misdiagnosed as other spindle cell tumors. Here, we present the first case of a primary SS of the esophagus in the presence of SS18-SSX2 fusion transcripts.

Case Presentation: A 47-year-old Japanese woman was initially diagnosed with thyroid papillary carcinoma in the left lobe and leiomyoma of the cervical esophagus and subsequently underwent left thyroid lobectomy and enucleation of the esophageal tumor. Four years after the first surgery, the esophageal tumor recurred. Endoscopic biopsy of the tumor revealed atypical cell proliferation with spindle cell features and mitoses. Immunohistochemistry showed focal positivity for bcl-2 and HHF35. Furthermore, the presence of SS18-SSX2 fusion transcripts was confirmed by reverse transcription-polymerase chain reaction analysis, using a paraffin-embedded tumor specimen. Therefore, the tumor was diagnosed as monophasic SS of the cervical esophagus. We re-evaluated the surgical specimen enucleated 3 years previously, which was initially diagnosed as leiomyoma, and the diagnosis of SS was confirmed. The patient underwent cervical esophagectomy with isolated jejunal interposition reconstruction. Three years after the second surgery, SS recurred in the distal anastomotic site between the jejunum and the esophagus, and the patient underwent thoracoscopic esophagectomy with gastric conduit reconstruction. The pathological grade of the lesion worsened with every recurrence.

Conclusions: Monophasic SS can be difficult to discriminate from other spindle cell tumors based on microscopy alone, and molecular analysis could be useful for confirming the precise diagnosis of monophasic SS.
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http://dx.doi.org/10.1186/s40792-020-00940-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371770PMC
July 2020

[Single Liver Metastasis of Breast Cancer Mimicking Intrahepatic Cholangiocarcinoma 13 Years after the Primary Surgery-A Case Report].

Gan To Kagaku Ryoho 2020 Jan;47(1):129-131

Dept. of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences.

A 78-year-old woman underwent left total mastectomy for breast cancer at 65 years of age.Thirteen years after the primary surgery, CT showed a single 46mm tumor located in liver segment 4.The tumor was difficult to distinguish between cholangiocellular carcinoma and liver metastasis of the breast cancer.We did not perform biopsy, considering dissemination, and performed left hemihepatectomy and left caudate lobectomy.Pathological findings revealed liver metastasis of breast cancer.Hepatic resection is a useful option in cases of single liver metastasis from breast cancer that are difficult to distinguish from cholangiocellular carcinoma.
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January 2020

Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning.

Clin Cancer Res 2020 05 28;26(10):2411-2421. Epub 2020 Jan 28.

Department of Pathology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

Purpose: Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery.

Experimental Design: We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathologic features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier.

Results: Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also nonneoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system.

Conclusions: Analysis of epigenetic changes in genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.
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http://dx.doi.org/10.1158/1078-0432.CCR-19-1247DOI Listing
May 2020

A case of gallbladder neuroendocrine carcinoma diagnosed preoperatively using somatostatin receptor scintigraphy.

Oncol Lett 2020 Jan 14;19(1):247-254. Epub 2019 Nov 14.

Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.

Gallbladder neuroendocrine carcinoma (NEC) is a rare gallbladder tumor. The current report is a case of a patient preoperatively diagnosed with gallbladder NEC using somatostatin receptor scintigraphy (SRS). A 63-year-old man was admitted to our hospital by a family doctor after abdominal ultrasonography revealed thickened walls of the neck of his gallbladder. At Kagoshima University Hospital, CT and MRI of the abdomen and endoscopic ultrasonography confirmed the thickening of the walls of the neck of the gallbladder. However, it did not resemble a typical gallbladder cancer or tumor, such as a neuroendocrine tumor or malignant lymphoma. Positron emission tomography and SRS showed abnormal accumulation at the tumor site. Endoscopic retrograde cholangiopancreatography was performed, adenocarcinoma was suspected based on intra-gallbladder bile cytology, and a cholecystectomy with lymphadenectomy was performed. The postoperative pathological diagnosis was small cell NEC (pT3a, N0, M0, stage II). Immunohistochemistry indicated that the gallbladder tumor cells were positive for synaptophysin, chromogranin A, and cluster of differentiation (CD) 56, and negative for somatostatin receptors (SSTR) 2 and 5. Gene expression assays revealed the expression of all SSTR subtypes (SSTR1-5) in the tumor. Generally, NECs exhibit poor accumulation in SRS, however, the results of the current case suggest that SRS may be useful in the preoperative diagnosis of NEC.
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http://dx.doi.org/10.3892/ol.2019.11101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6924094PMC
January 2020

Lung recurrence and its therapeutic strategy in patients with pancreatic cancer.

Pancreatology 2020 Jan 26;20(1):89-94. Epub 2019 Nov 26.

Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University, 8-35-1, Sakuragaoka Kagoshima, 890-8520, Japan.

Background: /Objectives: The lung is a major metastatic site of pancreatic cancer (PC). We aimed to assess the features and prognosis of patients with PC according to the recurrence pattern and the effect of resection of recurrent lung lesion.

Methods: We enrolled 168 PC patients who had undergone macroscopically curative resection. All resected lung tumors were evaluated immunohistochemically for expressions of thyroid transcription factor-1 (TTF-1) and napsin A.

Results: The most common site of first recurrence was the liver and local site, followed by the lung, peritoneum, and lymph node. Lung recurrence was observed significantly later than was liver recurrence. The median survival time (MST) after recurrence in patients with first recurrence in the lung was significantly longer than MST in patients with first recurrence in the liver (15.2 months vs 5.2 months, p = 0.039). Seven patients with lung recurrence underwent resection of the recurrent lesion. Surgical resection of single metastasis limited to the lung showed favorable overall survival after recurrence (MST = 36.5 months). Patients with single metastasis limited to the lung showed significantly lower value of FDG-PET SUV of the primary pancreatic tumor.

Conclusions: Patients with first recurrence in the lung showed better prognosis than did patients with first recurrence in the liver. Single metastasis limited to the lung could benefit from surgical resection and was significantly associated with lower FDG-PET SUV of the primary pancreatic tumor.
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http://dx.doi.org/10.1016/j.pan.2019.11.015DOI Listing
January 2020

Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence.

J Cutan Pathol 2020 Feb 1;47(2):154-160. Epub 2019 Sep 1.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka, Kagoshima, Japan.

Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.
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http://dx.doi.org/10.1111/cup.13569DOI Listing
February 2020

Diagnostic utility of linked color imaging in the evaluation of colonic mucosal inflammation in ulcerative colitis: a pilot study.

Endosc Int Open 2019 Aug 24;7(8):E937-E943. Epub 2019 Jul 24.

Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

 Recent studies recommend histological mucosal healing of intestinal tissue as a treatment goal in ulcerative colitis (UC). Linked-color imaging (LCI) is a new endoscopy system that enhances the color differences of the gastrointestinal mucosa. We investigated the efficacy of LCI in the evaluation of intestinal activity, including the histological activity in UC.  A total of 21 UC patients who were evaluated by the LASEREO system (FUJIFILM Co., Tokyo, Japan) were enrolled from August to December in 2016. All of the target points were observed by conventional white-light imaging (WLI) and LCI and biopsied from the region of interest in each view. We quantified the color tones of 73 biopsied points on WLI and LCI using the L*a*b* color value (WLI-L, WLI-a, WLI-b, and LCI-L, LCI-a, LCI-b). We then investigated the relationships among the L*a*b* color values, endoscopic findings, and histological healing.  The average LCI-a and LCI-b values of patients with high mucosal activity disease were significantly higher than in those with mucosal healing (  < 0.01), and only LCI-a was significantly correlated with the score for histological healing. With regard to the other color values (LCI-L and all WLI values), there were no statistically significant differences in terms of average color value and correlation between patients with high mucosal activity and those with mucosal healing. In addition, the difference in the average color values with LCI and WLI was 7.1 and 3.1, respectively.  LCI is more useful than WLI for the visualization and evaluation of mucosal inflammation in UC.
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http://dx.doi.org/10.1055/a-0810-0398DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656553PMC
August 2019

Vascular leiomyosarcoma originating from the right ovarian vein: a case report and literature review.

Surg Case Rep 2019 Jul 24;5(1):120. Epub 2019 Jul 24.

Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Sakuragaoka 8-35-1, Kagoshima, 890-8520, Japan.

Background: Primary leiomyosarcoma (LMS) of vascular origin is a rare lesion, and patients with LMS of vascular origin have poorer prognoses than patients with LMS of other origins. The inferior vena cava is the most commonly affected vessel and accounts for 60% of all vascular cases. However, LMS originating from the ovarian vein is extremely rare, and we are only aware of 15 reported cases. Therefore, we report our experience with a case of LMS originating from the right ovarian vein and review the related literature.

Case Presentation: A 71-year-old Japanese woman with no symptoms was admitted to our hospital because of abnormal findings in a routine abdominal ultrasonography check-up. Contrast-enhanced computed tomography of the abdomen revealed a well-defined, lobulated solid mass with a diameter of 5.5 cm in the right retroperitoneal space. The mass exhibited relatively low uptake during F-fluorodeoxyglucose positron emission tomography. Based on these findings, the differential diagnosis included a retroperitoneal tumor, such as a desmoid tumor, leiomyoma, LMS, and malignant mesothelioma. Operative findings confirmed that the mass had originated from the right ovarian vessels, and en bloc excision was performed for the mass and the right ovarian vessels. The final pathological diagnosis was LMS originating from the right ovarian vein, and the surgical resection margins were free from tumor cells. After histological findings confirmed the LMS diagnosis, the patient underwent adjuvant radiation therapy and has not exhibited signs of local recurrence or metastasis in the 6 months after surgery.

Conclusions: We encountered a 71-year-old woman with LMS originating from her right ovarian vein. The prognosis of vascular LMS is generally poor. Therefore, careful follow-up will be required for our patient.
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http://dx.doi.org/10.1186/s40792-019-0679-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6656842PMC
July 2019

Comprehensive validation of liquid-based cytology specimens for next-generation sequencing in cancer genome analysis.

PLoS One 2019 14;14(6):e0217724. Epub 2019 Jun 14.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

In addition to conventional cytology, liquid-based cytology (LBC) is also used for immunocytochemistry and gene analysis. However, an appropriate method to obtain high quality DNA for next-generation sequencing (NGS) using LBC specimens remains controversial. We determined the optimal conditions for fixation with an alcohol-based fixative for LBC and DNA extraction using cultured cancer cell lines and clinical specimens. The extracted DNA was processed for NGS after the DNA quality was confirmed based on the DNA concentration and degree of degradation. The optimal conditions for cultured cells to obtain high quality DNA were to fix the cells at a density of 6 × 103 or 2 × 104 cells/mL and to use the magnetic bead-based DNA extraction method. Even after storing the fixed cells for 90 days, DNA extracted using the above and other extraction kits, including membrane-based methods, did not undergo degradation. Furthermore, 5-year-old residual LBC samples demonstrated high DNA quality that was suitable for NGS. Furthermore, a cancer genome panel analysis was successfully performed with DNA extracted from cultured cells fixed at 6 × 103 cells/mL for 90 days, and with DNA from residual LBC samples even after 1 year of storage. Residual LBC samples may be a useful source of DNA for clinical NGS to promote genome-based cancer medicine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0217724PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6568385PMC
February 2020

CT and MRI features of undifferentiated carcinomas with osteoclast-like giant cells of the pancreas: a case series.

Abdom Radiol (NY) 2019 04;44(4):1246-1255

Department of Radiology, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.

Purpose: The purpose of this case series was to describe computed tomography (CT) and magnetic resonance imaging (MRI) features of undifferentiated carcinoma with osteoclast-like giant cells of the pancreas.

Methods: Institutional ethics review board approval was obtained, and informed consent was waived for this case series. We reviewed CT and MRI of patients with pathologically confirmed undifferentiated carcinoma with osteoclast-like giant cells of the pancreas found in the medical records of our hospital between 2006 and 2016.

Results: Seven patients (3 males and 4 females; age, 59-82 years (mean, 71)) with confirmation by surgical resection (n = 3) or biopsy (n = 4) were identified. They underwent CT (n = 7) and MRI (n = 6). The tumors 26-83 mm in diameter (mean, 44 mm) were located in the head (n = 4) or body (n = 3) of the pancreas. They were demonstrated as lower attenuation areas relative to the adjacent pancreas on CT images obtained in both pancreatic and portal vein phases (n = 7) with a well-defined smooth margin (n = 5). They were demonstrated as hypointense areas relative to the pancreas on T2-weighted images (n = 4) and T2*-weighted images (n = 4) and diffusion-weighted images (n = 3). They contained hemosiderin deposits on histology (n = 7).

Conclusions: Undifferentiated carcinoma with osteoclast-like giant cells of the pancreas might be present as low attenuation areas with a well-defined smooth margin on CT images obtained in pancreatic and portal vein phases, and hypointense areas on T2-, T2*-, and diffusion-weighted images caused by hemosiderin deposits.
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http://dx.doi.org/10.1007/s00261-019-01958-9DOI Listing
April 2019

An autopsy case of epignathus (immature teratoma of the soft palate) with intracranial extension but without brain invasion: case report and literature review.

Diagn Pathol 2018 Dec 22;13(1):99. Epub 2018 Dec 22.

Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8544, Japan.

Background: Epignathus is a rare congenital orofacial teratoma infrequently associated with intracranial extension. Intracranial extension of an epignathus indicates a poor prognosis; however, only a small number of such cases have been reported. While there have been some studies reporting cases of epignathus expanding directly into the cranium, others have reported no communication between an epignathus and an intracranial tumor.

Case Presentation: A fetus at gestational week 27 was suspected of having an epignathus with intracranial tumor as shown by ultrasonographic and magnetic resonance imaging. The fetus was stillborn and an autopsy was performed. An epignathus measuring 12 × 6 × 6 cm and weighing 270 g protruded from the mouth, with its base on the soft palate. An intracranial tumor weighing 14 g was located at the middle intracranial fossa and connected to the epignathus through the right side of the sella turcica. The intracranial tumor was encapsulated, and there was no invasion into the brain. Histologically, both the epignathus and intracranial tumor were immature teratomas, with neural and pulmonary components that were especially immature as compared to those of the internal organs and brain tissues of the fetus.

Conclusion: There have been several reports of epignathus and intracranial tumors that did not communicate; therefore, careful evaluation is needed when a fetus is suspected of having an epignathus extending into an intracranial lesion. Our case supports the findings that an epignathus can directly expand into the cranium. Moreover, this is a rare case of an epignathus in which the intracranial lesion was encapsulated and did not invade the brain. These rare but important findings will provide additional, potential therapeutic strategies for gynecologists, neurosurgeons, and pathologists.
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http://dx.doi.org/10.1186/s13000-018-0776-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303979PMC
December 2018

Oxidative stress induced by portal vein embolization in fatty liver: Experimental study of a nonalcoholic steatohepatitis model.

Biomed Rep 2018 Oct 8;9(4):357-363. Epub 2018 Aug 8.

Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima 890-8544, Japan.

The present study aimed to investigate whether excessive oxidative stress production or reduction of antioxidative stress potential may occur following portal vein embolization (PVE) in an experimental animal nonalcoholic steatohepatitis (NASH) model. A NASH rabbit model (n=11) was established by feeding of a fat diet for 4 weeks, and a normal diet rabbit model (n=11) was prepared as a control. The oxidative status of NASH was examined by measuring derivatives of reactive oxygen metabolites (d-ROM) for oxidative stress and biological antioxidative potential (BAP) for antioxidative potential in the NASH model and normal group. Additionally, oxidative status of PVE after 2 weeks was assessed by measuring d-ROM and BAP in the NASH and normal liver models. Oxidative status in a PVE+NASH model was also detected. In the process of NASH creation (fat diet for 4 weeks), total cholesterol was increased in the NASH group (P<0.0001). In the NASH group, PVE induced an increase in serum aspartate transaminase (P=0.0318). At 4 weeks after initiation of the fat diet, a decrease in BAP was determined as statistically significant (P<0.0001). In normal liver, d-ROM production was stimulated in the Sham group after 2 weeks (P=0.0152), but BAP was not altered (P=0.6119). In NASH liver, d-ROM production was stimulated in PVE and Sham groups (P<0.0001 and P=0.0189, respectively), but BAP did not change (P>0.05). In conclusion, decrease of antioxidant potential may promote NASH progression. Additionally, PVE appeared to cause a surge in oxidative stress in NASH liver.
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http://dx.doi.org/10.3892/br.2018.1141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6142040PMC
October 2018

PCP4/PEP19 upregulates aromatase gene expression via CYP19A1 promoter I.1 in human breast cancer SK-BR-3 cells.

Oncotarget 2018 Jul 3;9(51):29619-29633. Epub 2018 Jul 3.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

The Purkinje cell protein 4/peptide 19 (PCP4/PEP19) is a novel breast cancer cell expressing peptide, originally found in the neural cells as an anti-apoptotic factor, could inhibit cell apoptosis and enhance cell migration and invasion in human breast cancer cell lines. The expression of PCP4/PEP19 is induced by estrogens in estrogen receptor-positive (ER) MCF-7 cells but also highly expressed in ER SK-BR-3 cells. In this study, we investigated the effects of PCP4/PEP19 on aromatase gene expression in MCF-7 and SK-BR-3 human breast cancer cells. In SK-BR-3 cells but not in MCF-7 cells, PCP4/PEP19 knockdown by siRNA silencing decreased the aromatase expression in gene transcriptional level. When PCP4/PEP19 was overexpressed by CMV promoter-driven PCP4/PEP19 expressing plasmid transfection, aromatase gene transcription increased in SK-BR-3 cells. This aromatase gene transcription is mainly mediated through promoter region PI.1, which is usually active in the placental tissue but not in the breast cancer tissue. These results indicate a new function of PCP4/PEP19 that would enhance aromatase gene upregulation to supply estrogens in heterogeneous cancer microenvironment.
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http://dx.doi.org/10.18632/oncotarget.25651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6049867PMC
July 2018

Extracellular volume fraction determined by equilibrium contrast-enhanced multidetector computed tomography as a prognostic factor in unresectable pancreatic adenocarcinoma treated with chemotherapy.

Eur Radiol 2019 Jan 19;29(1):353-361. Epub 2018 Jun 19.

Department of Radiology, Graduate School of Medical and Dental Sciences, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima City, 890-8544, Japan.

Objectives: To assess whether extracellular volume (ECV) fraction with equilibrium contrast-enhanced multidetector computed tomography (MDCT) predicts outcomes for unresectable pancreatic adenocarcinoma patients treated with chemotherapy METHODS: Sixty-seven patients (42 men, 25 women; mean age, 67.5 years; range, 45-83 years) with histologically confirmed surgically unresectable pancreatic adenocarcinoma underwent contrast-enhanced MDCT before systemic chemotherapy. Tumour contrast enhancement (CE) and ECV fraction were calculated using region-of-interest measurement within the pancreatic adenocarcinoma and aorta on unenhanced and equilibrium phase-enhanced CT. The effect on survival variables including age, sex, tumour location, tumour size, TNM stage, carbohydrate antigen (CA) 19-9, carcinoembryonic antigen (CEA), tumour CE and tumour ECV fraction was determined on univariate and multivariate analyses using Cox proportional hazards regression model.

Results: Median overall survival was 10.5 months. On univariate analysis, elevated serum CA19-9 (hazard ratio (HR), 1.00; p = 0.006) and CEA (HR, 1.02; p = 0.011) levels were found to be associated with a negative effect on overall survival. Increasing tumour CE (HR, 0.98; p < 0.001) and ECV fraction (HR, 0.97; p = 0.001) were associated with a positive effect. Multivariate analysis revealed that only tumour ECV fraction was an independent predictor of overall survival (HR, 0.97; p = 0.012).

Conclusions: ECV fraction with equilibrium contrast-enhanced MDCT could be a useful imaging biomarker for predicting patient survival after chemotherapy for unresectable pancreatic adenocarcinoma.

Key Points: • Tumour aggressiveness and response to therapy are influenced by the extravascular extracellular space. • Extracellular volume (ECV) fraction can be quantified with equilibrium contrast-enhanced CT. • Patients with higher tumour ECV fraction had better prognosis after chemotherapy.
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http://dx.doi.org/10.1007/s00330-018-5570-4DOI Listing
January 2019

Steroidogenesis in ovarian-like mesenchymal stroma of hepatic and pancreatic mucinous cystic neoplasms.

Hepatol Res 2018 Nov 16;48(12):989-999. Epub 2018 Jul 16.

Department of Pathology, Graduate School of Medicine, Tohoku University, Sendai, Japan.

Steroidogenesis In Hepatic Mucinous Cystic Neoplasm: Aim Mucinous cystic neoplasms (MCNs) occur in the ovary, pancreas, and retroperitoneum but very rarely in the liver. Mucinous cystic neoplasms are known to harbor ovarian-like mesenchymal stroma (OLS) expressing progesterone and estrogen receptors. In this study we evaluated steroidogenesis in OLS of 25 hepatic MCNs and 24 pancreatic MCNs. Methods Both steroid receptors and steroidogenic factors were immunohistochemically evaluated using H-scores and results were compared with those in 15 ovarian MCNs and 10 normal ovaries. Results Androgen receptor (AR) H-scores in OLS were significantly higher in hepatic, pancreatic, and ovarian MCN than those in normal ovaries. H-scores of cytochrome P450 17α-hydroxylase/c17-20 lyase (P450c17) and 5α-reductase-1 (5αRED-1) in the stroma were significantly higher in OLS of hepatic and pancreatic MCN than in the stroma of ovarian MCN and normal ovary. In tumor epithelium, AR H-scores were significantly higher in hepatic and pancreatic MCN than in ovarian MCN. In both hepatic and pancreatic MCN, a significant positive correlation was detected between AR H-score in the epithelium and P450c17 H-score in OLS (hepatic MCN: Pearson's r = 0.446, P = 0.025; pancreatic MCN: r = 0.432, P = 0.035). In pancreatic MCN, a significantly positive correlation was detected between AR H-score in the tumor epithelium and 5αRED-1 H-score in OLS (Pearson's r = 0.458, P = 0.024). Conclusions These results indicated that locally produced androgens in OLS could be pivotal for tumorigenesis of both hepatic and pancreatic MCN and influence epithelial cells, possibly in a paracrine fashion, which could represent biological significance of OLS in these neoplasms.
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http://dx.doi.org/10.1111/hepr.13201DOI Listing
November 2018

A new embolic liquid agent comprised of amino acid.

Minim Invasive Ther Allied Technol 2018 Feb 13;27(1):17-21. Epub 2017 Dec 13.

a Department of Diagnostic Radiology , Hiroshima University , Hiroshima , Japan.

Transcatheter arterial or venous embolization has been widely used to address solid tumors by occluding the tumor-feeding vessels. It is also performed to treat portosystemic shunts and to stop bleeding by repair of the site of trauma. Commonly used embolic materials are gelatin sponges, coils, beads, and liquid agents such as absolute ethanol, histoacyryl, and onyx. In the field of interventional radiology, embolotherapy is performed routinely. Liquid embolization agents have different characteristics. Their coagulation time, the inflammatory reaction of the vascular wall or surrounding tissue, and their adhesion to the vascular wall vary. PuraMatrix, a liquid embolic agent not yet available for clinical use, is comprised of amino acid. We introduce and discuss preliminary experimental studies to examine its potential for use in humans.
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http://dx.doi.org/10.1080/13645706.2017.1416409DOI Listing
February 2018

Aortic fibromuscular dysplasia complicated by dissection: a case report and review of literature.

Cardiovasc Pathol 2017 Nov - Dec;31:41-46. Epub 2017 Aug 9.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan. Electronic address:

Fibromuscular dysplasia (FMD) is an idiopathic, segmental, nonatherosclerotic, non-inflammatory vascular disease, which is often complicated by the occurrence of dissection. Although it is known to occur in all arteries, aortic involvement is relatively rare. To date, 33 cases of aortic FMD have been reported in available English literature, among which only three cases have been complicated by the occurrence of dissection. We describe the case of a 40-year-old woman diagnosed with aortic FMD complicated by the occurrence of a type A aortic dissection. Non-invasive imaging revealed an ascending to descending thoracic aneurysm measuring 8 cm in diameter associated with dissection. Histopathologically, a segment of the wall of the aneurysm showed architectural disorganization of the aortic wall with loss of elastic fibers, collagen deposition, and irregular proliferation of smooth muscle cells in the intima and media-features suggesting FMD. No atheromatous plaque or medial cystic degeneration was observed in the aorta. Although aortic FMD is sometimes fatal, it is often very difficult to diagnose using imaging techniques. Therefore, performing a histopathological diagnosis is very important and should be emphasized.
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http://dx.doi.org/10.1016/j.carpath.2017.07.007DOI Listing
July 2018

TET1-mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer.

Genes Cancer 2017 Mar;8(3-4):517-527

Department of Pathology, Research Field in Medicine and Health Sciences, Medical and Dental Sciences Area, Research and Education Assembly, Kagoshima University, Sakuragoaka, Japan.

Lung cancer remains a disease of high mortality, despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in lung neoplasms. Our immunohistochemistry (IHC) studies have shown that high MUC4 expression correlates with a poor outcome. We have also shown that the expression of several mucin genes in cancer cell lines is regulated by DNA methylation. We evaluated the expression level of MUC4, mRNA and several DNA hypomethylation factors in lung tissue samples from 33 patients with various lung lesions. The results indicated that the DNA methylation status of matched the expression level of mRNA. In addition, the (Ten-Eleven Translocation) mRNA showed a significant correlation with the status of DNA methylation of . Furthermore, the treatment of a lung cancer cell line with siRNA caused a reduction in mRNA expression. Thus, we suggest that mediated DNA hypomethylation plays a key role in the expression of MUC4. This is the first report that TET1 mediated DNA hypomethylation regulates the expression of MUC4 in lung cancer. The analysis of these epigenetic changes may be useful for diagnosing carcinogenic risk.
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http://dx.doi.org/10.18632/genesandcancer.139DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5489649PMC
March 2017

Immunohistochemical expression profiles of mucin antigens in salivary gland mucoepidermoid carcinoma: MUC4- and MUC6-negative expression predicts a shortened survival in the early postoperative phase.

Histol Histopathol 2018 Feb 26;33(2):201-213. Epub 2017 Jun 26.

Department of Pathology, Field of Oncology, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, Japan.

In mucoepidermoid carcinoma (MEC), the most common salivary gland carcinoma, there is a lack of novel prognostic markers, but post-operative early recurrence strongly affects the clinical course and a poor outcome. It is critical to predict which MEC patients are prone to develop recurrence/metastases. Mucins play pivotal roles in influencing cancer biology, thus affecting cell differentiation, adhesion, carcinoma invasion, aggressiveness and/or metastatic potential. Our aim is to elucidate the significance of expression profiles for mucins, particularly MUC4 and MUC6, and their correlations with various clinicopathological features and recurrence in salivary gland MECs. We performed immunohistochemical analyses on patients with surgically resected primary MEC using antibodies against mucin core proteins MUC4/8G7 and MUC6/CLH5 in 73 paraffin-embedded samples. Recurrence was noted in 15 of 73 (20.5%) patients. MUC4 or MUC6 expression was considered to be negative when <30% or 0% of the MEC cells showed positive staining, respectively. MUC4- and/or MUC6-negative expression respectively and variably showed a significant relationship to pathological tumor high-grade, the presence of lymphovascular invasion, lymph node metastasis and/or tumor-related death. In addition, MUC4 showed significantly negative co-expression with MUC6. Kaplan-Meier analyses revealed that not only single MUC4/6-negative expression but also the combination of both predicted significantly shorter disease-free and disease-specific survivals in MECs, especially within the first two years postoperatively. Therefore, each mucin plays a pivotal role in the pathogenesis of MEC progression. The detection of MUC4 and/or MUC6 might be a powerful parameter in the clinical management of MECs in the early postsurgical phase.
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http://dx.doi.org/10.14670/HH-11-913DOI Listing
February 2018

Assessment of tumor characteristics based on glycoform analysis of membrane-tethered MUC1.

Lab Invest 2017 09 5;97(9):1103-1113. Epub 2017 Jun 5.

Glycomedicine Technology Research Center (GTRC), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.

Clinical tissue specimens are useful for pathological diagnosis, which is, in some cases, supported by visualization of biomolecule localization. In general, diagnostic specificity in molecular pathology is increased by the acquisition of a probe to distinguish the modification of isomers. Although glycosylation is one of the candidate modifications in a protein, comparative glycan analysis of disease-associated proteins derived from a single tissue section is still challenging because of the lack of analytical sensitivity. Here we demonstrate a possible method for differential glycoform analysis of an endogenous tumor-associated glycoprotein MUC1 by an antibody-overlay lectin microarray. Tissue sections (5 μm thick) of patients with cholangiocarcinoma (CCA; n=21) and pancreatic ductal adenocarcinoma (PDAC; n=50) were stained with an anti-MUC1 antibody MY.1E12 that was established as a monoclonal antibody recognizing an MUC1 glycosylation isoform with a sialyl-core 1 structure (NeuAcα2-3galactosyl β1-3-N-acetylgalactosamine). MY.1E12-positive tissue areas (2.5 mm) were selectively dissected with a laser capture microdissection procedure. The membrane MUC1 was enriched by immunoprecipitation with MY.1E12 and subjected to lectin microarray analysis. Even though the reactivities of MY.1E12 between CCA and PDAC were similar, the lectin-binding patterns varied. We found Maackia amurensis leukoagglutinin and pokeweed lectin distinguished MY.1E12-reactive MUC1 of CCA from that of PDAC. Moreover, MUC1 with M. amurensis hemagglutinin (MAH) reactivity potentially reflected the degree of malignancy. These results were confirmed with MAH-MY.1E12 double fluorescent immunostaining. These glycan changes on MUC1 were detected with high sensitivity owing to the cluster effect of immobilized lectins on a tandem repeat peptide antigen covered with highly dense glycosylation such as mucin. Our approach provides the information to investigate novel glycodynamics in biology, for example, glycoalteration, as well as diseases related to not only MUC1 but also other membrane proteins.
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http://dx.doi.org/10.1038/labinvest.2017.53DOI Listing
September 2017

Unusual morphology of a pulmonary blastoma having an epithelial component with focally significant nuclear pleomorphism.

Pathol Int 2017 07 23;67(7):370-372. Epub 2017 May 23.

Department of Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.

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http://dx.doi.org/10.1111/pin.12541DOI Listing
July 2017

Bilateral Tibial Osteofibrous Dysplasia on 18F-FDG PET/CT.

Clin Nucl Med 2017 Aug;42(8):e375-e376

From the Departments of *Radiology, and †Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

A 17-year-old girl had pain in the right front lower leg while road racing 2 months earlier. Radiography and CT showed osteolytic lesions in the medial part of the bilateral tibia. Bone scintigraphy showed focally increased radiotracer uptake in the bilateral tibia. The lesions showed hypermetabolism on FDG PET/CT. Osteofibrous dysplasia was suspected from the radiographic findings, but adamantinoma or metastases could not be excluded. Surgical biopsies were performed, and histopathologic studies confirmed the diagnosis of bilateral osteofibrous dysplasia.
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http://dx.doi.org/10.1097/RLU.0000000000001702DOI Listing
August 2017

A case of metachronous liver metastasis from neuroendocrine carcinoma of the stomach at 1 year and 10 months after endoscopic submucosal dissection.

Nihon Shokakibyo Gakkai Zasshi 2017 ;114(2):238-247

Department of Gastroenterology, Kirishima Medical Center.

A 77-year-old man underwent endoscopic submucosal dissection (ESD) of a type 0-IIc tumor located in the cardiac part of the stomach. The pathological diagnosis of the tumor was poorly differentiated tubular adenocarcinoma with submucosal invasion depth;therefore, radical gastrectomy was also performed. After 1 year and 10 months, liver metastasis was detected because of which partial liver resection was performed. The pathological diagnosis of the tumor was neuroendocrine carcinoma (NEC). The pathology of the ESD specimen was re-examined, and a diagnosis of gastric NEC was made;furthermore, the liver tumor was regarded as metachronous metastasis. Despite the radical excision of the stage IA tumor, metastasis occurred. Chemotherapy with S-1 alone was successfully performed after the liver resection while considering the advanced age of the patient. Follow-up revealed no signs of recurrence at 1 year and 4 months after the treatment, indicating that the S-1 therapy may be considered for treating NEC in elderly and medically compromised patients owing to its mild side effects.
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http://dx.doi.org/10.11405/nisshoshi.114.238DOI Listing
June 2017

Diagnostic efficacy of liquid-based cytology for solid pancreatic lesion samples obtained with endoscopic ultrasound-guided fine-needle aspiration: Propensity score-matched analysis.

Dig Endosc 2017 Jul 21;29(5):608-616. Epub 2017 Mar 21.

Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.

Background And Aim: There is a paucity of data on the diagnostic efficacy of liquid-based cytology (LBC) for pancreatic samples obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Using propensity score matching, we retrospectively analyzed the additional diagnostic value of LBC compared to a conventional Papanicolaou smear (CPS) for samples of solid pancreatic lesions obtained by EUS-FNA.

Methods: This cohort study included 126 matched patients who underwent initial EUS-FNA for solid pancreatic lesions between January 2009 and August 2014. CPS was used for cytology of EUS-FNA samples obtained until May 2012 (63 patients). Subsequently, LBC was used for cytological analysis (63 patients). Diagnostic yields of CPS and LBC for malignancy were compared. Risk factors for cytological misdiagnosis with LBC were investigated.

Results: Overall rate of malignancy was 86% after matching. LBC had higher diagnostic sensitivity and accuracy than CPS (96.6% vs 84.0%, P = 0.03; and 96.8% vs 87.3%, P = 0.05). LBC was significantly more sensitive for diagnosing pancreatic head lesions (96.4% vs 78.1%, P = 0.04). The sensitivity for pancreatic ductal adenocarcinoma (PDAC) with LBC was higher (98.1% vs 83.0%, P = 0.009). Multivariate analysis revealed that malignant tumors other than PDAC (P = 0.004) and lesion size ≤20 mm (P = 0.046) were risk factors for LBC misdiagnosis in all participants.

Conclusions: For solid pancreatic lesions, LBC of EUS-FNA samples contributes to the diagnosis of malignancy. Malignant tumors other than PDAC and small tumors are difficult to diagnose using EUS-FNA and LBC.
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http://dx.doi.org/10.1111/den.12827DOI Listing
July 2017
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