Background Pancreatic cancer has a dismal prognosis that is attributed to common local invasiveness and metastasis. Epithelial-to-mesenchymal transition (EMT) plays an important role in cancer ...invasion and metastasis and is associated with early dissemination. The aim of this study was to evaluate the association between EMT and the prognoses for patients with pancreatic cancer. Methods Immunohistochemistry of E-cadherin and vimentin was performed on surgical specimens from 174 patients who underwent resection of their pancreatic cancers. Tumoral stainings of E-cadherin and vimentin were graded, and EMT statuses were determined by calculating the ratio of vimentin to E-cadherin, whereby patients were categorized into 3 groups: epithelial, intermediate, and mesenchymal. The correlations between EMT statuses and clinicopathologic factors and prognoses were analyzed. Results There was a significant correlation between EMT status and CA19-9 levels ( P = .020); peritoneal washing cytology ( P = .025); portal vein invasion ( P = .038); and lymph node metastasis ( P = .030). The median survival for patients with epithelial tumors was 40.2 months as compared to 13.7 months for patients with mesenchymal tumors. Multivariate analysis demonstrated that perineural invasion ( P = .024); lymph node metastasis ( P = .033); and EMT status ( P < .0001) were significant prognostic factors. It is interesting that adjuvant chemotherapy (gemcitabine and/or S-1) improved the median survival time from 10.8 to 16.1 months in patients with mesenchymal tumors ( P = .002); however, no significant difference was seen in patients with epithelial tumors. Conclusion EMT status is an important prognostic factor for pancreatic cancer and is associated with portal vein invasion and lymph node metastasis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background and Aims In the International Consensus Diagnostic Criteria (ICDC), autoimmune pancreatitis (AIP) is classified into types 1 and 2, and its definite histopathology diagnosis can be made ...based only on surgical or core biopsy specimens. Although EUS-guided FNA (EUS-FNA) biopsy is a safe technique for the collection of pancreatic tissue, no consensus viewpoint has been reached with regard to the role of EUS-FNA biopsy in the diagnosis of AIP. This study investigated the utility of pancreatic tissue collected by EUS-FNA biopsy by using a standard 22-gauge aspiration needle in the diagnosis of AIP. Methods Patients with suspected AIP were prospectively enrolled in Nagoya University Hospital and Nagoya University–affiliated institutions. Pancreatic tissue was collected from each by EUS-FNA biopsy with a standard 22-gauge aspiration needle. Results Fifty patients were registered, including 45 with a final diagnosis of AIP. Lymphoplasmacytic infiltration and abundant immunoglobulin G4 –positive plasmacyte infiltration (>10/high-power field) were detected in 36 (72%) and 27 (54%) patients, respectively. Obliterative phlebitis and storiform fibrosis were not detected in our study. Granulocytic epithelial lesions (GEL) were observed in 3 patients. The sensitivity, specificity, positive predictive value, and negative predictive value of EUS-FNA biopsy to definitively diagnose AIP were 7.9% (3/38), 100% (12/12), 100% (3/3), and 25.5% (12/47), respectively. Pathology evaluation of pancreatic tissue collected by EUS-FNA biopsy improved the diagnostic accuracy in 8 (16%) of the 50 patients. Conclusions In this study, EUS-FNA biopsy by using a standard 22-gauge aspiration needle is not an effective diagnostic method for most patients with AIP. The combination of level 2 histology diagnosis of AIP with other findings specified in the ICDC slightly improved the diagnostic accuracy, although it still remains insufficiently accurate for routine clinical use.(Clinical trial registration number: 000006297.)
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
In gastric cancer, the non‐canonical Wnt signaling pathway is activated by Wnt5a, which has a critical role in disease outcome. Previous studies have shown that Wnt5a mediates the expression of the ...extracellular matrix protein laminin γ2 through Rac and JNK activation to promote gastric cancer progression. However, the mechanism of this regulatory pathway has not been completely addressed. The scaffold protein Dvl is a major component of the Wnt signaling pathway. Here, we show that Dvl‐associating protein with a high frequency of leucine residues (Daple) mediates Wnt5a‐induced laminin γ2 expression. Immunohistochemical analysis showed marked expression of Daple in advanced clinical stages of gastric cancer, where it highly correlated with Wnt5a/b and laminin γ2 expression, the depth of wall invasion, and the frequency of lymph node metastasis. In cultured cancer cells, Daple depletion led to the suppression of Wnt5a‐induced Rac and JNK activation, laminin γ2 expression, and cell migration and invasion. Accordingly, Daple depletion also suppressed liver metastasis in a mouse xenograft model of gastric cancer. These results suggest that the non‐canonical Wnt signaling pathway contributes to gastric cancer progression at least in part via Daple, which provides a new therapeutic opportunity for the treatment of the disease.
In the present study, we focused on the function of Daple (Dvl‐associating protein with a high frequency of leucine residues), which we previously showed mediates the non‐canonical Wnt signaling pathway. Histological analysis on human gastric cancer tissues showed marked expression of Daple, which was correlated with Wnt5a/b and laminin γ2 expression in invasive gastric cancer. We also found that Daple mediates Wnt5a‐induced Rac and JNK activation, laminin γ2 expression, and migration and invasion in gastric cancer cells. Daple depletion suppressed liver metastasis in a mouse xenograft model of gastric cancer. Our data collectively showed that Daple is an essential protein that mediates the non‐canonical Wnt signaling pathway to regulate gastric cancer progression.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
In patients with neurofibromatosis type 1 (NF1), it is important to accurately determine when plexiform neurofibroma (pNF) transforms to a malignant peripheral nerve sheath tumor (MPNST). The purpose ...of this study is to investigate the usefulness of diffusion-weighted imaging (DWI) in differentiating pNF and MPNST in NF1 patients.
Among the NF1 patients who were referred to our hospital between 1985 and 2015, 10 cases of MPNST and 19 cases of pNF were included. We evaluated features of standard magnetic resonance imaging according to the differentiation criteria of malignancy from benignancy as previously reported, apparent diffusion coefficient (ADC) value based on the DWI and the correlation between ADC value and benignancy/malignancy. ROC analysis was performed to determine the appropriate cutoff value of ADC.
There were significant differences between MPNST and pNF in the size of the tumor (P = 0.009), peripheral enhancement pattern (P = 0.002), perilesional edema-like zone (P = 0.0008), and intratumoral cystic change (P = 0.02). The mean and minimum values of ADC were significantly lower in MPNST than those in pNF (P = 0.03 and P = 0.003, respectively). When we set a cutoff value of mean ADC as 1.85 × 10–3 mm2/s, the sensitivity and specificity were 80% and 74%, respectively. The area under the curve value improved by adding the Wasa score to the mean ADC evaluation.
ADC values determined by DWI are useful in differentiating MPNST from pNF and adding ADC evaluation to standard MRI evaluation improved the diagnostic accuracy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The gastrointestinal tract is a rare site for metastatic lung cancer. Programmed cell death‐ligand 1 (PD‐L1) expression in lung cancer is a biomarker for the response to anti‐PD‐1/PD‐L1 therapy. We ...investigated clinicopathological features and PD‐L1 expression in 25 gastrointestinal metastatic tumors from the lung and primary adenocarcinoma of the small bowel. The small bowel was the most common site (16/25; 64%) of gastrointestinal tract lung cancer metastasis. A total of 19 (76%) of the gastrointestinal metastasis showed PD‐L1 expression in ≥5% of tumor cells, with 14 (56%) showing high expression levels (≥50%). In contrast, 21 (84%) expressed PD‐L1 in ≥5% immune cells, including 4 (16%) showing a high expression levels (≥50%). The PD‐L1 expression on tumor cells and immune cells in primary lung cancer and corresponding gastrointestinal metastasis was concordant in 13 (68%) and 11 (58%) of the 19 paired cases, respectively. Small‐bowel metastasis of lung cancer was characterized by a higher incidence of perforation (31% vs. 0%), ulcerated mass (83% vs. 60%), and neoplastic PD‐L1 expression (75% vs. 0%) compared to primary small‐bowel adenocarcinoma. Gastrointestinal metastasis from lung cancer might be a potential target for immune checkpoint inhibitor therapy, given its high expression of PD‐L1.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Amelanotic melanoma is a rare type of melanoma that shows little or no melanin pigmentation. When tumor lesions are not detected in cutaneous sites, the presence of melanin is the hallmark sign of ...malignant melanoma. We herein report a case of amelanotic melanoma with a BRAF V600E mutation mimicking primary lung cancer that was finally diagnosed on an autopsy. The current case suggests important caveats for the differential diagnosis of patients with BRAF V600E mutation-positive poorly differentiated lung tumors. In terms of the pathological diagnosis, routine immunohistochemical staining may be useful, especially in patients with a poorly differentiated lung tumor without TTF-1 expression.
Epstein–Barr virus (EBV) is associated with some disease entities of malignant lymphomas, including Burkitt lymphoma, Hodgkin lymphoma, immunodeficiency‐associated lymphoproliferative disorders ...(LPD), and a part of diffuse large B‐cell lymphoma. We have recently identified a series of elderly patients with EBV‐associated (or EBV+) B‐cell LPD (B‐LPD) showing similarities in many respects to immunodeficiency‐associated LPD, although no evidence of underlying immunodeficiency was found. Therefore, the nosological category of senile or age‐related EBV+ B‐LPD has been proposed for those patients. A larger series of patients with this disease revealed that the relative ratios of such EBV+ B‐LPD to all diffuse large B‐cell lymphoma cases were higher with increasing with age, reaching a peak (20–30%) at ≥90 years of age, with a median of 71 years, providing additional evidence for our assertion that this disease may be related to immunological deterioration as a result of the aging process. This new disease entity is characterized pathologically by centroblasts, immunoblasts, and Hodgkin and Reed–Sternberg‐like giant cells with a varying degree of reactive components, often posing therapeutic and diagnostic problems for hematologists and pathologists, respectively. The aim of the present review is to briefly summarize the overall clinicopathological profile of this newly recognized age‐related (also called ‘senile’) EBV+ B‐LPD and EBV+ Hodgkin lymphoma for a practical diagnostic approach. (Cancer Sci 2008; 99: 1085–1091)
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
We encountered a rare case of low-grade fibromyxoid sarcoma, which is generally known as Evans tumor, with massive calcification originating from the lung. The patient was a 22-year-old man with ...Duchenne muscular dystrophy who was referred for a detailed investigation of an intrathoracic tumor with massive calcification. Although our preoperative diagnosis was a solitary fibrous tumor originating from the mediastinum or diaphragm, intraoperative thoracoscopy revealed the tumor arising from the left lower lobe without adhesion to the other organs. Considering his medical history, we aimed to preserve lung function and chose wedge resection, which completely removed the tumor. Based on the pathological findings, the tumor was diagnosed as low-grade fibromyxoid sarcoma with massive calcification originating from the lung. Although extremely rare, this tumor should be considered as a differential diagnosis for a solitary lung mass with massive calcification in young adults.
Phosphaturic mesenchymal tumor (PMT) is a rare tumor that secretes fibroblast growth factor 23 (FGF23) and causes hypophosphatemia and tumor-induced osteomalacia (TIO). Fusion genes
and
have been ...detected in some PMTs, but the pathogenesis of PMTs without these fusion genes remains unclear. Here, we report a 12-year-old boy with persistent muscle weakness and gait disturbance. Roentgenographic examination revealed a radiolucent lesion with endosteal scalloping in the left fibula, while his serum level of FGF23 was markedly increased. Combined with simple X-ray findings of other body parts, we suspected that TIO was caused by PMT, and resected the tumor. After resection, the serum level of FGF23 started to decrease immediately and normalized within 3 hours after resection, with this being earlier than normalization of the serum phosphorus level. In RNA sequencing,
and
were not detected, but a novel
fusion gene was identified. When we forcedly expressed this fusion gene in HEK293T cells and MG63 cells, cell proliferation was enhanced in both cell lines. Furthermore, Gene set enrichment analysis of HEK293T cells showed significant upregulation of MYC-target genes. Our results suggest that this novel
fusion gene promotes cell proliferation possibly
the MYC pathway and might be one of the etiologies of PMTs other than
or
.
Neonatal necrotizing enterocolitis (NEC) is a serious disease of premature infants that necessitates intensive care and frequently results in life-threatening complications and high mortality. ...Dedifferentiated fat cells (DFATs) are mesenchymal stem cell-like cells derived from mature adipocytes. DFATs were intraperitoneally administrated to a rat NEC model, and the treatment effect and its mechanism were evaluated. The NEC model was created using rat pups hand fed with artificial milk, exposed to asphyxia and cold stress, and given oral lipopolysaccharides after cesarean section. The pups were sacrificed 96 h after birth for macroscopic histological examination and proteomics analysis. DFATs administration significantly improved the survival rate from 25.0 (vehicle group) to 60.6% (DFAT group) and revealed a significant reduction in macroscopical, histological, and apoptosis evaluation compared with the vehicle group. Additionally, the expression of C-C motif ligand 2 was significantly decreased, and that of interleukin-6 decreased in the DFAT group. DFAT administration ameliorated 93 proteins mainly related to proteins of fatty acid metabolism of the 436 proteins up-/down-regulated by NEC. DFATs improved mortality and restored damaged intestinal tissues in NEC, possibly by improving the abnormal expression of fatty acid-related proteins and reducing inflammation.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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