Publications by authors named "Yoshinao Oda"

876 Publications

A novel fast kilovoltage switching dual-energy computed tomography technique with deep learning: Utility for non-invasive assessments of liver fibrosis.

Eur J Radiol 2022 Aug 6;155:110461. Epub 2022 Aug 6.

Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Purpose: To investigate whether the iodine density of liver parenchyma in the equilibrium phase and extracellular volume fraction (ECV) measured by deep learning-based spectral computed tomography (CT) can enable noninvasive liver fibrosis staging.

Method: We retrospectively analyzed 63 patients who underwent dynamic CT using deep learning-based spectral CT before a hepatectomy or liver transplantation. The iodine densities of the liver parenchyma (I-liver) and abdominal aorta (I-aorta) were independently measured by two radiologists using iodine density images at the equilibrium phase. The iodine-density ratio (I-ratio: I-liver/I-aorta) and CT-ECV were calculated. Spearman's rank correlation analysis was used to evaluate the relationship between the I-ratio or CT-ECV and liver fibrosis stage, and receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performances of the I-ratio and CT-ECV.

Results: The I-ratio and CT-ECV showed significant positive correlations with liver fibrosis stage (ρ = 0.648, p < 0.0001 and ρ = 0.723, p < 0.0001, respectively). The areas under the ROC curve for the CT-ECV were 0.882 (F0 vs ≥ F1), 0.873 (≤F1 vs ≥ F2), 0.848 (≤F2 vs ≥ F3), and 0.891 (≤F3 vs F4).

Conclusions: Deep learning-based spectral CT may be useful for noninvasive assessments of liver fibrosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ejrad.2022.110461DOI Listing
August 2022

An efficient procedure for the recovery of DNA from formalin-fixed paraffin-embedded tissue sections.

Biol Methods Protoc 2022 26;7(1):bpac014. Epub 2022 Jul 26.

Department of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-Ku, Fukuoka 812-8582, Japan.

With the advent of new molecular diagnostic techniques, retrieving DNA from the formalin-fixed paraffin-embedded (FFPE) tissues has become an essential yet challenging step for efficient downstream processes. Owing to low quality and quantity of DNA retrieved from the FFPE sections, the process is often impractical and needs significant improvements. Here, we established an efficient method for the purification of DNA from FFPE specimens by optimizing incubation temperature, incubation time, and the concentration of a formalin scavenger tris(hydroxymethyl)aminomethane (Tris) for reverse-crosslinking. The optimized method, named "Highly concentrated Tris-mediated DNA extraction" (HiTE), yielded three times the DNA yield per tissue slice compared with a representative DNA extraction kit. Moreover, the use of HiTE-extracted DNA increased the yield of the sequencing library three times and accordingly yielded a log higher and more reproducible sequencing library compared with that obtained using the commonly used commercial kit. The sequencing library prepared from HiTE-extracted FFPE-DNA had longer inserts and produced reads that evenly covered the reference genome. Successful application of HiTE-extracted FFPE-DNA for whole-genome and targeted gene panel sequencing indicates its practical usability.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biomethods/bpac014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9351614PMC
July 2022

Giant cranial angiolipoma with arteriovenous fistula: A case report.

Surg Neurol Int 2022 22;13:314. Epub 2022 Jul 22.

Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Angiolipomas are benign mesenchymal tumors comprising mature adipocytes and abnormal blood vessels, commonly found in the subcutaneous tissue of the trunk and rarely in the skull. Furthermore, sporadic cases of angiolipoma with arteriovenous fistula (AVF) have been reported.

Case Description: We reported the case of a 72-year-old woman who presented with head swelling, seizures, and cognitive dysfunction. Computed tomography and magnetic resonance imaging revealed a right frontal bone tumor exceeding a sagittal suture of up to 10.7 cm. Angiography revealed AVF and varices formation. Endovascular embolization was performed to treat the AVF and reduce blood loss during surgical resection. Two days after the embolization, a craniotomy was performed; however, uncontrollable bleeding was observed at the time of tumor resection. Postoperatively, the patient was symptom-free and has been stable for 2 years without recurrence.

Conclusion: Despite careful preoperative evaluation and treatment planning, the patient in this case report was difficult to treat. Such cases require adequate preparation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.25259/SNI_422_2022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9345094PMC
July 2022

Nuclear β-catenin translocation plays a key role in osteoblast differentiation of giant cell tumor of bone.

Sci Rep 2022 Aug 4;12(1):13438. Epub 2022 Aug 4.

Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka City, 812-8582, Japan.

Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-17728-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9352730PMC
August 2022

The utility of core-needle tumor biopsy for pediatric patients.

Pediatr Int 2022 Apr 29;64(1):e15228. Epub 2022 Apr 29.

Department of Pediatric Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Core-needle biopsy (CNB) is used less frequently for the diagnosis of tumors in pediatric patients. In this report, the utility and safety of CNB for pediatric patients are described.

Methods: The medical records of patients who underwent CNB at the Department of Pediatric Surgery, Kyushu University Hospital from April 2020 to November 2021 were retrospectively reviewed. A 14 G or 16 G BARDMISSION Disposable Needle Instrument was used. For the diagnosis of neuroblastoma, a 14 G needle was selected; for the diagnosis of other tumors a 16 G needle was selected.

Results: During the above period 17 CNBs were performed in 17 patients, and the median patient age was 8 years (range, 15 days-19 years). The pathological diagnoses of the tumors were as follows: neuroblastoma, n = 6; lymphoma, n = 3; hepatoblastoma, n = 2; and others, n = 6. The quantity and quality of all tumor samples obtained by CNB was sufficient to make a diagnosis. The postoperative course after CNB was uneventful in most cases, with the exception of one case of hepatoblastoma (pseudoaneurysm).

Conclusions: Core-needle biopsy is useful for pediatric patients. Sufficient tumor specimens were able to be obtained in all cases, irrespective of the type of tumor, and an accurate diagnosis could be made.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.15228DOI Listing
April 2022

Impact of JMJD6 on intrahepatic cholangiocarcinoma.

Mol Clin Oncol 2022 Aug 23;17(2):131. Epub 2022 Jun 23.

Department of Surgery and Science, School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan.

The association of Jumonji domain-containing 6 (JMJD6) with the prognosis of various types of cancer has been demonstrated, except in intrahepatic cholangiocarcinoma (ICC). The present study aimed to clarify the impact of JMJD6 on ICC. The liver specimens of 51 patients who underwent surgery for ICC were analyzed for JMJD6 expression using immunohistochemistry staining. The relationship between clinicopathological factors and JMJD6 expression was investigated. The cellular activity was also evaluated in JMJD6 knocked down cells with Transwell migration assay and viability assay. In the immunohistochemistry staining of clinical samples, high expression of JMJD6 was seen in 32 of 51 samples. High expression was also associated with improved overall survival (OS) and recurrence-free survival (RFS) (P=0.0033 and 0.048, respectively). Further analyses revealed that higher JMJD6 expression was one of the improved independent prognostic factors of OS and RFS. Expression of JMJD6 was knocked down in commercial culture cell lines of ICC, and RNA and protein were extracted to analyze the downstream gene expression using RNA-sequencing and western blotting. JMJD6 knockdown was associated with higher programmed death-ligand 1 (PD-L1) expression in RNA-sequencing and western blotting. In addition, PD-L1 expression was higher in JMJD6 low expression clinical samples when measured using immunohistochemistry staining. In conclusion, high expression of JMJD6 was an independent favorable prognostic factor of ICC. JMJD6 may influence the prognosis of ICC through the regulation of PD-L1 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/mco.2022.2564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326512PMC
August 2022

Tropomyosin-related Kinase B Is Potentially a Biomarker of Prognosis and Therapeutic Target for Malignant Thymic Epithelial Tumors.

Anticancer Res 2022 Aug;42(8):3779-3787

Department of Anatomic Pathology, Graduate School of Medical Science, Kyushu University, Fukuoka, Japan;

Background/aim: Thymic epithelial tumors (TETs) mainly consist of thymoma and thymic carcinoma. Complete surgical resection is vital for the successful management of these TETs, and adjuvant therapy such as systematic chemotherapy and/or radiotherapy plays important roles in the management of recurrent or metastasized disease. However, there is still a lack of a standard treatment after the failure of these adjuvant therapies. There is thus a need to develop molecular targeted therapies for advanced malignant TETs. In the present study, we evaluated the biological significance of brain-derived neurotrophic factor (BDNF)/tropomyosin receptor kinase B (TrkB) signaling for TETs.

Materials And Methods: The expression of TrkB in 48 formalin-fixed, paraffin-embedded TET specimens (43 thymoma and 5 thymic carcinoma) collected by surgical resection was evaluated immunohistochemically. A thymic carcinoma cell line was evaluated for the role of BDNF/TrkB signaling pathway in an in vitro assay.

Results: High TrkB expression was related to significantly poor prognosis in patients with TETs. In vitro experiments showed that BDNF/TrkB signaling was involved in the proliferation of Ty-82 cells, but not their invasion and migration.

Conclusion: TrkB expression is a biomarker of the prognosis for TETs and the BDNF/TrkB signaling pathway is potentially a new therapeutic target for mTETs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.15868DOI Listing
August 2022

NECTIN4 expression in sebaceous and sweat gland carcinoma

Eur J Dermatol 2022 04;32(2):181-186

Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Background: Sebaceous carcinoma and sweat gland carcinoma (malignant tumours with apocrine and eccrine differentiation) are rare malignant adnexal tumours that differentiate toward sebaceous glands and eccrine and apocrine glands, respectively. Because of the rarity of these malignancies, standard treatments for advanced disease have yet to be established. The outcomes of patients with systemic metastasis remain poor, highlighting the need for novel treatment strategies. Nectin cell adhesion molecule 4 (NECTIN4) and its antibody-drug conjugate, enfortumab vedotin, have attracted attention as potential treatments for solid tumours.

Objectives: To examine the potential use of NECTIN4-target therapy for sebaceous and sweat gland carcinoma.

Materials & Methods: We immunohistochemically investigated NECTIN4 expression in 14 sebaceous carcinoma samples and 18 sweat gland carcinoma samples, and examined whether NECTIN4-targeted therapy could be applied to these cancers.

Results: We found strong and frequent expression of NECTIN4 in both cancers. All tumours exhibited positive staining at least in a part of the lesion, and the mean H-score, a semiquantitative score ranging from 0 to 300, was 259.4 for sebaceous carcinoma and 253.1 for sweat gland carcinoma.

Conclusion: Our results suggest that both sebaceous carcinoma and sweat gland carcinoma could be potentially treated with NECTIN4-targeted antibody-drug conjugates, such as enfortumab vedotin.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1684/ejd.2022.4241DOI Listing
April 2022

Relationship between consolidation tumor ratio and tumor-infiltrating lymphocytes in small-sized lung adenocarcinoma.

Thorac Cancer 2022 Aug 6;13(15):2134-2141. Epub 2022 Jul 6.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Consolidation tumor ratio (CTR) is associated with cancer progression and histological invasiveness in lung adenocarcinoma (LAD). However, little is known about the association between CTR and immune-related factors, including tumor-infiltrating lymphocytes (TILs) density or tumor expression of programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase 1 (IDO1) in small-sized LAD.

Methods: This study included 258 patients with LAD (<3 cm) who underwent surgery. Patients were assigned to four groups: CTR = 0; 0 < CTR <0.5; 0.5 ≤ CTR <1 (ground-glass opacity [GGO] group); and CTR = 1 (pure-solid group). CD4 , CD8 , and FoxP3 TIL density and PD-L1 and IDO1 tumor expression were assessed by immunohistochemistry.

Results: Among the GGO group, CD8 and FoxP3 TIL density increased significantly with increasing CTR (p < 0.001 and p < 0.001, respectively). Moreover, PD-L1 and IDO1 expression was significantly higher in the pure-solid group than in the GGO group (p < 0.001 and p < 0.001, respectively).

Conclusions: CTR was correlated with the abundance of CD8 and FoxP3 TILs in the GGO group. PD-L1 and IDO1 positivity rates were significantly higher in the pure-solid group than in the GGO group. Increased CTR may be correlated with immunosuppressive condition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.14524DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9346188PMC
August 2022

Pancreatic hamartoma: detection of harbouring NAB2::STAT6 fusion gene.

Histopathology 2022 Sep 14;81(3):319-328. Epub 2022 Jul 14.

Department of Pathology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan.

Hamartomas in the pancreas are rare and are often histologically and morphologically similar to solitary fibrous tumours (SFTs). We examined the differences between hamartomas and SFTs at the molecular level. METHODS AND RESULTS: Thirteen patients histopathologically diagnosed with pancreatic hamartoma were included in the study. We also performed STAT6 immunohistochemistry (IHC), which is used in the diagnosis of SFT. Furthermore, for the three cases in which RNA was extracted, reverse transcription polymerase chain reaction to search for NAB2::STAT6 fusions was used. Macroscopically, 13 patients had well-demarcated tumour lesions. Histologically, no islets of Langerhans were observed in the lesions, acinar tissue and ducts were unevenly distributed and elastic fibres were not observed around the ducts by Elastica van Gieson staining. One case contained a lipomatous hamartoma composed mainly of adipose tissue. Seven of the 13 cases demonstrated expression of STAT6 in the nuclei of intervening spindle cells. NAB2::STAT6 fusions were observed in two of the three cases in which RNA was extracted. These two cases also demonstrated STAT6 expression in spindle cells using STAT6 IHC. In one case of lipomatous hamartoma, we did not confirm NAB2::STAT6 fusion or STAT6 expression in STAT6 IHC. CONCLUSION: Of the 13 patients histopathologically diagnosed with hamartoma, two demonstrated NAB2::STAT6 fusions, suggesting the existence of pancreatic hamartomas with molecular-level components identical to those of SFT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/his.14703DOI Listing
September 2022

Clinical significance of signal regulatory protein alpha and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain expression in undifferentiated pleomorphic sarcoma.

J Cancer Res Clin Oncol 2022 Jun 23. Epub 2022 Jun 23.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Purpose: Undifferentiated pleomorphic sarcoma (UPS) is associated with poor prognosis. Recently, signal regulatory protein alpha (SIRPα), which is the immune checkpoint of macrophages, and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), which is the immune checkpoint of T cells and natural killer cells, have been considered as potential targets for cancer immunotherapy. This study aimed to assess the value of SIRPα and TIGIT as prognostic factors of UPS.

Materials And Methods: The cBio Cancer Genomics Portal was used to analyze mRNA expression data of 50 UPS cases in the Cancer Genome Atlas. We retrieved 49 UPS cases and performed immunohistochemistry (IHC) to detect programmed death ligand 1 (PD-L1), SIRPα, CD68, CD163, TIGIT, CD155, and CD8.

Results: SIRPα was positively associated with CD163 (Pearson's r = 0.51, p = 0.0002) as per open access data and IHC of the cohort (p = 0.002), which revealed that SIRPα-positive macrophage infiltration was higher in UPS cells with ≥ 1% PD-L1 expression than that in UPS cells with < 1% PD-L1 expression (p = 0.047). TIGIT was positively correlated with PD-L1 (r = 0.54, p < 0.0001) and CD8A (r = 0.98, p < 0.0001). In 35 of 49 cases, IHC revealed high levels of TIGIT expression on tumor cells. Furthermore, TIGIT expression on tumor cells was negatively correlated with CD155-positive (p = 0.0144) and CD8-positive (p = 0.0487) cell infiltration. Survival analysis showed that the high degree of SIRPα-positive macrophage infiltration was associated with poor overall survival and metastasis (p < 0.0001, p = 0.0006, respectively).

Conclusion: SIRPα-positive macrophages infiltrated UPS cells, which predicted poor prognosis. High TIGIT expression on tumor cells was associated with decreased levels of tumor-infiltrating macrophages in UPS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00432-022-04078-yDOI Listing
June 2022

Substantial improvement of histopathological diagnosis by whole-slide image-based remote consultation.

Virchows Arch 2022 Aug 7;481(2):295-305. Epub 2022 Jun 7.

Department of Pathology, Graduate School of Biomedical Sciences, Nagasaki University, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.

Consultation by subspecialty experts is the most common mode of rendering diagnosis in challenging cases in pathological practice. Our study aimed to highlight the diagnostic benefits of whole-slide image (WSI)-based remote consultation. We obtained diagnostically challenging cases from two institutions from the years 2010 and 2013, with histological diagnoses that contained keywords "probable," "suggestive," "suspicious," "inconclusive," and "uncertain." A total of 270 cases were selected for remote consultation using WSIs scanned at 40 × . The consultation process consisted of three rounds: the first and second rounds each with 12 subspecialty experts and the third round with six multi-expertise senior pathologists. The first consultation yielded 44% concordance, and a change in diagnosis occurred in 56% of cases. The most frequent change was from inconclusive to definite diagnosis (30%), followed by minor discordance (14%), and major discordance (12%). Out of the 70 cases which reached the second round, 31 cases showed discrepancy between the two consultants. For these 31 cases, a consensus diagnosis was provided by six multi-expertise senior pathologists. Combining all WSI-based consultation rounds, the original inconclusive diagnosis was changed in 140 (52%) out of 266 cases. Among these cases, 80 cases (30%) upgraded the inconclusive diagnosis to a definite diagnosis, and 60 cases (22%) changed the diagnosis with major or minor discordance, accounting for 28 cases (10%) and 32 cases (12%), respectively. We observed significant improvement in the pathological diagnosis of difficult cases by remote consultation using WSIs, which can further assist in patient healthcare. A post-study survey highlighted various benefits of WSI-based consults.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00428-022-03327-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9172976PMC
August 2022

Potential therapeutic targets discovery by transcriptome analysis of an in vitro human gastric signet ring carcinoma model.

Gastric Cancer 2022 Sep 4;25(5):862-878. Epub 2022 Jun 4.

Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Background: Loss of E-cadherin expression is frequently observed in signet ring carcinoma (SRCC). People with germline mutations in CDH1, which encodes E-cadherin, develop diffuse gastric cancer at a higher rate. Loss of E-cadherin expression is thus assumed to trigger oncogenic development.

Methods: To investigate novel therapeutic targets for gastric SRCC, we engineered an E-cadherin-deficient SRCC model in vitro using a human gastric organoid (hGO) with CDH1 knockout (KO).

Results: CDH1 KO hGO cells demonstrated distinctive morphological changes similar to SRCC and high cell motility. RNA-sequencing revealed up-regulation of matrix metalloproteinase (MMP) genes in CDH1 KO hGO cells compared to wild type. MMP inhibitors suppressed cell motility of CDH1 KO hGO cells and SRCC cell lines in vitro. Immunofluorescent analysis with 95 clinical gastric cancer tissues revealed that MMP-3 was specifically abundant in E-cadherin-aberrant SRCC. In addition, CXCR4 molecules translocated onto the cell membrane after CDH1 KO. Addition of CXCL12, a ligand of CXCR4, to the culture medium prolonged cell survival of CDH1 KO hGO cells and was abolished by the inhibitor, AMD3100. In clinical SRCC samples, CXCL12-secreting fibroblasts showed marked infiltration into the cancer area.

Conclusions: E-cadherin deficient SRCCs might gain cell motility through upregulation of MMPs. CXCL12-positive cancer-associated fibroblasts could serve to maintain cancer-cell survival as a niche. MMPs and the CXCL12/CXCR4 axis represent promising candidates as novel therapeutic targets for E-cadherin-deficient SRCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10120-022-01307-8DOI Listing
September 2022

Cyclin-dependent kinase 8 is an independent prognosticator in uterine leiomyosarcoma.

Pathol Res Pract 2022 Jul 26;235:153920. Epub 2022 Apr 26.

Department of Anatomic Pathology, Pathological Sciences, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Cyclin-dependent kinase 8 (CDK8) is associated with the transcriptional mediator complex and regulates several transcription factors implicated in cancer. CDK8 expression is a poor prognostic marker in colon and breast cancer by immunohistochemistry. However, somatic mutations in exon 2 of the RNA polymerase II transcriptional mediator subunit MED12 occur in 7-30% of cases of uterine leiomyosarcoma (ULMS), suggesting that these alterations contribute to tumorigenesis. Public genomic mutation data of 80 patients with ULMS were used for MED12 and CDK8 mutation analysis. The expression of MED12, CDK8 and β-catenin was evaluated by immunohistochemistry in our cohort of 60 patients with ULMS, in addition with MED12 mutation status and survival stage. Univariate analysis was performed using the log-rank test, and Cox regression was used to identify independent prognostic factors. Multivariate Cox regression analysis revealed that advanced stage (p < 0.0001) and high CDK8 expression (p = 0.0014) were independent predictors of poor prognosis. MED12 mutation status was not significantly associated with CDK8 expression (p = 0.6873) and DSS (p = 0.8075). In conclusion, our data suggest that CDK8 expression may identify a subset of ULMS patients with a poor prognosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2022.153920DOI Listing
July 2022

M-CSFR expression in the embryonal component of hepatoblastoma and cell-to-cell interaction between macrophages and hepatoblastoma.

Med Mol Morphol 2022 Sep 21;55(3):236-247. Epub 2022 May 21.

Department of Pediatric Surgery and Transplantation, Kumamoto University Graduate School of Medical Sciences, Kumamoto, Japan.

Tumor-associated macrophages (TAMs) have protumor functions in various cancers. However, their significance in hepatoblastoma, the most common liver tumor in children, remains unclear. The aim of this study was to explore the potential roles of TAMs in hepatoblastoma. Immunohistochemical analysis revealed that the density of CD204-positive TAMs was significantly higher in the embryonal component than in other histological subtypes of hepatoblastoma. An in vitro co-culture study with Huh6 cells and human monocyte-derived macrophages (HMDMs) showed that macrophage-colony-stimulating factor receptor (M-CSFR) was strongly up-regulated in the Huh6 cells that were directly co-cultured with HMDMs. The expressions of M-CSFR ligands (interleukin-34 and M-CSF) were also increased by co-culture with HMDMs. The proliferation of HepG2 cells (another hepatoblastoma cell line expressing M-CSFR) was inhibited by an M-CSFR inhibitor. M-CSFR was found to be highly expressed in the embryonal component and in recurrent lesions. The number of CD204-positive macrophages was also higher in the M-CSFR-positive areas than in the M-CSFR-negative areas. Thus, M-CSFR expression appeared to be induced by cell-cell contact with macrophages in hepatoblastoma cells, and M-CSFR inhibitor is potentially effective against M-CSFR-positive hepatoblastoma, especially recurrent cases.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00795-022-00323-yDOI Listing
September 2022

Cancer genomic profiling identified dihydropyrimidine dehydrogenase deficiency in bladder cancer promotes sensitivity to gemcitabine.

Sci Rep 2022 05 20;12(1):8535. Epub 2022 May 20.

Department of Clinical Chemistry and Laboratory Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.

Chemotherapy is a standard therapy for muscle-invasive bladder cancer (MIBC). However, genomic alterations associated with chemotherapy sensitivity in MIBC have not been fully explored. This study aimed to investigate the genomic landscape of MIBC in association with the response to chemotherapy and to explore the biological role of genomic alterations. Genomic alterations in MIBC were sequenced by targeted exome sequencing of 409 genes. Gene expression in MIBC tissues was analyzed by western blotting, immunohistochemistry, and RNA microarray. Cellular sensitivity to gemcitabine and gemcitabine metabolite was examined in bladder cancer cells after modulation of candidate gene. Targeted exome sequencing in 20 cases with MIBC revealed various genomic alterations including pathogenic missense mutation of DPYD gene encoding dihydropyrimidine dehydrogenase (DPD). Conversely, high DPYD and DPD expression were associated with poor response to gemcitabine-containing chemotherapy among patients with MIBC, as well as gemcitabine resistance in bladder cancer cells. DPD suppression rendered cells sensitive to gemcitabine, while DPD overexpression made cells gemcitabine-resistant through reduced activity of the cytotoxic gemcitabine metabolite difluorodeoxycytidine diphosphate. This study revealed the novel role of DPD in gemcitabine metabolism. It has been suggested that DPYD genomic alterations and DPD expression are potential predictive biomarkers in gemcitabine treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-12528-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9122908PMC
May 2022

Ampullary Neuroendocrine Neoplasm: Clinicopathological Characteristics and Novel Endoscopic Entity.

Dig Dis 2022 May 19. Epub 2022 May 19.

Background: Neuroendocrine neoplasms of the ampulla of Vater (ampullary NEN) have features of both gastrointestinal and pancreato-biliary (PB) NEN. However, the limited number of studies examining ampullary NEN makes it difficult to clarify their unique characteristics. This study aimed to elucidate the clinical characteristics of ampullary NEN.

Methods: We enrolled 162 patients with PB-NEN diagnosed at Kyushu University Hospital between 2011 and 2020. Clinical features, pathological diagnoses, treatments, and prognoses were retrospectively analyzed. We also compared ampullary NEN with pancreatic NEN (PanNEN).

Results: We analyzed 10 ampullary NEN cases and 149 PanNEN cases. The ampullary NEN cases consisted of four cases of NET G1 (neuroendocrine tumor Grade 1), one NET G2 (Grade 2), and five NECs (neuroendocrine carcinoma). The incidences of NEC and cholangitis were significantly higher in ampullary NEN than in PanNEN. All ampullary NETs had a submucosal tumor-like appearance, as identified by endoscopic ultrasound-guided fine needle aspiration. We treated small NET G1 (<10 mm) with endoscopic papillectomy and large NET G1 with pancreaticoduodenectomy. There were no cases of recurrence after resection. All ampullary NECs presented with the characteristic endoscopic finding of a ''crater sign" similar to deep-mining ulcers seen in gastric malignant lymphoma. Four cases underwent surgical resection, and one case was unresectable. Two patients who underwent multidisciplinary treatment were maintained without recurrence for over 2 years.

Conclusions: Endoscopic findings showed identifiable distinctions between ampullary NETs and NECs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000525013DOI Listing
May 2022

Application of contralateral osteotomy for the en bloc resection of paraspinal and spinal tumours: a report of three cases.

Br J Neurosurg 2022 May 19:1-7. Epub 2022 May 19.

Faculty of Medicine, Department of Orthopaedic Surgery, Saga University, Saga, Japan.

We herein report the effectiveness of contralateral osteotomy of the pedicle and posterolateral elements for en bloc resection (COPPER) of paraspinal and spinal tumours. This surgical method allows for complete resection of the localized tumour in the lateral posterior lesion without removing the entire vertebral body, as in total en bloc spondylectomy. Complete resection of paraspinal and spinal tumours is challenging for spinal surgeons because of anatomical complexities. Although the COPPER method has been introduced as a less invasive surgical procedure for wide resection of spinal tumours, no studies have reported the usefulness of this technique. We identified three patients with paraspinal or spinal tumours who underwent wide resection using the COPPER method and reviewed their clinical, radiological, and pathological outcomes. In all cases, we resected the spinal and paraspinal tumours extending to the anterior column and extravertebral component using the modified COPPER method. All patients underwent en bloc resection with a negative margin. We report three cases of spinal and paraspinal tumours extending to the anterior column and extravertebral component.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/02688697.2022.2076809DOI Listing
May 2022

A deep learning-based approach for the diagnosis of adrenal adenoma: a new trial using CT.

Br J Radiol 2022 Jul 9;95(1135):20211066. Epub 2022 May 9.

Department of Clinical Radiology, Kyushu University, Fukuoka, Japan.

Objective: To develop and validate deep convolutional neural network (DCNN) models for the diagnosis of adrenal adenoma (AA) using CT.

Methods: This retrospective study enrolled 112 patients who underwent abdominal CT (non-contrast, early, and delayed phases) with 107 adrenal lesions (83 AAs and 24 non-AAs) confirmed pathologically and with 8 lesions confirmed by follow-up as metastatic carcinomas. Three patients had adrenal lesions on both sides. We constructed six DCNN models from six types of input images for comparison: non-contrast images only (Model A), delayed phase images only (Model B), three phasic images merged into a 3-channel (Model C), relative washout rate (RWR) image maps only (Model D), non-contrast and RWR maps merged into a 2-channel (Model E), and delayed phase and RWR maps merged into a 2-channel (Model F). These input images were prepared manually with cropping and registration of CT images. Each DCNN model with six convolutional layers was trained with data augmentation and hyperparameter tuning. The optimal threshold values for binary classification were determined from the receiver-operating characteristic curve analyses. We adopted the nested cross-validation method, in which the outer fivefold cross-validation was used to assess the diagnostic performance of the models and the inner fivefold cross-validation was used to tune hyperparameters of the models.

Results: The areas under the curve with 95% confidence intervals of Models A-F were 0.94 [0.90, 0.98], 0.80 [0.69, 0.89], 0.97 [0.94, 1.00], 0.92 [0.85, 0.97], 0.99 [0.97, 1.00] and 0.94 [0.86, 0.99], respectively. Model E showed high area under the curve greater than 0.95.

Conclusion: DCNN models may be a useful tool for the diagnosis of AA using CT.

Advances In Knowledge: The current study demonstrates a deep learning-based approach could differentiate adrenal adenoma from non-adenoma using multiphasic CT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1259/bjr.20211066DOI Listing
July 2022

One-year clinical efficacy and safety of indigo naturalis for active ulcerative colitis: a real-world prospective study.

Intest Res 2022 Apr 29;20(2):260-268. Epub 2022 Apr 29.

Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Fukuoka, Japan.

Background/aims: Recent studies suggested a favorable effect of indigo naturalis (IN) in inducing remission for refractory ulcerative colitis (UC), however, the maintenance effect of IN for patients with UC remains unknown. Therefore, we conducted a prospective uncontrolled open-label study to analyze the efficacy and safety of IN for patients with UC.

Methods: Patients with moderate to severe active UC (clinical activity index [CAI] ≥ 8) took 2 g/day of IN for 52 weeks. CAI at weeks 0, 4, 8, and 52 and Mayo endoscopic subscore (MES) and Geboes score (GS) at weeks 0, 4, and 52 were assessed. Clinical remission (CAI ≤ 4), mucosal healing (MES ≤ 1), and histological healing (GS ≤ 1) rates at each assessment were evaluated. Overall adverse events (AEs) during study period were also evaluated. The impact of IN on mucosal microbial composition was assessed using 16S ribosomal RNA gene sequences.

Results: Thirty-three patients were enrolled. The rates of clinical remission at weeks 4, 8, and 52 were 67%, 76%, and 73%, respectively. The rates of mucosal healing at weeks 4 and 52 were 48% and 70%, respectively. AEs occurred in 17 patients (51.5%) during follow-up. Four patients (12.1%) showed severe AEs, among whom 3 manifested acute colitis. No significant alteration in the mucosal microbial composition was observed with IN treatment.

Conclusions: One-year treatment of moderate to severe UC with IN was effective. IN might be a promising therapeutic option for maintaining remission in UC, although the relatively high rate of AEs should be considered.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5217/ir.2021.00124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9081999PMC
April 2022

Nivolumab therapy for a pediatric-onset primary intracranial melanoma.

Pediatr Int 2022 01;64(1):e14956

Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ped.14956DOI Listing
January 2022

Dental pulp stem cells as a therapy for congenital entero-neuropathy.

Sci Rep 2022 04 28;12(1):6990. Epub 2022 Apr 28.

Department of Pediatric Surgery, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan.

Hirschsprung's disease is a congenital entero-neuropathy that causes chronic constipation and intestinal obstruction. New treatments for entero-neuropathy are needed because current surgical strategies have limitations5. Entero-neuropathy results from enteric nervous system dysfunction due to incomplete colonization of the distal intestine by neural crest-derived cells. Impaired cooperation between the enteric nervous system and intestinal pacemaker cells may also contribute to entero-neuropathy. Stem cell therapy to repair these multiple defects represents a novel treatment approach. Dental pulp stem cells derived from deciduous teeth (dDPSCs) are multipotent cranial neural crest-derived cells, but it remains unknown whether dDPSCs have potential as a new therapy for entero-neuropathy. Here we show that intravenous transplantation of dDPSCs into the Japanese Fancy-1 mouse, an established model of hypoganglionosis and entero-neuropathy, improves large intestinal structure and function and prolongs survival. Intravenously injected dDPSCs migrate to affected regions of the intestine through interactions between stromal cell-derived factor-1α and C-X-C chemokine receptor type-4. Transplanted dDPSCs differentiate into both pacemaker cells and enteric neurons in the proximal colon to improve electrical and peristaltic activity, in addition to their paracrine effects. Our findings indicate that transplanted dDPSCs can differentiate into different cell types to correct entero-neuropathy-associated defects.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-022-10077-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9051124PMC
April 2022

Clinical, Radiological, and Histopathological Characteristics of Periosteal Chondrosarcoma with a Focus on the Frequency of Medullary Invasion.

J Clin Med 2022 Apr 6;11(7). Epub 2022 Apr 6.

Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.

Periosteal chondrosarcoma is an extremely rare malignant cartilage-forming tumour that originates from the periosteum and occurs on the surface of bone. Often, it is difficult to distinguish periosteal chondrosarcoma from other tumours, and reports in the literature are scarce. This study aims to investigate the characteristics of periosteal chondrosarcoma, focusing particularly on medullary invasion. Among 33 periosteal cartilaginous tumours, seven patients with pathologically proven periosteal chondrosarcoma were identified retrospectively. The average tumour size was 5.4 cm in the long axis; two tumours were smaller than 3.0 cm. Six tumours were resected with a wide margin, and the remaining tumour had a marginal margin. Histology revealed that six tumours (85.7%) had invaded the medullary cavity; three of these did not show invasion into the medullary cavity on MRI evaluation. Neither local recurrence nor metastasis was observed among these patients. The frequency of invasion of the medullary cavity was higher than that reported previously. The recommended treatment for periosteal chondrosarcoma is resection with an adequate margin. Therefore, surgeons should consider the possibility of medullary invasion when attempting to achieve a histologically negative margin, even if the tumour does not show invasion into the medullary cavity on MRI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm11072062DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8999951PMC
April 2022

Rectal Phenotype of Perianal Paget Disease: Rare Concomitant Phenomena.

Cancer Diagn Progn 2021 Nov-Dec;1(5):387-392. Epub 2021 Nov 3.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Aim: Classically, 'Paget disease' refers to a distinct histological pattern in breast carcinoma. Here, we review the clinicopathological features of anorectal adenocarcinoma with 'pagetoid' spread.

Materials And Methods: Histological and immunohistochemical records for 11 cases of anorectal adenocarcinoma with pagetoid spread among 958 Japanese patients with primary rectal/anal carcinoma were reviewed.

Results: Grossly, nine of 11 cases had areas of invasive carcinoma: Tubular adenocarcinoma in eight and neuroendocrine carcinoma in one. Pagetoid components were positive for cytokeratin 7 in eight cases, cytokeratin 20 and caudal type homeobox 2 in all 11 cases, and p63 in one case, but were negative for estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), gross cystic disease fluid protein-15, and GATA binding protein 3.

Conclusion: The prevalence of perianal Paget disease in this series was 1.1%, with two cases of genuine perianal Paget disease with a rectal phenotype without invasive carcinoma. The rectal phenotype of perianal Paget disease may not be associated with HER2 overexpression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/cdp.10051DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8962862PMC
November 2021

Palisading-like arrangement of immature ganglion cell in myenteric ganglia is a unique pathological feature of immaturity of ganglia.

J Pediatr Surg 2022 Jul 13;57(7):1269-1273. Epub 2022 Mar 13.

Fukuoka College of Health Sciences, 2-15-1 Tamura, Sawara-ku, Fukuoka 814-0193, Japan.

Background: Immaturity of ganglia (IG), an allied disorder of Hirschsprung disease (AD-HSCR), develops as neonatal ileus, but the dysmotility spontaneously resolves after several months. The diagnosis of IG using HE staining is often difficult. We herein report a new pathological finding of IG called the 'palisading-like pattern', which may be helpful for improving the diagnostic accuracy.

Methods: Cases of IG that were managed over the past 28 years were retrospectively reviewed. We investigated the clinical course and pathological findings for Hematoxylin-Eosin (HE) staining. The conventional diagnostic criteria for IG were (1) a normal or slightly increased number of ganglion cells and (2) ganglion cells with small nuclei.

Results: Among the 155 cases, 28 were diagnosed with IG, and 10 were retrospectively confirmed by HE staining. A palisading-like pattern was confirmed at the time of the initial ileostomy (median age, 2.5 days), and the palisading-like pattern had completely disappeared by the time of stoma closure (median age, 215 days) in all 10 cases. A palisading-like pattern is not present in other diseases.

Conclusions: Even if immunostaining data are not available for a further analysis, the detection of a palisading-like pattern on HE staining makes an accurate diagnosis possible.

Level Of Evidence: LEVEL IV.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpedsurg.2022.02.035DOI Listing
July 2022

Three-dimensional imaging of intramural perineural invasion in colorectal cancer: Three-dimensional reconstruction approach with multiple immunohistochemically stained sections.

Pathol Int 2022 May 30;72(5):293-299. Epub 2022 Mar 30.

Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Perineural invasion (PNI) at Auerbach's plexus in colorectal cancer (CRC), known as intramural PNI, is associated with adverse prognostic outcomes. This study aimed to characterize the three-dimensional (3D) architecture of CRC with intramural PNI and to evaluate the morphological features of tumor invasion around nerve tissue. Serial tissue sections from two cases of CRC were stained with cytokeratin AE1/AE3 and an anti-S-100 protein antibody. 3D models were reconstructed by scanning the virtual slides. In one case, intramural PNI was observed at the horizontal invasive front. The 3D reconstruction model showed tumor cells that appeared to infiltrate along the nervous meshwork, the structure of which was preserved. In the other case, intramural PNI was observed both at and behind the horizontal invasive front, and the 3D reconstruction model showed that the tumor cells appeared to be involved with nerve cells at the focal part of the horizontal invasive front. However, the nervous meshwork structure was not well identified in cancer-involved areas. This is the first study to characterize the 3D structure of tumor invasion around nerve tissue in CRC, demonstrating the morphological features of intramural PNI in CRC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/pin.13222DOI Listing
May 2022

Spontaneous Regression of Metachronous Intra-Abdominal Desmoid Tumor in a Patient with Familial Adenomatous Polyposis.

Case Rep Oncol 2022 Jan-Apr;15(1):71-77. Epub 2022 Feb 7.

Department of Oncology and Social Medicine, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.

Desmoid tumors are clonal fibroblastic neoplasms that arise in soft tissues. Patients with familial adenomatous polyposis (FAP) can develop intra-abdominal desmoid tumors. However, metachronous appearance of intra-abdominal desmoid tumor is rare, and its clinical course is not well known. Here, we report a case of spontaneous regression of metachronous intra-abdominal desmoid tumor in a 36-year-old man with FAP. The patient was diagnosed with FAP and underwent laparoscopic total colorectomy. Intra-abdominal desmoid tumor appeared 2 years later and progressed despite treatment with tamoxifen and sulindac. He received four cycles of combinatory therapy with dacarbazine and adriamycin, resulting in shrinkage and stabilization of the desmoid tumor even after cessation of chemotherapy. A new intra-abdominal desmoid tumor developed 2 years later at a different site from the first lesion and progressed from 65 mm to 70 mm in diameter within a month. The size of the first lesion, however, remained unchanged. We prepared for chemotherapy because the second lesion progressed, but follow-up computed tomography showed spontaneous shrinkage of the second lesion. The patient still has not needed additional therapy as of more than 4 years after the appearance of the second lesion. Immunohistochemical staining showed the presence of macrophages in the second lesion. Although metachronous intra-abdominal desmoid tumor is rare and management protocols have yet to be established, this case suggests that an active surveillance approach may be applicable under careful follow-up in asymptomatic patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000521920DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921902PMC
February 2022

Diagnostic utility of ERG immunostaining in dermatofibroma.

J Clin Pathol 2022 Mar 22. Epub 2022 Mar 22.

Department of Anatomic Pathology, Kyushu University, Fukuoka, Japan

Aims: Dermatofibroma/fibrous histiocytoma (DF/FH) is a common cutaneous mesenchymal neoplasm exhibiting benign biological behaviour. However, the immunohistochemical utility of erythroblast transformation-specific-related gene (ERG) for diagnosing DF remains unknown. The authors reviewed the immunohistochemical status of ERG in different subtypes of DF and in its differential diagnoses.

Methods: Overall, 97 cases of ordinary DF/FH, 6 cases of aneurysmal FH, 10 cases of cellular FH, 5 cases of angiomatoid FH, 2 cases of epithelioid FH, 64 cases of dermatofibrosarcoma protuberans (DFSP) and 52 cases of fibrous scar were retrieved. As the other histological types of cutaneous neoplasms, 6 cases of myxofibrosarcoma, 4 cases of undifferentiated pleomorphic sarcoma, 11 cases of atypical fibroxanthoma, 19 cases of malignant melanoma, 20 cases of nevocellular nevus, 20 cases of neurofibroma, 19 cases of schwannoma, 8 cases of angioleiomyoma and 1 case of pilar leiomyoma were included.

Results: Immunohistochemical positivity for ERG was demonstrated in 87 of 97 cases (89.6%) of ordinary DF/FH, 7 of 10 cases (70%) of cellular FH, 3 of 6 cases (50%) of aneurysmal FH, 1 of 5 cases (20%) of angiomatoid FH and 1 of 52 cases (0.1%) of fibrous scar. All cases of DFSP, epithelioid FH and other types of cutaneous neoplasms included in the current investigation were negative for ERG. The intensity of ERG immunohistochemical staining in spindle-shaped cells appeared weaker than that in endothelial cells.

Conclusions: DF/FH was frequently positive for ERG immunostaining. ERG immunostaining may thus be useful to distinguish DF/FH from DFSP.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/jclinpath-2022-208158DOI Listing
March 2022

Approach for reclassification of collecting duct carcinoma and comparative histopathological analysis with SMARCB1/INI1-deficient renal cell carcinoma and fumarate hydratase-deficient renal cell carcinoma.

Hum Pathol 2022 06 16;124:36-44. Epub 2022 Mar 16.

Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. Electronic address:

Collecting duct carcinoma (CDC) is a rare subset of high-grade renal cell carcinoma (RCC). To diagnose CDC, it is necessary to rule out other renal tumors including renal medullary carcinoma and fumarate hydratase (FH)-deficient RCC. However, there is overlap in the morphology of these three tumors, which all have poor outcomes. There is also still a need to sufficiently examine the therapeutic strategies for each of these tumors. In this study, we retrospectively reclassified invasive/infiltrating high-grade RCC and investigated its pathological features. We reviewed 18 cases previously diagnosed as "CDC," "FH-deficient RCC," and "unclassified RCC," which were reclassified as SMARCB1/INI1-deficient RCC, FH-deficient RCC, and CDC by SMARCB1/INI1, FH, and 2SC immunohistochemistry (IHC) and FH gene mutational status. As the result, 18 cases were reclassified into 2 cases of SMARCB1/INI1-deficient RCC, 7 cases of FH-deficient RCC, and 9 cases of CDC. The morphological features of each group overlapped, and no specific immunohistochemical expression except for SMARCB1/INI1, FH, and 2SC was detected. These results suggest that invasive/infiltrating high-grade RCC should be diagnosed by the combination of immunohistochemistry and molecular biological technique.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.humpath.2022.03.002DOI Listing
June 2022

Subtypes in pancreatic ductal adenocarcinoma based on niche factor dependency show distinct drug treatment responses.

J Exp Clin Cancer Res 2022 Mar 10;41(1):89. Epub 2022 Mar 10.

Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Fukuoka, 812-8582, Japan.

Background: Pancreatic ductal adenocarcinoma (PDAC) is characterized by abundant stroma in which microenvironmental (niche) factors promote PDAC progression. In mouse models, reduction of the stroma increased the proportion of poorly differentiated PDAC with a worse prognosis. Here, we aimed to clarify the effects of stroma on PDAC that may define the PDAC phenotype and induce distinct therapeutic responses.

Methods: The molecular features of PDAC based on differentiation grade were clarified by genome and transcriptome analysis using PDAC organoids (PDOs). We identified the dependency on niche factors that might regulate the differentiation grade. A three-dimensional co-culture model with cancer-associated fibroblasts (CAFs) was generated to determine whether CAFs provide niche factors essential for differentiated PDAC. PDOs were subtyped based on niche factor dependency, and the therapeutic responses for each subtype were compared.

Results: The expression profiles of PDOs differed depending on the differentiation grade. Consistent with the distinct profiles, well differentiated types showed high niche dependency, while poorly differentiated types showed low niche dependency. The three-dimensional co-culture model revealed that well differentiated PDOs were strongly dependent on CAFs for growth, and moderately differentiated PDOs showed plasticity to change morphology depending on CAFs. Differentiated PDOs upregulated the expression of mevalonate pathway-related genes correlated with the niche dependency and were more sensitive to simvastatin than poorly differentiated PDOs.

Conclusions: Our findings suggest that CAFs maintain the differentiated PDAC phenotype through secreting niche factors and induce distinct drug responses. These results may lead to the development of novel subtype-based therapeutic strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13046-022-02301-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8908673PMC
March 2022
-->