Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 66
Filter
1.
Appl Immunohistochem Mol Morphol ; 32(1): 24-31, 2024 01 01.
Article in English | MEDLINE | ID: mdl-37859432

ABSTRACT

Recently, the US Food and Drug Administration (FDA) approved the Ventana MMR RxDx Panel as the first immunohistochemical companion diagnostic test for identification of tumors with mismatch repair (MMR) status. The aim of this study was to investigate the accuracy of this test in comparison with polymerase chain reaction (PCR)-based microsatellite instability (MSI) analysis. We assessed the MMR/MSI concordance rate in 140 cases of endometrioid carcinoma. MMR status was evaluated by immunohistochemistry (MMR-IHC), and MSI status was evaluated by PCR-based analysis (MSI-PCR). Potential molecular mechanisms responsible for MSH6 staining variations were also analyzed. Immunohistochemistry showed that 34 tumors (24.3%) were MMRd; these included 26 with combined MLH1/PMS2 loss, 2 with combined MSH2/MSH6 loss, and 6 with isolated MSH6 loss. Heterogeneous MSH6 loss was found in 10 tumors and was recognized only in tumors with combined MLH1/PMS2 loss. Eight of 10 tumors with heterogeneous MSH6 loss harbored MSH6 C8 tract instability, suggesting a secondary somatic event after MLH1/PMS2 loss. MSI-PCR revealed that 102 tumors were MSS, 4 were MSI-low, and 34 were MSI-high. Consequently, MMR-IHC and MSI-PCR showed perfect concordance (kappa=0.080, P <0.0001). However, 10 of the 34 MSI-high tumors, including the 6 tumors with isolated MSH6 loss, showed only minimal microsatellite shift by MSI-PCR, which may have been erroneously interpreted as MSS or MSI-low. On the basis of these findings, we consider that the FDA-approved immunohistochemical panel can detect MMR variations consistently and is more accurate than MSI-PCR for determining the applicability of immune checkpoint inhibitors for treatment of endometrioid carcinomas.


Subject(s)
Carcinoma, Endometrioid , Colorectal Neoplasms , United States , Female , Humans , Carcinoma, Endometrioid/diagnosis , Carcinoma, Endometrioid/genetics , Mismatch Repair Endonuclease PMS2 , United States Food and Drug Administration , Microsatellite Instability , DNA Mismatch Repair , Phenotype , MutL Protein Homolog 1/genetics , MutS Homolog 2 Protein/genetics , Colorectal Neoplasms/pathology
2.
Quant Imaging Med Surg ; 13(1): 441-448, 2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36620149

ABSTRACT

Background: Hemorrhoids are a common benign disorder that can require surgery for treatment. Aluminum potassium sulfate and tannic acid (ALTA) have been used as a sclerotherapy agent that induces noninvasive sclerosis and regression of hemorrhoids without surgery. However, there is no objective index for determining its effectiveness. In this study, we prospectively investigated the usefulness of our method as an objective indicator of the effectiveness of ALTA sclerotherapy. Methods: From April 2015 to April 2019, 241 patients underwent ALTA sclerotherapy. We standardized a simple evaluation method using the lumen of the lower rectum as observed through a clear plastic proctoscope. Patients' hemorrhoids were evaluated preoperatively and their subjective satisfaction with treatment by our new method was evaluated on postoperative day 7. Results: Our method showed that among patients who lost the rectal lumen before treatment, the lumen was reacquired after ALTA sclerotherapy in 96.1% (224/233). McNemar test showed the effect of ALTA sclerotherapy to be significantly associated with lumen gain [κ value, 0.0027; 95% confidence interval (CI): 0.0001-0.0052], P<0.001]. Patients' subjective satisfaction with the treatment was significantly higher in the group reacquiring the lumen (Fisher's exact test, P=0.0186). Among those patients needing re-treatment, 59.4% (19/32) had lost their lumen during follow-up [mean difference, 0.578; standard deviation (SD): 0.502, P<0.001]. Conclusions: Our simple method using a clear plastic proctoscope could objectively indicate the effect of ALTA sclerotherapy and patients who needed re-treatment on losing their lumen during follow-up. We believe this method is highly advantageous for patients, can advocate the concept of the hemorrhoid shrinking sign, and will contribute to the development of new indication criteria for ALTA sclerotherapy.

3.
Gan To Kagaku Ryoho ; 50(13): 1507-1509, 2023 Dec.
Article in Japanese | MEDLINE | ID: mdl-38303323

ABSTRACT

The aim of this study was to evaluate the inflammatory/nutritional index in patients with colorectal cancer. A total of 600 patients with pStage Ⅱ-Ⅲ colorectal cancer who underwent radical resection at our hospital between January 2008 and September 2022 were retrospectively reviewed. Onodera's prognostic nutritional index(OPNI), CRP-to-albumin ratio, modified Glasgow prognostic score, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, lymphocyte-to-monocyte ratio were measured preoperatively. Clinical and pathological data were assessed using univariate and multivariate analysis to determine prognostic factors for overall survival(OS), relapse-free survival(RFS)and post-relapse overall survival (PROS). Moreover, these patients were divided into high and low groups based on OPNI, these survival outcome for OS, RFS and PROS were assessed using Kaplan-Meier analysis with the logrank test. In multivariate analysis, the independent prognostic factors were gender, age, OPNI, histological type, pStage for OS, gender, OPNI, venous invasion and pStage for RFS, and OPNI, histological type and resection of recurrent site for PROS. In Kaplan-Meier analysis, patients in the low OPNI group had significant poor prognosis for OS, RFS and PROS. OPNI is a useful prognostic factor in colorectal cancer.


Subject(s)
Colorectal Neoplasms , Nutrition Assessment , Humans , Retrospective Studies , Prognosis , Neoplasm Recurrence, Local , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology
4.
Environ Pollut ; 311: 119962, 2022 Oct 15.
Article in English | MEDLINE | ID: mdl-35981638

ABSTRACT

We measured the concentrations of cesium isotopes (133Cs, 134Cs, and 137Cs) in zooplankton samples collected in waters off the east coast of Japan from May 2015 to June 2020. By combining these data with those obtained previously from May 2012 to February 2015, we evaluated the long-term impacts of the Fukushima Dai-ichi Nuclear Power Plant accident on marine zooplankton. Relatively high 137Cs concentrations in zooplankton, exceeding 10 Bq/kg-dry weight, were sporadically observed until June 2016, regardless of year or station. After May-June 2017, 137Cs concentrations decreased to below 1 Bq/kg-dry at most stations, and by May 2020, concentrations were below 0.5 Bq/kg-dry except those off Fukushima Prefecture. Since the accident, the 137Cs/133Cs atom ratios of zooplankton samples were higher than those of ambient seawater until 2019, but in May-June 2020 the ratios matched those of seawater except off Fukushima Prefecture. Highly radioactive particles were not detected in zooplankton samples by autoradiography using imaging plates after May-June 2017, although they were before. Therefore, the persistence of elevated 137Cs/133Cs ratios in zooplankton relative to seawater for nine years after the accident was probably due to the incorporation of highly radioactive particles (cesium-bearing particles or clay-mineral aggregates with highly adsorbed radiocesium) onto/into zooplankton for several years after the accident. However, since at least May-June 2017, these elevated ratios have likely been caused by small highly radioactive particles (or larger particles disaggregated into small pieces) entering the ocean from land via rivers or directly discharged from the Fukushima Nuclear Power Plant. Microplastics enriched with radiocesium with higher 137Cs/133Cs ratios than seawater may have also contributed 137Cs to the zooplankton.


Subject(s)
Fukushima Nuclear Accident , Radiation Monitoring , Water Pollutants, Radioactive , Animals , Cesium , Cesium Radioisotopes/analysis , Japan , Nuclear Power Plants , Plastics , Water Pollutants, Radioactive/analysis , Zooplankton
5.
Surg Case Rep ; 8(1): 102, 2022 May 25.
Article in English | MEDLINE | ID: mdl-35610493

ABSTRACT

BACKGROUND: Mesh infection after inguinal hernia repair is a very rare complication. The incidence of late-onset mesh infection is approximately 0.1-0.2% of total hernia repair cases and can lead to serious complications if not treated promptly. Here, we report a rare case of discitis due to late-onset mesh infection, occurring 14 years after an inguinal hernia repair. CASE PRESENTATION: An 89-year-old man was brought to our hospital with right-sided abdominal pain and signs of hypoglycemia. He had a history of type 2 diabetes mellitus and had undergone inguinal hernia repair 14 years ago. Upon admission, laboratory tests revealed no elevated inflammatory markers. Computed tomography (CT) revealed a peri-appendicular abscess. Although the patient was administered empiric antibiotics, on day 3 of admission, his white blood cell count and C-reactive protein levels increased to 38,000/µl and 28 mg/dl, respectively. CT-guided drainage was attempted but was not successful. Escherichia coli was detected in both blood culture collections. On day 7 of admission, the patient complained of back pain; CT on day 10 revealed a peri-appendicular abscess with a soft tissue shadow anterior to the thoracic vertebrae at the 8th/9th level. Thoracic discitis, due to bacteremia originating from the mesh abscess, was suspected. We surgically resected the appendix, followed by removal of the plug and mesh abscess. The post-operative course of the patient was uneventful. For treating discitis, it is known that antibiotic therapy is required for a minimum of 6 weeks. Therefore, on the 30th day post-surgery, the patient was transferred to the orthopedic ward for continued treatment. CONCLUSIONS: This report discusses a rare case of late-onset mesh infection leading to thoracic discitis. Since late-onset mesh infection cannot be treated solely with antibiotics, expeditious surgery should be selected when subcutaneous drainage fails. When an immunocompromised patient with bacteremia has a complaint of back pain, purulent spinal discitis should also be suspected.

6.
Diagn Cytopathol ; 49(6): E203-E206, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33237605

ABSTRACT

We present a case of bronchial mucous gland adenoma (MGA) and discuss the results of its cytomorphological and cytogenetic examination serving as a basis for the differential diagnosis. To our best knowledge, this is a first report that demonstrate a GNAS gene (R201C) mutation in mucous gland adenoma, which may play an important role in MGA tumorigenesis, as is the case in other mucinous-type epithelial neoplasms of various organs.


Subject(s)
Adenoma/genetics , Adenoma/pathology , Bronchial Neoplasms/genetics , Bronchial Neoplasms/pathology , Chromogranins/genetics , GTP-Binding Protein alpha Subunits, Gs/genetics , Aged, 80 and over , Female , Humans , Mutation
7.
AME Case Rep ; 3: 43, 2019.
Article in English | MEDLINE | ID: mdl-31872178

ABSTRACT

Gastric volvulus is the medical situation that a stomach is twisted beyond the physiological range. It is a rare disease which is hard to experience in routine medical examination. Principally surgical treatment is essential for the acute type. However, the conservative therapy should be attempted in some cases, such as decompression of a stomach with a nasogastric tube, endoscopic reduction and so forth. Concerning surgical operation, the base is reduction of the torsion and immobilization of stomach. Recently, laparoscopic surgery is performed for the case that the general condition is stable or chronically progressive in the early stages. Percutaneous endoscopic gastrostomy (PEG) had also been performed for gastric immobilization. However, the recurrences and problems of twisting around the gastrostomy site were reported in addition to the problem of cosmetic outcomes. Therefore, the case is decreasing. In this paper, we present two cases on adult primary gastric volvulus. For the first case, endoscopic reduction was not good enough to release the torsion state. Then laparoscopic gastropexy was performed successfully. For the second case, we succeeded in endoscopic reduction. Since the patient had already experienced gastric volvulus, laparoscopic surgery was performed. The upper and middle gastric bodies were secured to the anterior abdominal wall, and gastric antrum to the ligamentum teres hepatis with interrupted absorbable sutures respectively. However, partial gastric volvulus recurred after ten and a several days postoperatively due to cutting off of the suture at the antrum secured to the ligamentum teres hepatis at previous surgery. Then, PEG for 2 points of lower body and antrum were performed to secure the antrum. The gastrostomies were removed 6 months after the surgery. Immobilization by laparoscopic gastropexy and PEG are useful for gastric volvulus due to their significant merit of minimum invasiveness. Concerning gastropexy, the number of sutures is very important for the secured part not to be torn off.

8.
Pediatr Dermatol ; 36(3): 397-399, 2019 May.
Article in English | MEDLINE | ID: mdl-30811625

ABSTRACT

Both medallion-like dermal dendrocyte hamartoma and fibroblastic connective tissue nevus are rare benign dermal lesions composed of CD34-positive spindle cells. Although regarded as different diseases, it is sometimes difficult to distinguish between them due to their clinical and pathological similarities. We present a case of medallion-like dermal dendrocyte hamartoma that could also be diagnosed as fibroblastic connective tissue nevus and propose the possibility of overlap in these diseases.


Subject(s)
Hamartoma/congenital , Hamartoma/diagnosis , Nevus/diagnosis , Skin Diseases/congenital , Skin Diseases/diagnosis , Antigens, CD34 , Child , Diagnosis, Differential , Female , Humans
9.
J Stroke Cerebrovasc Dis ; 28(5): e37-e38, 2019 May.
Article in English | MEDLINE | ID: mdl-30797641

ABSTRACT

Our objective is to study a 53-year-old woman with Down syndrome presented with massive lobar hematoma in the left fronto-parietal lobe, and who underwent craniotomy and hematoma evacuation. Histopathological diagnosis of surgical specimen was amyloid angiopathy. Postoperative magnetic resonance studies were performed. The lesion this time showed mixed intensity on susceptibility-weighted imaging. In addition, multiple hypointense lesions were evident. An old previously unidentified hemorrhage in the right temporo-parietal lobe was accompanied by superficial cortical siderosis. Old bleeds were apparent in subcortical areas. These various kinds of hemorrhagic lesion were consistent with findings of amyloid angiopathy reported in the elderly. Most reported cases of Down syndrome associated with intracerebral hemorrhage have involved middle-aged patients. Magnetic resonance studies for Down syndrome patients before old age may disclose the degree to which amyloid angiopathy progresses in the brain of these patients.


Subject(s)
Cerebral Amyloid Angiopathy/diagnostic imaging , Cerebral Hemorrhage/diagnostic imaging , Diffusion Magnetic Resonance Imaging , Down Syndrome/complications , Age Factors , Cerebral Amyloid Angiopathy/etiology , Cerebral Hemorrhage/etiology , Cerebral Hemorrhage/surgery , Craniotomy , Disease Progression , Down Syndrome/diagnosis , Female , Hematoma/diagnostic imaging , Hematoma/etiology , Humans , Middle Aged , Predictive Value of Tests , Treatment Outcome
10.
Acta Cytol ; 61(6): 447-454, 2017.
Article in English | MEDLINE | ID: mdl-28954257

ABSTRACT

OBJECTIVE: To demonstrate the usefulness of a direct-smear processing technique employing two-step centrifugation/fixation processing (TSCFP) in the cytoscreening of high-grade urothelial carcinoma (HGUC). STUDY DESIGN: Using the T24 HGUC cell line, we compared the cell yield and the morphological preservation of preparations concurrently processed by direct-smear, SurePath, ThinPrep, and TSCFP techniques. A total of 287 urine cytology cases subjected to TSCFP over a period of 6 years were reviewed and reclassified according to the Paris System for Reporting Urinary Cytology (PSRUC) and correlated with histology results. RESULTS: TSCFP of T24 cells demonstrated good cell yield with a recovery rate of about 70%. Diagnostic features of HGUC, such as a high nuclear/cytoplasmic ratio and irregular/hyperchromatic chromatin, were better discovered in TSCFP smears than in smears prepared with the other methods. Cytological evaluation of 287 voided urine specimens revealed that the rate of unsatisfactory preparations was quite low (0.30%) and the overall sensitivity, specificity, and positive and negative predictive values for urothelial carcinoma were 0.719, 0.923, 0.973, and 0.462, respectively. CONCLUSION: TSCFP was able to provide adequate preparations for detecting HGUC in urine cytology and could be considered as a promising processing method according to the principal purpose of PSRUC.


Subject(s)
Carcinoma, Transitional Cell/pathology , Urologic Neoplasms/pathology , Urothelium/pathology , Carcinoma, Transitional Cell/diagnosis , Centrifugation/methods , Cytoplasm/pathology , Histological Techniques/methods , Humans , Neoplasm Grading/methods , Urologic Neoplasms/diagnosis
11.
J Gastrointest Surg ; 21(11): 1851-1858, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28785935

ABSTRACT

BACKGROUND: We compared tumor growth activity during treatment associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) with that in classical 2-stage hepatectomy. METHODS: Short-term outcomes, serial changes in volume of the future liver remnant (FLR), and tumor growth activity during the treatment period were compared between 12 patients treated with ALPPS and 20 patients treated with 2-stage hepatectomy for colorectal liver metastases. This study was registered in UMIN Clinical Trials Registry (registration number, UMIN000018622). RESULTS: The FLR hypertrophy ratio at 1 week after the first operation was greater in the ALPPS group (1.43 ± 0.24) than the 2-stage group (1.21 ± 0.28, P = 0.043). The mean kinetic growth rate (mKGR) of tumors in the ALPPS group (0.548 ± 7.29 mL/day) did not differ significantly from that in the 2-stage group (-3.53 ± 7.02 mL/day) in the first week after the initial procedure (P = 0.210). However, mKGR between 1 and 3 weeks after the first procedure (1.29 ± 2.34 mL/day) was significantly greater than that in first week after the procedure in the 2-stage group (P = 0.034). CONCLUSIONS: ALPPS induces a rapid FLR volume increase while avoiding remnant tumor progression.


Subject(s)
Hepatectomy/methods , Liver Neoplasms/surgery , Liver Regeneration , Portal Vein/surgery , Embolization, Therapeutic , Female , Humans , Male , Middle Aged
12.
Cancer Sci ; 108(10): 2088-2101, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28746769

ABSTRACT

Analysis of our original microRNA (miRNA) expression signature of patients with advanced renal cell carcinoma (RCC) showed that microRNA-10a-5p (miR-10a-5p) was significantly downregulated in RCC specimens. The aims of the present study were to investigate the antitumor roles of miR-10a-5p and the novel cancer networks regulated by this miRNA in RCC cells. Downregulation of miR-10a-5p was confirmed in RCC tissues and RCC tissues from patients treated with tyrosine kinase inhibitors (TKI). Ectopic expression of miR-10a-5p in RCC cell lines (786-O and A498 cells) inhibited cancer cell migration and invasion. Spindle and kinetochore-associated protein 1 (SKA1) was identified as an antitumor miR-10a-5p target by genome-based approaches, and direct regulation was validated by luciferase reporter assays. Knockdown of SKA1 inhibited cancer cell migration and invasion in RCC cells. Overexpression of SKA1 was observed in RCC tissues and TKI-treated RCC tissues. Moreover, analysis of The Cancer Genome Atlas database demonstrated that low expression of miR-10a-5p and high expression of SKA1 were significantly associated with overall survival in patients with RCC. These findings showed that downregulation of miR-10a-5p and overexpression of the SKA1 axis were highly involved in RCC pathogenesis and resistance to TKI treatment in RCC.


Subject(s)
Carcinoma, Renal Cell/genetics , Chromosomal Proteins, Non-Histone/genetics , Down-Regulation , Drug Resistance, Neoplasm , Kidney Neoplasms/genetics , MicroRNAs/genetics , 3' Untranslated Regions , Aged , Aged, 80 and over , Carcinoma, Renal Cell/drug therapy , Cell Line, Tumor , Cell Movement , Female , Gene Expression Regulation, Neoplastic , Humans , Kidney Neoplasms/drug therapy , Male , Middle Aged , Neoplasm Invasiveness , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , Survival Analysis
13.
Br J Cancer ; 117(3): 409-420, 2017 Jul 25.
Article in English | MEDLINE | ID: mdl-28641312

ABSTRACT

BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC). Genome-wide gene expression studies and in silico analyses were carried out to predict miRNA regulation and investigate the functional significance and clinical utility of the novel oncogenic pathways regulated by these miRNAs in prostate cancer (PCa). RESULTS: Based on the novel miRNA expression signature of CRPC, miR-145-5p and miR-145-3p were downregulated in CRPC. By focusing on miR-145-3p, which is a passenger strand and has not been well studied in previous reports, we showed that miR-145-3p targeted 4 key molecules, i.e., MELK, NCAPG, BUB1, and CDK1, in CPRC. These 4 genes significantly predicted survival in patients with PCa. CONCLUSIONS: Small RNA sequencing for lethal CRPC and in silico analyses provided novel therapeutic targets for CRPC.


Subject(s)
Gene Expression Regulation, Neoplastic , MicroRNAs/genetics , Prostatic Neoplasms, Castration-Resistant/genetics , Prostatic Neoplasms, Castration-Resistant/pathology , Argonaute Proteins/genetics , CDC2 Protein Kinase , Cell Cycle Proteins/genetics , Cell Line, Tumor , Computer Simulation , Cyclin-Dependent Kinases/genetics , Disease-Free Survival , Down-Regulation , Gene Expression , Genome-Wide Association Study , Humans , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Metastasis , Neoplasm Staging , Protein Serine-Threonine Kinases/genetics , RNA-Induced Silencing Complex , Sequence Analysis, RNA , Survival Rate
14.
Ann Surg Oncol ; 24(9): 2456-2464, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28612126

ABSTRACT

BACKGROUND: We studied histologic changes of bile canalicular-ductule networks in the future liver remnant (FLR) while associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS), since little is known about regeneration of these networks during the relatively short interval between procedures in ALPPS. METHODS: Bile canalicular-ductule networks were examined in specimens from eight patients treated with ALPPS and six patients undergoing hepatectomy following portal vein embolization (PVE). Expression of multidrug resistance-1 (MDR1), a membrane transporter in bile canaliculi (BC), was analyzed immunohistochemistcally. Morphologic changes of BC and tight junctions (TJs) adjoining BC were also assessed electron microscopically. RESULTS: Extrapolated kinetic growth of the FLR was greater during ALPPS (17.2 ± 6.8 mL/day) than after PVE (6.3 ± 3.4 mL/day; p = 0.005), and continuity of the MDR1-positive bile canalicular networks was less evident in ALPPS than PVE (p < 0.001). Electron microscopically, no significant difference was evident in numbers of BC or BC lumen size between the two groups; however, development of microvilli in BC was poorer in the ALPPS group than in the PVE group (p < 0.001). TJ/desmosome complexes were shorter in the ALPPS group (0.69 ± 0.52 µm) than in the PVE group (1.09 ± 0.50 µm; p < 0.001), and leaky TJs were seen more frequently in the ALPPS group (64.9 vs. 23.6%; p = 0.001). CONCLUSIONS: Regeneration of bile canalicular-ductule networks in the FLR was poorer in ALPPS than PVE, which may be associated with prolonged cholestasis following final hepatectomy in ALPPS.


Subject(s)
Bile Canaliculi/pathology , Bile Canaliculi/ultrastructure , Embolization, Therapeutic , Hepatectomy/methods , Liver Neoplasms/therapy , Portal Vein , ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism , Adult , Aged , Aged, 80 and over , Bile Canaliculi/metabolism , Desmosomes/ultrastructure , Female , Humans , Immunohistochemistry , Liver/growth & development , Male , Microscopy, Electron, Transmission , Microvilli/ultrastructure , Middle Aged , Tight Junctions/ultrastructure
15.
Int Immunol ; 29(1): 31-45, 2017 01 01.
Article in English | MEDLINE | ID: mdl-28177443

ABSTRACT

It has been reported that splenic immune responses play pivotal roles in the development of allergic diseases; however, the precise role of the spleen remains unclear. Herein, we demonstrated a novel role of the spleen in the pathogenesis of food allergy (FA). We found that mast cells (MCs) developed from progenitor cells present in spleen during an antigen-specific T-cell response in vitro. In a Th2 response-mediated FA model, significant expansion of MCs was also observed in spleen. The incidence of allergic diarrhea was profoundly reduced in splenectomized mice, whereas adoptive transfer of in vitro-induced splenic MCs into these mice restored allergic symptoms, suggesting that the splenic MCs functioned as the pathogenic cells in the development of FA. The in vitro-generated MCs required not only IL-3 but also IFN-γ, and treatment of FA-induced mice with anti-IFN-γ antibody suppressed expansion of MCs in spleen as well as diarrhea development, highlighting that IFN-γ in the spleen orchestrated the development of FA, which was followed by a Th2 response in the local lesion. Overall, we propose that the role of the spleen in the development of FA is to provide a unique site where antigen-specific T cells induce development of pathogenic MCs.


Subject(s)
Food Hypersensitivity/immunology , Mast Cells/immunology , Spleen/immunology , Th2 Cells/immunology , Animals , Female , Food Hypersensitivity/pathology , Interferon-gamma/immunology , Interleukin-3/immunology , Mast Cells/pathology , Mice , Mice, Inbred BALB C , Spleen/pathology , Th2 Cells/pathology
16.
Oncotarget ; 7(37): 59070-59086, 2016 Sep 13.
Article in English | MEDLINE | ID: mdl-27487138

ABSTRACT

Molecular targeted therapy is a standard treatment for patients with advanced renal cell carcinoma (RCC). Sunitinib is one of the most common molecular-targeted drugs for metastatic RCC. Molecular mechanisms of sunitinib resistance in RCC cells is still ambiguous. The microRNA (miRNA) expression signature of patients with sunitinib failure in RCC was constructed using a polymerase chain reaction (PCR)-based array. Several miRNAs that were aberrantly expressed in RCC tissues from patients treated with sunitinib were identified in this analysis. MicroRNA-101 (miR- 101) was markedly suppressed in sunitinib treated RCC tissues. Restoration of miR-101 significantly inhibited cell migration and invasion in Caki-1 and 786-O cells. Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) was directly suppressed by miR-101 in RCC cells, and overexpression of UHRF1 was confirmed in sunitinib-treated RCC tissues. The pathways of nucleotide excision repair and mismatch repair were significantly suppressed by knockdown of UHRF1. Our findings showed that antitumor miR-101- mediated UHRF1 pathways may be suppressed by sunitinib treatment.


Subject(s)
Antineoplastic Agents/therapeutic use , CCAAT-Enhancer-Binding Proteins/genetics , Carcinoma, Renal Cell/drug therapy , Indoles/therapeutic use , MicroRNAs/genetics , Pyrroles/therapeutic use , Biomarkers, Pharmacological , CCAAT-Enhancer-Binding Proteins/metabolism , Carcinoma, Renal Cell/genetics , Cell Line, Tumor , Drug Resistance, Neoplasm , Humans , RNA, Small Interfering/genetics , Sunitinib , Transcriptome , Treatment Failure , Ubiquitin-Protein Ligases
17.
Ann Surg Oncol ; 23(13): 4384-4391, 2016 12.
Article in English | MEDLINE | ID: mdl-27439417

ABSTRACT

BACKGROUND: Chemotherapy-induced liver injury after potent chemotherapy is a considerable problem in patients undergoing liver resection. The aim of this study was to assess the relationship between the fractal dimension (FD) of Tc-99m diethylenetriaminepentaacetic acid (DTPA) galactosyl human serum albumin (GSA) and pathologic change of liver parenchyma in liver cancer patients who have undergone chemotherapy. METHODS: We examined 34 patients (10 female and 24 male; mean age, 68.5 years) who underwent hepatectomy. Hepatic injury was defined as steatosis more than 30 %, grade 2-3 sinusoidal dilation, and/or steatohepatitis Kleiner score ≥4. Fractal analysis was applied to all images of Tc-99m DTPA GSA using a plug-in tool on ImageJ software (NIH, Bethesda, MD). A differential box-counting method was applied, and FD was calculated as a heterogeneity parameter. Correlations between FD and clinicopathological variables were examined. RESULTS: FD values of patients with steatosis and steatohepatitis were significantly higher than those without (P > .001 and P > .001, respectively). There was no difference between the FD values of patients with and without sinusoidal dilatation (P = .357). Multivariate logistic regression showed FD as the only significant predictor for steatosis (P = .005; OR 36.5; 95 % CI 3.0-446.3) and steatohepatitis (P = .012; OR, 29.1; 95 % CI 2.1-400.1). CONCLUSIONS: FD of Tc-99m DTPA GSA was the significant predictor for fatty liver disease in patients who underwent chemotherapy. This new modality is able to differentiate steatohepatitis from steatosis; therefore, it may be useful for predicting chemotherapy-induced pathologic liver injury.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chemical and Drug Induced Liver Injury/diagnostic imaging , Fatty Liver/diagnostic imaging , Fractals , Liver Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Camptothecin/administration & dosage , Camptothecin/analogs & derivatives , Chemical and Drug Induced Liver Injury/pathology , Fatty Liver/chemically induced , Fatty Liver/pathology , Female , Fluorouracil/administration & dosage , Hepatectomy , Humans , Irinotecan , Leucovorin/administration & dosage , Liver Neoplasms/surgery , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Predictive Value of Tests , ROC Curve , Radionuclide Imaging , Radiopharmaceuticals , Risk Factors , Technetium Tc 99m Aggregated Albumin , Technetium Tc 99m Pentetate
19.
Surgery ; 159(5): 1289-98, 2016 May.
Article in English | MEDLINE | ID: mdl-26775576

ABSTRACT

OBJECTIVE: We compared histologic findings in nonneoplastic portions of liver resected during surgery associating liver partition with portal vein ligation for staged hepatectomy (ALPPS) with those from hepatectomy after portal vein embolization (PVE). SUMMARY BACKGROUND DATA: Effects of congestion and ischemia in ALPPS on hepatocyte regeneration are incompletely understood, as are those on hepatocyte maturity. METHODS: Specimens obtained from 8 patients treated with ALPPS and from 14 patients treated with hepatectomy after PVE were examined by light and electron microscopy. RESULTS: Extrapolated kinetic growth of the future liver remnant (FLR) for ALPPS was 14.4 ± 4.8 mL/d, which was faster than for PVE (3.6 ± 2.2 mL/d; P < .001). Microscopically, the FLR showed greater hepatocyte cell density and smaller hepatocyte size in ALPPS than in PVE (P < .01 for each). Bright-appearing hepatocytes and sinusoidal narrowing were more frequent in ALPPS (50% and 50%) than in PVE (0% and 8.3%; P = .025 for each). In the deportalized ventral aspect of the anterior section, hepatocyte atrophy, hepatocyte degeneration or necrosis, sinusoidal dilation, fibrosis, and congestion were more frequent in ALPPS than in PVE (P = .001, P = .002, P < .001, and P < .001, respectively). Electron microscopy frequently showed vacant-appearing hepatocytic cytoplasm filled with glycogen granules in the FLR in ALPPS. Fewer cytoplasmic organelles and lipofuscin granules were observed in ALPPS than in PVE. CONCLUSION: In the FLR, regenerative hepatocytes in ALPPS were morphologically immature compared with PVE. ALPPS should be performed with caution, considering limited functional increase in the FLR reflecting immaturity of the regenerative hepatocytes.


Subject(s)
Embolization, Therapeutic , Hepatectomy/methods , Liver Neoplasms/surgery , Liver Regeneration , Liver/pathology , Portal Vein/surgery , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms/pathology , Female , Hepatocytes/pathology , Hepatocytes/physiology , Humans , Liver/physiology , Liver/surgery , Liver Neoplasms/pathology , Liver Neoplasms/secondary , Liver Regeneration/physiology , Male , Middle Aged , Treatment Outcome
20.
Pancreatology ; 16(3): 464-8, 2016.
Article in English | MEDLINE | ID: mdl-26804004

ABSTRACT

We encountered a 62-year-old female patient with a distinctive pancreatic myoepithelial hamartoma characterized by dilated loops formed by pancreatic branch ducts. The patient, who experienced recurrent acute pancreatitis caused by pancreatic juice stasis, underwent subtotal stomach-preserving pancreatoduodenectomy, achieving remission of pancreatitis. Computed tomography (CT) and magnetic resonance cholangiopancreatography (MRCP) demonstrated a honeycomb appearance of the pancreatic head, consisting largely of loop-forming dilated pancreatic branch ducts. Radiography of resected specimens demonstrated a tortuous main pancreatic duct that narrowed in the head, but communicated with the pancreatic branch ducts forming intricate loops within the lesion. Histologic examination showed dilated pancreatic ducts embedded in thick layers of smooth muscle, leading to a diagnosis of myoepithelial hamartoma. Her son shared a similar clinical course, radiologic findings, and histopathologic findings with his mother. MRCP demonstrated a honeycomb appearance of the pancreatic head in her daughter, who complained of persistent diarrhea. To our knowledge, this is the first English-language reports of such a myoepithelial hamartoma of the pancreas showing familial occurrence.


Subject(s)
Hamartoma/pathology , Pancreatic Diseases/pathology , Adult Children , Female , Hamartoma/diagnostic imaging , Humans , Male , Middle Aged , Mothers , Pancreatic Diseases/diagnostic imaging
SELECTION OF CITATIONS
SEARCH DETAIL
...