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BACKGROUND/OBJECTIVES: Decrease in skeletal muscle mass and function is associated with a poor prognosis following surgical resection of pancreatic ductal adenocarcinomas (PDAs). This study evaluated whether skeletal muscle mass decrease affects PDA outcomes. METHODS: Data of 112 patients with advanced and unresectable PDA who underwent chemotherapy in a single institution were retrospectively analyzed. Information on age, sex, hematological investigations, including systemic inflammation-based markers and nutritional assessment biomarkers, and imaging parameters of skeletal muscle mass and visceral adipose tissue were retrieved from the patients' medical records. The efficiency of the Cox, Weibull, and standardized exponential models were compared using hazard ratios and the Akaike Information Criterion (AIC). RESULTS: Results from the Weibull, Cox, and standardized exponential model analyses indicated that low skeletal muscle mass, Eastern Cooperative Oncology Group performance status (PS), and the requirement of biliary drainage were associated with the highest risk of death, followed by carcinoembryonic antigen (CEA) levels and the presence of ascites. The AIC value from the four significant parameters was lowest for the Weibull-exponential distribution (222.3) than that of the Cox (653.7) and standardized exponential models (265.7). We developed a model for estimating the 1-year survival probability using the Weibull-exponential distribution. CONCLUSIONS: Low-skeletal muscle index, PS, requirement of biliary drainage, CEA levels, and presence of ascites are independent factors for predicting poor patient survival after chemotherapy. Improved survival modeling using a parametric approach may accurately predict the outcome of patients with advanced-stage PDA.
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Neoplasias Pancreáticas , Sarcopenia , Ascite/patologia , Antígeno Carcinoembrionário , Humanos , Músculo Esquelético/patologia , Neoplasias Pancreáticas/patologia , Prognóstico , Estudos Retrospectivos , Sarcopenia/patologia , Análise de Sobrevida , Neoplasias PancreáticasRESUMO
SYNOPSIS: A new combination therapy consisting of intraarterial chemotherapy plus radiotherapy was demonstrated to have the potential to improve the response rate and survival time in patients with unresectable biliary tract cancer. PURPOSE: We retrospectively investigated the effectiveness and safety of a new combination therapy consisting of intraarterial chemotherapy plus radiation therapy (AI+RT), which may have the potential to improve unresectable biliary tract cancer (BTC). METHODS: We retrospectively reviewed 52 BTC cases treated with AI+RT and analyzed the anti-tumor effect, survival time and adverse events. The AI+RT regimen consisted of one-shot intraarterial chemotherapy (AI) at the first angiography session, almost 6 months of reservoir AI (5-FU and cisplatin, q/week) and external radiation with a maximum dose of 50.6 Gy. RESULTS: The response rate and disease control rate were high, at 40.4% and 96.2%, respectively, and the median overall and progression-free survival time were 463 and 431 days; thus, long-term survival was achieved. A univariate analysis identified 12 prognostic factors, and a performance status of 2 (hazard ratio [HR]: 4.82, p=0.02), jaundice (HR: 3.22, p<0.01), peritoneal dissemination (HR: 22.5, p<0.01), number of AI (HR: 0.35, p=0.01) and response to AI+RT (HR: 0.23, p<0.01) were extracted as significant prognostic factors in a multivariate analysis. The following: grade ≥3 adverse events occurred: leucopenia (11.5%), neutropenia (1.9%), anemia (15.4%), thrombocytopenia (11.5%), anorexia (3.8%), gastroduodenal ulcer (25.0%), and cholangitis (23.1%). There were no cases of treatment-related death. CONCLUSIONS: AI+RT was shown to contribute to a high response rate and prolonged survival in patients with unresectable BTC. A sufficient number of AI and the response to this therapy were thought to be significant prognostic factors in patients receiving AI+RT. Advances in multidisciplinary therapies, such as AI+RT, which was described in the present study, are also considered to be important for the future.
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BACKGROUND: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). METHODS: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. RESULTS: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. CONCLUSIONS: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.
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Carcinoma Ductal Pancreático/diagnóstico , Neoplasias Intraductais Pancreáticas/diagnóstico , Neoplasias Pancreáticas/diagnóstico , Reação em Cadeia da Polimerase/métodos , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno CA-19-9/sangue , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Estudos de Casos e Controles , Ácidos Nucleicos Livres/sangue , Cromograninas/genética , Estudos de Viabilidade , Feminino , Subunidades alfa Gs de Proteínas de Ligação ao GTP/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Neoplasias Intraductais Pancreáticas/genética , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto JovemRESUMO
INTRODUCTION: Surgical management is not a standard treatment option for metastatic recurrence of pancreatic adenocarcinoma. However, the surgical management of a solitary metastasis is useful in selected cases. PATIENT CONCERNS: A 42-year-old woman was referred to our hospital on account of epigastric pain associated with a mass in the pancreatic body. The patient had a family history of branch duct-type intraductal papillary mucinous neoplasm of the pancreas. DIAGNOSIS: The patient was diagnosed with pancreatic ductal adenocarcinoma (PDA) complicated with pancreatitis due to pancreatic duct involvement. INTERVENTIONS: The patient underwent distal pancreatectomy, and pathological examination revealed a tubular adenocarcinoma. Solitary liver and lung metastatic tumors were found 6 and 43 months after the initial presentation, respectively, and sequential metastasectomies were performed. OUTCOMES: The patient survived until 8 years after her initial presentation. The genetic profiles of the resected specimens, primary PDA, and recurrent tumors in the liver and lung possessed identical KRAS mutations at codon 12, whereas there were no mutations in the main tumor suppressor genes, such as TP53, CDKN2A, and SMAD4. Multiplex polymerase chain reaction-based microsatellite instability assay demonstrated microsatellite stability. CONCLUSION: In our case, the patient with pancreatic adenocarcinoma survived for over 8 years following the resection of the primary tumor and resections of metachronous metastatic tumors. The outcome of PDA may be associated with the genetic profile that regulates its biological behavior. Operative management of solitary metastatic tumors may be a therapeutic options for selected patients with pancreatic cancer.
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Carcinoma Ductal Pancreático/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/cirurgia , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)RESUMO
Pancreatobiliary tumors frequently contain multiple malignant and precancerous lesions; however, the origin of the driver mutations and the mechanisms that underlie the generation of distinct clones within an organ field remain unclear. Herein, we describe a 76-year-old male suffering from moderately differentiated adenocarcinomas of the pancreas that primarily involved the distal bile duct and multiple "dispersing" invasive lesions in the pancreatic head. The patient underwent pylorus-preserving pancreaticoduodenectomy with superior mesenteric vein resection, and targeted sequencing of 18 genes associated with pancreatic tumorigenesis and immunohistochemical analysis of RNF43 and ARID1A were performed on each tumor compartment, including the invasive and non-invasive areas. Multi-region sequencing revealed shared KRAS and TGFBR1 mutations in all invasive foci, including those involving the distal bile duct. Distinct KRAS variants were found to be present in other non-continuous and non-invasive lesions in the pancreas. Intraductal lesions with KRAS G12D and RNF43 V50R mutations were evident in the main pancreatic duct. This appeared to be a founder clone, given that the mutation profile was common to the invasive foci as well as the additional high-grade dysplasia harboring ARID1A mutations, thereby suggesting a clonal branch-off during tumor evolution. In addition, we also observed independent intraductal papillary mucinous neoplasms with KRAS G12V and GNAS R201H mutations. Our theory, learned from this patient, was that lesions skipped dissemination and wide-spread movement potentially through the pancreatic ductal system as a process of pancreatic cancer development.
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Background and study aims Needle tract seeding during endoscopic ultrasound fine-needle biopsy (EUS-FNB) remains a concern. We investigated whether such seeding occurred in a patient with pancreatic ductal adenocarcinoma (PDA). Patient and methods Surgically resected and EUS-FNB-derived specimens were genotyped to determine if a gastric wall tumor that emerged 3 years after curative resection of an early-stage PDA was clonally related to the original tumor. Results The gastric tumor histologically resembled the primary PDA; the lesions also shared KRAS , SMAD4 , and RNF43 mutations. Genotyping of the preoperative EUS-FNB specimen, in which cancer was not detected, nevertheless revealed mutations that were identical to those in the resected primary and recurrent tumors. While the primary PDA had a low frequency of mutant SMAD4 , such mutations were highly prevalent in both the EUS-FNB and recurrent tumor specimens. Conclusions The genetic lineages of sampled tissues from our patient revealed that needle tract seeding may have incidentally occurred when a subset of neoplastic cells within a heterogeneous tumor ( i.âe. , an aggressive clone) was targeted during EUS-FNB.
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Adenocarcinoma/terapia , Neoplasias Esofágicas/terapia , Junção Esofagogástrica/patologia , Neoplasias Hepáticas/terapia , Neoplasias Gástricas/terapia , alfa-Fetoproteínas/metabolismo , Técnicas de Ablação , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patologia , Esofagectomia , Etanol/administração & dosagem , Gastrectomia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Excisão de Linfonodo , Masculino , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Fatores de Tempo , Resultado do Tratamento , alfa-Fetoproteínas/análiseRESUMO
BACKGROUND & AIMS: Intraductal papillary mucinous neoplasms (IPMNs) are regarded as precursors of pancreatic ductal adenocarcinomas (PDAs), but little is known about the mechanism of progression. This makes it challenging to assess cancer risk in patients with IPMNs. We investigated associations of IPMNs with concurrent PDAs by genetic and histologic analyses. METHODS: We obtained 30 pancreatic tissues with concurrent PDAs and IPMNs, and 168 lesions, including incipient foci, were mapped, microdissected, and analyzed for mutations in 18 pancreatic cancer-associated genes and expression of tumor suppressors. RESULTS: We determined the clonal relatedness of lesions, based on driver mutations shared by PDAs and concurrent IPMNs, and classified the lesions into 3 subtypes. Twelve PDAs contained driver mutations shared by all concurrent IPMNs, which we called the sequential subtype. This subset was characterized by less diversity in incipient foci with frequent GNAS mutations. Eleven PDAs contained some driver mutations that were shared with concurrent IPMNs, which we called the branch-off subtype. In this subtype, PDAs and IPMNs had identical KRAS mutations but different GNAS mutations, although the lesions were adjacent. Whole-exome sequencing and methylation analysis of these lesions indicated clonal origin with later divergence. Ten PDAs had driver mutations not found in concurrent IPMNs, called the de novo subtype. Expression profiles of TP53 and SMAD4 increased our ability to differentiate these subtypes compared with sequencing data alone. The branch-off and de novo subtypes had substantial heterogeneity among early clones, such as differences in KRAS mutations. Patients with PDAs of the branch-off subtype had a longer times of disease-free survival than patients with PDAs of the de novo or the sequential subtypes. CONCLUSIONS: Detailed histologic and genetic analysis of PDAs and concurrent IPMNs identified 3 different pathways by which IPMNs progress to PDAs-we call these the sequential, branch-off, and de novo subtypes. Subtypes might be associated with clinical and pathologic features and be used to select surveillance programs for patients with IPMNs.
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Adenocarcinoma Mucinoso/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Papilar/genética , Diferenciação Celular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Adenocarcinoma Mucinoso/patologia , Idoso , Carcinoma Ductal Pancreático/patologia , Carcinoma Papilar/patologia , Estudos de Coortes , Procedimentos Clínicos , Análise Mutacional de DNA , Bases de Dados Factuais , Progressão da Doença , Feminino , Seguimentos , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/patologia , Estudos Retrospectivos , Medição de Risco , Análise de SobrevidaRESUMO
Background Despite advances in the diagnosis of pancreatic ductal adenocarcinoma (PDA), histological evaluation of small and poorly defined masses in the pancreas is uncomfortable and unsafe. Methods We herein report a case of early stage PDA, in which multiple KRAS mutations were detected in the pancreatic juice preoperatively. A small hypoechoic area adjacent to the portal vein was detected through endoscopic ultrasound in the pancreatic body. KRAS mutations were evaluated using plasma, and the pancreatic juice by digital PCR. Results Pancreatic duct biopsy and pancreatic juice cytology were performed with no evidence of malignancy; however, KRAS mutations, KRAS G12V and G12D, were detected in the pancreatic juice. Histological assessment of the resected specimen demonstrated a solid tumor with desmoplastic reaction accompanied by carcinoma in situ in the main pancreatic duct where KRAS G12V mutation was identified. More detailed analysis demonstrated KRAS G12D mutation in the cluster of low grade pancreatic intraepithelial neoplasia, implying that the lesion developed independently. Conclusions Our study indicates the potential of "endoscopic liquid biopsy" to capture the driver gene for PDA diagnosis.
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BACKGROUND: Takayasu's arteritis (TA) is a large-vessel vasculitis pathologically characterized by granulomatous necrotizing vasculitis with giant cells. Although the cause of TA is still unclear, genetic factors as well as immunological abnormalities, particularly the overactivation of Th1 and Th-17, are considered to play important roles in the pathogenesis of this disease. Eosinophilic gastroenteritis (EGE) is a type of refractory inflammation in which numerous eosinophils infiltrate the inflammatory area. It is known that the overactivation of Th2 is associated with the pathogenesis of EGE, although the cause of EGE is still unclear. The immunological abnormalities in TA are therefore thought to be different from those in EGE. To date, no cases of complication of TA and EGE have been reported. CASE PRESENTATIONS: An 18 year-old female was diagnosed with EGE and treated with prednisolone. At 6 months after completion of the treatment, the patient experienced chest pain, and was diagnosed with TA. TH1 and TH17 immunity are thought to be involved with TA, while TH2 are considered to be involved with EGE. In this case, the expression of IL-17 mRNA in the colon mucosa greatly decreased after prednisolone treatment for EGE. CONCLUSIONS: This is the first report of TA complicated with EGE, and the overactivation of TH17 is considered to be associated with the pathogenesis of these two diseases.
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BACKGROUND: Pancreatic cancer is associated with an extremely poor prognosis, so new biomarkers that can detect the initial stages are urgently needed. The significance of serum microRNA (miR) levels in pancreatic neoplasm such as pancreatic cancer and intraductal papillary mucinous neoplasm (IPMN) diagnosis remains unclear. We herein evaluated the usefulness of miRs enclosed in serum exosomes (ExmiRs) as diagnostic markers. METHODS: The ExmiRs from patients with pancreatic cancer (n = 32) or IPMN (n = 29), and patients without neoplasms (controls; n = 22) were enriched using ExoQuick-TC™. The expression of ExmiRs was evaluated using a next-generation sequencing analysis, and the selected three miRs through this analysis were confirmed by a quantitative real-time polymerase chain reaction. RESULTS: The expression of ExmiR-191, ExmiR-21 and ExmiR-451a was significantly up-regulated in patients with pancreatic cancer and IPMN compared to the controls (p < 0.05). A receiver operating characteristic curve analysis showed that the area under the curve and the diagnostic accuracy of ExmiRs were 5-20% superior to those of three serum bulky circulating miRs (e.g.; ExmiR-21: AUC 0.826, accuracy 80.8%. Circulating miR-21: AUC 0.653, accuracy 62.3%). In addition, high ExmiR-451a was associated with mural nodules in IPMN (p = 0.010), and high ExmiR-21 was identified as a candidate prognostic factor for the overall survival (p = 0.011, HR 4.071, median OS of high-ExmiR-21: 344 days, median OS of low-ExmiR-21: 846 days) and chemo-resistant markers (p = 0.022). CONCLUSIONS: The level of three ExmiRs can thus serve as early diagnostic and progression markers of pancreatic cancer and IPMN, and considered more useful markers than the circulating miRs (limited to these three miRs).
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MicroRNAs/sangue , Neoplasias Pancreáticas/sangue , Adenocarcinoma Mucinoso/sangue , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/patologia , Idoso , Biomarcadores Tumorais/sangue , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Intervalo Livre de Doença , Exossomos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , PrognósticoRESUMO
OBJECTIVE: Helicobacter pylori (H. pylori) eradication rarely develops into antibiotic-associated hemorrhagic colitis (AAHC), in which the etiology of colitis remains unclear. We herein report a rare case of AAHC caused by second-line therapy for H. pylori eradication. RESULTS: A 65-year-old female was administered second-line therapy for H. pylori composed of 1500 mg of amoxicillin, 500 mg of metronidazole and 40 mg of vonoprazan for 7 days because of first-line therapy failure. A day after completing second-line therapy, she complained of abdominal pain and hematochezia. Colonoscopy revealed a hemorrhage and edematous mucosa with no transparent vascular pattern in the transverse colon. A bacterial culture detected Klebsiella oxytoca (K. oxytoca), but no other pathogenic bacteria. A drug-induced lymphocyte stimulation test (DLST) showed positive reactions for both amoxicillin and metronidazole. According to these findings, the patient was diagnosed with AAHC. Bowel rest for 6 days relieved her abdominal pain and hematochezia. CONCLUSIONS: The present case developed AAHC caused by second-line therapy for H. pylori eradication. The pathogenesis is considered to be associated with microbial substitution as well as a delayed-type allergy to antibiotics, suggesting that AAHC is a potential adverse event of second-line therapy for H. pylori eradication.
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Amoxicilina/efeitos adversos , Colite/etiologia , Colo/efeitos dos fármacos , Infecções por Helicobacter/complicações , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/patogenicidade , Metronidazol/efeitos adversos , Pirróis/efeitos adversos , Sulfonamidas/efeitos adversos , Dor Abdominal , Idoso , Amoxicilina/uso terapêutico , Biópsia , Colite/diagnóstico por imagem , Colite/microbiologia , Colite/fisiopatologia , Colo/diagnóstico por imagem , Colonoscopia , Feminino , Hemorragia Gastrointestinal , Hemorragia , Humanos , Klebsiella oxytoca , Metronidazol/uso terapêutico , Mucosa/patologia , Pirróis/uso terapêutico , Doenças Raras , Sulfonamidas/uso terapêuticoRESUMO
Genetic alterations responsible for the initiation of cancer may serve as immediate biomarkers for early diagnosis. Plasma levels of cell-free DNA (cfDNA) in patients with cancer are higher than those in healthy individuals; however, the major technical challenge for the widespread implementation of cfDNA genotyping as a diagnostic tool is the insufficient sensitivity and specificity of detecting early-stage tumors that shed low amounts of cfDNA. To establish a protocol for ultrasensitive droplet digital polymerase chain reaction (ddPCR) for quantification of low-frequency alleles within a limited cfDNA pool, two-step multiplex ddPCR targeting eight clinically relevant mutant KRAS variants was examined. Plasma samples from patients with colorectal (n = 10) and pancreatic cancer (n = 9) were evaluated, and cfDNA from healthy volunteers (n = 50) was utilized to calculate reference intervals. Limited cfDNA yields in patients with resectable colorectal and pancreatic cancers did not meet the requirement for efficient capture and quantification of rate mutant alleles by ddPCR. Eight preamplification cycles followed by a second-run ddPCR were sufficient to obtain approximately 5000-10 000 amplified copies per ng of cfDNA, resolving the subsampling issue. Furthermore, the signal-to-noise ratio for rare mutant alleles against the extensive background presented by the wild-type allele was significantly enhanced. The cutoff limit of reference intervals for mutant KRAS was determined to be ~ 0.09% based on samples from healthy individuals. The modification introduced in the ddPCR protocol facilitated the quantification of low-copy alleles carrying driver mutations, such as oncogenic KRAS, in localized and early-stage cancers using small blood volumes, thus offering a minimally invasive modality for timely diagnosis.
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Ácidos Nucleicos Livres/genética , Neoplasias Colorretais/genética , Análise Mutacional de DNA/métodos , Mutação , Neoplasias Pancreáticas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Linhagem Celular Tumoral , Ácidos Nucleicos Livres/sangue , Neoplasias Colorretais/sangue , Feminino , Humanos , Biópsia Líquida , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Reação em Cadeia da Polimerase/métodos , Adulto JovemRESUMO
Ferrichrome is known to be a siderophore, but it was recently identified as a tumor-suppressive molecule derived from Lactobacillus casei ATCC334 ( L. casei). In the present study, we investigated the effects of ferrichrome in gastric cancer cells. Cell lines and xenograft models treated with ferrichrome demonstrated growth suppression. The expression levels of cleaved poly (adenosine diphosphate-ribose) polymerase, and cleaved caspase-9 were increased by ferrichrome treatment. Although the tumor-suppressive effects of ferrichrome were almost completely diminished by the iron chelation, the reduction in the intracellular iron by ferrichrome did not correlate with its tumor-suppressive effects. An exhaustive docking simulation indicated that iron-free ferrichrome can make stable conformations with various mammalian molecules, including transporters and receptors. In conclusion, probiotic-derived ferrichrome induced apoptosis in gastric cancer cells. The iron binding site of ferrichrome is the structure responsible for its tumor suppressive function.
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Apoptose/efeitos dos fármacos , Ferricromo/administração & dosagem , Ferricromo/química , Neoplasias Gástricas/tratamento farmacológico , Animais , Sítios de Ligação , Caspase 9/biossíntese , Linhagem Celular Tumoral , Ferricromo/isolamento & purificação , Humanos , Ferro/metabolismo , Lacticaseibacillus casei/química , Camundongos , Simulação de Acoplamento Molecular , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Epidermoid cysts arising from both the pancreas and spleen are rare. We herein report a case of a surgically resected epidermoid cyst in the pancreatic tail invaginated from the spleen. A multi-locular cyst, 2 cm in diameter, without a solid component was discovered incidentally in the pancreatic tail. During the 11-year follow-up, the emergence of satellite cystic lesions with distinct appearances was seen, and surgical resection was selected despite the lack of any associated symptoms or evidence of cytological abnormalities. Histologically, these cysts were lined with benign multi-layered flattened epithelium surrounded by a thin layer consisting of cells positive for CD8 and CD68 and connecting to the spleen.
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Coristoma/patologia , Cisto Epidérmico/patologia , Pâncreas/patologia , Pancreatectomia , Cisto Pancreático/patologia , Baço/patologia , Coristoma/diagnóstico por imagem , Coristoma/cirurgia , Cisto Epidérmico/diagnóstico por imagem , Cisto Epidérmico/cirurgia , Feminino , Seguimentos , Humanos , Achados Incidentais , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/cirurgia , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Baço/diagnóstico por imagem , Baço/cirurgia , Resultado do TratamentoRESUMO
Previous reports have suggested that some probiotics inhibit tumorigenesis and cancer progression. However, the molecules involved have not yet been identified. Here, we show that the culture supernatant of Lactobacillus casei ATCC334 has a strong tumour-suppressive effect on colon cancer cells. Using mass spectrometry, we identify ferrichrome as a tumour-suppressive molecule produced by L. casei ATCC334. The tumour-suppressive effect of ferrichrome is greater than that of cisplatin and 5-fluorouracil, and ferrichrome has less of an effect on non-cancerous intestinal cells than either of those agents. A transcriptome analysis reveals that ferrichrome treatment induces apoptosis, which is mediated by the activation of c-jun N-terminal kinase (JNK). Western blotting indicates that the induction of apoptosis by ferrichrome is reduced by the inhibition of the JNK signalling pathway. This we demonstrate that probiotic-derived ferrichrome exerts a tumour-suppressive effect via the JNK signalling pathway.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ferricromo/farmacologia , Lacticaseibacillus casei/metabolismo , Probióticos/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Cisplatino/farmacologia , Colo/citologia , Colo/efeitos dos fármacos , Colo/patologia , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Progressão da Doença , Ferricromo/uso terapêutico , Fluoruracila/farmacologia , Perfilação da Expressão Gênica/métodos , Humanos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Probióticos/farmacologia , Ratos , Resultado do Tratamento , Regulação para CimaRESUMO
BACKGROUND: Pancreatic involvement of angiosarcoma is extremely rare. METHODS: We herein report a rare case of angiosarcoma associated with chronic lymphedema (Stewart-Treves syndrome) with pancreatic metastasis that was diagnosed using endoscopic ultrasound (EUS)/fine needle aspiration (FNA). RESULTS: A 43-year-old woman with a history of radical hysterectomy with bilateral inguinal lymphadenectomy and chemoradiotherapy for cervical cancer 15 years prior noticed the presence of erythematous indurative plaques on her right femoral region, where chronic lymphedema had developed. Contrast-enhanced computed tomography (CT) revealed not only multiple nodules in the subcutaneous tissue of the right femoral region but also a 25âmmâ×â20âmm solid mass in the region of the pancreatic tail. A histological analysis of the specimens obtained using EUS/FNA revealed angiosarcoma that was immunohistochemically positive for platelet/endothelial cell adhesion molecule-1 but negative for cytokeratin. The patient was diagnosed as Stewart-Treves syndrome that had metastasized to the pancreas. Chemotherapy was performed, but the patient died 14 months after her diagnosis. CONCLUSION: Unfortunately, this patient was not followed up, even though she had chronic lymphedema of the right femoral region due to the repeated occurrence of phlegmon. To improve the survival rate of this fatal secondary malignant complication of radical lymphadenectomy, an early diagnosis with consecutive and long-term clinical follow-up and close monitoring for Stewart-Treves syndrome is therefore important.
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Hemangiossarcoma/diagnóstico , Linfangiossarcoma/diagnóstico , Neoplasias Pancreáticas/secundário , Adulto , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Feminino , Hemangiossarcoma/patologia , Humanos , Linfangiossarcoma/patologia , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Neoplasias Pancreáticas/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
While the gastric involvement of pancreatic cancer is occasionally observed as the result of direct invasion, hematogenous gastric metastasis is rare. A 72-year-old Japanese male presented with general fatigue, pollakiuria, and thirst. Computed tomography revealed a 4.6-cm solid mass in the pancreatic tail and a 4.2-cm multilocular cystic mass in the pancreatic head with multiple liver and lymphatic metastasis. Notably, two solid masses were detected in the gastric wall of the upper body and the antrum; both were separated from the primary pancreatic cancer and seemed to be located in the submucosal layer. Esophagogastroduodenoscopy revealed a submucosal tumor with a normal mucosa in the posterior wall of the upper body of the stomach, suggesting the gastric hematogenous metastasis of pancreatic cancer. The suspected diagnosis was unresectable pancreatic cancer with multiple metastases that was concomitant with the intraductal papillary mucinous neoplasm of the pancreas.
RESUMO
AIM: To compare previously reported randomized controlled studies (RCTs) of cold and hot polypectomy, we systematically reviewed and clarify the utility of cold polypectomy over hot with respect to efficacy and adverse events. METHODS: A meta-analysis was conducted to evaluate the predominance of cold and hot polypectomy for removing colon polyps. Published articles and abstracts from worldwide conferences were searched using the keywords "cold polypectomy". RCTs that compared either or both the effects or adverse events of cold polypectomy with those of hot polypectomy were collected. The patients' demographics, endoscopic procedures, No. of examined lesions, lesion size, macroscopic and histologic findings, rates of incomplete resection, bleeding amount, perforation, and length of procedure were extracted from each study. A forest plot analysis was used to verify the relative strength of the effects and adverse events of each procedure. A funnel plot was generated to assess the possibility of publication bias. RESULTS: Ultimately, six RCTs were selected. No significant differences were noted in the average lesion size (less than 10 mm) between the cold and hot polypectomy groups in each study. Further, the rates of complete resection and adverse events, including delayed bleeding, did not differ markedly between cold and hot polypectomy. The average procedural time in the cold polypectomy group was significantly shorter than in the hot polypectomy group. CONCLUSION: Cold polypectomy is a time-saving procedure for removing small polyps with markedly similar curability and safety to hot polypectomy.
Assuntos
Pólipos do Colo/cirurgia , Neoplasias Colorretais/prevenção & controle , Ressecção Endoscópica de Mucosa/efeitos adversos , Ressecção Endoscópica de Mucosa/métodos , Duração da Cirurgia , Colonoscopia , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo , Resultado do TratamentoRESUMO
Squamous cell carcinoma of the extrahepatic bile duct is quite rare. A 77-year-old woman with jaundice and general fatigue was referred to our hospital. Multiphase contrast-enhanced computed tomography visualized a 17-mm solid mass in the junction of the cystic and common bile ducts. The patient underwent pylorus-preserving pancreaticoduodenectomy. The pathological findings demonstrated keratin-positive poorly differentiated squamous cell carcinoma of the extrahepatic bile duct (T3N0M0, stage IIIA). Although adjuvant chemotherapy with gemcitabine was administered, the patient exhibited local recurrence at the site of anastomosis of biliojejunostomy 20 months after resection and died 32 months after resection.