RESUMO
Despite continuing advances in the development of effective new therapies, including immunotherapies, the prognosis of pancreatic cancer remains extremely poor. Gap junction proteins have become attractive targets for potential cancer therapy. However, the role of gap junction beta-4 (GJB4) protein remains unexplored in pancreatic cancer. Through bioinformatic analyses we discovered pancreatic cancer tissues showed higher levels of GJB4 transcripts compared to normal pancreatic tissues and this had a negative effect on overall survival in patients that had pancreatic cancer. The high expression of nuclear GJB4 was identified as a negative prognostic factor in such patients. Knockdown of GJB4 in cultured pancreatic cancer cells resulted in G0/G1 arrest followed by decreased cell proliferation and suppression of metastatic potential. The overexpression of GJB4 accelerated cell proliferation, migration, and invasion in a SUIT-2 cell line, whereas MET inhibitor canceled the acceleration. GJB4 suppression with siRNA significantly inhibited tumor growth in a mouse xenograft model. Mechanistically, suppression of GJB4 inhibited MET-AKT activities. Such data suggest that targeting the GJB4-MET axis could represent a promising new therapeutic strategy for pancreatic cancer.
Assuntos
Proliferação de Células , Conexinas , Neoplasias Pancreáticas , Proteínas Proto-Oncogênicas c-akt , Proteínas Proto-Oncogênicas c-met , Animais , Feminino , Humanos , Masculino , Camundongos , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Conexinas/metabolismo , Conexinas/genética , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Metástase Neoplásica , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/genética , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Proteínas Proto-Oncogênicas c-met/genética , Transdução de Sinais , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND AND AIMS: EUS-guided hepaticogastrostomy (EUS-HGS) is a rescue procedure when ERCP fails. Peritonitis and recurrent biliary obstruction (RBO) are adverse events (AEs) associated with EUS-HGS. Antegrade stent placement across a malignant distal biliary obstruction (DBO) followed by EUS-HGS (EUS-HGAS) creates 2 biliary drainage routes, potentially reducing peritonitis and prolonging time to RBO (TRBO). We compared the outcomes of the 2 techniques. METHODS: Data of consecutive patients with malignant DBO who underwent attempted EUS-HGS or EUS-HGAS across 5 institutions from January 2014 to December 2020 were retrospectively analyzed. A matched cohort of patients was obtained using 1-to-1 propensity score matching. The primary outcome was TRBO, and secondary outcomes were AEs except for RBO and overall survival. RESULTS: Among 360 patients, 283 (176 and 107 in the HGS and HGAS groups, respectively) were eligible. The matched cohorts included 81 patients in each group. AEs developed in 10 (12.3%) and 15 (18.5%) patients (P = .38) in the HGS and HGAS groups, respectively. RBO occurred in 18 and 2 patients in the HGS and HGAS groups, respectively (P < .001). TRBO was significantly longer in the HGAS group (median, 194 days vs 716 days; hazard ratio, .050; 95% confidence interval, .0066-.37; P < .01). However, no significant differences occurred in overall survival between the groups (median, 97 days vs 112 days; hazard ratio, .97; 95% confidence interval, .66-1.4; P = .88). CONCLUSIONS: EUS-HGAS extended TRBO compared with EUS-HGS, whereas AEs, except for RBO and overall survival, did not differ. The longer TRBO of EUS-HGAS could benefit patients with longer life expectancy.
Assuntos
Colestase , Endossonografia , Pontuação de Propensão , Stents , Humanos , Masculino , Feminino , Colestase/cirurgia , Colestase/etiologia , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Casos e Controles , Gastrostomia/métodos , Drenagem/métodos , Neoplasias dos Ductos Biliares/complicações , Neoplasias dos Ductos Biliares/cirurgia , Ultrassonografia de Intervenção , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Accumulating evidence has demonstrated platinum-based chemotherapy followed by maintenance therapy with a poly Adenosine diphosphate (ADP)-ribose polymerase inhibitor (olaparib) show benefits in unresectable pancreatic cancer with a germline (g)BRCA1/2 mutation. Evaluation of the germline BRCA1 and BRCA2 mutation is essential for making decisions on a treatment strategy for patients with unresectable pancreatic cancer. However, the detection rates of germline BRCA1 and BRCA2 mutations and efficacy of maintenance with olaparib remain undetermined, prospectively, in Japan. METHODS & RESULTS: In this prospective analysis, the rate of germline BRCA1 and BRCA2 mutations and efficacy of chemotherapy were analyzed in 136 patients with pancreatic cancer who underwent BRACAnalysis® (85 patients) or FoundationOne® CDx (51 patients) between January 2020 and July 2022. A total of six patients (4.4%) had a germline BRCA1 and BRCA2 mutation. Five patients were treated with modified FOLFIRINOX and one with fluorouracil and oxaliplatin. All patients continued platinum-based chemotherapy for Ë4 months and were subsequently treated with olaparib as a maintenance therapy. The response rate to platinum-based chemotherapy in the germline BRCA1 and BRCA2 mutation-positive group was significantly better than that of the germline BRCA1 and BRCA2 mutation-negative group (66% vs 23%, P = 0.04). All patients harbouring a germline BRCA1 and BRCA2 mutation were able to switch to olaparib. The median progression-free survival using olaparib was 5.7 months (range 3.0-9.2). CONCLUSIONS: The rate of germline BRCA1 and BRCA2 mutations found in patients with unresectable pancreatic cancer was comparable to those of previous studies.An analysis of germline BRCA1 and BRCA2 mutations has benefits for all patients with unresectable pancreatic cancer with regard to decisions on therapeutic strategies in a clinical practice setting.
Assuntos
Antineoplásicos , Neoplasias Ovarianas , Neoplasias Pancreáticas , Feminino , Humanos , Proteína BRCA1/genética , Antineoplásicos/uso terapêutico , Estudos Prospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Proteína BRCA2/genética , Neoplasias Ovarianas/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Genes BRCA1 , Genes BRCA2 , Mutação , Ftalazinas/uso terapêutico , Ftalazinas/efeitos adversos , Mutação em Linhagem GerminativaRESUMO
BACKGROUND AND AIM: Optimal tumor samples are crucial for successful analysis using commercially available comprehensive genomic profiling (CACGP). However, samples acquired by endoscopic ultrasound-guided tissue acquisition (EUS-TA) are occasionally insufficient, and no consensus on the optimal number of needle passes required for CACGP exists. This study aimed to explore the optimal number of needle passes required for EUS-TA to procure an ideal sample fulfilling the prerequisite criteria of CACGPs. METHODS: Patients who underwent EUS-TA for solid masses between November 2019 and July 2021 were retrospectively studied. The correlation between the acquisition rate of an ideal sample and the number of needle passes mounted on a microscope slide was evaluated. Additionally, the factors predicting a successful analysis were investigated in patients scheduled for CACGP using EUS-TA-obtained samples during the same period. RESULTS: EUS-TAs using 22- and 19-gauge (G) needles were performed in 336 and 57 patients, respectively. There was a positive correlation between the acquisition rate and the number of passes using a 22-G needle (38.9%, 45.0%, 83.7%, and 100% for 1, 2, 3, and 4 passes, respectively), while no correlation was found with a 19-G needle (84.2%, 83.3%, and 85.0% for 1, 2, and 3 passes, respectively). The analysis success rate in patients with scheduled CACGP was significantly higher with ideal samples than with suboptimal samples (94.1% vs 55.0%, P < 0.01). CONCLUSIONS: The optimal estimated number of needle passes was 4 and 1-2 for 22- and 19-G needles, respectively.
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Endossonografia , Agulhas , Neoplasias Pancreáticas/patologia , Pâncreas/diagnóstico por imagemRESUMO
BACKGROUND: Microsatellite instability (MSI) is a key marker for predicting the response of immune checkpoint inhibitors (ICIs) and for screening Lynch syndrome (LS). AIM: This study aimed to see the characteristics of cancers with high level of MSI (MSI-H) in genetic medicine and precision medicine. METHODS: This study analyzed the incidence of MSI-H in 1000 cancers and compared according to several clinical and demographic factors. RESULTS: The incidence of MSI-H was highest in endometrial cancers (26.7%, 20/75), followed by small intestine (20%, 3/15) and colorectal cancers (CRCs)(13.7%, 64/466); the sum of these three cancers (15.6%) was significantly higher than that of other types (2.5%)(P < 0.0001). MSI-H was associated with LS-related cancers (P < 0.0001), younger age (P = 0.009), and family history, but not with smoking, drinking, or serum hepatitis virus markers. In CRC cases, MSI-H was significantly associated with a family history of LS-related cancer (P < 0.0001), Amsterdam II criteria [odds ratio (OR): 5.96], right side CRCs (OR: 4.89), and multiplicity (OR: 3.31). However, MSI-H was very rare in pancreatic (0.6%, 1/162) and biliary cancers (1.6%, 1/64) and was null in 25 familial pancreatic cancers. MSI-H was more recognized in cancers analyzed for genetic counseling (33.3%) than in those for ICI companion diagnostics (3.1%)(P < 0.0001). Even in CRCs, MSI-H was limited to 3.3% when analyzed for drug use. CONCLUSIONS: MSI-H was predominantly recognized in LS-related cancer cases with specific family histories and younger age. MSI-H was limited to a small proportion in precision medicine especially for non-LS-related cancer cases.
Assuntos
Neoplasias Colorretais Hereditárias sem Polipose/genética , Neoplasias Colorretais/genética , Anamnese/estatística & dados numéricos , Instabilidade de Microssatélites , Neoplasias/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Medicina de PrecisãoRESUMO
BACKGROUND: Metallic stents placed in the descending duodenum can cause compression of the major duodenal papilla, resulting in biliary obstruction and pancreatitis. These are notable early adverse events of duodenal stent placement; however, they have been rarely examined. This study aimed to assess the incidence of and risk factors for biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum. METHODS: We retrospectively reviewed data of consecutive patients who underwent metallic stent placement in the descending duodenum for malignant gastric outlet obstruction at a tertiary referral cancer center between April 2014 and December 2019. Risk factors for biliary obstruction and/or pancreatitis were analyzed using a logistic regression model. RESULTS: Sixty-five patients were included. Biliary obstruction and/or pancreatitis occurred in 12 patients (18%): 8 with biliary obstruction, 2 with pancreatitis, and 2 with both biliary obstruction and pancreatitis. Multivariate analysis indicated that female sex (odds ratio: 9.2, 95% confidence interval: 1.4-58.6, P = 0.02), absence of biliary stents (odds ratio: 12.9, 95% confidence interval: 1.8-90.2, P = 0.01), and tumor invasion to the major duodenal papilla (odds ratio: 25.8, 95% confidence interval: 2.0-340.0, P = 0.01) were significant independent risk factors for biliary obstruction and/or pancreatitis. CONCLUSIONS: The incidence of biliary obstruction and/or pancreatitis after duodenal stent placement in the descending duodenum was non-negligible. Female sex, absence of biliary stents, and tumor invasion to the major duodenal papilla were the primary risk factors. Risk stratification can allow endoscopists to better identify patients at significant risk and permit detailed informed consent.
Assuntos
Ampola Hepatopancreática , Colestase , Obstrução Duodenal , Pancreatite , Ampola Hepatopancreática/patologia , Colestase/etiologia , Colestase/patologia , Obstrução Duodenal/etiologia , Duodeno/patologia , Feminino , Humanos , Pancreatite/epidemiologia , Pancreatite/etiologia , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: Endoscopic biliary drainage using metal stent (MSs) is an established palliative treatment for patients with unresectable malignant distal biliary obstruction (MDBO). However, a major drawback of MS is recurrent biliary obstruction (RBO). Uncovered MSs with a diameter of 14 mm (UMS-14) were developed to overcome this. We aimed to compare the clinical outcomes of UMS-14 with those of conventional covered MSs having a diameter of 10 mm (CMS-10). METHODS: Consecutive patients with MDBO caused by unresectable pancreatic cancer, who underwent UMS-14 or CMS-10 placement at two tertiary-care centers, were retrospectively examined according to the Tokyo Criteria 2014. RESULTS: Two hundred and thirty-eight patients who underwent UMS-14 (the UMS-14 group, n = 80) or CMS-10 (the CMS-10 group, n = 158) over a 62-month period were included. The technical and clinical success rates were similar between the two groups. RBO occurred in 20 (25%) and 59 (37%) patients of the UMS-14 and CMS-10 groups, respectively (p = 0.06). Median time till RBO was significantly longer in the UMS-14 group than in the CMS-10 group (not reached vs. 290 days, p = 0.04). Multivariate analysis revealed that CMS-10 placement was an independent risk factor for RBO (hazard ratio: 1.66, 95% confidence interval: 1.00-2.76). The incidence of early complications, including pancreatitis, and the overall survival (UMS-14 vs. CMS-10: 169 vs. 167 days, p = 0.83) were comparable between the two groups. CONCLUSIONS: UMS-14 stents were safe and effective for treating patients with MDBO secondary to unresectable pancreatic cancer. The insertion of UMS-14 is recommended, because it is less likely to get occluded as compared to CMS-10.
Assuntos
Colestase , Neoplasias Pancreáticas , Colestase/etiologia , Colestase/cirurgia , Drenagem/efeitos adversos , Humanos , Neoplasias Pancreáticas/complicações , Estudos Retrospectivos , Stents/efeitos adversosRESUMO
OBJECTIVES: Measurement of the macroscopic visible core (MVC) length during macroscopic on-site quality evaluation (MOSE) may allow estimation of sample adequacy for next-generation sequencing (NGS), and prediction of correct diagnosis in endoscopic ultrasound-guided tissue acquisition (EUS-TA) of pancreatic masses. METHODS: This multicenter prospective study included consecutive patients who underwent EUS-TA for pancreatic masses using a 22-G Franseen needle. MVC length and pathological samples obtained from two needle passes were analyzed on a per-pass basis. Outcome measures included respective correlations of MVC length with histological sample quantity and diagnostic yields. RESULTS: The analysis included 204 passes from 102 EUS-TAs. MVC length correlated positively with histological sample quantity (P < 0.01). On the receiver operating characteristic curve for MVC length, the cut-off value and area under the curve for obtaining a candidate sample for NGS were 30 mm and 0.74 (95% confidence interval [CI] 0.65-0.83), respectively. On multivariate analysis, MVC length ≥30 mm was a significant factor affecting suitability for NGS (odds ratio 6.19; 95% CI 2.72-14.10). Histologic diagnostic yield correlated positively with MVC length (P = 0.01); however, there was no positive correlation between MVC length and overall (histology plus cytology) diagnostic yield. CONCLUSIONS: Measuring MVC length to predict histological sample quantity on MOSE may be of clinical significance during EUS-TA using a 22-G Franseen needle. It may be an effective method, particularly while submitting samples for NGS. REGISTRATION: University Hospital Medical Information Network Trials Registry (UMIN000036528).
Assuntos
Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Neoplasias Pancreáticas , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Endossonografia , Humanos , Agulhas , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Estudos ProspectivosRESUMO
BACKGROUND/OBJECTIVES: The diagnostic ability of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been fully studied; however, the efficacy of other endoscopic samplings (OESs) is less clear. The aim of this study was to examine the diagnostic efficacies of OESs for pancreatic head cancer (PHC). METHODS: The diagnostic efficacies of endoscopic samplings were retrospectively analyzed in 448 PHC cases and 63 cases of mass-forming pancreatitis (MFP) during initial transpapillary biliary drainage. The OESs included duodenal biopsy (118 PHCs and 50 MFPs), biliary biopsy (218 and 51) with cytology (368 and 53), and pancreatic duct biopsy (23 and 13) with cytology (56 and 43). EUS-FNA was conducted in a different session (149 and 62). Factors associated with OES sensitivity were analyzed. The sensitivity of biliary biopsy was compared between 1.95 mm and 1.8 mm forceps. RESULTS: Cancer cells were confirmed in 87.9% of the EUS-FNA samplings and in 64.1% (268/418) obtained by combined OESs (average 1.7 OES types per case): 68.6% by duodenal biopsy, 59.6% by biliary biopsy, 32.6% by biliary cytology, 73.9% by pancreatic duct biopsy, and 33.9% by pancreatic duct cytology. No MFP cases revealed cancer by any sampling. OESs did not increase adverse events. Duodenal stenosis, serum bilirubin, tumor size, and pancreatic juice amounts were associated with OES sensitivity. Biliary biopsy had the same sensitivity with different forceps. CONCLUSION: EUS-FNA was the most diagnostic protocol; however, OESs can be safely applied during the initial biliary drainage to reduce the demand for EUS-FNA while providing good diagnostic yields.
Assuntos
Neoplasias Pancreáticas , Pancreatite , Colangiopancreatografia Retrógrada Endoscópica , Drenagem , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Humanos , Neoplasias Pancreáticas/diagnóstico , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias PancreáticasRESUMO
BACKGROUND/OBJECTIVES: International consensus diagnostic criteria (ICDC) include characteristic images of autoimmune pancreatitis (AIP); however, reports on atypical cases are increasing. The aims of this study were to compare CT findings between AIP and pancreatic cancer (PC), and to analyze type 1 AIPs showing atypical images. METHODS: Five-phase CT images were compared between 80 type 1-AIP lesions and 80 size- and location-matched PCs in the case-control study. Atypical AIPs were diagnosed based on the four ICDC items. RESULTS: ICDC items were recognized in most AIP lesions; pancreatic enlargement (87.7%), narrowing of the main pancreatic duct (98.8%), delayed enhancement (100%), and no marked upstream-duct dilation (97.5%). CT values of AIPs increased rapidly until the pancreatic phase and decreased afterward, while those of PCs gradually increased until the delayed phase (P < 0.0001). Atypical images were recognized in 14.8% of AIPs, commonly without pancreatic enlargement (18.5 mm) and sometimes mimicking intraductal neoplasms. The CT values and their ratios were different between atypical AIPs and size-matched PCs most significantly in the pancreatic phase, but similar in the delayed phase. CONCLUSIONS: Ordinary type 1 AIPs can be diagnosed with the ICDC, but atypical AIPs represented a small fraction. "Delayed enhancement" is characteristic to ordinary AIPs, however, "pancreatic-phase enhancement" is more diagnostic for atypical AIPs.
Assuntos
Adenocarcinoma/diagnóstico por imagem , Pancreatite Autoimune/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
A woman in her 70s with main pancreatic duct dilatation was referred to our hospital. Various imaging examinations showed an extensive mass within the lumen of the main pancreatic duct in the head and body of the pancreas. The microscopic examination of a biopsy specimen revealed an adenocarcinoma. She was diagnosed with intraductal tubulopapillary adenocarcinoma of the pancreas;a pylorus-preserving total pancreatectomy was subsequently performed. However, 30 days after surgery, the patient presented with neck pain and left upper arm numbness. Results of magnetic resonance imaging and bone scintigraphy revealed a cervical spinal tumor that was subsequently biopsied. The patient was diagnosed with intraductal tubulopapillary adenocarcinoma with bone metastasis.
Assuntos
Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/cirurgia , Idoso , Carcinoma Ductal Pancreático/cirurgia , Feminino , Humanos , Pâncreas/cirurgia , Pancreatectomia , Ductos Pancreáticos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgiaAssuntos
Sistema Biliar , Colestase , Neoplasias Pancreáticas , Stents Metálicos Autoexpansíveis , Colestase/diagnóstico por imagem , Colestase/etiologia , Colestase/cirurgia , Humanos , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Recidiva , Estudos Retrospectivos , Stents/efeitos adversos , Resultado do TratamentoRESUMO
Hepatitis C virus (HCV) reactivation is relatively rare compared with hepatitis B reactivation in patients treated with immunosuppressive or anticancer drugs. Here, we present the first case of genotype 2 HCV reactivation due to antiemetic steroid therapy during chemotherapy for hepatocellular carcinoma (HCC), which was verified by not only increased viral load but also pathological exacerbation of liver injury during HCV reactivation. Further chemotherapy for HCC could be continued without steroid therapy. This present case highlights the awareness of HCV reactivation and the management of complex situation.
Assuntos
Antieméticos/efeitos adversos , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Neoplasias Hepáticas/tratamento farmacológico , Esteroides/efeitos adversos , Ativação Viral/efeitos dos fármacos , Idoso , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/virologia , Feminino , Humanos , Neoplasias Hepáticas/virologia , Esteroides/uso terapêuticoRESUMO
BACKGROUND: Preoperative chemotherapy is a promising strategy for downstaging advanced gastric cancer before radical resection, although severe adverse events can occur and clinical outcomes are often unsatisfactory. To identify predictive biomarkers of drug sensitivity, we used a well-designed functional apoptosis assay and assessed the correlations between chemosensitivity and clinical outcomes. METHODS: Drug sensitivity to docetaxel, cisplatin, and 5-fluorouracil was examined in 11 gastric cancer cell lines. BCL2-homology domain 3 (BH3) profiling was performed and assessed for correlations with drug sensitivity. Immunohistochemical staining of clinical gastric cancer specimens was performed before preoperative chemotherapy, and correlations with histopathological responses and clinical outcomes were assessed. RESULTS: BIM (BCL2L11)-BH3 profiling results correlated with docetaxel sensitivity and BAK protein expression, whose knockdown caused docetaxel resistance. The BAK expression indexes of 69 gastric cancer specimens before preoperative chemotherapy (including docetaxel treatment) were determined by multiplying numerical values describing the degrees of BAK positivity and staining intensity observed. Patients whose specimens showed good chemotherapeutic histopathological responses had higher BAK indexes than those with poor responses. Patients with BAK index values ≥3 showed improved progression-free survival (HR, 2.664; 95 % CI, 1.352-5.248; P = 0.005) and overall survival (HR, 3.390; 95 % CI, 1.549-7.422; P = 0.002). CONCLUSIONS: BH3 profiling clearly showed that BIM expression, which depends on BAK expression, correlated with docetaxel sensitivity. BAK expression in gastric cancer is thus predictive of chemotherapeutic responses to docetaxel and clinical prognosis in patients treated with preoperative chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Proteína Killer-Antagonista Homóloga a bcl-2/metabolismo , Adulto , Idoso , Cisplatino/administração & dosagem , Docetaxel , Combinação de Medicamentos , Feminino , Seguimentos , Gastrectomia , Humanos , Técnicas Imunoenzimáticas , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Ensaios Clínicos Controlados não Aleatórios como Assunto , Ácido Oxônico/administração & dosagem , Fragmentos de Peptídeos/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas/metabolismo , Neoplasias Gástricas/patologia , Taxa de Sobrevida , Taxoides/administração & dosagem , Tegafur/administração & dosagem , Adulto JovemRESUMO
OBJECTIVES: To prevent the onset of lifestyle-related diseases associated with metabolic syndrome (MetS) in Japan, research into the development of a useful screening method is strongly desired. We developed a new screening questionnaire (JAMRISC) utilizing a logistic regression model and evaluated its ability to predict the development of MetS, type 2 diabetes and other lifestyle-related diseases in Japanese populace. METHODS: JAMRISC questionnaire was sent to 1,850 individuals in Rumoi, a small city in Hokkaido. We received a total of 1,054 valid responses. To maximize the target individuals accurately diagnosed with MetS, logistic regression analysis was used to generate a unique metabolic syndrome score calculation formula as taking into consideration the clinical relevance of each question item as individual coefficients. RESULTS: The results of our comparative research utilizing both JAMRISC and Finnish Diabetes Risk Score (FINDRISC) questionnaires revealed the usefulness of JAMRISC for its ability to detect risks for MetS, pre-MetS, diabetes, and pre-diabetes. Study of disease risk detection via JAMRISC questionnaire targeting the 4283 residents of Rumoi indicated a high detection rate for pre-MetS (98.8 %), MetS (94.2 %), pre-diabetes (85.1 %) and type 2 diabetes (94.9 %). In addition, JAMRISC was useful not only as a MetS risk score test, but also as a screening tool for diagnosing insulin resistance. CONCLUSIONS: JAMRISC questionnaire is a useful instrument for the detection of early risk of not only MetS and type 2 diabetes but also insulin resistance.
Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Resistência à Insulina , Programas de Rastreamento/métodos , Síndrome Metabólica/diagnóstico , Inquéritos e Questionários/normas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Programas de Rastreamento/instrumentação , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
PURPOSE: To predict side effects and optimize injection doses in the dosimetry of 177Lu imaging, highly accurate quantitative SPECT images are required. Monte Carlo simulations were performed to verify the accuracy and variability of quantitative values for 177Lu imaging under various imaging conditions. METHODS: SPECT data of NEMA body phantom were assumed to simulate intrahepatic tumors 6 h after administration of 7.4 GBq of 177Lu-Dotatate. SPECT data were acquired using the SIMIND program with different combinations of collimators and energy windows. For variability evaluation, 30 SPECT images with Poisson noise were generated for each acquisition time. The relative error was evaluated for accuracy evaluation, and the coefficient of variation was estimated for variability evaluation. RESULTS: The accuracy of BG quantification was less than 10% relative error. The accuracy of hot sphere quantification was highest with the combination of MEGP and an energy window of 208 keV±10%. However, the accuracy of hot sphere quantification decreased significantly with decreasing hot sphere diameter. Variability varied with imaging conditions and improved with longer acquisition time. CONCLUSION: Monte Carlo simulations revealed the accuracy and variability of quantitative values for each SPECT imaging condition for 177Lu imaging.
Assuntos
Lutécio , Método de Monte Carlo , Imagens de Fantasmas , Tomografia Computadorizada de Emissão de Fóton Único , Tomografia Computadorizada de Emissão de Fóton Único/métodos , Humanos , RadioisótoposRESUMO
BACKGROUND: Pancreatic acinar cell carcinoma (PACC) is a rare pancreatic neoplasm. Recently, molecular analysis revealed that PACC shows a high frequency of the BRCA1/2 mutation and is likely to be considered a cancer associated with hereditary breast and ovarian cancer (HBOC). Hereditary cancers, including HBOC, are characterized by multifocal and/or metachronous tumors. However, no case reports exist of germline BRCA1-mutated synchronous and metachronous PACC. CASE: A 58-year-old man was diagnosed with synchronous and metachronous PACC at the age of 56 and underwent two surgeries. Ten months after the second surgery, the patient developed multiple liver metastases. Gemcitabine plus nab-paclitaxel therapy was administered as first-line chemotherapy. After seven cycles, computed tomography examination revealed progressive disease (PD). Therefore, modified FOLFIRINOX (mFFX) was administered as second- line chemotherapy. After 19 cycles of mFFX, comprehensive cancer genomic profiling (CGP) identified a BRCA1 pathogenic variant that was confirmed to be germline origin. Accordingly, we treated the patient with olaparib; however, he was diagnosed with PD after 4 months. He subsequently died 5 years and 9 months after the initial surgery, and 3 years and 10 months after chemotherapy. Based on the genetic data of the patients, his family members received genetic counseling followed by cascade testing. Consequently, the same gBRCA1 pathogenic variant was detected in the son and his surveillance for HBOC-related cancers was initiated. CONCLUSION: We diagnosed a 58-year-old man with a synchronous and metachronous PACC with germline BRCA1 pathogenic variant. Considering that PACC is likely to have BRCA1/2 mutations responsible for HBOC, we need to be aware of the possible presence of multifocal and/or metachronous tumors in patients with PACC. Additionally, patients with PACC should undergo genetic examinations, which would be beneficial in determining treatment strategies and health care for blood relatives.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Proteína BRCA1 , Carcinoma de Células Acinares , Mutação em Linhagem Germinativa , Neoplasias Pancreáticas , Humanos , Pessoa de Meia-Idade , Masculino , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Proteína BRCA1/genética , Carcinoma de Células Acinares/genética , Carcinoma de Células Acinares/patologia , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Segunda Neoplasia Primária/genética , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/diagnóstico , Neoplasias Primárias Múltiplas/genética , Neoplasias Primárias Múltiplas/patologia , Neoplasias Primárias Múltiplas/terapia , Oxaliplatina/administração & dosagem , Leucovorina/administração & dosagem , Irinotecano/administração & dosagem , Paclitaxel/administração & dosagem , Fluoruracila/administração & dosagemRESUMO
Background: Endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) is an alternative for failed endoscopic retrograde cholangiopancreatography (ERCP), with current success rates of 65-84% considered suboptimal. A novel ERCP catheter (SHOREN, Kaneka Corporation, Osaka, Japan) with a tapered 3.3-French tip may facilitate smoother insertion, potentially improving outcomes. Methods: This retrospective analysis encompassed EUS-HGS procedures conducted from January 2021 to August 2023 at four institutions. The aim of this study was to compare the performance of conventional and novel ERCP contrast catheters regarding the success rate of single-attempt catheter insertion, failure rates, technical success rates, and incidence of adverse events. Results: The study included 48 patients; 26 underwent EUS-HGS using conventional catheters and 22 with the novel catheter. The novel catheter achieved higher success rates in single-attempt insertions (96.5% vs. 80.8%) and lower failure rates (4.6% vs. 7.7%). The occurrence of bile peritonitis was comparable between the two groups. Conclusions: The novel ERCP contrast catheter with a tapered tip appears to contribute to successful catheter insertion and is useful for EUS-HGS.