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BACKGROUND/OBJECTIVES: The association between autoimmune pancreatitis (AIP) and pancreatic cancer (PC) remains controversial. This study aimed to clarify the long-term prognosis and risk of malignancies in AIP patients in Japan. METHODS: We conducted a multicenter retrospective cohort study on 1364 patients with type 1 AIP from 20 institutions in Japan. We calculated the standardized incidence ratio (SIR) for malignancies compared to that in the general population. We analyzed factors associated with overall survival, pancreatic exocrine insufficiency, diabetes mellitus, and osteoporosis. RESULTS: The SIR for all malignancies was increased (1.21 [95 % confidence interval: 1.05-1.41]) in patients with AIP. Among all malignancies, the SIR was highest for PC (3.22 [1.99-5.13]) and increased within 2 years and after 5 years of AIP diagnosis. Steroid use for ≥6 months and ≥50 months increased the risk of subsequent development of diabetes mellitus and osteoporosis, respectively. Age ≥65 years at AIP diagnosis (hazard ratio [HR] = 3.73) and the development of malignancies (HR = 2.63), including PC (HR = 7.81), were associated with a poor prognosis, whereas maintenance steroid therapy was associated with a better prognosis (HR = 0.35) in the multivariate analysis. Maintenance steroid therapy was associated with a better prognosis even after propensity score matching for age and sex. CONCLUSIONS: Patients with AIP are at increased risk of developing malignancy, especially PC. PC is a critical prognostic factor for patients with AIP. Although maintenance steroid therapy negatively impacts diabetes mellitus and osteoporosis, it is associated with decreased cancer risk and improved overall survival.
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Doenças Autoimunes , Pancreatite Autoimune , Diabetes Mellitus , Osteoporose , Neoplasias Pancreáticas , Humanos , Idoso , Pancreatite Autoimune/complicações , Japão , Estudos Retrospectivos , Doenças Autoimunes/diagnóstico , Recidiva Local de Neoplasia , Prognóstico , Esteroides , Neoplasias Pancreáticas/complicações , Osteoporose/complicaçõesRESUMO
BACKGROUND: Opportunistic infections associated with immunosuppressive treatments for inflammatory bowel disease pose an important safety concern. Here we report the case of a patient with active ulcerative colitis and cryptococcal pneumonia who was treated with vedolizumab combined with fluconazole. CASE PRESENTATION: A 56-year-old Japanese man with ulcerative colitis and a history of Sweet's syndrome who was taking prednisolone and azathioprine presented with a moderate exacerbation of ulcerative colitis, abdominal pain, diarrhea, and bloody stools along with cytomegalovirus infection. Increasing the prednisolone dose without using antiviral drugs improved cytomegalovirus infection; however, ulcerative colitis did not improve, and cryptococcal pneumonia occurred. Thus, treatment with fluconazole followed by vedolizumab was initiated for ulcerative colitis. The patient gradually recovered and achieved clinical remission without the exacerbation of pneumonia. CONCLUSIONS: We reported the first case of a patient with ulcerative colitis who was treated with vedolizumab and concomitant fluconazole for active cryptococcal pneumonia. Vedolizumab constitutes a high-potential treatment regimen owing to its safety in inflammatory bowel disease associated with opportunistic infections.
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Colite Ulcerativa , Infecções por Citomegalovirus , Doenças Inflamatórias Intestinais , Infecções Oportunistas , Masculino , Humanos , Pessoa de Meia-Idade , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Fluconazol/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Prednisolona/uso terapêutico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/tratamento farmacológicoRESUMO
Objective Steroid pulse therapy is a regimen involving the intravenous administration of supra-pharmacological doses of corticosteroids in the short term. It is used to treat various inflammatory and autoimmune conditions. However, the strengths and limitations of steroid pulse therapy for induction of remission in type 1 autoimmune pancreatitis (AIP) are unknown. Methods Depending on the steroid therapy regimen administered, the 104 patients with type 1 AIP included in this retrospective study were divided into three groups: conventional oral prednisolone (PSL) regimen (PSL group), intravenous methylprednisolone (IVMP) pulse followed by oral PSL regimen (Pulse+PSL group), and IVMP pulse-alone regimen (Pulse-alone group). We then examined the relapse rate and adverse events among the three groups. Results The Kaplan-Meier estimates of the relapse rate at 36 months after steroid therapy were 13.6% in the PSL group, 13.3% in the Pulse+PSL group, and 46.2% in the Pulse-alone group. The log-rank test revealed that the relapse-free survival in the Pulse-alone group was significantly shorter than that in the PSL (p=0.024) and Pulse+PSL groups (p=0.014). The exacerbation of glucose tolerance after steroid therapy was less frequently observed in the Pulse-alone group (0%) than in the PSL group (17%, p=0.050) and Pulse+PSL groups (26%, p=0.011). Conclusion Although treatment with IVMP pulse alone resulted in unsatisfactory relapse prevention outcomes compared with conventional steroid therapy, the IVMP pulse-alone regimen might be an alternative treatment strategy for type 1 AIP from the perspective of avoiding adverse events from steroids.
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Pancreatite Autoimune , Humanos , Pancreatite Autoimune/tratamento farmacológico , Estudos Retrospectivos , Prednisolona , Metilprednisolona/uso terapêutico , Esteroides/uso terapêutico , Recidiva , Resultado do TratamentoRESUMO
Vascular endothelial growth factor inhibitors and checkpoint inhibitors are effective treatments for solid tumors. These new classes of anti-cancer agents frequently cause kidney-related side effects. Although their anti-cancer effects may be enhanced when used in combination, the severity of their kidney-related side effects is unknown. We herein report the first case of thrombotic microangiopathy and mesangial proliferative glomerulonephritis caused by combined treatment with atezolizumab and bevacizumab in a 74-year-old man with hepatocellular carcinoma. The combination therapy was discontinued and replaced with intravenous methylprednisolone followed by oral prednisolone. Subsequently, the urinary protein excretion levels declined.
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Carcinoma Hepatocelular , Glomerulonefrite , Neoplasias Hepáticas , Microangiopatias Trombóticas , Masculino , Humanos , Idoso , Bevacizumab/efeitos adversos , Fator A de Crescimento do Endotélio Vascular , Microangiopatias Trombóticas/tratamento farmacológico , Glomerulonefrite/induzido quimicamente , Glomerulonefrite/tratamento farmacológico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológicoRESUMO
IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder recognized as a novel clinical entity with either synchronous or metachronous multiorgan involvement. Autoimmune pancreatitis (AIP) is classified into two types: type 1 AIP as a pancreatic manifestation of IgG4-RD and type 2 AIP with granulocytic epithelial lesion and occasional association with ulcerative colitis. Although the pathogenic mechanism still remains unclear, possible multipathogenic factors such as genetic factors, disease-specific or related antigens, and abnormal innate or adaptive immunity may be involved in the development of IgG4-RD. Many immunocytes including M2 macrophages, plasmablasts, B cells, and T-cells (Th2-CD4+T, follicular helper T-cells, and CD4+SLAMF7+cytotoxic T-cells) play important roles in the pathogenesis. Conventional induction and maintenance therapies with glucocorticoid or rituximab are recommended in all symptomatic patients with active IgG4-RD. In those at risk for irreversible damage in any organs, this should be done urgently, regardless of symptoms. As no randomized clinical trials other than glucocorticoid maintenance therapy for type 1 AIP have been performed, the comprehensive management for IgG4-RD has not been established yet. Targeted treatment approaches against the plasmablast to B cell lineage and the CD4+ SLAMF7+ cytotoxic T-cell seem to be promising for the future-directed treatment.
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Doenças Autoimunes , Pancreatite Autoimune , Doença Relacionada a Imunoglobulina G4 , Pancreatite , Humanos , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/tratamento farmacológico , Pancreatite Autoimune/diagnóstico , Pancreatite Autoimune/tratamento farmacológico , Glucocorticoides/uso terapêutico , Pancreatite/tratamento farmacológico , Pancreatite/diagnóstico , Linfócitos T CD4-Positivos , Doenças Autoimunes/diagnósticoRESUMO
In 1995, Yoshida et al. proposed first the concept of "autoimmune pancreatitis" (AIP). Since then, AIP has been accepted as a new pancreatic inflammatory disease and is now divided two subtypes. Type 1 AIP affected immunoglobulin G4 (IgG4) and implicates the pancreatic manifestation of IgG4-related disease, while type 2 is characterized by neutrophil infiltration and granulocytic epithelial lesions (GEL). Recent research has clarified the clinical and pathophysiological aspects of type 1 AIP, which is more than type 2 among the Japanese population. However, many details remain unclear about the pathogenesis and progression of this disease. In this review, we discuss the current knowledge and recent advances relating to type 1 AIP.
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Doenças Autoimunes , Pancreatite Autoimune , Doença Relacionada a Imunoglobulina G4 , Pancreatopatias , Pancreatite , Pancreatite Autoimune/diagnóstico , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Pancreatite/diagnóstico , Pancreatite/etiologiaRESUMO
BACKGROUND: Pancreatic acinar cell carcinoma is rare; it accounts for 1% of all malignant pancreatic exocrine tumors. Although surgical resection is an option for curative treatment, the safety and efficacy of conversion surgery in patients with pancreatic acinar cell carcinoma with metastasis remain unknown. CASE: A 67-year-old man with epigastric pain and a pancreatic tumor was referred to our hospital. Computed tomography revealed a large tumor with a maximum diameter of 67 mm at the pancreatic head and a 23-mm mass in the left upper abdominal cavity. Because a definitive diagnosis could not be made based on endoscopic ultrasonography-guided fine needle aspiration biopsy findings, a diagnostic laparoscopy was performed. The tumor in the greater omentum at the left upper abdomen, resected under laparoscopy, was histopathologically diagnosed as pancreatic acinar cell carcinoma. Therefore, the pancreatic tumor was diagnosed as an unresectable pancreatic acinar cell carcinoma with a solitary peritoneal dissemination. The size of the main pancreatic tumor decreased to 15 mm after 18 courses of FOLFIRINOX (5-fluorouracil, leucovorin, irinotecan, and oxaliplatin). Subsequently, the patient underwent conversion surgery, and the initial diagnosis of pancreatic acinar cell carcinoma was confirmed on pathological examination. The patient was discharged 31 days postoperatively, following which he received adjuvant chemotherapy with S-1. No sign of recurrence has been observed for 32 months after surgical resection. CONCLUSION: FOLFIRINOX may be effective in patients with pancreatic acinar cell carcinoma, and conversion surgery after FOLFIRINOX may be applicable to selective patients.
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Carcinoma de Células Acinares , Neoplasias Pancreáticas , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Acinares/diagnóstico , Carcinoma de Células Acinares/tratamento farmacológico , Carcinoma de Células Acinares/cirurgia , Fluoruracila , Humanos , Irinotecano/uso terapêutico , Leucovorina , Masculino , Oxaliplatina/uso terapêutico , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias PancreáticasRESUMO
BACKGROUND AND AIM: To clarify the clinicoepidemiological characteristics of immunoglobulin G4 (IgG4)-related disease (IgG4-RD) with malignancy, a nationwide epidemiological survey was conducted. METHODS: Immunoglobulin G4-related disease patients with malignancy who had visited selected hospitals in Japan were surveyed. The study consisted of two stages: the number of IgG4-RD patients with malignancy was estimated by the first questionnaire and their clinicoepidemiological characteristics were assessed by the second questionnaire. RESULTS: The frequencies of autoimmune pancreatitis (AIP), IgG4-related sialadenitis, IgG4-related eye disease, IgG4-related kidney disease, and IgG4-related retroperitoneal fibrosis were 44.7%, 20.8%, 14.0%, 5.16%, and 5.12%, respectively. The overall prevalence of malignant disease in IgG4-RD cases was estimated to be 10 900 per 100 000 cases, which was significantly higher than that of malignant disease in the general population. The prevalence of malignant lymphoma in IgG4-RD cases was the highest and was estimated to be 1985 per 100 000 cases. IgG4-related kidney disease had the highest frequency of malignant disease (17.1%). In data from 200 patients, 61 (30.5%) cases of cancer were found 2 years or more before the IgG4-RD diagnosis, 92 cases (46%) during the 1 year preceding or following IgG4-RD diagnosis, and 62 cases of cancer (31%) 2 or more years following IgG4-RD diagnosis. CONCLUSIONS: The nationwide survey for IgG4-RD with malignancy in Japan showed that IgG4-RD may be related with malignant diseases.
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Doenças Autoimunes , Doença Relacionada a Imunoglobulina G4 , Neoplasias , Doenças Autoimunes/diagnóstico , Humanos , Imunoglobulina G , Doença Relacionada a Imunoglobulina G4/diagnóstico , Doença Relacionada a Imunoglobulina G4/epidemiologia , Japão/epidemiologia , Neoplasias/epidemiologia , Inquéritos e QuestionáriosRESUMO
In response to the latest knowledge and the amendment of the Japanese diagnostic criteria for autoimmune pancreatitis (AIP) in 2018, the Japanese consensus guidelines for managing AIP in 2013 were required to be revised. Three committees [the professional committee for developing clinical questions (CQs) and statements by Japanese specialists; the expert panelist committee for rating statements by the modified Delphi method; and the evaluating committee of moderators] were organized. Twenty specialists in AIP extracted the specific clinical statements from a total of 5218 articles (1963-2019) from a search in PubMed and the Cochrane Library. The professional committee made 14, 9, 5, and 11 CQs and statements for the current concept and diagnosis, extra-pancreatic lesions, differential diagnosis, and treatment, respectively. The expert panelists regarded the statements as valid after a two-round modified Delphi approach with individually rating these clinical statements, in which a clinical statement receiving a median score greater than 7 on a 9-point scale from the panel was regarded as valid. After evaluation by the moderators, the amendment of the Japanese consensus guidelines for AIP has been proposed in 2020.
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Pancreatite Autoimune , Consenso , Técnica Delphi , Diagnóstico Diferencial , Humanos , JapãoRESUMO
BACKGROUND: Stimulation of Toll-like receptor 3 (TLR3) induces autoimmune-mediated pancreatitis in susceptible mice, whereas stimulation of TLR4 causes nonautoimmune-mediated pancreatitis. However, the effects of TLR2 stimulation on the pancreas are unknown. AIMS: We investigated the role of TLR2 stimulation on pancreatic damage by repeatedly stimulating mice with TLR2 ligands. METHODS: Wild-type (WT) and interleukin 10-deficient (IL-10-knockout (KO)) mice were administered zymosan and lipoteichoic acid (LTA) intraperitoneally at various doses twice weekly for 4 weeks. Syngeneic T-cell-deficient mice, B-cell-deficient mice, recombination activating gene 2-deficient (RAG2-KO) mice and RAG2-KO mice that had been reconstituted with CD4+ or CD8+ T cells isolated from WT mice were treated with zymosan similarly. Mice were killed, the severity of pancreatitis was graded histologically, and serum cytokine levels were measured. RESULTS: Repeated administration of zymosan induced pancreatitis dose dependently in both WT and IL-10-KO mice. Administration of LTA induced pancreatitis only in IL-10-KO mice. Adoptive transfer of splenocytes obtained from IL-10-KO mice with pancreatitis did not cause pancreatitis in recipient RAG2-KO mice. Pancreatitis was scarcely observed in RAG2-KO mice and was attenuated in T-cell-deficient and B-cell-deficient mice compared with WT mice. A single administration of zymosan significantly increased the serum level of monocyte chemoattractant protein 1 (MCP-1) in WT mice. CONCLUSIONS: Repeated stimulation of TLR2 and dectin-1 induced nonautoimmune-mediated pancreatitis in mice. Participation of acquired immunity seems to play an important role in the pathogenesis of pancreatitis in association with the increase in serum MCP-1 level.
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Imunidade Adaptativa , Lectinas Tipo C , Pancreatite Crônica , Receptor 2 Toll-Like , Animais , Linfócitos T CD8-Positivos/metabolismo , Interleucina-10/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pancreatite Crônica/patologia , Receptor 2 Toll-Like/genética , Receptor 2 Toll-Like/metabolismo , ZimosanRESUMO
The effectiveness of azathioprine (AZA) in preventing relapse and maintaining autoimmune pancreatitis (AIP) remission has been reported; however, most of these studies are case series with no randomized control trials available in the literature. Therefore, this study performed a systematic review and meta-analysis of the existing literature on this subject to determine the clinical efficacy of AZA as maintenance therapy for AIP patients. A systematic search was performed to identify studies on the clinical efficacy of AZA as maintenance therapy in AIP patients. The crude multiple relapse rate was estimated to assess the ability of AZA to control relapses in AIP. Pooled estimates were obtained using a random-effects model with the DerSimonian-Laird method. We identified AIP patients who did not respond to initial steroid treatment, experienced steroid weaning failure, or those who relapsed during remission as refractory cases. After reviewing the studies, ten articles fulfilled the inclusion criteria and were selected for meta-analysis. Of all 4504 patients, 3534 patients were treated with steroids, and 346 patients were treated with AZA for relapsed AIP. In this meta-analysis, 14/73 (19.2%) patients receiving AZA for refractory AIP relapsed. Meanwhile, 14/47 (29.8%) patients without AZA experienced relapse. The integrated odds ratio for relapse risk in patients receiving AZA was estimated to be 0.52 (p = 0.15). This systematic review and meta-analysis demonstrated the efficacy of AZA in preventing relapse of AIP, which supports the use of AZA as a maintenance treatment in patients with AIP who relapse upon withdrawal of steroid therapy.
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Pancreatite Autoimune , Azatioprina , Humanos , Pancreatite Autoimune/tratamento farmacológico , Azatioprina/administração & dosagem , Imunossupressores/administração & dosagem , Indução de Remissão/métodos , Resultado do TratamentoRESUMO
BACKGROUND: /Object: Some patients with type 1 autoimmune pancreatitis (AIP), the pancreatic manifestation of IgG4-related disease, have normal serum IgG4. The aim of this study is to investigate the diagnostic value of measuring serum free light chains (FLCs) in type 1 AIP. MATERIALS AND METHODS: Thirty-seven patients with type 1 AIP, and 21 healthy, 17 alcoholic chronic pancreatitis (ACP), 21 idiopathic chronic pancreatitis (ICP) and 20 pancreatic cancer (PC) patients were enrolled. Serum IgG4 and FLC concentrations were measured using sFLC Freelite assays on a nephelometric analyzer. RESULTS: Active AIP patients have significantly higher serum levels of κ (median 30.97 (12.3-227.0) mg/L) and λFLC (median 20.53 (12.36-102.7) mg/L)) than healthy controls (κFLC; median 12.5 (3.1-52.1) mg/L), λFLC: median 12.45 (5.4-39.5) mg/L) (p < 0.05) correlating with raised serum IgG4, and significantly higher summated FLCs (∑) (median 53.09 (25.0-218.0) mg/L) than ICP patients (median 26.77 (15.0-89.2) mg/L) and healthy controls (median 24.43 (8.5-91.6) mg/L) (p < 0.05). AIP patients (median 1.43 (0.84-3.24)) showed significantly higher κ/λ ratios than ACP (median 0.83 (0.42-1.18)), ICP (median 0.87 (0.47-2.16)), PC patients (median 0.90 (0.48-1.27)) and healthy controls (median 0.963 (0.51-1.32)). There was a correlation between increased κ and λ FLCs levels and the number of affected organs involved in IgG4 related disease. CONCLUSION: Patients with type 1 AIP have increased serum k and λ FLC concentrations, Σ FLC, and κ/λ ratios. These novel biomarkers may be useful in the diagnosis of type 1 AIP and in monitoring disease activity.
Assuntos
Pancreatite Autoimune/diagnóstico , Doença Relacionada a Imunoglobulina G4/diagnóstico , Cadeias Leves de Imunoglobulina/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Pancreatite Autoimune/sangue , Pancreatite Autoimune/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Regras de Decisão Clínica , Diagnóstico Diferencial , Feminino , Humanos , Imunoglobulina G/sangue , Doença Relacionada a Imunoglobulina G4/sangue , Doença Relacionada a Imunoglobulina G4/imunologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e Especificidade , Índice de Gravidade de DoençaRESUMO
To evaluate the breakdown of unexpected pancreatic 18F-fluorodeoxyglucose (FDG) uptake and the proportion of secondary primary pancreatic cancer on follow-up, patients with cancer underwent positron emission tomography/computed tomography (PET/CT). The participants consisted of 4,473 consecutive patients with cancer who underwent follow-up PET/CT between January 2015 and March 2019 at Kochi Medical School. Among the participants, 225 with a history of pancreatic cancer were excluded from the present study. Retrospective and blinded PET/CT evaluations of 4,248 patients were performed. In patients with pancreatic FDG uptake, the distribution of FDG uptake in the pancreas was evaluated. The final diagnosis was determined pathologically. A total of 14 (0.3%) of the 4,248 patients exhibited FDG uptake in the pancreatic area. Pancreatic abnormalities were detected in 14 patients, and included five cases of pancreatic metastases (36%), four cases of secondary primary pancreatic cancer (29%), two cases of lymph node metastases (14%), one case of malignant lymphoma (7%), one case of autoimmune pancreatitis (7%) and one case of pseudolesion (7%). One patient with early-stage secondary primary pancreatic cancer had a maximum standardized uptake value (SUVmax) <3.0. The remaining 13 patients had a SUVmax >3.0 in the pancreas. Of the 14 patients, two had multiple foci of FDG uptake in the pancreas. Patients with multiple foci of FDG uptake exhibited pancreatic metastasis from renal cell carcinoma and malignant lymphoma. In conclusion, the majority of patients with unexpected pancreatic FDG uptake on follow-up PET/CT exhibited malignancies; furthermore, ~30% of the malignancies detected in patients with pancreatic FDG uptake were secondary primary pancreatic cancers. In patients with unexpected pancreatic FDG uptake on follow-up PET/CT, primary cancer should be considered as well as metastatic tumors.
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IgG4-related disease (IgG4-RD) represents an immune-mediated fibroinflammatory condition with peculiar histopathologic changes that can affect various organs. In 2012 its unified nomenclature was published, which allows to abandon other synonymous names. Up to now, only little is known about its epidemiology around the world. However, although it is generally considered a rare condition, the number of patients with IgG4-RD is increasing enormously. Likewise, the annual number of publications on this subject has increased progressively. The spectrum of clinical manifestations in IgG4-RD is highly variable, depending on the severity of the disease as well as the presence of organ(s) involvement. This review gives an overview on changing epidemiology of IgG4-RD focusing the attention on the large cohorts of patients published in the literature.
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An asymptomatic 76-year-old man presented to our department for the treatment of gastric cancer. Esophagogastroduodenoscopy revealed a superficial elevated lesion with an irregular central depression in the lower third of the stomach; this was confirmed to be adenocarcinoma by biopsy, while abdominal contrast-enhanced CT revealed no abnormal lesions. Based on the patient's clinical diagnosis of early gastric cancer, we planned laparoscopic gastrectomy with preoperative placement of four endoscopic marking clips equipped with indocyanine green-conjugated resin to determine the resection margin. During surgery, a dedicated laparoscopic system was used to detect indocyanine green fluorescence emitted by the clips and determine their precise position. The clips helped to identify an accurate resection line for the stomach, enabling accurate laparoscopic distal gastrectomy with regional lymphadenectomy. We successfully demonstrated the usefulness of clips with fluorescent resin for detecting gastric cancer in patients. We report the first case using the clips to accurately locate a site of interest.
Assuntos
Laparoscopia , Neoplasias Gástricas , Idoso , Gastrectomia , Humanos , Verde de Indocianina , Masculino , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Instrumentos CirúrgicosRESUMO
AIM: The optimal choice between sorafenib (SOR) or lenvatinib (LEN) as the first-line treatment for unresectable hepatocellular carcinoma (u-HCC) remains debatable. Using propensity score matching, this study compares the outcomes of SOR and LEN in the molecular-targeted agent (MTA) sequential treatment of u-HCC patients. METHODS: This retrospective, multicenter, observational study recruited 137 u-HCC patients who underwent primary treatment with LEN (n = 52) or SOR (n = 85) between June 2017 and June 2020 after regorafenib was approved as the secondary treatment for u-HCC. Propensity score matching was used to reduce confounding, resulting in the selection of 104 patients (n = 52 for the SOR and LEN cohorts). RESULTS: The median overall survival was 21.8 months for LEN and 20.4 months for SOR. LEN exhibited significantly greater therapeutic efficacy as compared to SOR (objective response rate: 3.8% [SOR] vs. 42.3% [LEN], p < 0.01; progression-free survival: 10 months [LEN] vs. 5.1 months [SOR], p < 0.01). No significant intergroup differences were noted in the rate of transition to secondary MTA treatments (SOR: 58.7%; LEN: 48.4%), adverse events (SOR: 86%; LEN: 95%), and maintenance of the Child-Pugh (CP) score during treatment. Compared to non-MTA treatments, secondary MTA treatment achieved a greater improvement in survival (4.3 vs. 2.8 months, p = 0.0047). Multivariate analysis demonstrated that the CP score (p < 0.01) and alpha-fetoprotein level (p < 0.01) were independent prognostic factors. CONCLUSIONS: Both SOR and LEN treatments showed a clinically comparable therapeutic efficacy as the first-line treatments for u-HCC patients in an MTA sequential therapy.
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OBJECTIVES: The objective of this study was to clarify the role of pancreatectomy for patients with resectable and borderline resectable pancreatic ductal adenocarcinoma aged 80 years or older using a nationwide audit by the Japan Pancreas Society. METHODS: Data were collected from 39 institutions from 2007 to 2014. The primary endpoint was overall survival, and secondary endpoints were surgical outcomes and predictive factors for prognosis. RESULTS: Data were obtained from 556 octogenarians who underwent pancreatectomy (n = 369, 66%), chemo(radio)therapy (n = 99, 18%), and palliative therapy (n = 88, 16%). Median survival times were 20.6, 18.6, and 8.8 months in each group, respectively. Even after propensity score matching, median survival time in the surgery group (22.8 months) was significantly higher than that in the chemotherapy group (18.5 months; hazard ratio, 0.64 [95% confidence interval, 0.44-0.93]; P = 0.020). Significant independent prognostic factors were body mass index, lymph node metastasis, and tumor diameter in the surgery group, and serum albumin level, American Society of Anesthesiologists classification, body mass index, modified Glasgow prognostic score, second-line chemotherapy, and tumor diameter in the chemotherapy group. CONCLUSIONS: Octogenarians with resectable/borderline resectable pancreatic ductal adenocarcinoma can be recommended for pancreatectomy according to mental and physical fitness for surgical procedures.
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Carcinoma Ductal Pancreático/terapia , Tratamento Farmacológico/métodos , Cuidados Paliativos/métodos , Pancreatectomia/métodos , Neoplasias Pancreáticas/terapia , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Feminino , Humanos , Masculino , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND/AIM: We evaluated urinary levels of porphyrin metabolites, such as uroporphyrin (UP) and coproporphyrin (CP), after 5-Aminolevulinic acid (ALA) administration in patients with or without pancreatic cancer (PaC). PATIENTS AND METHODS: Sixty-seven subjects with PaC, 11 with pancreatitis, and 9 with normal pancreas (NP) were enrolled. Urine samples from all subjects were collected prior to ALA administration and at more than 4 hours after ALA administration. We measured the urinary levels of UP and CP by high-performance liquid chromatography analysis. RESULTS: The PaC group showed significantly higher UP levels compared to NP groups (104.9 nmol/g Cre vs. 53.4 nmol/g Cre, p=0.014). Moreover, PaC patients with long-term survival had significantly lower urinary levels of UP at diagnosis (98.8 nmol/gCre) than the short-term survival group (125.2 nmol/gCre) (p=0.042). CONCLUSION: The urinary levels of UP after ALA administration might serve as a promising biomarker for diagnosis and prognosis prediction of PaC.
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Ácidos Levulínicos , Luz , Imagem Molecular , Neoplasias Pancreáticas/diagnóstico , Fármacos Fotossensibilizantes , Idoso , Biomarcadores , Biomarcadores Tumorais , Detecção Precoce de Câncer , Feminino , Humanos , Ácidos Levulínicos/metabolismo , Masculino , Programas de Rastreamento , Pessoa de Meia-Idade , Imagem Molecular/métodos , Imagem Molecular/normas , Neoplasias Pancreáticas/metabolismo , Fármacos Fotossensibilizantes/metabolismo , Porfirinas , Sensibilidade e Especificidade , Ácido AminolevulínicoRESUMO
PURPOSE: Intraoperative identification of the cancer location is often difficult to conduct during laparoscopic surgery, especially in early-stage cancers. This study aimed to investigate the feasibility and accuracy of a novel endoscopic clip resin-conjugated fluorescent indocyanine green during laparoscopic surgery for gastrointestinal cancer. METHODS: Preoperative placement of endoscopic marking clips equipped with resin-conjugated fluorescent indocyanine green was performed to determine the resection margin in eight patients with gastrointestinal cancer. During laparoscopic surgery, a dedicated laparoscopic system with a xenon light source was used to detect fluorescence. The evaluation determined whether the fluorescent from the clips was visualized during laparoscopic surgery. RESULTS: Fluorescent signal emitted from ICG in the resin of the clips was detected in six patients from the outer layer of the serosal surfaces of the gastrointestinal tract, and the clips aided in accurate resection line of the organ. There were no significant differences of age, gender, and BMI between the patients in whom we could and could not detect ICG fluorescence. CONCLUSIONS: The results demonstrated the usefulness of a novel clip-equipped fluorescent resin, which is a promising diagnostic tool to detect accurate tumor location during laparoscopic surgery.