RESUMO
We present the case of a 61-year-old man who developed nephrotic syndrome as a result of syphilis-associated secondary membranous nephropathy (MN). The patient showed nephrotic syndrome remission following antibiotic treatment for syphilis alone. Pathologically, the target antigen of immune complexes accumulated on glomerular basement membranes (GBM) in secondary MN caused by syphilis has been reported to be neuron-derived neurotrophic factor (NDNF). His renal histopathology was consistent with secondary MN caused by syphilis, with a full-house pattern on immunofluorescence microscopy, in addition to NDNF deposits that colocalized with IgG deposits granularly on the GBM. However, to date, there is no serological evidence for the involvement of NDNF in the GBM. In the present study, we found that anti-NDNF autoantibodies in the acute-phase serum disappeared in the convalescent-phase serum of a patient who recovered from syphilis and nephrotic syndrome after antibiotic therapy alone. This result supports the hypothesis that treatment of syphilis with antibiotics suppresses NDNF's antigenicity. In summary, we found new serological evidence emphasizing that NDNF is an etiological antigen in secondary MN caused by syphilis.
Assuntos
Autoanticorpos , Glomerulonefrite Membranosa , Sífilis , Humanos , Glomerulonefrite Membranosa/imunologia , Glomerulonefrite Membranosa/tratamento farmacológico , Glomerulonefrite Membranosa/complicações , Glomerulonefrite Membranosa/diagnóstico , Masculino , Pessoa de Meia-Idade , Sífilis/tratamento farmacológico , Sífilis/complicações , Sífilis/diagnóstico , Autoanticorpos/imunologia , Autoanticorpos/sangue , Antibacterianos/uso terapêuticoRESUMO
BACKGROUND: March hemoglobinuria is caused by a hemolytic mechanism due to transient hematuria after physical exercise which, although rare, may lead to acute kidney injury. We report a case of a patient with march hemoglobinuria induced by kendo, which was diagnosed by the presence of Berlin blue iron staining in the proximal tubules through renal biopsy. CASE PRESENTATION: A 15-year-old male complained of fever (37 °C), general malaise, and nausea after hard kendo sessions. Laboratory findings revealed indirect bilirubin dominant hyperbilirubinemia (total bilirubin 3.8 mg/dL), high lactate dehydrogenase (LDH), and acute kidney injury (serum creatinine: 3.11 mg/dL and estimated glomerular filtration rate: 26 mL/min/1.73m2). Urine test was positive for occult blood but without hematuria. Renal biopsy was performed to clarify the cause of renal injury, which showed minor glomerular abnormalities. Meanwhile, hemosiderin deposition was identified in the proximal tubules by Berlin blue iron staining, and lysosomes were observed to contain granular iron. In addition to clinical background of strenuous kendo exercise, renal biopsy led to a definitive diagnosis of march hemoglobinuria. CONCLUSIONS: March hemoglobinuria is a hemolytic disease that can occur after intense exercise, especially kendo. Considering its rarity due to the lack of critical symptoms, it is important to note that occult blood-positive findings may be indicative of march hemoglobinuria if the patient underwent strenuous exercise. Therefore, clinicians should be aware of this possibility to provide timely and appropriate treatment.
Assuntos
Injúria Renal Aguda , Anemia Hemolítica , Masculino , Humanos , Adolescente , Hemoglobinúria/etiologia , Hematúria/complicações , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/terapia , Hemólise , Bilirrubina , FerroRESUMO
BACKGROUND: Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13-14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities. CASE PRESENTATION: A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary ß2-microglobulin was high (805 µg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. CONCLUSIONS: NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas do Citoesqueleto/genética , Doenças Renais Císticas/congênito , Túbulos Renais , Insuficiência Renal , Adulto , Atrofia , Biópsia/métodos , Diagnóstico Diferencial , Feminino , Testes Genéticos/métodos , Taxa de Filtração Glomerular , Humanos , Queratina-7/metabolismo , Doenças Renais Císticas/diagnóstico , Doenças Renais Císticas/etiologia , Doenças Renais Císticas/genética , Doenças Renais Císticas/metabolismo , Doenças Renais Císticas/fisiopatologia , Túbulos Renais/diagnóstico por imagem , Túbulos Renais/patologia , Insuficiência Renal/diagnóstico , Insuficiência Renal/etiologia , Deleção de SequênciaRESUMO
OBJECTIVE: We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital. METHODS: According to the World Health Organization(WHO)diagnostic criteria. PATIENTS: All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019. RESULT: More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology. CONCLUSION: Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.
Assuntos
Policitemia Vera , Trombocitemia Essencial , Humanos , Policitemia Vera/diagnóstico , Policitemia Vera/epidemiologia , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/epidemiologiaRESUMO
A 42âyearâold woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/µL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/µL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/µL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/µL. Six days after delivery, she developed infarction. The Plt count was 915,000/µL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/µL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"lowârisk"by IPSETâthrombosis, and as"ultralow"risk by revised IPSETâthrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.
Assuntos
Trombocitemia Essencial , Adulto , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Cesárea , Feminino , Humanos , Período Pós-Parto , Gravidez , Trombocitemia Essencial/complicaçõesRESUMO
In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients. OBJECTIVE: The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated. METHODS: A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted. RESULT: In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases. CONCLUSION: The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.
Assuntos
Leucemia Linfocítica Crônica de Células B , Adenina/análogos & derivados , Humanos , Japão , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Piperidinas , Pirazóis/efeitos adversos , Estudos Retrospectivos , Resultado do TratamentoRESUMO
A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). BMbiopsy performed in 2016 showed overt fibrotic stage(Grade 2). She was classified according to the Dynamic International Prognostic Scoring System(DIPSS)as intermediate(Int)-â ¡risk. Ruxolitinib 10 mg daily was initiated. Ruxolitinib was suspended for hepatic dysfunction after the dose was increased to 15 mg. Subsequently, ruxolitinib was resumed at 10 mg. BM biopsy performed in 2017 showed progression of myelofibrosis(MF)to Grade 3. BM biopsy performed in 2018 showed improved to Grade 0-1, however, BM was fatty. Currently in 2019, she continues to be on ruxolitinib. Results of immunohistochemical staining of BM biopsy specimens for cytokines and CD34 suggested the role of cytokines in the pathogenesis of the PMF. It was speculated that ruxolitinib blocked the production of cytokines to ameliorate the MF and restore the hematopoietic function of the BM. Although the pathogenesis of the fatty marrow remained unclear, the possibility of involvement of ruxolitinib cannot be denied.
Assuntos
Mielofibrose Primária , Medula Óssea , Feminino , Fibrose , Humanos , Pessoa de Meia-Idade , Nitrilas , Mielofibrose Primária/tratamento farmacológico , Pirazóis , PirimidinasRESUMO
Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.
Assuntos
Carcinoma Medular/diagnóstico por imagem , Carcinoma de Células Renais/diagnóstico por imagem , Neoplasias Renais/diagnóstico por imagem , Traço Falciforme/diagnóstico por imagem , Adulto , Carcinoma Medular/genética , Carcinoma Medular/patologia , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Diagnóstico Diferencial , Humanos , Imuno-Histoquímica , Japão , Neoplasias Renais/genética , Neoplasias Renais/patologia , Masculino , Proteína SMARCB1/metabolismo , Traço Falciforme/patologia , Tomografia Computadorizada por Raios X , Adulto JovemRESUMO
OBJECTIVE: The clinical features(CF), laboratory data, disease transformation pattern and drug metabolism in essential thrombocythemia(ET)differ between Japan and Western countries. The CF of ET in clinical practice(CP)are more diverse than in prospective clinical studies. We should conduct retrospective analyses in CP. The present study was aimed at evaluating the efficacy, safety and tolerability of anagrelide(ANA)monotherapy and combined ANA plus hydroxycarbamide(HC)in Japanese ET. PATIENTS AND METHODS: We have a total of 35 cases. Sixteen patients received ANA monotherapy, 10 received ANA plus HC, and 9 received ANA plus other drugs. RESULTS: Comparison among three groups revealed the absence of differences in response rate(platelet count C60×10 / / 4/mL, platelet count C40×104/mL)(43.8%, 6.3% vs. 50.0%, 10.0% vs. 44.4%, 11.1%), treatment continuation rate(81.3% vs. 40.0% vs. 55.6%), median daily dose of ANA(1.00 mg in all three groups)or median treatment period(days)(259 vs. 198.5 vs. 161.0), the treatment continuation rate tended to be lower in the combined ANA plus HC. The incidence of all adverse events(AEs)was higher in the ANA monotherapy(45.7%)than ANA plus HC(28.6%)or ANA plus other drugs(25.7%), the AEs were mild in all groups. CONCLUSION: The tolerability of ANA monotherapy, ANA plus HC, and ANA plus other drugs were good.
Assuntos
Hidroxiureia/uso terapêutico , Quinazolinas/efeitos adversos , Trombocitemia Essencial , Protocolos de Quimioterapia Combinada Antineoplásica , Humanos , Japão , Estudos Retrospectivos , Trombocitemia Essencial/tratamento farmacológicoRESUMO
A 59-year-old female was diagnosed as pulmonary aspergillosis(IPA)while remission induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia. Liposomal amphotericin B improved the fungal serodiagnostic markers, however,the IPA worsened. She also developed an Aspergillus brain abscess,which, while being undetectable on CT,was detected as multiple nodular lesions by MRI. A definitive diagnosis was made by polymerase chain reaction(PCR)of brain biopsy specimens. Voriconazole(VRCZ)was effective,and cord blood transplantation was performed. She has received VRCZ for a long time. There are no relapse of either the IPA or the Aspergillus brain abscess.
Assuntos
Abscesso Encefálico , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Aspergilose Pulmonar Invasiva , Leucemia-Linfoma Linfoblástico de Células Precursoras , Antifúngicos , Feminino , Humanos , Aspergilose Pulmonar Invasiva/complicações , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , VoriconazolRESUMO
Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.
Assuntos
Linfoma Difuso de Grandes Células B , Transplante de Células-Tronco de Sangue Periférico , Protocolos de Quimioterapia Combinada Antineoplásica , Ciclofosfamida , Etoposídeo , Humanos , Linfoma Difuso de Grandes Células B/terapia , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
A 31-year-old woman with systemic lupus erythematosus and lupus nephritis was treated with prednisone and immunosuppressants. After her lupus nephritis symptoms worsened, both high-dose steroid and cyclophosphamide pulse therapy were administered. The patient developed an intestinal perforation, and laparoscopic Hartmann's surgery was performed on the sigmoid colon. Serum Cytomegalovirus (CMV) antigen C7HRP was detected, and the patient was diagnosed with CMV colitis and underwent a colon resection. Severe hematochezia continued despite ganciclovir administration, and the patient underwent laparoscopic total colectomy and partial ileostomy. CMV enteritis should be considered in patients treated with prednisone and immunosuppressants and those who have abdominal pain and hematochezia. Immunocompromised patients with intestinal perforation due to CMV enteritis have a poor prognosis. We report a case with along with the results of a literature review.
Assuntos
Colite/complicações , Infecções por Citomegalovirus/complicações , Enterite/complicações , Hospedeiro Imunocomprometido , Perfuração Intestinal/etiologia , Nefrite Lúpica/complicações , Adulto , Antivirais/uso terapêutico , Betametasona/administração & dosagem , Betametasona/efeitos adversos , Colo Sigmoide/cirurgia , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Enterite/virologia , Feminino , Ganciclovir/uso terapêutico , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Perfuração Intestinal/cirurgia , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/imunologia , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversosRESUMO
Background: Amyloidosis is a spectrum of disorders characterized by the deposition of amyloid that causes severe damage to many organ systems. However, conjunctival amyloidosis is thought to be the manifestation of a local immunologic disorder and rarely affects the organ systems. We present two cases of conjunctival amyloidosis found as unilateral ptosis at initial visit. Case 1: 43-year-old-woman presented with unilateral ptosis and discomfort for the left eye. She had been treated with topical antihistamines and corticosteroids for allergic conjunctivitis. However, as symptoms persisted she was referred to us. At initial visit, unilateral ptosis, subconjunctival hemorrhage and waxy-yellow mass were found. Incisional biopsy was performed and histpathological examination revealed amyloid in the conjunctival stroma. Case 2: 31-year-old woman presented with unilateral ptosis and discomfort of palpebral superior conjunctiva in the left eye. At initial visit, the examination of the left superior palpebral conjunctiva showed waxy-yellow mass and hemorrhage. Incisional biopsy was performed and histopathological examination revealed amyloid in the conjunctival stroma. Conclusion: Unilateral ptosis may be an indication of conjunctival amyloidosis.
Assuntos
Amiloidose/patologia , Blefaroptose/patologia , Doenças da Túnica Conjuntiva/patologia , Adulto , Amiloidose/cirurgia , Blefaroptose/cirurgia , Doenças da Túnica Conjuntiva/cirurgia , Feminino , HumanosRESUMO
The patient was a 48-year-old Japanese woman diagnosed as having systemic lupus erythematosus at the age of 21 years when she presented with fever and an erythematous skin rash on her face and extremities. Prednisolone was initiated at that time. Thirteen days before admission to our hospital, she was referred to us by her family physician. Upon admission, blood tests showed pancytopenia, hypocomplementemia, and renal dysfunction, as well as the presence of lupus anticoagulant. Urinalysis showed abundant proteinuria and heavy microscopic hematuria. After performing a renal biopsy, we initiated immunosuppressive therapy and an anticoagulant. On the 22nd hospital day, microangiopathic hemolytic anemia appeared with the progression of thrombocytopenia and renal failure, and the patient subsequently underwent ten sessions of plasma exchange. After the commencement of the plasma exchange, her general condition improved. Her renal dysfunction, however, continued to progress, and hemodialysis was started on the 36th hospital day. The light microscopy showed severe endo- and extra-capillary proliferative glomerulonephritis with abundant crescents, and massive thrombi in the capillary lumen of the glomeruli. The arterioles contained occlusive hyaline materials. An immunofluorescence study showed granular staining of immunoglobulins and complements along the glomerular capillary wall. An electron microscopy examination revealed the presence of electron-dense deposits in the subepithelial and intramembranous areas of the glomeruli, but subendothelial deposits were absent. For cases with lupus nephritis (LN), immunosuppressive therapy based on corticosteroid remains the mainstay of treatment. However, immunosuppression alone may be insufficient when antiphospholipid antibody syndrome and thrombotic microangiopathy (TMA) are also present, and other treatment modalities including antiplatelet therapy, anticoagulation, and plasma exchange are likely to be necessary, as illustrated by the present case. Although the mechanism responsible for LN remains uncertain, we report a case of LN suggesting that TMA is associated with renal dysfunction.
Assuntos
Síndrome Antifosfolipídica/terapia , Nefrite Lúpica/terapia , Microangiopatias Trombóticas/terapia , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Feminino , Humanos , Nefrite Lúpica/complicações , Nefrite Lúpica/diagnóstico , Pessoa de Meia-Idade , Microangiopatias Trombóticas/complicações , Microangiopatias Trombóticas/diagnóstico , Resultado do TratamentoRESUMO
BACKGROUND: "Skip" lymphovascular invasion presenting as discontinuous foci of tumor cells within the colon wall is now excluded from consideration when determining T stage in the TNM classification. The purpose of this study was to assess the clinicopathological characteristics of colorectal cancer (CRC) patients with such skip lymphovascular invasion. METHODS: First, a retrospective questionnaire survey of the incidence of skip lymphovascular invasion was performed for a total of 1,868 patients with CRCs at ten institutions. Next, we comparatively assessed clinicopathological data for 896 CRC patients with or without skip lymphovascular invasion. RESULTS: The incidence of skip lymphovascular invasion was 1.1 % (20 out of 1,868). Most of the affected cases were rectal, pT2, and node negative, with moderately differentiated histology. Skip lymphovascular invasion was present in the muscularis propria and subserosa, with the tumors directly invading submucosa (pT1) or muscularis propria (pT2). Hepatic metastasis was greater in CRC with skip lymphovascular invasion (25 %) than in pT1/2 CRC (0 %; P < 0.001) or pT3 CRC without such invasion (13.8 %; P = 0.185). CONCLUSIONS: Our study suggests that skip lymphovascular invasion is associated with hepatic metastasis in CRC cases. Thus, definition of a T category including such invasion would be useful for clinical practice.
Assuntos
Adenocarcinoma/patologia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/patologia , Neoplasias Vasculares/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Neoplasias Hepáticas/secundário , Linfonodos/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Vasculares/secundário , Adulto JovemRESUMO
OBJECTIVE: Colorectal cancer patients bearing wild-type KRAS benefit from anti-epidermal growth factor receptor (EGFR) antibody treatment. Since clinical studies showed the efficacy of anti-EGFR antibody treatment for metastatic colorectal cancer (mCRC), we analyzed KRAS mutations in mCRC to gain insight into the association between these mutations and clinicopathological characteristics. METHODS: KRAS mutations were analyzed in 109 tissue samples of mCRC using amplification refractory mutation system-Scorpion (ARMS/S) assay (68 samples) and direct sequencing (41 samples). RESULTS: In the ARMS/S assay, 36.5 and 7.4% of mCRCs harbored mutations at codons 12 and 13, respectively. In direct sequencing, corresponding values were 24.4 and 19.5%. Overall, 37.6% (codon 12/13, 25.7/11.9%) of mCRCs harbored KRAS mutations. No significant differences were found between KRAS mutations and clinicopathological variables. Among mCRC patients <65 years of age, the incidence of KRAS mutations at codon 13 was significantly higher in female than male patients (p = 0.035). CONCLUSION: The incidence of KRAS mutations in mCRC was similar to that of non-mCRC as previously reported. KRAS codon 13 mutations might be associated with younger female patients with mCRC, but further investigation is necessary to clarify the association between this type of mutation and metastatic potential in female CRC patients.
Assuntos
Povo Asiático/genética , Neoplasias Colorretais/etnologia , Neoplasias Colorretais/genética , Mutação/genética , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Códon/genética , Feminino , Humanos , Incidência , Japão , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/genética , Proteínas Proto-Oncogênicas p21(ras) , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
Japanese classification of colorectal carcinoma continues to develop several decades. In 2015, the Japanese Society for Cancer of the Colon and Rectum published the eighth edition of the general rules for clinical and pathological studies on cancer of the colon, rectum, and anus. The new Japanese classification of colorectal carcinoma based on new evidences including sessile serrated adenoma/polyp (SSA/P) of serrated polyp, budding, desmoplastic reaction, head/stalk invasion, submucosal invasion depth for early cancer, EX (extramural cancer deposit), and PN (perineural invasion) for advanced cancer. And recently molecular targeted therapy for anti EGFR has made rapidly progress in refractory advanced cancer. However, some issues still remain to be resolved in pathological diagnosis. We describe and discuss about assessment of pathological diagnosis for new therapy for colorectal carcinoma.
Assuntos
Neoplasias Colorretais/patologia , Neoplasias Colorretais/terapia , Humanos , Terapia de Alvo MolecularRESUMO
Background: Aggressive mature T-cell lymphoma (TCL) is a disease that carries a poor prognosis. Methods: We analyzed the expression of 22 tumor cell functional proteins in 16 randomly selected patients with TCL. Immunohistochemistry was performed in paraffin-embedded tumor tissue sections to determine the protein expression statuses in tumor cells. Results: Glucose-regulated protein 94 (GRP94), a protein that serves as a pro-survival component under endoplasmic reticulum (ER) stress in the tumor microenvironment, was significantly associated with a shortened survival. Furthermore, significant differences were observed when GRP94 was combined with six other factors. The six factors were (1) programmed cell death-ligand 1 (PD-L1); (2) programmed cell death 1 (PD-1); (3) aldo-keto reductase family 1 member C3 (AKR1C3); (4) P53, a tumor suppressor; (5) glucose-regulated protein 78 (GRP78), an ER stress protein; and (6) thymidine phosphorylase (TP). Based on the combination of GRP94 and the six other factors expressed in the tumors, we propose a new prognostic classification system for TCL (TCL Urayasu classification). Group 1 (relatively good prognosis): GRP94-negative (n = 6; median OS, 88 months; p < 0.01); Group 2 (poor prognosis): GRP94-positive, plus expression of two of the six factors mentioned above (n = 5; median OS, 25 months; p > 0.05); and Group 3 (very poor prognosis): GRP94-positive, plus expression of at least three of the six factors mentioned above (n = 5; median OS, 10 months; p < 0.01). Conclusions: Thus, the TCL Urayasu prognostic classification may be a simple, useful, and innovative classification that also explains the mechanism of resistance to treatment for each functional protein. If validated in a larger number of patients, the TCL Urayasu classification will enable a targeted treatment using selected inhibitors acting on the abnormal protein found in each patient.
RESUMO
The 6th Diagnostic Pathology Summer Fest, held in Tokyo on August 25-26, 2012, opened its gates for everyone in the medical profession. Basic pathology training can contribute to the improvement of algorithms for diagnosis and treatment. The 6th Summer Fest with the theme 'Pathology and Clinical Treatment of Gastrointestinal Diseases' was held at the Ito International Research Center, The University of Tokyo. On August 25, 'Treatment of Early Gastrointestinal Cancer and New Guidelines' was discussed in the first session, followed by 'Biopsy Diagnosis of Digestive Tract: Key Points of Pathological Diagnosis for Inflammation and Their Clinical Significance' in the second session. On August 26, cases were discussed in the third session, and issues on pathological diagnosis and classification of neuroendorcrine tumor in the fourth session. The summaries of speeches and discussions are introduced along with the statements of each speaker. This meeting was not a formal evidence-based consensus conference, and 20 experts gave talks on their areas of specialty. Discussion was focused on how the management strategy should be standardized on the algorithm of patient care.