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BACKGROUND & AIMS: SERENE UC (Study of a Novel Approach to Induction and Maintenance Dosing With Adalimumab in Patients With Moderate to Severe Ulcerative Colitis) evaluated the efficacy of higher adalimumab induction and maintenance dose regimens in patients with ulcerative colitis. METHODS: This phase 3, double-blind, randomized trial included induction and maintenance studies, with a main study (ex-Japan) and Japan substudy. Eligible patients (18-75 years, full Mayo score 6-12, centrally read endoscopy subscore 2-3) were randomized 3:2 to higher induction regimen (adalimumab 160 mg at weeks 0, 1, 2, and 3) or standard induction regimen (160 mg at week 0 and 80 mg at week 2); all received 40 mg at weeks 4 and 6. At week 8, all patients were rerandomized 2:2:1 (main study) to 40 mg every week (ew), 40 mg every other week (eow), or exploratory therapeutic drug monitoring; or 1:1 (Japan substudy) to 40 mg ew or 40 mg eow maintenance regimens. RESULTS: In the main study, 13.3% vs 10.9% of patients receiving the higher induction regimen vs standard induction regimen achieved clinical remission (full Mayo score ≤2 with no subscore >1) at week 8 (induction primary end point; P = .265); among week-8 responders, 39.5% vs 29.0% receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (maintenance primary end point; P = .069). In the integrated (main + Japan) population, 41.1% vs 30.1% of week-8 responders receiving 40 mg ew vs 40 mg eow achieved clinical remission at week 52 (nominal P = .045). Safety profiles were comparable between dosing regimens. CONCLUSION: Although primary end points were not met, a >10% absolute difference in clinical remission was demonstrated with higher adalimumab maintenance dosing. Higher dosing regimens were generally well tolerated and consistent with the known safety profile of adalimumab in ulcerative colitis. CLINICALTRIALS: gov, Number: NCT002209456.
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Colite Ulcerativa , Adalimumab/uso terapêutico , Protocolos Clínicos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/tratamento farmacológico , Método Duplo-Cego , Humanos , Indução de Remissão , Resultado do TratamentoRESUMO
INTRODUCTION: The efficacy of texture and color enhancement imaging (TXI) in the novel light-emitting diode endoscopic system for polyp detection has not been examined. We aimed to evaluate the noninferiority of the additional 30-second (Add-30-s) observation of the right-sided colon (cecum/ascending colon) with TXI compared with narrow band imaging (NBI) for detecting missed polyps. METHODS: We enrolled 381 patients ≥40 years old who underwent colonoscopy from September 2021 to June 2022 in 3 institutions and randomly assigned them to either the TXI or NBI groups. The right-sided colon was first observed with white light imaging in both groups. Second, after reinsertion from hepatic flexure to the cecum, the right-sided colon was observed with Add-30-s observation of either TXI or NBI. The primary endpoint was to examine the noninferiority of TXI to NBI using the mean number of adenomas and sessile serrated lesions per patient. The secondary ones were to examine adenoma detection rate, adenoma and sessile serrated lesions detection rates, and polyp detection rates in both groups. RESULTS: The TXI and NBI groups consisted of 177 and 181 patients, respectively, and the noninferiorities of the mean number of adenomas and sessile serrated lesions per patients in the second observation were significant (TXI 0.29 [51/177] vs NBI 0.30 [54/181], P < 0.01). The change in adenoma detection rate, adenoma and sessile serrated lesions detection rate, and polyp detection rate for the right-sided colon between the TXI and NBI groups were not different (10.2%/10.5% [ P = 0.81], 13.0%/12.7% [ P = 0.71], and 15.3%/13.8% [ P = 0.71]), respectively. DISCUSSION: Regarding Add-30-s observation of the right-sided colon, TXI was noninferior to NBI.
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BACKGROUND AND AIM: We investigated whether oral-dental conditions may be associated with the prevalence of irritable bowel syndrome (IBS) in a cross-sectional study in Japan. METHODS: Information on lifestyle and abdominal symptoms was collected, and oral-dental examinations were performed from 2013 to 2017. To investigate the association between oral-dental conditions and IBS, this study used logistic regression analyses adjusted for relevant confounding factors, such as age, sex, BMI, stress, and eating between meals. RESULTS: The prevalence of IBS was 484 (13.4%) among 3626 participants. The mean maximum occlusal force in the IBS group was significantly lower than that in the non-IBS group (0.306 ± 0.192 kN vs. 0.329 ± 0.205 kN, P = 0.014). The maximum occlusal force of the constipation-type IBS was significantly lower than that of other types of IBS without constipation type (0.269 ± 0.164 kN vs. 0.317 ± 0.198 kN, P = 0.010). Compared with those who had high values of maximum occlusal force (â§0.265 kN), those with a low value of maximum occlusal force (<0.265 kN) had a significantly greater risk for IBS (OR, 1.426; 95% CI, 1.135-1.792; P = 0.002), by multivariate analyses, across different categories of oral-dental condition in women, not in men. Women who had lowest third occlusal force (<0.206 kN) had approximately 35% significantly greater odds of having IBS compared with those who had highest third occlusal force (â§0.386 kN). CONCLUSIONS: Results suggest that a reduction in the maximum occlusal force increases the risk of IBS in Japanese women.
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Síndrome do Intestino Irritável , Masculino , Adulto , Humanos , Feminino , Síndrome do Intestino Irritável/etiologia , Síndrome do Intestino Irritável/complicações , Prevalência , Força de Mordida , Estudos Transversais , População do Leste Asiático , Constipação Intestinal/etiologia , Constipação Intestinal/complicações , Inquéritos e QuestionáriosRESUMO
OBJECTIVES: The incidence of colorectal neuroendocrine tumors (NETs) has increased with colorectal cancer screening programs and increased colonoscopies. The management of colorectal NETs has recently shifted from radical surgery to endoscopic resection. We aimed to evaluate the short-term outcomes of various methods of endoscopic resection for colorectal NETs. METHODS: Among those registered in the C-NET STUDY, patients with colorectal NETs who underwent endoscopic treatment as the initial therapy were included. Short-term outcomes, such as the en bloc resection rate and R0 resection (en bloc resection with tumor-free margin) rate, were analyzed based on treatment modalities. RESULTS: A total of 472 patients with 477 colorectal NETs received endoscopic treatment. Of these, 418 patients with 421 lesions who met the eligibility criteria were included in the analysis. The median age of the patients was 55 years, and 56.9% of them were men. The lower rectum was the most commonly affected site (88.6%), and lesions <10 mm accounted for 87% of the cases. Endoscopic submucosal resection with a ligation device (ESMR-L, 56.5%) was the most common method, followed by endoscopic submucosal dissection (ESD, 31.4%) and endoscopic mucosal resection using a cap (EMR-C, 8.5%). R0 resection rates <10 mm were 95.5%, 94.8%, and 94.3% for ESMR-L, ESD, and EMR-C, respectively. All 16 (3.8%) patients who developed treatment-related complications could be treated conservatively. Overall, 23 (5.5%) patients had incomplete resection without independent clinicopathological risk factors. CONCLUSION: ESMR-L, ESD, and EMR-C were equally effective and safe for colorectal NETs with a diameter <10 mm.
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A 59-year-old man was treated for early gastric cancer with endoscopic submucosal dissection (ESD) 10 years prior to the study. Two months after the first ESD, he was diagnosed with recurrence on the ESD scar and treated via ESD again. The horizontal margin could not be evaluated because of cauterization, and the patient was carefully observed. He was admitted to our hospital complaining of low backache and diagnosed with disseminated carcinomatosis of the bone marrow associated with gastric cancer after examination. Although he started chemotherapy, he died after 6 months. In this study, we report a rare case of disseminated carcinomatosis of the bone marrow associated with gastric cancer, which developed 10 years after ESD.
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Ressecção Endoscópica de Mucosa , Neoplasias Peritoneais , Neoplasias Gástricas , Medula Óssea , Ressecção Endoscópica de Mucosa/efeitos adversos , Mucosa Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Neoplasias Gástricas/cirurgia , Resultado do TratamentoRESUMO
An advanced small bowel mucinous adenocarcinoma with Peutz-Jeghers syndrome was resected, and we started capecitabine plus oxaliplatin (CapeOX) as adjuvant therapy. However, local recurrence was noted, and the tumor increased even after CapeOX plus bevacizumab and fluorouracil plus leucovorin plus irinotecan plus panitumumab (FOLFIRI plus panitumumab). Pembrolizumab was administered after confirming high-frequency microsatellite instability, and the tumor shrank markedly and remained shrunk for 20 months.
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Adenocarcinoma Mucinoso , Neoplasias Colorretais , Síndrome de Peutz-Jeghers , Adenocarcinoma Mucinoso/tratamento farmacológico , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/uso terapêutico , Camptotecina/uso terapêutico , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Recidiva Local de Neoplasia , Síndrome de Peutz-Jeghers/tratamento farmacológicoRESUMO
A 53-year-old man who had been diagnosed with moderate ulcerative colitis and treated with mesalazine and glucocorticoid steroid was admitted due to fever of unknown origin and diarrhea. Intravenous feeding and treatment with cephem antibiotics were started, but the febrile reaction did not improve at all. Physical examination and various tests showed no specific symptoms, including headache or meningeal irritation. However, the blood culture test showed a positive result of Gram-positive bacilli. Thus, a lumbar puncture was performed and the patient was finally diagnosed with Listeria monocytogenes bacteremia and meningitis. Administration of intravenous meropenem and ampicillin led to the improvement of symptoms without any neurological sequelae. In addition, several cases with opportunistic infection of L. monocytogenes have been reported in recent years in cases of inflammatory bowel disease (IBD) during immunosuppressive therapy. Consequently, L. monocytogenes infection should be considered as one of differential diagnosis when patients present with IBD patient and are treated by biological or immunosuppressive agents with a fever of unknown origin.
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Colite Ulcerativa , Listeria monocytogenes , Meningite por Listeria , Ampicilina , Antibacterianos/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Humanos , Japão , Masculino , Meningite por Listeria/diagnóstico , Meningite por Listeria/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Nonalcoholic fatty liver disease is characterized by excessive hepatic fat accumulation. Some individuals frequently present elevated gamma-glutamyl transferase (GGT) levels without fatty liver ultrasound images and other abnormal liver enzymes levels. However, whether these individuals are at an elevated risk for developing fatty liver is unclear. We compared fatty liver change rates and risk factors between individuals with frequently elevated GGT levels and those with normal levels. METHODS: We designed a retrospective cohort study on the basis of complete medical checkup records. One group of individuals had presented normal serum GGT levels during the observation period (Normal-GGT group, n = 2713). Another group had had abnormal elevated serum GGT levels frequently (Abnormal-GGT group, n = 264). We determined the fatty liver change incident rates before and after propensity score matching. We explored confounding factors affecting fatty changes in each group using univariate and multivariate Cox models. RESULTS: The change incidence rates were 5.80/1000 and 10.02/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively. After propensity score matching, the incidence rates were 3.08/1000 and 10.18/1000 person-years in the Normal-GGT and Abnormal-GGT groups, respectively (p = 0.026). The factors associated with fatty liver changes in the Normal-GGT group included body mass index (BMI), hemoglobin, alanine aminotransferase (ALT), albumin, triglyceride (TG), fasting blood sugar, and high-density lipoprotein levels. Those in the Abnormal-GGT group were platelet counts and TG. In our multivariable analysis, BMI, ALT, albumin, and TG levels were independent predictors of fatty changes in the Normal-GGT group, and high TG level was the only independent predictor in the Abnormal-GGT group. CONCLUSIONS: The incidence rate of fatty liver change in the Abnormal-GGT group was higher than that in the Normal-GGT group. Consecutive elevated GGT levels increase the risk for fatty liver, and high TG levels in those individuals further independently increase the risk.
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Hepatopatia Gordurosa não Alcoólica , gama-Glutamiltransferase , Alanina Transaminase , Humanos , Testes de Função Hepática , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estudos RetrospectivosRESUMO
BACKGROUND/AIMS: This study investigated the effect of Helicobacter pylori eradication therapy on latent digestive symptoms in chronic atrophic gastritis. METHODS: We enrolled 650 health checkup patients who underwent eradication therapy for chronic gastritis and completed a self-report questionnaire before and after the treatment between January 2014 and December 2016 at the Japanese Red Cross Society Kyoto Daiichi Hospital. RESULTS: H. pylori eradication therapy for chronic atrophic gastritis improved latent digestive symptoms, including both the acid reflux and dyspepsia components in the frequency scale for the symptoms of gastroesophageal reflux disease (FSSG) scores. The effect was sustained until 1 year after the treatment. Higher FSSG scores (≥8 points) before H. pylori eradication therapy and age <70 years were significantly associated with the improvement of digestive symptoms after H. pylori eradication therapy. CONCLUSION: H. pylori eradication therapy may improve patients' quality of life through the resolution of latent abdominal symptoms.
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Antibacterianos/uso terapêutico , Antiulcerosos/uso terapêutico , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Helicobacter pylori/efeitos dos fármacos , Idoso , Feminino , Gastrite Atrófica/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Estudos Retrospectivos , Autorrelato , Resultado do TratamentoRESUMO
A 17-year-old boy developed prominent mediastinal and subcutaneous emphysema while receiving treatment with 5-aminosalicylic acid (5-ASA) and oral corticosteroids for severe ulcerative colitis. We ruled out infection and initiated oral administration of tacrolimus, after which both the underlying disease and mediastinal and subcutaneous emphysema improved. However, he continued to experience repeated bouts of ulcerative colitis, so we ultimately opted for surgical intervention. Although mediastinal and subcutaneous emphysema is rare, it is one of the known extra-intestinal complications and can be particularly concerning. In this patient, mediastinal and subcutaneous emphysema might have been caused by the vulnerability of pulmonary alveolar walls to steroid medication and the increase of pulmonary alveolar pressure with abdominal pain and breath holding. Here, we report a case of inflammatory bowel disease with mediastinal and subcutaneous emphysema, along with a review of the literature.
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Colite Ulcerativa/complicações , Enfisema Mediastínico/etiologia , Enfisema Subcutâneo/etiologia , Adolescente , Humanos , MasculinoRESUMO
A 40-year-old man admitted to our hospital with diarrhea underwent abdominal computed tomography (CT) which showed multiple masses in the liver and pancreatic tail. Although there were no abnormal accumulations with fluorodeoxyglucose ((18)F) positron emission tomography (FDG-PET), (68)Ga-DOTATOC-PET/CT detected obvious abnormal accumulations for the both lobes of liver and pancreatic tail tumors. The serum gastrin was markedly high, and liver tumor biopsy demonstrated the presence of malignant cells with round nuclei that were positive for gastrin and somatostatin receptor. The patient was diagnosed with pancreatic tail gastrinoma with multiple liver metastases and treated with octreotide, everolimus, and a proton pump inhibitor which functionally controlled tumor growth. This case demonstrates (68)Ga-DOTATOC-PET/CT as a useful modality for the localization, qualitative diagnosis, and treatment of gastrinoma.
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Gastrinoma/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Pancreáticas/diagnóstico por imagem , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Everolimo/administração & dosagem , Radioisótopos de Gálio , Gastrinoma/tratamento farmacológico , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Masculino , Octreotida/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Resultado do TratamentoRESUMO
BACKGROUND: Patients with ulcerative colitis (UC) have elevated/activated myeloid lineage leucocytes and may respond favorably to adsorptive granulocyte/monocyte apheresis (GMA). However, there are patients who respond well to GMA, and patients who do not benefit. Therefore, predictive factors of GMA efficacy need to be defined. METHODS: In a prospective multicenter setting, 200 UC patients at 32 institutes received one GMA session per week over 10 weeks. Patients who achieved remission were followed for 12 months. The Clinical Activity Index (CAI) ≤3 meant remission, and response meant CAI decreased by ≥3. Quality of life was evaluated by the Inflammatory Bowel Disease Questionnaire (IBDQ). RESULTS: After final GMA, remission, response and no response rates were 67.0%, 15.0% and 18%, respectively. The remission group had a significant decrease in myeloid leucocytes and platelets. Corticosteroid dose decreased (P < 0.001); 49 of 97 patients on corticosteroids became steroid-free. Baseline CAI was lower in the remission group versus non-remission (P < 0.01), whereas IBDQ was higher in the remission group versus non-remission (P < 0.05). After 12 months, 52 of 134 patients had maintained remission. Disease duration was longer in the relapsed group versus maintained remission group (P = 0.041). Male gender, first UC episode and corticosteroid responder were significant factors for maintaining remission, whereas corticosteroid dependent UC was associating with relapse. DISCUSSION: Selective myeloid leucocyte depletion was effective for remission induction and improving patients' quality of life. Baseline demographics such as disease activity level, duration and corticosteroid dependency appear to predict response to GMA. Additionally, patients with a first UC episode who were drug naive responded well to GMA and achieved a favorable long-term disease course by avoiding pharmacologics from an early stage of their inflammatory bowel disease. These findings should help to end unnecessary use of medical resources by targeting GMA to patients who may respond well.
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Linhagem da Célula , Colite Ulcerativa/terapia , Granulócitos/citologia , Leucócitos/citologia , Células Mieloides/citologia , Adsorção , Adulto , Remoção de Componentes Sanguíneos , Colite Ulcerativa/sangue , Feminino , Humanos , Estimativa de Kaplan-Meier , Contagem de Leucócitos , Masculino , Monócitos/citologia , Prognóstico , Estudos Prospectivos , Fatores de Tempo , Resultado do TratamentoRESUMO
A 66-year-old man was admitted to our hospital with high fever. We diagnosed a gas-containing liver abscess and performed percutaneous abscess drainage. However, 15 hours after admission, he developed massive intravascular hemolysis and acidosis. Sepsis due to Clostridium perfringens was suspected and we treated the patient intensively with multidisciplinary approaches, including antibiotics, mechanical ventilation, and renal replacement therapy. Furthermore, we administered freeze-dried gas gangrene antitoxin. Despite intensive care, the patient died 43 hours after admission.
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Antitoxinas/uso terapêutico , Gangrena Gasosa/terapia , Idoso , Liofilização , Humanos , Abscesso Hepático Piogênico/terapia , MasculinoRESUMO
BACKGROUND: To investigate the associations between serum concentrations of carotenoids and the presence of colorectal polyps and cancers in Japanese using a cross-sectional study. METHODS: 893 subjects who underwent colorectal endoscopy between 2001 and 2002 provided serum samples and information on lifestyle factors. Serum concentrations of six carotenoids were compared among patients with polyps, cancers, and controls. RESULTS: In males, high serum zeaxanthin was associated with decreased rates of polyps [odds ratio (OR) = 0.48, 95 % confidence interval (CI) 0.27-0.87] and cancer (OR = 0.35, 95 % CI 0.12-1.06), adjusting for age, body mass index, serum cholesterol, smoking status, and alcohol intake. In females, zeaxanthin (OR = 0.25, 95 % CI 0.07-0.82), lutein (OR = 0.30, 95 % CI 0.10-0.94), alpha-carotene (OR = 0.30, 95 % CI 0.10-0.90), and beta-carotene (OR = 0.27, 95 % CI 0.09-0.85) showed significant inverse associations with cancer development. These associations were consistent with findings of inverse associations between the ingestion of green-yellow vegetables (OR = 0.44, 95 % CI 0.23-0.84), carrots and pumpkins (OR = 0.46, 95 % CI 0.25-0.86), and fruits (OR = 0.53, 95 % CI 0.30-0.94) and polyp in males, and between carrots and pumpkins (OR = 0.30, 95 % CI 0.09-0.99), legumes (OR = 0.14, 95 % CI 0.04-0.44), and seaweed (OR = 0.23, 95 % CI 0.07-0.75) and cancer development in females. CONCLUSIONS: These results provide further support for the protective effects of carotenoids contained in green-yellow vegetables and fruits against colorectal neoplasm in Japanese.
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Neoplasias Colorretais/sangue , Pólipos/sangue , Xantofilas/sangue , Idoso , Carotenoides/sangue , Neoplasias Colorretais/dietoterapia , Neoplasias Colorretais/patologia , Endoscopia , Feminino , Frutas , Humanos , Japão , Luteína/sangue , Masculino , Pessoa de Meia-Idade , Pólipos/patologia , Fatores de Risco , Verduras , Zeaxantinas , beta Caroteno/sangueRESUMO
A 70-year-old man was admitted to our hospital for the treatment of a large granular-type laterally spreading tumor in the splenic flexure of the descending colon. The preoperative diagnosis was intramucosal colon carcinoma and endoscopic submucosal dissection was performed. During treatment, a small perforation occurred accidentally. After conservative treatment with endoscopic suturing, the patient was discharged without additional surgery. The pathological diagnosis was an intramucosal carcinoma. One year after treatment, no local recurrence was observed on endoscopy, and abdominal computed tomography showed no obvious metastasis. Two years later, fluorodeoxyglucose-positron emission tomography/computed tomography, laparoscopic findings, and histopathologic findings by experimental excision of omentum revealed several disseminated peritoneal metastases from previously treated colon carcinoma. To the best of our knowledge, this is the first report of peritoneal dissemination after a small perforation during endoscopic submucosal dissection and conservative therapy for early-stage colon carcinoma. This report suggests the possibility of tumor dissemination in patients with small perforations during endoscopic procedures. Endoscopists should be aware of these rare potential risks and perform later surveillance carefully.
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Neoplasias do Colo , Tratamento Conservador , Ressecção Endoscópica de Mucosa , Perfuração Intestinal , Neoplasias Peritoneais , Humanos , Masculino , Idoso , Neoplasias do Colo/patologia , Neoplasias do Colo/cirurgia , Neoplasias do Colo/secundário , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Peritoneais/secundário , Perfuração Intestinal/etiologia , Colonoscopia/efeitos adversosRESUMO
An 83-year-old male underwent three transgastric punctures with endoscopic ultrasound-guided fine-needle aspiration for the examination of a pancreatic body tumor. After a diagnosis of resectable pancreatic cancer and undergoing distal pancreatectomy, the patient was administered postoperative adjuvant chemotherapy with oral S-1 for 6 months, and carcinoembryonic antigen and carbohydrate antigen 19-9 levels were bimonthly evaluated. Carbohydrate antigen 19-9 levels continually increased to 4638.1 U/mL at 45 months post-fine-needle aspiration. Endoscopic ultrasound-guided showed a 25 mm low-echoic, irregularly shaped, and heterogeneous tumor with clear margins protruding from the mucosa outside the gastric wall, and biopsy confirmed adenocarcinoma. Since the immunostaining findings of the specimen matched those of the previously resected specimen, needle tract seeding (NTS) due to puncture of the pancreatic cancer was identified as the cause. After a pylorus-preserving gastrectomy at 46 months post-fine-needle aspiration, postoperative chemotherapy initiation, comprising gemcitabine and nab-paclitaxel, was initiated; however, the patient died despite these interventions as he developed multiple peritoneal dissemination. Although rare, the incidence of NTS will increase in the future owing to the expected extended survival in post-pancreatic cancer resection cases. We suggest regular upper gastrointestinal endoscopy and endoscopic ultrasound-guided evaluations for patients who are at risk for NTS can facilitate early detection. Furthermore, it is extremely relevant to share experiences of encountered NTS cases in practice and extend knowledge of its varying endoscopic appearances.
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UNLABELLED: Retrospective studies have suggested that UDP-glucuronosyltransferase (UGT)1A1, UGT1A7, and UGT1A9 predict severe toxicity and efficacy of irinotecan-containing regimens. We prospectively evaluated the impact of UGT1A genotypes and haplotypes on severe toxicity and efficacy in patients treated with fluorouracil, leucovorin, and irinotecan combination chemotherapy (FOLFIRI) for metastatic colorectal cancer (mCRC) from the two prospective multicenter phase II studies in Japan. The FLIGHT1 study was a first-line FOLFIRI trial, and FLIGHT2 was a FOLFOX-refractory, second-line FOLFIRI trial. A total of 73 patients agreed to additional analysis, and were genotyped for UGT1A polymorphisms, UGT1A1*28 (TA6>TA7), UGT1A1*6 (211G>A), UGT1A1*27 (686C>A), UGT1A1*60 (-3279T>G), UGT1A1*93 (-3156G>A), UGT1A7 (-57T>G), UGT1A7*3 (387T>G, 622T>C), and UGT1A9*22 (T9>T10). Of 73 patients, 34 developed G3/4 severe hematological toxicities. The toxicities were significantly more frequent in patients with UGT1A1*6 (211A), UGT1A7 (387G), and UGT1A9*22 reference alleles (T9). Haplotype I, which consists of all favorable alleles, was associated with a significant reduction in hematologic toxicity (P = 0.031). In contrast, haplotype II, which contains four high-risk alleles, showed significantly higher hematologic toxicity than the other haplotypes (P = 0.010). Six out of seven patients who were homozygous for UGT1A1*28 or *6 experienced severe hematological toxicity despite the fact that their response rate was not impaired (42.9%). We concluded that UGT1A polymorphisms, especially UGT1A1*6, are important for the prediction of severe toxicity of FOLFIRI in northeast Asian populations. In this regard, haplotype analyses should substantially impact the prediction of severe hematological toxicities of FOLFIRI. ( CLINICAL TRIAL REGISTRATION: UMIN000002388 and UMIN000002476).
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Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias Colorretais/tratamento farmacológico , Glucuronosiltransferase/genética , Neutropenia/induzido quimicamente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/uso terapêutico , Neoplasias Colorretais/genética , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Frequência do Gene , Genótipo , Haplótipos/genética , Humanos , Irinotecano , Japão , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neutropenia/genética , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , UDP-Glucuronosiltransferase 1ARESUMO
OBJECTIVE: This study aimed to assess the efficacy and tolerability of leukocytapheresis (LCAP) and to investigate predictive factors for mucosal healing and a sustained clinical response in steroid-free and steroid-refractory patients with ulcerative colitis (UC). MATERIAL AND METHODS: Thirty-one steroid-free or steroid-refractory patients with active UC were enrolled. Five or ten consecutive sessions of LCAP were performed in each patient. The efficacy and tolerability was then evaluated at weeks 3 and 6. Endoscopic examination was performed at week 6 to evaluate the mucosal healing, and the sustained cumulative response rate was evaluated at 12 months. RESULTS: At week 6, the mean Mayo clinical activity score had decreased significantly from 8.0 to 4.6 in the steroid-free patients and from 8.3 to 3.9 in the steroid-refractory patients. Rachmilewitz's endoscopic index had also decreased significantly from 9.1 to 6.1 in the steroid-free patients and from 10.0 to 5.7 in the steroid-refractory patients. Forty-seven percent of the steroid-free patients and 33% of the steroid-refractory patients achieved mucosal healing. The peripheral platelet counts had decreased significantly at weeks 3 and 6 in the mucosal healing group, compared with the non-mucosal healing group. The patients with a more than 15% platelet reduction had a significantly higher cumulative response rate, compared with the patients without a platelet reduction (p = 0.015). CONCLUSIONS: LCAP is beneficial for the induction of mucosal healing in steroid-free and steroid-refractory patients with UC. The degree of platelet reduction during LCAP might be a predictive marker for mucosal healing and a sustained clinical response.
Assuntos
Colite Ulcerativa/terapia , Leucaférese/métodos , Adulto , Biomarcadores/sangue , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Colite Ulcerativa/sangue , Colite Ulcerativa/patologia , Feminino , Glucocorticoides/uso terapêutico , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
Poorly differentiated neuroendocrine cell carcinomas of the gallbladder are rare and patients with such tumors have a poor prognosis. We describe a 64-year-old male with a large cell neuroendocrine carcinoma of the gallbladder and multiple lymph node metastases. Diagnostic excisional biopsy of the left axillary lymph nodes revealed atypical cells with predominantly large-sized round-to-oval nuclei, proliferating in a solid and focal nesting pattern. The tumor cells were positive for synaptophysin and chromogranin A, and strongly positive for Ki-67, leading to a diagnosis of poorly differentiated neuroendocrine cell carcinoma of the gallbladder, of large cell type. Using (18)F-fluorodeoxy glucose-positron emission tomography/computed tomography to determine the origin of these tumors, we observed the accumulation of (18)F-fluorodeoxy glucose in multiple large lymph nodes, a small part of the liver and the fundus of the gallbladder. Computed tomography-guided aspiration of the gallbladder showed the same pleomorphic tumor cells as the lymph nodes. The patient was diagnosed with a large cell neuroendocrine carcinoma of the gallbladder, only â¼25 mm in diameter. Combination chemotherapy with cisplatin and docetaxel, the regimen used for non-small cell lung carcinomas, and probably large cell lung carcinomas, resulted in the disappearance of the lymph node metastases and a marked improvement in the performance status for â¼22 months. The poor prognosis of patients with these aggressive tumors may be improved by the use of minimally invasive diagnostic procedures and combined systemic chemotherapy as soon as possible.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Grandes/diagnóstico , Carcinoma Neuroendócrino/diagnóstico , Fluordesoxiglucose F18 , Neoplasias da Vesícula Biliar/diagnóstico , Imagem Multimodal , Tomografia por Emissão de Pósitrons , Tomografia Computadorizada por Raios X , Neoplasias Ósseas/secundário , Carcinoma de Células Grandes/tratamento farmacológico , Carcinoma Neuroendócrino/tratamento farmacológico , Cisplatino/administração & dosagem , Coagulação Intravascular Disseminada/etiologia , Docetaxel , Evolução Fatal , Neoplasias da Vesícula Biliar/tratamento farmacológico , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Imagem Multimodal/métodos , Compostos Radiofarmacêuticos , Taxoides/administração & dosagem , Falha de TratamentoRESUMO
OBJECTIVE: In Japan, there had been no prospective clinical studies conducted in terms of modified FOLFOX6 + bevacizumab therapy. We performed a post-marketing Phase II multicenter clinical study to examine the efficacy and safety of this regimen as first-line therapy for Japanese patients with advanced/recurrent colorectal cancer. METHODS: Bevacizumab (5 mg/kg) was administered intravenously, and then oxaliplatin (85 mg/m(2)) and levofolinate calcium (200 mg/m(2)) were infused intravenously over 2 h. Subsequently, a bolus dose of 5-fluorouracil (400 mg/m(2)) was injected, followed by infusion of 5-fluorouracil (2400 mg/m(2)) for 46 h. This regimen was repeated every 2 weeks until 24 cycles unless there was disease progression, unacceptable toxicity or patient refusal. The primary end point was the response rate. RESULTS: Among the 70 patients enrolled, two patients withdrew the study before treatment, and 68 patients were eligible for analysis of efficacy and safety. The response rate was 51.5% (95% confidence interval: 39.0-63.8%). The median progression-free survival and median overall survival time were 12.6 months (95% confidence interval: 10.4-14.5 months) and 28.5 months [95% confidence interval: 23.1 months-(not applicable)], respectively. There were no treatment-related deaths observed. The most common Grade 3 and 4 adverse events included neutropenia in 35.3% of the patients, peripheral neuropathy in 16.2% and hypertension in 16.2%. All adverse events were manageable and tolerable. The exploratory analysis of polymorphisms of three genes, ERCC1, XPD and GSTP1, did not show any trends in terms of correlation with the efficacy or safety of modified FOLFOX6 + bevacizumab therapy. CONCLUSIONS: Modified FOLFOX6 + bevacizumab therapy was manageable and tolerable in Japanese patients, achieving a high response rate.