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INTRODUCTION: Unsedated peroral endoscopy, including ultrathin endoscopy (UE) and conventional endoscopy (CE), is feasible in clinical practice but requires improved endoscopic operability and patient tolerance. Currently, the impact of breathing method on these factors remains unclear. We conducted the first randomized controlled trial comparing oral breathing (OB) and nasal breathing (NB) during both UE and CE to assess their influence. METHODS: 252 eligible patients undergoing CE or UE were randomly assigned to OB or NB groups. Endoscopists and patients rated endoscopic operability and patient tolerance using a 100-mm visual analog scale (VAS). Visibility from the oral cavity to the middle pharynx was recorded. RESULTS: OB led to a higher rate of improved visibility from the oral cavity to the middle pharynx compared to NB, ranging from 79.3% to 81.0%. Multivariate correlation analyses showed significantly lower VAS scores for endoscopic operability with OB compared to NB in both UE and CE groups (p < 0.05). No significant differences were found in the overall evaluation of patient tolerance between OB and NB groups in UE and CE, while the smaller diameter of UE exhibited better patient tolerance compared to CE. Discriminant analysis comparing endoscope types and breathing methods revealed that UE with OB outperformed other combinations in the overall evaluation of endoscopic operability and patient tolerance (p < 0.05). CONCLUSIONS: OB facilitates endoscopic operability compared to NB in peroral endoscopy. UE with OB is recommended as the preferred choice for unsedated peroral endoscopy in daily practice.
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Background and study aims Gastric adenocarcinoma of the fundic gland type (GA-FG) is characterized by an elevated lesion with vessel dilation exhibiting branching architecture (DVBA). However, this feature is also found in fundic gland polyps (FGPs), posing a challenge in their differentiation. In this study, we aimed to investigate the clinicopathological features of gastric elevated lesions with DVBA and assess the efficacy of the white ring sign (WRS) as a novel marker for distinguishing between FGPs and GA-FGs. Methods We analyzed 159 gastric elevated lesions without DVBA and 51 gastric elevated lesions with DVBA, further dividing the latter into 39 in the WRS-positive group and 12 in the WRS-negative group. The clinicopathological features, diagnostic accuracy, and inter-rater reliability were analyzed. Results Univariate and multivariate analyses for gastric elevated lesions with DVBA identified the histological type consistent with FGPs and GA-FGs, along with the presence of round pits in the background gastric mucosa, as independent predictors. FGPs were present in 92.3% (36/39) of the WRS-positive group and GA-FGs were observed in 50.0% (6/12) of the WRS-negative group. WRS positivity and negativity exhibited high diagnostic accuracy, with 100% sensitivity, 80.0% specificity, and 94.1% accuracy for FGPs, and 100% sensitivity, 86.7% specificity, and 88.2% accuracy for GA-FGs. Kappa values for WRS between experts and nonexperts were 0.891 and 0.841, respectively, indicating excellent agreement. Conclusions WRS positivity and negativity demonstrate high diagnostic accuracy and inter-rater reliability for FGPs and GA-FGs, respectively, suggesting that WRS is a useful novel marker for distinguishing between FGPs and GA-FGs.
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Background: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. Methods: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. Results: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. Conclusions: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.
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INTRODUCTION: Carbazochrome sodium sulfonate (CSS) is a hemostatic agent that reduces capillary permeability and enhances capillary resistance. However, its specific effects on colorectal endoscopic submucosal dissection (ESD) outcomes remain uncertain. This study aimed to assess the risk factors for post-ESD bleeding and the effect of CSS on colorectal ESD outcomes. METHODS: First, we retrospectively analyzed the risk factors for post-ESD bleeding using data from 1,315 lesions in 1,223 patients who underwent ESD for superficial colorectal neoplasms at eight institutions. Second, patients were divided into CSS and non-CSS groups using propensity score matching, and their outcomes from colorectal ESD were analyzed. RESULTS: The risk factors for post-colorectal ESD bleeding were identified as age of ≥70 years, tumor located in the rectum, tumor size of ≥40 mm, and post-ESD defect unclosure in both univariate and multivariate analyses. The CSS and non-CSS groups each consisted of 423 lesions after propensity score matching. The post-colorectal ESD bleeding rate was 3.5% (15/423) and 3.3% (14/423) in the CSS and non-CSS groups, respectively, indicating no significant differences. Among patients with the high-risk factors for post-ESD bleeding, the administration of CSS also did not demonstrate a significant reduction in the post-ESD bleeding rate compared to the non-CSS group. CONCLUSION: CSS administration is ineffective in preventing post-colorectal ESD bleeding in both the general population and individuals at a high risk for such bleeding. Our results indicate the necessity to reconsider the application of CSS for preventing post-colorectal ESD bleeding.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Hemorragia Posoperatoria , Puntaje de Propensión , Humanos , Estudios Retrospectivos , Masculino , Neoplasias Colorrectales/cirugía , Femenino , Anciano , Factores de Riesgo , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Persona de Mediana Edad , Hemorragia Posoperatoria/prevención & control , Hemorragia Posoperatoria/etiología , Hemorragia Posoperatoria/epidemiología , Resultado del Tratamiento , Hemostáticos/administración & dosificación , Hemostáticos/uso terapéutico , Colonoscopía/métodos , Colonoscopía/efectos adversos , Anciano de 80 o más Años , Hemorragia Gastrointestinal/prevención & control , Hemorragia Gastrointestinal/etiología , Hemorragia Gastrointestinal/epidemiología , Adrenocromo/análogos & derivadosRESUMEN
Colorectal cancer is the third most commonly diagnosed cancer and the second leading cause of cancer-related death, thus a novel chemotherapeutic agent for colon cancer therapy is needed. In this study, analogues of echinomycin, a cyclic peptide natural product with potent toxicity to several human cancer cell lines, were synthesized, and their biological activities against human colon cancer cells were investigated. Analogue 3 as well as 1 inhibit HIF-1α-mediated transcription. Notably, transcriptome analysis indicated that the cell cycle and its regulation were involved in the effects on cells treated with 3. Analogue 3 exhibited superior in vivo efficacy to echinomycin without significant toxicity in mouse xenograft model. The low dose of 3 needed to be efficacious in vivo is also noteworthy and our data suggest that 3 is an attractive and potentially novel agent for the treatment of colon cancer.
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Neoplasias del Colon , Equinomicina , Humanos , Animales , Ratones , Equinomicina/farmacología , Neoplasias del Colon/tratamiento farmacológico , Subunidad alfa del Factor 1 Inducible por HipoxiaRESUMEN
BACKGROUND AND AIM: Image enhancement endoscopy techniques, such as linked color imaging (LCI) and autofluorescence imaging (AFI), have shown promise in diagnosing mucosal inflammation in ulcerative colitis (UC). However, no studies have directly compared the diagnostic efficacy of LCI and AFI. This prospective observational study aimed to compare their diagnostic accuracy for histological healing in UC. METHODS: This study included 81 UC patients, resulting in a total of 204 endoscopic images captured using LCI and AFI, respectively. Spearman's rank correlation coefficients assessed the correlation between LCI and AFI coloration and Geboes histopathology score (GHS). Six endoscopists, who were blinded to clinicopathological features, evaluated these images, and subsequently, the diagnostic accuracy was evaluated. RESULTS: Spearman's rank correlation coefficients between LCI index, AFI index (reverse gamma value), and GHS were 0.324 and -0.428, respectively (P < 0.001), indicating a significant correlation between LCI and AFI coloration and histological healing. In LCI and AFI classifications, mean values for diagnostic accuracy, sensitivity, specificity, positive predictive value, and negative predictive value were 76.3 ± 2.2 versus 77.8 ± 2.7, 91.8 ± 4.0 versus 83.2 ± 7.6, 53.4 ± 10.0 versus 70.0 ± 5.3, 74.0 ± 3.5 versus 80.0 ± 1.6, and 82.9 ± 5.2 versus 75.5 ± 7.5, respectively. No significant difference in diagnostic accuracy existed between LCI and AFI classifications. However, LCI displayed higher sensitivity than AFI while AFI showed higher specificity compared with LCI (P < 0.05). CONCLUSIONS: LCI and AFI offer comparable diagnostic accuracy for histological healing. Clinically, it is necessary to recognize diagnostic features characterized by higher sensitivity in LCI and greater specificity in AFI.
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Colitis Ulcerosa , Imagen Óptica , Sensibilidad y Especificidad , Colitis Ulcerosa/patología , Colitis Ulcerosa/diagnóstico por imagen , Colitis Ulcerosa/diagnóstico , Humanos , Estudios Prospectivos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Imagen Óptica/métodos , Valor Predictivo de las Pruebas , Color , Colonoscopía/métodos , Anciano , Mucosa Intestinal/patología , Mucosa Intestinal/diagnóstico por imagen , Adulto Joven , Aumento de la Imagen/métodosRESUMEN
The combination or sequential use of systemic therapies, such as lenvatinib and locoregional therapies, can improve the curability rate of hepatocellular carcinoma. This is based on the notion that lenvatinib remodels abnormal tumor vessels into normal vessels, potentially enhancing the efficacy of locoregional therapies. In this case report, we achieved noninvasive visualization of tumor blood vessels by applying superb microvascular imaging (SMI) to contrast-enhanced ultrasonography (CEUS). A man in his 80s with a borderline resectable hepatocellular carcinoma received preoperative therapy using lenvatinib. The patient achieved a complete response after lenvatinib therapy, underwent hepatectomy, and maintained a cancer-free status. CEUS and SMI revealed a decrease in tumor blood vessels at 1 week after lenvatinib administration and a decrease in tumor perfusion at 2 weeks. Although CEUS alone is adequate for noninvasive real-time evaluation of tumor perfusion, it is not sufficient to achieve accurate assessments of tumor blood vessels. We performed a noninvasive time-course evaluation of vascular normalization after lenvatinib administration by applying SMI. The evaluation of vascular normalization with lenvatinib therapy using CEUS and SMI can support the decision to proceed to conversion therapies.
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BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.
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Ampolla Hepatopancreática , Neoplasias del Conducto Colédoco , Humanos , Ampolla Hepatopancreática/diagnóstico por imagen , Ampolla Hepatopancreática/patología , Neoplasias del Conducto Colédoco/patología , Endosonografía , Estudios Retrospectivos , AguaRESUMEN
Esophageal cancer, which is common among the elderly, has the poorest prognosis among gastrointestinal cancers. Previously, we demonstrated that ferrichrome, produced by the probiotic Lactobacillus casei, exhibited anti-tumor effects in various gastrointestinal cancers, including colorectal and gastric cancers, with minimal effects on non-cancerous intestinal cells. However, it remains unclear whether ferrichrome exerts anti-tumor effects in esophageal cancer. A sulforhodamine B assay revealed that ferrichrome suppressed esophageal adenocarcinoma (OE33, OE19) and squamous cell carcinoma (KYSE70) cells. Ki-67 staining indicated that ferrichrome inhibited the proliferation of esophageal cancer cells. Cell cycle analysis showed that ferrichrome inhibited the DNA synthesis. TUNEL staining revealed that ferrichrome-induced DNA fragmentation. We also confirmed the cleavage of caspase-9 and PARP in ferrichrome-treated cells. Reverse transcription polymerase chain reaction demonstrated an increase in the mRNA of DNA damage-inducible transcript 3 (DDIT-3), a key regulator of programmed cell death, in ferrichrome-treated OE33 cells. In an in vivo OE33 xenograft model, intraperitoneal administration of 5-mg/kg ferrichrome for 14 days resulted in an almost complete inhibition of tumor growth. However, 14 days of intraperitoneal administration of 20-mg/kg 5-fluorouracil (5-FU), but not 20-mg/kg ferrichrome, induced weight loss and myelosuppression in both young and aged mice. Our findings indicate that ferrichrome induces DNA damage-inducible transcript-3, thereby producing anti-tumor effects, including cell cycle arrest and apoptosis, with minimal adverse effects in esophageal cancer cells. This illustrates the high potential of ferrichrome as an anti-tumor drug against esophageal carcinoma.
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A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.
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OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA , in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA , which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC , which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA , HULC , or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.
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Biomarcadores de Tumor , Carcinoma Ductal Pancreático , Vesículas Extracelulares , Neoplasias Pancreáticas , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/sangre , ARN Largo no Codificante/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangre , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Biopsia Líquida/métodos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/sangre , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Estudios de Casos y ControlesRESUMEN
Background and Aims: EUS-guided biliary drainage (EUS-BD) has been performed increasingly worldwide, especially in patients with malignant tumors in which ERCP is difficult, patients with surgically altered GI tracts, and older patients who are at high risk for surgery. EUS-BD requires high-level skills and has limited options for managing adverse events, particularly when stent migration and cholangitis occur. Adverse events, such as persistent bile leakage from the fistula and continuous reflux from the GI tract, are believed to always have a risk of severe exacerbation that could threaten the patient's life. Methods: We encountered 2 cases of stent migrations and 1 case with repeated cholangitis in patients with malignant tumors among the patients who underwent EUS-BD. The migrated stent was visualized under EUS in 2 patients with stent migration, and an EUS-guided FNA needle was used to puncture the mesh of the stent. The cannulation catheter was directly inserted into the mesh of the stent in 1 case with repeated retrograde cholangitis, while the stent was visualized with an endoscope. Subsequently, a guidewire was inserted through the puncture site, and a second metal stent was deployed between the meshes of the first stent, bridging the GI wall again (Lambda stenting technique). All procedures were performed with the patient under general anesthesia, and the patients safely completed the intervention. Results: Patients' conditions significantly improved after the second stent insertion, allowing for chemotherapy resumption while maintaining their activities of daily living. The second stent remained in place without any migration, and the stent successfully prevented further cholangitis. Conclusions: The Lambda stenting technique is considered highly effective for managing stent migration and repeated cholangitis, which is a major EUS-BD adverse event. This procedure helps avoid more invasive surgeries when stent migration and cholangitis occur and contributes to expanding EUS-BD applicability.
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BACKGROUND: Hospitalization for ulcerative colitis (UC) is potentially life-threatening. Severe disease in the Japanese criteria which modifies the Truelove-Witts' criteria might encompass more fulminant cases than the definition for acute severe UC. However, few studies have investigated the predictive factors for clinical remission (CR) after medical treatments for severe hospitalized patients by Japanese criteria. METHODS: Medical treatment selection, CR rates, and factors contributing to CR on day 14 were assessed in severe patients by Japanese criteria. We also investigated whether the reduction rate in patient-reported outcome 2 (PRO2) on day 3 could predict short-term prognosis. RESULTS: Eighty-five severe hospitalized patients were selected. Corticosteroids, tacrolimus, and infliximab were mainly selected as first-line treatments (76/85; 89.4%). The CR rates on day 14 were 26.8%, 21.4%, and 33.3% in patients receiving corticosteroids, tacrolimus, and infliximab, respectively. Extensive disease (odds ratio [OR] 0.022; 95% confidence interval [CI] 0.002-0.198), higher PRO2 (OR 0.306; 95% CI 0.144-0.821), and higher reduction rate in PRO2 on day 3 (OR 1.047; 95% CI 1.019-1.075) were independent factors predicting CR on day 14. If the cutoff value for the reduction rate in PRO2 on day 3 was 18.3%, sensitivity was 0.714 and specificity was 0.731 to predict CR on day 14. A higher reduction rate in PRO2 on day 3 (OR 0.922; 95% CI 0.853-0.995) was a negative factor to predict surgery within 28 days. CONCLUSIONS: Tacrolimus and infliximab in addition to corticosteroids were used as first-line treatment in severe hospitalized patients. PRO2 on day 3 is a useful marker for switching to second-line therapy or colectomy.
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Colitis Ulcerosa , Humanos , Colitis Ulcerosa/diagnóstico , Colitis Ulcerosa/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Infliximab/uso terapéutico , Inmunosupresores/uso terapéutico , Tacrolimus/uso terapéutico , Japón , Corticoesteroides/uso terapéutico , Resultado del Tratamiento , Colectomía , Estudios RetrospectivosRESUMEN
INTRODUCTION: A remission induction therapy of granulocyte and monocyte adsorptive apheresis (GMA) was given to patients with Crohn's disease (CD). However, establishing an appropriate treatment strategy for GMA in patients with CD remains unclear. METHODS: This study evaluated the clinical efficacy and subsequent clinical progression after GMA in patients with CD who underwent GMA in seven independent institutions in Japan from 2010 to 2023. RESULTS: Sixteen patients were enrolled. The overall remission and response rates were 25.0% and 68.8%, respectively. All patients responding to GMA received biologics that were continuously used and 36.4% of patients remained on the same biologics 52 weeks after GMA. Notably, all patients who continued the same biologics had previously experienced a loss of response to biologics. CONCLUSION: GMA may exhibit effectiveness even in cases with refractory CD. Moreover, it represents a potential novel therapeutic option for refractory CD with loss of response to biologics.
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Eliminación de Componentes Sanguíneos , Enfermedad de Crohn , Granulocitos , Monocitos , Humanos , Enfermedad de Crohn/terapia , Masculino , Femenino , Proyectos Piloto , Adulto , Estudios Retrospectivos , Eliminación de Componentes Sanguíneos/métodos , Japón , Resultado del Tratamiento , Persona de Mediana Edad , Inducción de Remisión/métodos , Adsorción , Productos Biológicos/uso terapéutico , Adulto JovenRESUMEN
RATIONALE: Both ulcerative colitis (UC) and sarcoidosis are chronic inflammatory diseases with unknown etiologies and are rare. However, the odds ratio in UC patients has been reported to range from 1.7 to 2.1, suggesting a potential etiology between sarcoidosis and UC. Furthermore, the underlying etiologies of UC and sarcoidosis remain unidentified. Sharing the experience of a UC patient with cardiac sarcoidosis could provide valuable insights to prevent sudden death in UC patients. PATIENT CONCERNS: A 71-year-old Japanese woman was diagnosed with UC at 58-year-old and maintained remission on mesalazine treatment. She complained of just palpitation; therefore, she consulted a cardiologist. DIAGNOSES: The patient received a diagnosis of cardiac sarcoidosis with complicating ulcerative colitis based on the results of N-terminal prohormone of the brain natriuretic peptide (NT-proBNP), imaging examinations, and histology. INTERVENTION: The patient was treated with prednisolone and methotrexate. The prednisolone was then tapered, and the methotrexate dose was adjusted based on her symptoms, imaging results, and laboratory findings. OUTCOME: She no longer had any symptoms, and the abnormal FDG uptake had disappeared after 2 years. LESSON: In UC patients, periodic or additional (in case of symptomatic) electrocardiography and NT-proBNP are recommended for the early detection of cardiac sarcoidosis, a life-threatening complication.
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Colitis Ulcerosa , Miocarditis , Sarcoidosis , Humanos , Femenino , Anciano , Persona de Mediana Edad , Colitis Ulcerosa/complicaciones , Colitis Ulcerosa/tratamiento farmacológico , Metotrexato/uso terapéutico , Sarcoidosis/complicaciones , Sarcoidosis/diagnóstico , Sarcoidosis/tratamiento farmacológico , Prednisolona/uso terapéuticoRESUMEN
A male patient in his 70s with recurrent hepatocellular carcinoma (HCC) after surgery received atezolizumab plus bevacizumab (Atezo+Bev) therapy. Initial computed tomography (CT) revealed tumor growth along with an increase in tumor markers, and contrast-enhanced ultrasonography (CEUS) showed multiple round avascular areas within the nodules with an appearance similar to a slice of Swiss cheese. Continuation of immunotherapy with consideration of the potential for pseudoprogression produced a dramatic response. Although it is difficult to distinguish between true progression and pseudoprogression, the Swiss cheese-like appearance on CEUS may be important for the early diagnosis of pseudoprogression.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Masculino , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patología , Medios de Contraste , Ultrasonografía/métodos , InmunoterapiaRESUMEN
Introduction: There have been limited reports on the clinical efficacy of golimumab (GLM) in Japanese patients with ulcerative colitis (UC) in real clinical practice. This study aimed to explore the real-life effectiveness and factors associated with response to GLM in Japanese patients with UC. Methods: This observational, retrospective, multicenter study was conducted in hospitals with expertise in inflammatory bowel disease treatment. Sixty-three patients treated with GLM and active UC were included in the analysis. Clinical remission (CR) (partial Mayo (pMayo) score ≤2) in the induction and maintenance phases after GLM treatment and associated factors were evaluated. Results: The proportion of patients achieving CR in the induction and maintenance phases was 41.3% (26/63) and 46.0% (29/63, the last observation carried forward method was used for patients who discontinued treatment for reasons other than inadequate response), respectively. The median pMayo score was 5 (interquartile range (IQR): 4-6) at baseline, 3 (IQR: 1-5) in the induction phase, and 1 (IQR: 0-3) in the maintenance phase. Hemoglobin, platelet, and C-reactive protein levels changed, consistent with the pMayo score. Multivariate logistic analysis revealed that biologic-naive status was an independent factor associated with CR in the induction (p = 0.0200) and maintenance (p = 0.0459) phases, and a disease duration of >60 months until GLM initiation was associated with CR in the induction phase (p = 0.0427). Conclusions: The effectiveness of GLM in daily clinical practice has been confirmed in Japanese patients with active UC. Biologic-naive patients responded more to GLM in the induction and maintenance phases, and patients with disease duration of >60 months until initiation of GLM were more responsive in the induction phase.
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BACKGROUND: This multicenter observational cohort study aimed to evaluate the utilization and short-term efficacy of advanced therapy (AT) in hospitalized patients with acute severe ulcerative colitis (ASUC). METHODS: In total, 221 patients with ASUC were enrolled between August 2020 and July 2021. The primary endpoint was clinical remission (CR, defined as a patient-reported outcome score < 2 with no blood in the stool) rate on Day 7 and 14 in hospitalized patients who received corticosteroids (CS) and AT. RESULTS: Among patients with ASUC, 120 and 101 patients received CS or any AT as first-line treatment, respectively. The CR rates on Day 7 and 14 were 22.5% and 35.0%, respectively, in hospitalized patients who received CS as first-line treatment. Most patients who used ATs had CS-dependent or frequent recurrences. Eight different ATs (apheresis, tacrolimus, infliximab, golimumab, tofacitinib, vedolizumab, ustekinumab, and cyclosporine) were used as first-line treatment in patients with ASUC, and the CR rates on Day 7 and 14 were 16.8% and 29.7%, respectively. Twenty-five patients received the second ATs after hospitalizations, and the CR rates on Day 7 and 14 were 0% and 12%, respectively. The CR rates on Day 14 were significantly higher in patients who changed to AT than in those whose dose of CS increased (34.0% vs 10.7%, p = 0.020) among patients who had already used CS before hospitalization. CONCLUSION: Most first-use ATs were effective for patients with ASUC, while second-use ATs might have had limited benefits in inducing CR. These findings may contribute to considerations for the management of hospitalized patients.
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Colitis Ulcerosa , Humanos , Colitis Ulcerosa/tratamiento farmacológico , Resultado del Tratamiento , Infliximab/efectos adversos , Tacrolimus/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
OBJECTIVE: Antithrombotic medications pose a challenge for conducting surgical or invasive procedures, because their discontinuation is required to avoid postprocedural hemorrhagic complications but potentially increases the ischemic risk for the patient. This study aimed to estimate the increased risk of developing cerebral ischemic events during hospitalization requiring discontinuation of antithrombotic therapy. METHODS: This investigation was a single-center retrospective observational study. Clinical data in patients scheduled for admission between January 1, 2021, and December 31, 2022, were collected. Patients requiring discontinuation of antithrombotic therapy were identified by referring to the admission database. Patients who developed cerebral ischemia were identified by referring to the institution's stroke center database. RESULTS: Seven hundred ninety-six patients scheduled for nonneurosurgical procedures and 39 scheduled for neurosurgical procedures underwent discontinuation of antithrombotic therapy. Anticoagulation therapy was prescribed in 40.0%, and antiplatelet therapy was prescribed in 69.1% of the patients. A total of 9.2% of the entire cohort of patients were receiving both anticoagulation and antiplatelet therapy. Bridging therapy was administered in 20.9% of nonneurosurgical patients. No ischemic event was observed in the patients undergoing neurosurgical procedures. Among the entire cohort, 3 patients encountered some kind of thrombotic event-2 of which were cerebral ischemia-accounting for an incidence of 0.24%, which was significantly higher than incidental in-hospital stroke unrelated to discontinuation of antithrombotic therapy (p = 0.04). Patients undergoing both anticoagulation and antiplatelet therapy harbored a significantly higher risk for cerebral ischemia related to discontinuation of antithrombotic therapy (p < 0.0001). CONCLUSIONS: Discontinuing antithrombotic therapy during hospitalization for elective invasive procedures-including neurosurgical procedures-entailed a relatively small risk of developing cerebral ischemic events, but the risk was significantly higher compared to hospitalized patients without discontinuation of antithrombotic therapy.
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Isquemia Encefálica , Accidente Cerebrovascular , Humanos , Fibrinolíticos/efectos adversos , Inhibidores de Agregación Plaquetaria/efectos adversos , Accidente Cerebrovascular/prevención & control , Accidente Cerebrovascular/tratamiento farmacológico , Isquemia Encefálica/epidemiología , Isquemia Encefálica/complicaciones , Anticoagulantes/efectos adversosRESUMEN
BACKGROUND: Infliximab (IFX) effectively treats patients with inflammatory bowel disease (IBD). IFX-biosimilar (IFX-BS) has the same amino acid sequence as that of the IFX originator, and its increasing use is expected to reduce national healthcare costs. Long-term efficacy and safety of IFX-BS in patients with Crohn's disease (CD) and ulcerative colitis (UC) have not been completely investigated. METHODS: We conducted a retrospective, multicenter observational study of patients with IBD who received IFX-BS treatment at three hospitals between October 2016 and April 2022. Clinical data were collected from electronic medical records and evaluated for achieving clinical remission (CR) using Crohn's disease activity index (CDAI) and partial Mayo (pMayo) score, persistency of long-term IFX-BS administration, and clinical response rate in the bio-naïve and bio-failure groups. RESULTS: A total of 117 patients with IBD (90 CD and 27 UC) were included. The study findings indicated that both bio-naïve and bio-failure groups of patients with UC showed similar effectiveness of IFX-BS. The treatment persistence rate in patients with CD was significantly higher in the bio-naïve (P = 0.042) and switch (P = 0.010) groups than in the bio-failure group. In the former two groups, the treatment persistence rate was high at two years after administration (more than 80%). In patients with UC, the findings indicated higher treatment persistence rate in the switch group than in the bio-naïve group. Univariable and multivariable analyses for treatment persistence rate showed that the albumin level at the initial IFX-BS administration and groups (bio-naïve, bio-failure and switch) were effective factors for patients with CD. Adverse events were reported in 18 patients (15.4%). CONCLUSION: The present study demonstrates the long-term effectiveness and safety of IFX-BS. In addition to the favorable remission induction in the bio-naïve and bio-failure groups, we demonstrated remission maintenance and treatment persistence rates beyond two years. Albumin level and groups were associated with better treatment persistence in patients with CD.