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INTRODUCTION: Fatigue is reportedly associated with a poor prognosis in dialysis patients. The aim of the present study was to investigate whether fatigue on dialysis days or non-dialysis days is associated with mortality in patients on chronic hemodialysis. METHODS: This was a prospective study of 134 hemodialysis patients. The level of fatigue was evaluated using a visual analog scale (VAS). The association between high fatigue evaluated by the highest quartile of the VAS value and all-cause death was investigated. RESULTS: The fatigue scale score was significantly higher on dialysis than on non-dialysis days. During the follow-up period (median 6.8 years), 42 patients died. Patients with high post-dialysis fatigue in the higher quartiles died more frequently compared to those with in the lower quartiles (p = 0.012). Multivariate Cox regression analysis showed that high post-dialysis fatigue was an independent predictor of all-cause death (adjusted hazard ratio 2.12, 95% confidence interval 1.10-4.07). CONCLUSION: Higher post-dialysis fatigue is related to increased mortality.
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BACKGROUND AND AIMS: Endoscopic interventions for bile duct stones (BDSs) with benign choledochojejunal anastomotic stenosis (bCJS) are challenging. Therefore, we investigated endoscopic interventions for BDSs with bCJS. METHODS: Seventeen patients with BDSs with bCJS were retrospectively analyzed. Patient characteristics, technical success, adverse events (AEs), and recurrence were evaluated. RESULTS: In 17 patients, the median diameters of the bile duct and BDSs were both 8 mm. The median number of BDSs was 3. The technical success rate was 94% (16/17). Ten patients underwent balloon dilation at the choledochojejunal anastomotic site (CAS), the median diameter of balloon dilation was 10.5 mm, and waist disappearance was achieved in 2. Six patients had fully covered self-expandable metal stents (FCSEMSs) with a diameter of 10 mm placed at the CAS. BDSs were removed after balloon dilation or FCSEMS removal, and 6 of 16 patients were treated with a combination of lithotripsy and 5 with peroral direct cholangioscopy (PDCS). Regarding AEs, perforation at the CAS by balloon dilation occurred in 1 patient. The median follow-up was 3701 days. Nine of 16 patients (56%) had recurrence. The patients treated with a combination of PDCS at BDS removal (P = .022) and waist disappearance at the CAS by balloon dilation (P = .035) had significantly fewer recurrences. CONCLUSIONS: Endoscopic interventions for BDSs with bCJS are useful and relatively safe; however, long-term follow-up showed frequent recurrences. Recurrence was common in patients not treated with the combination of PDCS at BDS removal and those without waist disappearance at the CAS by balloon dilation.
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Hiperpigmentación , Liquen Plano , Humanos , Administración Cutánea , Hiperpigmentación/tratamiento farmacológico , Hiperpigmentación/diagnóstico , Hiperpigmentación/patología , Liquen Plano/tratamiento farmacológico , Liquen Plano/patología , Liquen Plano/diagnóstico , Pirroles/administración & dosificación , Pirroles/uso terapéutico , Piel/patología , Piel/efectos de los fármacos , Resultado del TratamientoRESUMEN
Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD.
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Enfermedad de Paget Extramamaria , Silicatos , Titanio , Humanos , Femenino , Enfermedad de Paget Extramamaria/tratamiento farmacológico , Enfermedad de Paget Extramamaria/patología , Recurrencia Local de Neoplasia/patología , Pronóstico , Estadificación de NeoplasiasAsunto(s)
Adapaleno , Peróxido de Benzoílo , Fármacos Dermatológicos , Humanos , Masculino , Adapaleno/administración & dosificación , Administración Cutánea , Administración Tópica , Peróxido de Benzoílo/administración & dosificación , Peróxido de Benzoílo/uso terapéutico , Fármacos Dermatológicos/administración & dosificación , Fármacos Dermatológicos/uso terapéutico , Dermatosis Facial/tratamiento farmacológico , Dermatosis Facial/patología , Resultado del Tratamiento , Persona de Mediana EdadRESUMEN
The identification of immune cell profiles (ICP) involved in anti-tumor immunity is crucial for immunotherapy. Therefore, we herein investigated cholangiocarcinoma patients (CCA) who received adoptive T-cell immunotherapy (ATI). Eighteen unresectable or recurrent CCA received ATI of αß T cells alone or combined with chemotherapy. ICP were evaluated by flow cytometry. There were 14 patients with intrahepatic cholangiocarcinoma (iCCA) and four with distal cholangiocarcinoma (dCCA). After one course of treatment, nine iCCA and four dCCA had progressive disease (PD), while five iCCA had stable disease (SD). Median overall survival (OS) was prolonged to 21.9 months. No significant differences were observed in OS between the PD and SD groups of iCCA. The frequency of helper T cells (HT) in iCCA decreased from 70.3% to 65.5% (P = .008), while that of killer T cells (KT) increased from 27.0% to 30.6% (P = .005). dCCA showed no significant changes of immune cells. OS was prolonged in iCCA with increased frequencies of CD3+ T cells (CD3) (P = .039) and αß T cells (αß) (P = .039). dCCA showed no immune cells associated with OS. The frequencies of CD3+ T cells and αß T cells in the PD group for iCCA decreased from 63.5% to 53% (P = .038) and from 61.6% to 52.2% (P = .028), respectively. In the SD group, the frequency of HT decreased from 65.8% to 56.9% (P = .043), whereas that of KT increased from 30.1% to 38.3% (P = .043). In conclusions, ATI affected ICP and prolonged OS. Immune cells involved in treatment effects differed according to the site of cholangiocarcinoma.
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Neoplasias de los Conductos Biliares , Colangiocarcinoma , Humanos , Colangiocarcinoma/terapia , Pronóstico , Inmunoterapia , Conductos Biliares Intrahepáticos/patología , Neoplasias de los Conductos Biliares/terapia , Neoplasias de los Conductos Biliares/patologíaRESUMEN
BACKGROUND: Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different. METHODS: We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan. RESULTS: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p < 0.001); median progression-free survival (PFS) was 14.7, 5.4, and 5.8 months (p = 0.003), and median overall survival (OS) was 34.6, 37.0 months, and not reached, respectively (p = 0.535). In multivariable analysis, hazard ratios (HRs) for PFS of Anti-PD-1 and PD-1/CTLA-4 compared with BRAF/MEKi were 2.30 (p < 0.001) and 1.38 (p = 0.147), and for OS, HRs were 1.37 (p = 0.111) and 0.56 (p = 0.075), respectively. In propensity-score matching, BRAF/MEKi showed a tendency for longer PFS and equivalent OS with PD-1/CTLA-4 (HRs for PD-1/CTLA-4 were 1.78 [p = 0.149]) and 1.03 [p = 0.953], respectively). For patients who received second-line treatment, BRAF/MEKi followed by PD-1/CTLA-4 showed poor survival outcomes. CONCLUSIONS: The superiority of PD-1/CTLA-4 over BRAF/MEKi appears modest in Asian patients. First-line BRAF/MEKi remains feasible, but it is difficult to salvage at progression. Ethnicity should be considered when selecting systemic therapies until personalized biomarkers are available in daily practice. Further studies are needed to establish the optimal treatment sequence for Asian patients.
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Melanoma , Proteínas Proto-Oncogénicas B-raf , Humanos , Antígeno CTLA-4 , Estudios Retrospectivos , Proteínas Proto-Oncogénicas B-raf/genética , Receptor de Muerte Celular Programada 1 , Japón , Melanoma/tratamiento farmacológico , Melanoma/genética , Inhibidores de Proteínas Quinasas/uso terapéutico , Quinasas de Proteína Quinasa Activadas por MitógenosAsunto(s)
Conductos Biliares Extrahepáticos , Endoscopía , Humanos , Constricción Patológica/etiología , Constricción Patológica/cirugía , Conductos Biliares Intrahepáticos/diagnóstico por imagen , Conductos Biliares Intrahepáticos/cirugía , Colangiopancreatografia Retrógrada Endoscópica , Esfinterotomía EndoscópicaRESUMEN
Japanese patients with very high-risk cutaneous squamous cell carcinomas (cSCCs), based on the National Comprehensive Cancer Network guidelines, have been reported to display a higher cumulative incidence of relapse and disease-specific death (DSD) than those with high-risk cSCC. Therefore, prognosis prediction is crucial for Japanese patients with very high-risk cSCCs. Herein, we aimed to evaluate the prognostic prediction ability of our novel Japanese Risk Factor Scoring Systems (JARF scoring) in a Japanese cohort of cSSC patients. Data of 424 Japanese patients with resectable very high-risk cSCCs were analysed. We compared the prognostic ability of the following three staging systems: Brigham and Women's Hospital (BWH) tumour staging, number of NCCN very high-risk factors, and JARF scoring, including recurrent tumour, high-risk histological features, deep tumour invasion and lymphatic or vascular involvement as risk factors. The prognostic ability of these staging systems was evaluated according to the cumulative incidence of local recurrence (LR), regional lymph node metastasis (RLNM), DSD, and overall survival (OS). When BWH staging was used, high T stage led to significantly poor outcomes only in the cumulative incidence of RLNM (p = 0.01). The presence of very high-risk NCCN factors led to significantly poor outcomes in terms of RLNM (p = 0.03) and OS (p = 0.02). Meanwhile, a high number of risk factors in the JARF scoring system clearly led to poor outcomes in terms of LR (p = 0.01), RLNM (p < 0.01), DSD (p = 0.03), and OS (p < 0.01). The JARF scoring system may accurately predict the risk of recurrence and death in very high-risk cSCC patients in Japan.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Humanos , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Estudios Transversales , Pueblos del Este de Asia , Japón , Recurrencia Local de Neoplasia/patología , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaAsunto(s)
Melanoma , Neoplasias Cutáneas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Pueblos del Este de Asia , Ipilimumab/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/etiología , Nivolumab/uso terapéutico , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/etiologíaRESUMEN
BACKGROUND: Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear. OBJECTIVE: To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM. METHODS: Japanese patients with advanced BRAF wild-type NACM who received first-line ICIs were recruited. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), and the degree of solar elastosis (SE) were evaluated. RESULTS: A total of 146 patients (PD1 group 113 and PD1 +CTLA4 group 33) were included. No significant differences in ORR were observed between the PD1 and PD1 +CTLA4 groups (35 % vs. 36 %; P = 0.67) or PFS and OS (median PFS 6.1 months vs. 8.5 months; P = 0.46, median OS 28.1 months vs. not reached; P = 0.59). Multivariate survival analysis revealed that PD1 +CTLA4 did not prolong the PFS and OS. The SE score had no effect on either PFS or OS. CONCLUSIONS: ICI efficacy was not as high as those reported in Western countries, and PD1 +CTLA4 did not present better clinical efficacy compared to PD1. Indicators of CSD did not serve as a predictor for clinical advantage. These findings may partially support the theory that ICI efficacy is affected by CSD; however, other unrecognized factors may also exist.
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Melanoma , Neoplasias Cutáneas , Humanos , Antígeno CTLA-4/genética , Pueblos del Este de Asia , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Melanoma/tratamiento farmacológico , Melanoma/genética , Proteínas Proto-Oncogénicas B-raf/genética , Estudios Retrospectivos , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/genética , Melanoma Cutáneo MalignoRESUMEN
Multiple myeloma (MM) and polycythemia vera (PV) rarely coexist; the clinical manifestations and treatment of this coexistence have not been described. An 81-year-old woman developed MM 15 years after undergoing PV treatment and was successfully treated using bortezomib. Herein, we share our experience of treating MM under such unusual conditions.
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BACKGROUND AND OBJECTIVES: In cutaneous squamous cell carcinoma (cSCC), adherence to guideline-recommended fixed surgical margins is often difficult, and narrower margins are preferable. This study aimed to evaluate relapse and disease-specific death with narrower margins for high or very high-risk cSCC. PATIENTS/METHODS: We retrospectively investigated high or very high-risk cSCC patients who underwent tumor excision. Patients were divided into guideline-recommended standard margin group (SMG) and narrower-margin group (NMG). Co-primary outcomes were local relapse, SCC relapse, and SCC death. Cumulative incidence function (CIF) was used to describe SCC death probability and competing risk mortality. Gray's test was used to compare differences in CIF between the groups. RESULTS: In total, 1,000 patients with cSCC (high-risk, 570; very high-risk, 430) were included. In the high-risk cohort, there were no significant differences in incomplete excision rate (IER) between SMG and NMG (2.6 % vs. 3.0 %, P > 0.99). However, in the very high-risk cohort, IER in SMG was significantly lower than in NMG (8.9 % vs. 16.2 %, P = 0.03). No significant differences were observed between SMG and NMG for local relapse (high-risk, P = 0.56; very high-risk, P = 0.70), SCC relapse (high-risk, P = 0.30; very high-risk, P = 0.47), and SCC death (high-risk, P = 0.23; very high-risk, P = 0.83). CONCLUSIONS: Surgical margin size has limited impact on margin control, relapse, and disease-specific death in high-risk cSCC.
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Carcinoma de Células Escamosas , Neoplasias Cutáneas , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Humanos , Márgenes de Escisión , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/cirugíaRESUMEN
HINTERGRUND UND ZIELE: Bei kutanen Plattenepithelkarzinomen (PEK) ist die Einhaltung der in Leitlinien empfohlenen festen Resektionsränder oft schwierig und knappere Ränder sind wünschenswert. Ziel dieser Studie war die Bewertung des Auftretens von Rezidiven und krankheitsspezifischen Todesfällen bei knapperen Resektionsrändern für PEK mit hohem oder sehr hohem Risiko. PATIENTEN/METHODEN: PEK-Patienten mit hohem oder sehr hohem Risiko, bei denen eine Tumorexzision durchgeführt wurde, wurden retrospektiv untersucht. Die Patienten wurden in eine Gruppe mit Standardrand gemäß Leitlinienempfehlung (standard margin group, SMG) und eine Gruppe mit knapperen Rändern (narrower-margin group, NMG) eingeteilt. Gemeinsame primäre Endpunkte waren lokales Rezidiv, PEK-Rezidiv und PEK-bedingter Tod. Die Wahrscheinlichkeit eines PEK-bedingten Tods und konkurrierender Mortalitätsrisiken wurde mittels kumulativer Inzidenzfunktion (CIF) beschrieben. Unterschiede bei der CIF zwischen den Gruppen wurden mit dem Test nach Gray verglichen. ERGEBNISSE: Insgesamt wurden 1.000 Patienten mit PEK (hohes Risiko, 570; sehr hohes Risiko, 430) eingeschlossen. In der Kohorte mit hohem Risiko gab es keine signifikanten Unterschiede bei der unvollständigen Exzisionsrate (IER) zwischen SMG und NMG (2,6 % vs. 3,0 %, P > 0,99). In der Kohorte mit sehr hohem Risiko war die IER in der SMG jedoch signifikant geringer als in der NMG (8.9 % vs. 16.2 %, P = 0,03). Keine signifikanten Unterschiede zwischen SMG und NMG wurden für Lokalrezidiv (hohes Risiko, P = 0.56; sehr hohes Risiko, P = 0,70), PEK-Rezidiv (hohes Risiko, P = 0,30; sehr hohes Risiko, P = 0,47) und PEK-bedingtem Tod (hohes Risiko, P = 0,23; sehr hohes Risiko, P = 0,83) beobachtet. SCHLUSSFOLGERUNGEN: Die Größe des Resektionsrands hat einen begrenzten Einfluss auf Randkontrolle, Rezidive und krankheitsspezifischen Tod bei PEK mit hohem Risiko.
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Lichen planopilaris (LPP) is a type of lymphocytic cicatricial alopecia, which can occur at unusual sites. It can be difficult to diagnose at an early stage and may be misdiagnosed as seborrheic dermatitis or psoriasis in early stages before alopecia occurs. We report a rare case in which alopecia occurred between two long surgical scars on the scalp several years after surgery. Dermoscopy and biopsy led to a diagnosis of LPP. The localization of the lesions in our case suggests that oxidative stress from the failure of lymph flow might have induced LPP. Oral roxithromycin, a macrolide antibiotic, with anti-oxidative and anti-inflammatory was effective at stopping its progression.
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BACKGROUND: Temporary fully covered self-expandable metal stent (FCSEMS) placement is performed for benign choledochojejunal anastomotic stenosis (bCJS). However, recurrence may develop after stricture resolution. We investigated endoscopic biliary stenting using FCSEMS for bCJS. METHODS: Sixteen bCJS patients with FCSEMS placement were retrospectively analyzed. FCSEMS was removed endoscopically after 2 months. Technical success, stricture resolution, recurrence, and adverse events were evaluated. RESULTS: The technical success rate for FCSEMS placement was 94% (15/16). Biliary stones were detected and extracted in four patients. FCSEMS removal was successfully performed on 14 patients, excluding one with stent migration. At FCSEMS removal, stricture resolution was noted in 14 patients; however, four had anastomotic ulcers. The median follow-up was 319 days. Three patients with a history of repeated plastic stent placement had no recurrence. Four out of 15 patients (27%) had recurrence, and three had no recurrence after additional interventions. Biliary stones before first FCSEMS placement (P = .003) or anastomotic ulcers at FCSEMS removal (P = .018) were associated with recurrence. CONCLUSIONS: Although FCSEMS placement was useful for stricture resolution, recurrence was detected in patients with biliary stones before first FCSEMS placement or anastomotic ulcers at FCSEMS removal. Anastomotic ulcers are a risk factor for recurrence and only detected by endoscopy.
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Colestasis , Cálculos Biliares , Stents Metálicos Autoexpandibles , Colangiopancreatografia Retrógrada Endoscópica/efectos adversos , Colestasis/etiología , Constricción Patológica/etiología , Constricción Patológica/cirugía , Remoción de Dispositivos/efectos adversos , Cálculos Biliares/etiología , Humanos , Membrana Mucosa , Plásticos , Estudios Retrospectivos , Stents/efectos adversos , Resultado del Tratamiento , Úlcera/complicacionesRESUMEN
BACKGROUND: In addition to 2-weekly nivolumab 240 mg or 3-weekly pembrolizumab 200 mg, extended dosing intervals of 4-weekly nivolumab 480 mg or 6-weekly pembrolizumab 200 mg were approved. To date, the clinical safety of the extended dosing schedules of immune checkpoint inhibitors (ICIs) has not been adequately investigated in patients with solid tumors. METHODS: This real-world study enrolled patients with solid tumors who received nivolumab 480 mg every 4 weeks or pembrolizumab 400 mg every 6 weeks at the Kyoto Prefectural University of Medicine in Japan, between August 2020 and December 2021. RESULTS: Sixty-nine patients with solid tumors received an extended-interval dosing schedule during this period. Among them, 60 received it during treatment (cohort A), and nine received it for the first time (cohort B). After the extended dosing interval of ICIs in cohort A, 13 (21.7%) patients developed immune-related adverse events (irAEs). Seven of the 13 patients (53.8%) developed irAEs during the first cycle of the extended dosing interval. All patients who developed irAEs during the first cycle of the extended dosing interval had pre-existing antibodies. Multivariate analysis indicated that patients with pre-existing anti-thyroid antibodies had a significantly higher irAE incidence after starting extended dosing intervals (odds ratio: 6.41; 95% confidence interval: 1.46-28.2, p = 0.01). CONCLUSIONS: Most patients were allowed to continue ICI therapy after an extended dosing interval. Patients with pre-existing antibodies, particularly anti-thyroid antibodies, may be prone to developing irAEs after starting extended dosing intervals and should be treated with caution.