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Coronavirus disease 2019 (COVID-19) vaccines are highly effective; however, vaccine-related adverse events, including autoimmunity, have been reported. Case reports describing relapse or new-onset of ulcerative colitis (UC) after COVID-19 mRNA vaccination are available. However, the molecular mechanisms underlying the development of colonic inflammation associated with COVID-19 mRNA vaccination are poorly understood. Furthermore, it is unclear whether the relapse of UC after COVID-19 vaccination is driven by unique cytokine responses that differ from those of UC not associated with vaccination. mRNAs derived from COVID-19 vaccines are potent inducers of type I IFN response. We encountered three cases of UC relapse after COVID-19 vaccination. mRNA expressions of IFN-α, IFN-ß, IL-1ß, and IL-12/23p40 showed higher tendency in the colonic mucosa of patients with UC associated with vaccination compared with those not associated with vaccination. In contrast, the expressions of C-X-C motif chemokine ligand 9 (CXCL9) and CXCL10 were comparable. Immunofluorescence analyses also showed higher expression of IFN-α in the colonic mucosa of patients with UC associated with COVID-19 vaccination than in those not associated with vaccination. Taken together, these data suggest that the colonic mucosa of patients with UC who relapsed after COVID-19 vaccination was characterized by enhanced type I IFN responses.
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The aim of this study was to determine the impact of nerve preservation confirmed by intraoperative electrical stimulation (IES) on subjective symptoms of urinary and sexual function in uterine cervical cancer patients who underwent radical hysterectomies. This study included 85 patients who underwent type C radical hysterectomy with IES. Pelvic splanchnic nerve preservation with IES after hysterectomy (nerve-stimulation positive group) was confirmed in 61 women and 24 women did not have nerve preservation (negative group). Urinary function was assessed with the Overactive Bladder Symptom Score (OABSS), International Prostate Symptom Score (IPSS), and International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) questionnaires. Sexual function was surveyed using the Female Sexual Function Index (FSFI). Longitudinal changes in those scores according to response to nerve-stimulation were evaluated using a generalized estimating equation. IPSS quality of life (QOL) scores were significantly better in the nerve-stimulation positive group compared with the scores in the negative group until 12 months after surgery, whereas OABSS, IPSS total, IPSS voiding, and ICIQ-SF scores evaluating urinary symptoms were not significantly different between the two groups. FSFI scores were better in the nerve-stimulation positive group 36 months after surgery compared with the scores in the negative group. In this study, we assessed self-reported urinary and sexual symptoms after nerve-sparing radical hysterectomy (NSRH) with IES in the long term. We demonstrated that nerve-sparing significantly reduced distress associated with QOL until 1 year, improved urinary storage symptoms at 2 years, and sexual symptoms 3 years after surgery.
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Histerectomía , Autoinforme , Humanos , Histerectomía/efectos adversos , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Calidad de Vida , Adulto , Factores de Tiempo , Tratamientos Conservadores del Órgano/métodos , Micción/fisiología , Neoplasias del Cuello Uterino/cirugía , Encuestas y Cuestionarios , AncianoAsunto(s)
Artralgia , COVID-19 , Exantema , Humanos , Artralgia/etiología , Artralgia/virología , Artralgia/diagnóstico , Vacuna BNT162/efectos adversos , Vacuna BNT162/administración & dosificación , Infección Irruptiva , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/efectos adversos , Vacunas contra la COVID-19/administración & dosificación , Exantema/virología , Exantema/diagnóstico , Exantema/etiología , RecurrenciaRESUMEN
Background and Aim: Serum leucine-rich alpha-2 glycoprotein level has been reported to be a useful biomarker in assessing mucosal healing in patients undergoing biotherapy, where mucosal lesions caused by ulcerative colitis are difficult to assess endoscopically. However, no such reports have been reported in biotherapy-naïve cases. Methods: Sixty-eight patients with ulcerative colitis (UC) who were biotherapy-naïve at Kindai University Hospital between October 2021 and October 2022 were enrolled. We prospectively examined the correlation between leucine-rich alpha-2 glycoprotein (LRG), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Geboes scores with clinical endoscopic activity using the Mayo endoscopic subscore (MES). Results: Mucosal healing was achieved in 39 (57%) patients. Univariate analysis revealed that the factors associated with mucosal healing were LRG (P = 0.0024), CRP (P = 0.1078), ESR (P = 0.0372), and Geboes scores (P = 0.0075). Logistic regression analysis identified LRG and Geboes scores as independent factors associated with mucosal healing assessed using MES (P = 0.0431 for LRG and P = 0.0166 for Geboes scores). Conclusion: LRG was found to be the easiest marker to monitor disease activity and mucosal inflammation in UC patients with biotherapy-naïve cases, with a performance equivalent to that of Geboes scores.
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Advantages of lymphadenectomy for early stage endometrial cancer remain controversial. Lymphadenectomy had been routinely omitted for patients aged ≥ 70 years at our institute if lymph node metastasis was unsuspected due to an increased risk of peri- and postsurgical complications. Since 2013, with the introduction of minimally invasive surgery and considering the heterogeneous medical conditions, we started performing lymphadenectomy in patients who were considered well-tolerated. We retrospectively investigated our clinical database to assess the effect of lymphadenectomy in older patients with early stage endometrial carcinoma. Patients aged ≥ 70 years, preoperatively diagnosed with stage I endometrial carcinoma, and who underwent lymphadenectomy between 2013 and 2021 at Tohoku University Hospital were included in the lymphadenectomy group (n = 33), whereas patients who underwent surgery without lymphadenectomy before the end of 2012 were included in the no-lymphadenectomy group (n = 49). Clinical parameters and patient outcomes, such as disease-free survival (DFS) and disease-specific survival (DSS), were compared. The median age was significantly higher and fewer patients received adjuvant chemotherapy in the no-lymphadenectomy group. Neither DSS nor DFS differed significantly between the two groups. Five-year-DFS rates were 77.2% and 82.5% and 5-year-DSS rates were 89.7% and 97.8% for the lymphadenectomy and no-lymphadenectomy groups, respectively. No significant differences were observed in the subsequent survival analysis by substage, histological subtype, or risk of recurrence. Our results suggest that the indications for lymphadenectomy in older patients should be individually optimized according to the risk of recurrence and postoperative complications.
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OBJECTIVE: This multicenter study aimed to evaluate the accuracy of the one-step nucleic acid amplification (OSNA) assay in diagnosing lymph node metastasis (LNM) in patients with cervical and endometrial cancers. METHODS: Surgically removed LNs from patients with cervical and endometrial cancer were sectioned at 2-mm intervals along the short axis direction and alternately examined using the OSNA assay and conventional histopathological examination. Ultrastaging (200-µm LN sections) was performed for metastatic LNs using hematoxylin and eosin staining and immunostaining with an anti-CK19 antibody in cases where the OSNA assay and histopathological examination (performed using 2-mm LN sections) results showed discordance. RESULTS: A total of 437 LNs from 133 patients were included; 61 patients (14%) showed metastasis by histopathological examination, with a concordance rate of 0.979 (95% confidence interval [CI]: 0.961-0.991) with the OSNA assay. The sensitivity and specificity of the OSNA assay were 0.918 (95% CI: 0.819-0.973) and 0.989 (95% CI: 0.973-0.997), respectively. Discordance between the two methods was observed in nine LNs (2.1%), and allocation bias of metastatic foci was identified as the major cause of discordance. CONCLUSIONS: The OSNA assay showed equally accurate detection of LN metastasis as the histopathological examination. We suggest that the OSNA assay may be a useful tool for the rapid intraoperative diagnosis of LN metastasis in patients with cervical and endometrial cancers.
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Neoplasias de la Mama , Neoplasias Endometriales , Ácidos Nucleicos , Humanos , Femenino , Metástasis Linfática/patología , Estudios Prospectivos , Técnicas de Amplificación de Ácido Nucleico/métodos , Neoplasias Endometriales/patología , Ganglios Linfáticos/patología , Biopsia del Ganglio Linfático Centinela , Queratina-19/genética , Neoplasias de la Mama/patologíaRESUMEN
Background: The standard therapy for acute severe ulcerative colitis (ASUC) is intravenous corticosteroids; however, 30% of ulcerative colitis (UC) patients do not recover with corticosteroids alone. Few studies have reported the efficacy and safety of tofacitinib for ASUC with steroid resistance. We report a case series of successful first-line treatment consisting of tofacitinib (20 mg/day) administered to ASUC patients with steroid resistance. Methods: Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered a high dose of tofacitinib (20 mg) after showing no response to steroid therapy in a dose of 1-1.5 mg/kg/day. Results: Eight patients with ASUC, 4 (50%) men, median age 47.1 (range 19-65) years, were included. Four patients were newly diagnosed, and the median UC duration was 4 (range 0-20) years. Six of the 8 patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. Only one patient (patient 4) experienced an adverse event, local herpes zoster, treated with acyclovir without tofacitinib discontinuation. Conclusions: Clinical remission without serious adverse events can be achieved with high probability and colectomy can be avoided by first administering high-dose tofacitinib to steroid-resistant ASUC patients. Tofacitinib may be one of the first-line treatment options for steroid-resistant ASUC.
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Poly(ADP-ribose) polymerase (PARP) inhibitors theoretically promote synthetic lethality in cancer cells with homologous recombination deficiency (HRD). However, clinical evidence indicates that PARP inhibitors are also effective for treating HRD-negative ovarian cancer. The PARP inhibitor olaparib became available in Japan as a maintenance therapy for platinum-sensitive recurrent ovarian cancer regardless of homologous recombination status in April 2018. The purpose of this study was to identify potential clinical biomarkers for olaparib sensitivity in patients with recurrent ovarian cancer. Clinical information about the patients with recurrent ovarian cancer treated with olaparib maintenance therapy (OMT) was retrospectively collected. OMT duration was used as an indicator for olaparib sensitivity. The relationship between OMT duration and clinical parameters was statistically analyzed. We found a positive correlation between OMT duration and progression-free survival (PFS) or treatment free interval (TFI). In some cases, OMT duration exceeded PFS before olaparib introduction. We also found that more than half of the patients with measurable target lesions at the time of OMT introduction showed partial or complete response to OMT. These results validated the effectiveness of OMT and identified PFS and TFI as potential clinical markers for olaparib sensitivity in the patients with recurrent ovarian cancer.
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Recurrencia Local de Neoplasia , Neoplasias Ováricas , Biomarcadores , Carcinoma Epitelial de Ovario/tratamiento farmacológico , Femenino , Humanos , Recurrencia Local de Neoplasia/tratamiento farmacológico , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/patología , Ftalazinas , Piperazinas , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Estudios RetrospectivosRESUMEN
BACKGROUND: Adjuvant therapy is usually considered for surgically treated patients with uterine cervical cancer harboring intermediate risk (IR) factors such as large tumor diameter, stromal invasion to the outer half, and lymphovascular space invasion (LVSI). However, the indications and types of adjuvant therapy for the IR group remain controversial. This study aimed to analyze the differences in patient outcomes in the IR group to provide novel insights for tailoring adjuvant therapy. METHODS: Data from 6192 patients with cervical cancer who underwent radical hysterectomy at 116 institutions belonging to the Japanese Gynecologic Oncology Group were reviewed. RESULTS: In total, 1688 patients were classified into the IR group, of whom 37.3% did not receive adjuvant therapy. Conversely, approximately equal proportions of the remaining patients received adjuvant radiotherapy, concurrent chemoradiotherapy, and chemotherapy. Patients with all three risk factors showed worse overall survival than those with one or two risk factors. In addition to LVSI, non-squamous cell carcinoma histology, and vaginal invasion were identified as independent risk factors for both recurrence and mortality in multivariate analyses. Tumor diameter greater than 40 mm and surgical center volume were identified as independent risk factors for recurrence. Stromal invasion to the outer half and ovarian metastasis were identified as independent risk factors for mortality. CONCLUSIONS: This study revealed the significant differences in prognosis in the IR group. The indications for adjuvant therapy should be further studied, focusing on conventional risk factors and other pathological findings.
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Histerectomía , Neoplasias del Cuello Uterino , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Femenino , Humanos , Japón , Radioterapia Adyuvante , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía , Neoplasias del Cuello Uterino/terapiaRESUMEN
MicroRNA-152 (miR-152) expression has been reported to be associated with poor prognosis in patients with endometrial serous carcinoma (ESC). However, the function of miR-152 in ESCs is not fully understood. The present study aimed to investigate the involvement of miR-152 in ESC progression. The influence of miR-152 overexpression on cell proliferation and motility was assessed by transfecting two human ESC cell lines, USPC-1 and SPAC-1-L, with a miR-152 precursor. MiR-152 overexpression increased apoptosis and inhibited the proliferation of the two ESC cell lines. Cell motility was also suppressed in both cell lines following precursor transfection. Conversely, miR-152 inhibitor transfection led to an increase in cell migration ability, suggesting the involvement of miR-152 in ESC cell motility. Results of the analysis of publicly available messenger RNA dataset indicated that high expression of matrix metalloproteinase 10 (MMP10), one of the predicted targets of miR-152 by microRNA target prediction database, was a poor prognostic factor for ESC. In vitro examination results revealed that miR-152 overexpression reduced MMP10 expression, and knockdown of MMP10 significantly reduced cell motility. This study elucidates the function of miR-152 as a tumor suppressor in ESCs. We demonstrated that miR-152 plays an important role in ESC cell motility by regulating MMP10 expression.
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Cistadenocarcinoma Seroso , Metaloproteinasa 10 de la Matriz , MicroARNs , Línea Celular Tumoral , Movimiento Celular , Cistadenocarcinoma Seroso/genética , Neoplasias Endometriales/genética , Femenino , Humanos , Metaloproteinasa 10 de la Matriz/genética , MicroARNs/genéticaRESUMEN
OBJECTIVE: The mainstay of treatment for uterine endometrial cancer is surgery, and recurrent-risk cases require multidisciplinary treatment, including surgery, chemotherapy and radiation therapy. METHODS: The standard surgery for uterine endometrial cancer is hysterectomy and bilateral salpingooophorectomy, with additional retroperitoneal lymph node dissection and omentectomy, depending on the case. The appropriate treatment is determined based on the risk classification, such as the depth of invasion into the myometrium, diagnosis of histological type and grade, and risk assessment of lymph node metastasis. RESULTS: Recently, minimally invasive surgery has been widely used not only in low-risk patients but also in intermediate- and high-risk patients. In low-risk patients, the possibility of ovarian preservation is discussed from a healthcare perspective for young women. Determining the need for retroperitoneal lymph node dissection based on sentinel lymph node evaluation may contribute in minimizing the incidence of post-operative lymphedema while ensuring accurate diagnosis of lymph node metastasis. Recently, many studies using sentinel lymph nodes have been reported for patients with uterine endometrial cancer, and the feasibility of sentinel lymph node mapping surgery has been proven. Unfortunately, sentinel lymph node biopsy and sentinel lymph node mapping surgery have not been widely adopted in surgery for uterine cancer in Japan. In addition, the search for biomarkers, such as RNA sequencing using The Cancer Genome Atlas, metabolic profile and lipidomic profile for early detection and prognostic evaluation, has been actively pursued. CONCLUSIONS: Gynecologic oncologists expect to be able to provide uterine endometrial cancer patients with appropriate treatment that preserves their quality of life without compromising oncologic outcomes in the near future.
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Neoplasias Endometriales , Calidad de Vida , Neoplasias Endometriales/patología , Neoplasias Endometriales/cirugía , Femenino , Humanos , Japón , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Metástasis Linfática/patología , Biopsia del Ganglio Linfático CentinelaRESUMEN
BACKGROUND: Treatment strategies based on histological subtypes are unestablished. AIMS: Rethinking the significance of surgery for uterine cervical cancer. METHODS: Using the database of cervical cancer stages IB-IIB with extensive hysterectomy (Federation of Gynecology and Obstetrics [FIGO] 2008) established by the Japanese Gynecologic Oncology Group network, we conducted a clinicopathological study of cervical cancer cases reclassified according to the FIGO 2018 staging. In stage IB (FIGO 2018) cervical cancer patients, there was no significant difference in treatment outcome according to histological type, but in stages IIA, IIB, and IIIC1 (FIGO 2018), the treatment outcome of nonsquamous cell carcinoma was significantly worse than that of squamous cell carcinoma. Considering post-treatment health care, it is important to consider ovarian preservation in young patients with cervical cancer, up to stage IIA (FIGO 2018) for squamous cell carcinoma and stage IB1 (FIGO 2018) for nonsquamous cell carcinoma, after careful evaluation of clinicopathological factors before surgery. DISCUSSION: Locally advanced adenocarcinoma of the cervix is a rare and refractory cancer that has been shown to have low radiosensitivity, and its treatment outcome is still unsatisfactory. A new therapeutic strategy involving multidisciplinary treatment in combination with perioperative chemotherapy at a facility that can provide highly curative surgical treatment is desired. CONCLUSION: Minimally invasive surgery is being introduced for the treatment of early-stage cervical cancer. However, the number of eligible cases should be expanded in a phased manner, based on an objective evaluation of surgical outcomes at the facilities. Omics analysis may be useful to develop a new treatment for human papillomavirus nonrelated cervical cancer, represented by gastric mucinous carcinoma.
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Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias del Cuello Uterino , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/cirugía , Femenino , Humanos , Histerectomía , Estadificación de Neoplasias , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
A 50s woman with a stomachache was referred to our hospital with diagnosed gastric cancer. Upper endoscopy showed a type 3 tumor in the lower gastric body, and CT demonstrated a pelvic tumor 10 cm in size. Laparoscopic surgery was performed; since the pelvic tumor was found to derive from the left ovary, left oophorectomy and total gastrectomy were performed. Pathological examination revealed that the ovarian tumor was a gastric cancer metastasis. Adjuvant chemotherapy with S-1 monotherapy was introduced. Four months after the operation, metastasis was suspected due to right ovary tumor edema. Due to the possibility of obtaining R0 resection and adverse events of chemotherapy, we chose right oophorectomy. Pathological examination demonstrated signet-ring cell cancer. Fourteen months after the first operation, the patient is alive with no recurrence or metastasis.
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Carcinoma de Células en Anillo de Sello , Tumor de Krukenberg , Neoplasias Ováricas , Neoplasias Pélvicas , Neoplasias Gástricas , Femenino , Humanos , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Neoplasias Pélvicas/cirugía , Tumor de Krukenberg/tratamiento farmacológico , Tumor de Krukenberg/cirugía , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/cirugía , Carcinoma de Células en Anillo de Sello/cirugía , Gastrectomía/efectos adversosRESUMEN
Immune checkpoint inhibitors (ICIs) are widely used to treat various malignancies. Although the gut microbiome is known to influence the efficacy of ICIs on epithelial tumors, the functional interactions between gut taxa and colonic mucosa remain poorly understood. Here we performed transcriptomic profiling and 16S rRNA sequencing to investigate the relationships between mucosal gene expression and microbial composition with ICI responses and gastrointestinal immune-related adverse events (GI irAEs). In responders, genes related to DNA repair and cell cycle signatures were enriched in responders whereas signatures related to innate immune response, NFAT and IFN-γ signaling pathways were enriched in nonresponders. Gut microbial composition revealed an association between moderate GI irAE and favorable response to ICI therapy. Favorable therapeutic responses to ICI and GI irAE treatments were associated with taxa classified as Enterobacteriaceae and were related to ribonucleoprotein complex biogenesis, cytokine-mediated signaling pathway, tRNA metabolic process, and ribonucleoprotein complex assembly in the colon. These findings open new perspectives for improving the efficacy and safety of cancer immunotherapy.
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Colitis , Microbioma Gastrointestinal , Colitis/inducido químicamente , Colitis/genética , Colitis/terapia , Microbioma Gastrointestinal/genética , Humanos , Inmunoterapia/efectos adversos , ARN Ribosómico 16S/genética , Transcriptoma/genética , Resultado del TratamientoRESUMEN
The impact of histologic subtype on definitive radiotherapy for patients with locally advanced cervical cancer remains unclear. The aim of this retrospective analysis was to assess clinicopathological findings and clinical outcome by histological type in patients with stage IIB-IVA cervical cancer. Ninety-two patients with stage IIB-IVA [International Federation of Gynecology and Obstetrics (FIGO) 2008] cervical cancer, who underwent definitive radiotherapy between 2013 to 2018, were identified as eligible for this study. The clinical information of the eligible patients was obtained from medical records of our hospital. Seventy-eight patients underwent concurrent chemoradiotherapy, and the remaining 14 patients received radiotherapy alone. Of 92 patients, 83 had squamous cell carcinoma (SCC) and 9 had non-SCC histology. Progression-free survival (PFS) rate of patients with non-SCC was significantly worse than of those with SCC (2-year PFS: 62.0% vs. 12.5%, p = 0.0020), but overall survival (OS) rate did not statistically differ between the two subtypes (2-year OS: 82.4% vs. 62.5%, p = 0.2157). Pelvic failure-free (PFF) rate of patients with non-SCC histology was significantly worse than of those with non-SCC (2-year PFF; 88.2% vs. 25.0%, p < 0.0001). In univariate analysis, non-SCC histology was associated with PFS rate, although there was no association with OS rate. In multivariate analysis, non-SCC histology and lymph node metastasis were independent prognostic factors for shorter PFS. In patients with stage IIB-IVA cervical cancer who underwent definitive radiotherapy, patients with non-SCC showed significantly worse PFS rate than those with SCC.
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Adenocarcinoma , Neoplasias del Cuello Uterino , Adenocarcinoma/patología , Quimioradioterapia , Supervivencia sin Enfermedad , Femenino , Humanos , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patologíaRESUMEN
Immune checkpoint inhibitors (ICIs) have become the standard of care for several cancers. However, ICI therapy has also been associated with various immune-related adverse events (irAEs). Clinical manifestations of immune-related colitis resemble those of inflammatory bowel diseases such as ulcerative colitis (UC). The composition of the bowel microflora is thought to influence the development of inflammatory bowel disease and irAE colitis. We profiled the gene expressions and microbe compositions of colonic mucosa from patients with solid cancers receiving anti-PD-L1 antibody treatment; we then compared the expression profiles associated with irAE colitis with those associated with UC. The pathway enrichment analysis revealed functional similarities between inflamed regions of irAE colitis and UC. The common enriched pathways included leukocyte extravasation and immune responses, whereas non-inflamed mucosa from patients with irAE colitis was distinct from patients with UC and was characterized by the recruitment of immune cells. A similarity between the microbiota profiles was also identified. A decreased abundance of Bacteroides species was observed in inflamed regions from both irAE colitis and UC based on a microbiota composition analysis of 16S rDNA sequencing. Pathways associated with molecule transport systems, including fatty acids, were enriched in inflamed and non-inflamed irAE colitis and inflamed UC, similar to Piphillin-inferred KEGG pathways. While UC is characterized by local regions of inflammation, ICI treatment extends to non-inflammatory regions of the colonial mucosa where immune cells are reconstituted. This analysis of the similarity and heterogeneity of irAE colitis and UC provides important information for the management of irAE colitis.
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Although the addition of bevacizumab to platinum-based combination chemotherapy has been recommended as a standard regimen for patients with advanced or recurrent cervical cancer, there is no clear evidence regarding the effectiveness of bevacizumab monotherapy as salvage chemotherapy. This study prospectively examined the efficacy and safety of switching from platinum-based chemotherapy combined with bevacizumab to single maintenance therapy in patients with advanced or recurrent cervical cancer. Patients were first treated with standard combination chemotherapy. However, if chemotherapy was discontinued because of an adverse event, bevacizumab monotherapy was continued for patients who agreed to participate in this study and provided written informed consent. The study protocol was approved by the Independent Review Board of Tohoku University School of Medicine (reception number 2017-1-540). A total of 15 patients (median age of 55 years, range 33-69 years) participated in this study. The median number of cycles of bevacizumab single maintenance administration was 8, and the main reasons for discontinuation were disease progression and adverse events. Bevacizumab single maintenance therapy had a disease control rate of 53.3% (CR 40%, PR 6.7%, SD 6.7%). The most frequent grade 3/4 clinical adverse events were proteinuria (5/15) and hypertension (4/15). No treatment-related deaths occurred. Bevacizumab single maintenance therapy was effective as salvage chemotherapy in patients with advanced or recurrent cervical cancer, and the safety profile was generally consistent with those reported in previous studies of bevacizumab monotherapy.
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Neoplasias del Cuello Uterino , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bevacizumab/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Proyectos Piloto , Platino (Metal)/uso terapéutico , Estudios Prospectivos , Neoplasias del Cuello Uterino/tratamiento farmacológicoRESUMEN
BACKGROUND: Preparation for colon capsule endoscopy (CCE) requires a large liquid laxative volume for capsule excretion, which compromises the procedure's tolerability. AIM: To assess the safety and utility of castor oil-boosted bowel preparation. METHODS: This prospective cohort study including 20 patients (age range, 16-80 years; six men and 14 women) suspected of having colorectal disease was conducted at Kindai University Hospital from September 2017 to August 2019. All patients underwent CCE because of the following inclusion criteria: previous incomplete colonoscopy in other facility (n = 20), history of abdominal surgery (n = 7), or organ abnormalities such as multiple diverticulum (n = 4) and adhesion after surgery (n = 6). The exclusion criteria were as follows: Dysphagia, history of allergic reactions to the drugs used in this study (magnesium citrate, polyethylene glycol, metoclopramide, and castor oil), possibility of pregnancy, possibility of bowel obstruction or stenosis based on symptoms, or scheduled magnetic resonance imaging within 2 wk after CCE. The primary outcome was the capsule excretion rate within the battery life, as evaluated by the total large bowel observation rate, large bowel transit time, and bowel creasing level using a five-grade scale in different colorectal segments. The secondary outcomes were complications, colorectal lesion detection rates, and patients' tolerability. RESULTS: The castor oil-based regimen was implemented in 17 patients. Three patients cancelled CCE because they could tolerate castor oil, but not liquid laxatives. The capsule excretion rate within the battery life was 88% (15/17). The mean large bowel transit time was 236 min. Approximately 70% of patients had satisfactory colon cleansing levels. CCE detected colon polyps (14/17, 82%) and colonic diverticulum (4/12, 33%). The sensitivity, specificity, and diagnostic accuracy rates for detecting colorectal polyps (size ≥ 6 mm) were 76.9%, 75.0%, and 76.4%, respectively. The sensitivity, specificity, and diagnostic accuracy rates for detection of diverticulum were 100% each. Twelve patients (71%) rated CCE as more than "good", confirming the new regimen's tolerability. No serious adverse events occurred during this study. CONCLUSION: The castor oil-based regimen could reduce bowel preparation dose and improve CCE tolerability.
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This study investigated the usefulness of conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) in distinguishing metastasis of pelvic sentinel lymph nodes (SLNs) in patients with gynecological cancer. We examined 74 SLNs of patients with endometrial cancer (nâ¯=â¯26) and cervical cancer (nâ¯=â¯11). Patients underwent US and CEUS followed by SLN biopsy; US and CEUS results were evaluated visually and quantitatively and compared between pathological metastasis-negative and -positive groups. To support CEUS results, the microvessel density of SLNs was evaluated immunohistochemically. Seventeen positive and 40 negative SLNs were evaluable. Margin and enhancement patterns by visual assessment revealed significant differences (pâ¯=â¯0.046 and 0.022, respectively). In quantitative time-intensity curve analyses, the weakest peak intensities (PImin), PI ratio and PI difference indicated significant differences (pâ¯=â¯0.045, p < 0.001 and p < 0.001, respectively). The areas under the receiver operating characteristic curves (AUCs) were 0.64, 0.82 and 0.83, respectively. The most effective PI ratio from the AUC was 1.3 (sensitivityâ¯=â¯82%, specificityâ¯=â¯70%), and the PI difference from the AUC was 20 (sensitivityâ¯=â¯88%, specificityâ¯=â¯70%). Microvessel density was significantly lower in metastatic lesions than in other areas. The quantitative analysis of CEUS seemed to be a reasonable method for distinguishing lymph node metastasis in patients with gynecological cancer.