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BACKGROUND The spring-and-loop with clip (S-O clip) consists of a spring and a nylon loop located on one side of the claws of the clip, and is used in gastric endoscopic submucosal dissection (ESD) to allow countertraction. This retrospective study included 290 patients with early gastric neoplasms (eGNs) and aimed to compare postoperative outcomes of ESD with and without the use of the S-O clip. MATERIAL AND METHODS We retrospectively reviewed the data of 347 patients with eGN who underwent ESD, with or without an S-O clip, at our institution between April 1, 2017 and March 31, 2023. Overall, 290 patients were analyzed after excluding ineligible participants. The control group (n=149; adenoma: 1, carcinoma: 148) underwent ESD without an S-O clip between April 2017 and March 2020, while the S-O group (n=141; adenoma: 4, carcinoma: 137) used the clip between April 2020 and March 2023. Primary outcomes included procedure time, en bloc resection rate, and complete resection rate. Subgroup analysis for examined procedure time concerning endoscopist expertise, submucosal fibrosis, and neoplasm locations. RESULTS The S-O group had a shorter procedure time (44.4±23.9 vs 61.1±40.9 min, P<0.001) and a higher complete resection rate (97.9% vs 92.6%, P<0.05) than the control group. Subgroup analysis revealed that the S-O clip significantly reduced procedure time for trainees compared to the control group (40.8±18.3 vs 61.1±35.6 min, P<0.05). CONCLUSIONS The scheduled use of S-O clips in gastric ESD is effective in improving procedural time and complete resection rates, benefiting endoscopists across all experience levels.
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Resección Endoscópica de la Mucosa , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/patología , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Resección Endoscópica de la Mucosa/métodos , Resección Endoscópica de la Mucosa/instrumentación , Anciano , Resultado del Tratamiento , Instrumentos Quirúrgicos , Gastroscopía/métodos , Gastroscopía/instrumentación , Adenoma/cirugía , Adenoma/patología , Tempo Operativo , Adulto , Periodo Posoperatorio , Tracción/métodos , Tracción/instrumentaciónRESUMEN
BACKGROUND: Self-medication using over-the-counter (OTC) medicines is one of the effective self-care measures in dealing with daily health problems. Health literacy (HL) is critical to ensuring the appropriate use of OTC medicines. The purpose of this study was to evaluate the association between HL and comprehension of medication package inserts among adults who use OTC medicines. METHODS: We conducted a cross-sectional study using a self-administered questionnaire and interviews at 14 drugstores in the Kanto region in Japan from January to February 2020. The study participants were adults aged 20 years or older who purchased OTC medicines. HL was measured using the 14-item HL scale for Japanese adults (Japanese version of HLS-14), and comprehension of medication package inserts was evaluated using an interview survey (label comprehension study [LCS] form). The association between HL and LCS correct response rate and that between HL and attitude toward reporting adverse drug events (ADEs) were assessed using multiple linear regression and logistic regression analyses, respectively. RESULTS: The analysis included the data of 140 adults, 50 men (35.7%) and 90 women (64.3%), with an average age of 55.2 years. The average HLS-14 score was 51.6, and the overall correct answer rate for reading comprehension was 57.5%. Multiple linear regression analysis revealed that a higher HLS-14 score was associated a higher LCS correct response rate (ß = 1.01, p = 0.001). In addition, logistic regression analysis revealed that higher HL was associated with positive attitude towards reporting ADEs to health professionals (adjusted odds ratio = 1.06, p = 0.031). CONCLUSIONS: Adults with higher HL had higher comprehension of OTC package inserts, and higher HL was associated with positive attitude toward reporting ADEs to healthcare professionals. These results indicate that optimal self-medication with OTC medicines requires improving HL among the general public through health education and effective health information provision from pharmacists and registered sales clerks at drug stores.
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Patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), a mitochondrial disease, develop various types of organ failure, including intestinal pseudo-obstruction (IPO). We treated a patient with IPO that improved with total parenteral nutrition. A 20-year-old woman with a two-year history of diabetes mellitus was taking sitagliptin but her hemoglobin A1c (HbA1c) levels began increasing. After receiving metformin, she suffered a stroke-like attack and was diagnosed with MELAS. After persistent anorexia, she presented with symptoms of IPO, such as vomiting and gastrointestinal dilatation. After about 10 days of total parenteral nutrition, intestinal peristalsis improved and bowel movements resumed. She was able to resume her normal diet, and glycemic control with insulin glargine has allowed her to return to her daily life without gastrointestinal symptoms for over six months. Total parenteral nutrition may be effective for MELAS with IPO, and good glycemic control can prevent the need for incretin-related drugs, thus reducing the likelihood of recurrent IPO.
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Potassium-sensing oligonucleotide, PSO, a conjugate of a quadruplex structure-forming oligonucleotide with a peptide incorporating a Förster Resonance Energy Transfer (FRET) chromophore pair, has been developed for fluorescent detection of potassium ion (K+) in aqueous medium. PSO 1 could be introduced into cells for real-time imaging of cytoplasmic K+ concentrations. To perform fluorescent imaging of K+ on the cell surface, we synthesized twelve PSO derivatives with different types of peptide types and lengths, and oligonucleotide sequences including thrombin-binding aptamer (TBA) sequences with FAM and TAMRA as a FRET chromophore pair, and evaluated their performance. 1 was shown to respond selectively to K+, not to most ions present in vivo, and to show reciprocal fluorescence changes in response to K+ concentration. For the peptide chains and oligonucleotide sequences examined in this study, the PSO derivatives had K d values for K+ in the range of 5-30 mM. All PSO derivatives showed high K+ selectivity even in the presence of excess Na+. The PSO derivatives were successfully localized to the cell surface by biotinylated concanavalin A (ConA) or sulfo-NHS-biotin via streptavidin (StAv). Fluorescence imaging of extracellular K+ upon addition of apoptosis inducers was successfully achieved by 1 localized to the cell surface.
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CO2 insufflation has proven effective in reducing patients' pain after colonoscopies but has not been examined in esophagogastroduodenoscopies. Therefore, we examined the effect of CO2 insufflation in examinees who underwent transnasal endoscopies without sedation. This study is a single-center, prospective, double-blind, case-control trial conducted between March 2017 and August 2018. Subjects were assigned weekly to receive insufflation with either CO2 or air. The primary outcome was improvement of abdominal pain and distension at 2 h and 1-day postprocedure. In total, 336 and 338 examinees were assigned to the CO2 and air groups, respectively. Visual analog scale (VAS) scores for abdominal distension (15.4 vs. 25.5; p < 0.001) and distress from flatus (16.0 vs. 28.8; p < 0.001) at 2 h postprocedure were significantly reduced in the CO2 group. VAS scores for pain during the procedure (33.5 vs. 37.1; p = 0.059) and abdominal pain after the procedure (3.9 vs. 5.7; p = 0.052) also tended to be lower at 2 h postprocedure, but all parameters showed no significant difference at 1-day postprocedure. All procedures were safely completed through the planned program, and no apparent adverse events requiring treatment or follow-up occurred. In conclusion, CO2 insufflation may reduce postprocedural abdominal discomfort from transnasal esophagogastroduodenoscopies. (UMIN000028543).
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OBJECTIVES: Endoscopic mucosal resection (EMR) is the gold standard for the treatment of noninvasive large colorectal lesions, despite challenges associated with nonlifting lesions and a high rate of local recurrence. Endoscopic submucosal dissection (ESD) offers the possibility of overcoming these EMR limitations. However, a higher risk of complications and longer procedure time prevented its dissemination. As ESD now provides more stable results because of standardized techniques compared with those used earlier, this study aimed to quantify the rates of en bloc and curative resections, as well as ESD complications, in the present situation. METHODS: A multicenter, large-scale, prospective cohort trial of ESD was conducted at 20 institutions in Japan. Consecutive patients scheduled for ESD were enrolled from February 2013 to January 2015. RESULTS: ESD was performed for 1883 patients (1965 lesions). The mean procedure time was 80.6 min; en bloc and curative resections were achieved in 1759 (97.0%) and 1640 (90.4%) lesions, respectively, in epithelial lesions ≥20 mm. Intra- and postprocedural perforations occurred in 51 (2.6%) and 12 (0.6%) lesions, respectively, and emergency surgery for adverse events was performed in nine patients (0.5%). CONCLUSIONS: This trial conducted after the standardization of the ESD technique throughout Japan revealed a higher curability, shorter procedure time, and lower risk of complications than those reported previously. Considering that the target lesions of ESD are more advanced than those of EMR, ESD can be a first-line treatment for large colorectal lesions with acceptable risk and procedure time. (Clinical Trial Registration: UMIN000010136).
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Resección Endoscópica de la Mucosa/efectos adversos , Resección Endoscópica de la Mucosa/métodos , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Recurrencia Local de Neoplasia/cirugía , Estudios Prospectivos , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND AND AIMS: Colorectal neoplastic lesions (≥ 20 mm) are commonly treated via piecemeal endoscopic mucosal resection (p-EMR) but have a high rate of local recurrence. We aimed to clarify the optimal surveillance interval after p-EMR for these neoplasias. METHODS: In this multicenter (15 participating institutions) prospective, randomized trial, 180 patients recruited over a 4-year period and were classified based on tumor location, tumor diameter, histological diagnosis, institution, and number of resected specimens. The patients underwent curative p-EMR followed by scheduled surveillance colonoscopy at 3, 6, 12, and 24 months after p-EMR (group A; n = 90) or at 6, 12, and 24 months after p-EMR (group B; n = 90). The primary endpoint was cumulative local recurrence at 6 months after p-EMR. Secondary endpoints included local recurrence and the cumulative surgical resection rate of recurrent tumors during the 24-month follow-up period. RESULTS: The median tumor diameter was 25 mm (IQR 20-30). Six months after p-EMR, 12 and 6 local recurrences were noted in groups A and B, which corresponded to 13 and 8 recurrences, respectively, during the 24-month surveillance period. The primary and secondary endpoints of recurrence were not significantly different between the groups on either intention-to-treat or per-protocol analysis; no surgery case was observed in group B when a strict surveillance protocol of 6-, 12-, and 24-month follow-up post-EMR was followed. CONCLUSIONS: For patients who underwent p-EMR for neoplastic lesions, additional postprocedural 3-month surveillance did not show superior results in detecting recurrence compared with a 6-month surveillance interval. CLINICAL TRIAL REGISTRATION: UMIN000015740.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/métodos , Humanos , Mucosa Intestinal/patología , Mucosa Intestinal/cirugía , Recurrencia Local de Neoplasia/patología , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND Cold polypectomy (CP) and hot polypectomy (HP) are both accepted methods for polypectomy. In recent years, the use of CP has increased for reasons of safety. However, there have been few investigations of conditions at follow-up early after resection. This prospective study from a single center aimed to compare colonic mucosal healing at 1 week following HP vs CP of benign colonic polyps <10 mm in diameter. MATERIAL AND METHODS Six patients with a total of 52 lesions under 10 mm in size were randomized to either the HP group (n=25) or CP group (n=27) using information in opaque envelopes. One week after endoscopic treatment, the site of treatment was evaluated using colonoscopy. We assessed the mean tumor size, ulcer diameter, exposed blood vessels, residual lesion, and complications. RESULTS Mean tumor size did not differ between the 2 groups (CP vs HP: 5.41 mm vs 5.68 mm). The CP group had a smaller ulcer base diameter (2.70 mm vs 4.84 mm; P<0.05) and fewer exposed blood vessels than the HP group (3.7% vs 36.0%; P<0.05). One residual lesion was found in the CP group. No patients experienced delayed perforation or post-polypectomy bleeding. CONCLUSIONS Our study findings showed that at 1-week follow-up, cold polypectomy resulted in improved colonic mucosal healing, with a smaller ulcer diameter and fewer blood vessels, when compared with hot polypectomy.
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Pólipos del Colon/cirugía , Colonoscopía/métodos , Resección Endoscópica de la Mucosa/métodos , Membrana Mucosa/citología , Hemorragia Posoperatoria/prevención & control , Cicatrización de Heridas , Adulto , Anciano , Anciano de 80 o más Años , Pólipos del Colon/patología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/fisiología , Pronóstico , Estudios Prospectivos , Adulto JovenRESUMEN
Condyloma acuminatum, in the form of genital warts, usually results from an infection by human papillomavirus, one of the most common causes of sexually transmitted diseases. It develops after an incubation period of 3 weeks to 8 months after infection; flat lesions are significantly rare. Condyloma acuminatum is prevalent in the genitals, particularly in the anus of immunodeficient patients. This also occurs in women during menstrual period and pregnancy. Although a common treatment option for rectal and anal lesions, surgical resection is highly invasive and results in a high rate of recurrence. Recently, endoscopic submucosal dissection has been performed for anorectal lesions, but data on its long-term follow-up are not available. We report the case of an immunocompromised patient due to pregnancy who remained recurrence-free 27 months after en-bloc resection by endoscopic submucosal dissection, with adequate visualisation of the flat lesion's safety margin, combined with magnifying narrow-band imaging.
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Condiloma Acuminado , Resección Endoscópica de la Mucosa , Canal Anal , Condiloma Acuminado/cirugía , Femenino , Humanos , Imagen de Banda Estrecha , Recurrencia Local de Neoplasia , EmbarazoRESUMEN
BACKGROUND: Sessile serrated lesion (SSL) is a colorectal polyp that has malignant potential. However, the dysplastic components within an SSL can be difficult to diagnose with conventional endoscopy, because most SSLs with dysplasia/carcinoma have subtle mucosal features. Many studies have indicated that narrow-band imaging (NBI) observations of colorectal polyps are very useful, accurate predictors of histology. We aimed to verify the usefulness of the Japan NBI Expert Team (JNET) classification system for the diagnosis of SSLs with dysplasia/carcinoma. METHODS: We examined 709 endoscopically or surgically resected lesions that were pathologically diagnosed as SSL, including 647 with no dysplasia, 37 with low-grade dysplasia, 15 with high-grade dysplasia, and 10 with submucosal invasive carcinoma. We retrospectively evaluated their clinicopathologic characteristics and conventional endoscopic and magnifying NBI endoscopic findings using the JNET system. RESULTS: Cases in all groups were more frequently located in the proximal colon. Submucosal invasive carcinomas were significantly larger than no dysplasia and low-grade dysplasia lesions. Almost all studied lesions (96.3%) were covered with a mucus cap. Five hundred and eighty (81.8%) lesions exhibited dark spots inside the crypts, which are NBI findings' characteristic of SSL. As for the JNET classification of magnifying NBI endoscopic findings, all 709 lesions showed Type 1. Six hundred and eighteen (95.5%) SSLs with no dysplasia lesions exhibited Type 1 only, whereas 52 (83.9%) SSLs with dysplasia/carcinoma had a combination of Type 1 and Type 2A, 2B, or 3, corresponding to SSL and dysplasia/carcinoma, respectively. The JNET classification had high sensitivity (83.9%), specificity (95.5%), and overall diagnostic accuracy (94.5%) for diagnosing SSLs with dysplasia/carcinoma. CONCLUSIONS: Use of magnifying NBI endoscopy with the JNET classification might be useful for diagnosing SSLs with dysplasia/carcinoma. This increased awareness may also improve the recognition of SSLs with dysplasia/carcinoma.
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Carcinoma , Pólipos del Colon , Neoplasias Colorrectales , Pólipos del Colon/diagnóstico por imagen , Colonoscopía , Neoplasias Colorrectales/diagnóstico por imagen , Humanos , Japón , Imagen de Banda Estrecha , Estudios RetrospectivosRESUMEN
BACKGROUND: Tacrolimus (TAC) is used for the management of ulcerative colitis (UC). However, there are few reports on the effectiveness of its long-term administration. TAC is also known to cause renal toxicity. The aim of this study was to evaluate long-term effectiveness and monitor changes in renal function during prolonged TAC use in patients with UC. METHODS: Medical records of 50 UC patients treated with TAC were retrospectively reviewed. Clinical outcomes were assessed at 6, 12, 24, and 36 months after initiating TAC. We also monitored chronological changes in renal function. RESULTS: Thirty-nine patients were treated with TAC for more than 3 months. Relapse-free survival among these patients at 6, 12, 24, and 36 months was 82%, 69%, 41%, and 23%, respectively. On the other hand, renal function was reduced in 35.9% of patients. We found that irreversible renal dysfunction was more likely to occur in cases in which the estimated glomerular-filtration rate (eGFR) was reduced by more than 30%. CONCLUSION: This study demonstrated the potential use of TAC as an effective option in the long-term medical management of UC, although it tended to increase the risk of nephrotoxicity. There is a need for the careful monitoring of renal function during TAC administration.
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AIMS: Colorectal adenocarcinoma with enteroblastic differentiation (CAED) is a rare malignancy, and its clinicopathological characteristics have not yet been fully elucidated. This study aimed to elucidate the clinicopathological features of CAED through immunostaining of enteroblastic lineage markers alpha-fetoprotein (AFP), glypican-3 (GPC3), and spalt-like transcription factor 4 (SALL4). METHODS AND RESULTS: We identified five CAED cases (0.3%) from 1666 colorectal carcinomas, analysed the clinicopathological characteristics and performed immunostaining for AFP, GPC3 and SALL4. Three patients were male and two were female. All cases were located in the sigmoid colon or rectum. Histologically, all cases showed adenocarcinoma composed of cuboidal or columnar cells, with clear cytoplasm resembling the primitive gut; one case exhibited a partial hepatoid pattern. The depth of invasion was T2 and T3 in two and three cases, respectively. Lymphatic/venous invasion was found in all cases (100%), lymph node metastases in four of five cases (80%) and distant metastases in three of five cases (60%) (liver, two cases; lung, one case). Two patients died as a result of their disease during follow-up. Immunohistochemically, SALL4 and GPC3 were each positive in four of five cases, whereas one case with a hepatoid component was positive for AFP. All three CAED cases with distant metastases were GPC3-positive. CONCLUSIONS: CAED was frequently located in the sigmoid colon or rectum, showed aggressive behaviour, such as lymph node metastasis and distant metastasis, and had a dismal prognosis. In addition, CAED was immunoreactive to AFP, GPC3 or SALL4, indicating that these markers may be characteristic of CAED.
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Adenocarcinoma/patología , Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Glipicanos/metabolismo , Factores de Transcripción/metabolismo , alfa-Fetoproteínas/metabolismo , Adenocarcinoma/metabolismo , Anciano , Anciano de 80 o más Años , Diferenciación Celular , Colon Sigmoide/metabolismo , Colon Sigmoide/patología , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Inmunohistoquímica , Metástasis Linfática , Masculino , Persona de Mediana Edad , Pronóstico , Recto/metabolismo , Recto/patologíaRESUMEN
BACKGROUND: Cytapheresis is a non-pharmacologic treatment option in which depleting elevated/activated leucocytes is known to exacerbate and perpetuate ulcerative colitis (UC) by releasing inflammatory cytokines. Therefore, it is a relevant treatment for elderly patients who wish to avoid pharmacologicals. METHODS: The efficacy of Cytapheresis for remission induction in 72 patients who received Cytapheresis for active UC at our hospital was retrospectively evaluated. Patients included 11 elderly cases, patients on steroids, biologics, calcineurin inhibitor, and 13 with extra-intestinal complications. Lichtiger's UC clinical activity index ≤4 meant remission was assessed at the end of therapy and then 1 month later. The efficacy on extra-intestinal manifestations meant improvement of the main morbidity. RESULTS: At the end of Cytapheresis therapy, the remission rate in the elderly was 36.4%, and 54.2% in the non-elderly patients. One-month post Cytapheresis, the remission rate in the elderly had increased to 72.7% (p = 0.042), but to 58.3% in the non-elderly, suggesting a delayed response phenomenon in the elderly. The efficacy of Cytapheresis in 4 cases with loss of response to biologics was 75%, and 84.6% in the 13 patients with extra-intestinal complications, indicating a dramatic efficacy on dermatitis and arthralgia. CONCLUSIONS: Unlike pharmacologicals, the efficacy of Cytapheresis appears to be time dependent. Accordingly, in the elderly, we observed a delayed response, indicating that elderly patients may respond beyond the end of Cytapheresis therapy. Therefore, patients who do not show efficacy at the end of Cytapheresis therapy should be followed up for delayed response. Further, Cytapheresis is favored by patients for its good safety profile.
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Colitis Ulcerosa/inmunología , Colitis Ulcerosa/terapia , Citaféresis/métodos , Adolescente , Adulto , Cuidados Posteriores , Factores de Edad , Anciano , Productos Biológicos/uso terapéutico , Citocinas/inmunología , Femenino , Humanos , Inmunosupresores/uso terapéutico , Leucaféresis/métodos , Leucocitos/inmunología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND In recent years, a plethora of therapeutic agents for ulcerative colitis (UC), especially novel biologics (Bio), have become available. Although it is now possible to use biological drugs, there should be no need for frequently changing medications. To avoid first-pass metabolism in the liver, thus reducing systemic bioavailability, budesonide foam has been applied as a topical steroid. We therefore evaluated whether budesonide foam has therapeutic value in UC patients who responded inadequately to Bio or to tacrolimus. MATERIAL AND METHODS We enrolled 10 patients who were experiencing an inadequate response to Bio (n=7) or to tacrolimus (n=3) at Juntendo University. We used Lichtiger's index to assess UC activity and clinical response. RESULTS Of the study patients, 4 were receiving adalimumab, 3 golimumab, and 3 tacrolimus. The average Lichtiger's index before budesonide administration was 7.1 (range 13-3), which improved to 3.4 (range 7-0) after budesonide therapy (p=0.01). Notably, 4 of the 6 cases with a Lichtiger's index >4 before budesonide administration achieved improvement of ≥3 points or remission. CONCLUSIONS Although the number of patients was small, budesonide foam had significant efficacy when added to the treatment of patients having an inadequate response to Bio or to tacrolimus. These results suggest that in cases responding poorly to Bio, adding budesonide foam as combination therapy can achieve a clinical remission.
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Budesonida/uso terapéutico , Colitis Ulcerosa/tratamiento farmacológico , Adalimumab/uso terapéutico , Adulto , Anticuerpos Monoclonales/uso terapéutico , Terapia Biológica , Quimioterapia Combinada , Femenino , Glucocorticoides/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Inducción de Remisión , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Tacrolimus/uso terapéutico , Resultado del TratamientoRESUMEN
Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in BRAF-mutated colorectal carcinomas with not only high levels of microsatellite instability but also microsatellite stable. SSA/Ps with advanced histology, including cytological dysplasia or minimally invasive carcinomas, are important lesions because SSA/Ps are considered major contributors to "interval cancers" and these lesions can rapidly become dysplastic or invasive carcinomas. Clinicopathologically, SSA/Ps with dysplasia or invasive carcinoma were associated with advanced age, female sex, and proximal colon. Although SSA/Ps with submucosal invasive carcinoma were smaller and invaded less deeply into the submucosal layer than conventional tubular adenomas with submucosal invasive carcinoma, SSA/Ps with submucosal invasive carcinoma frequently had a mucinous component and exhibited a higher potential for lymphatic invasion and lymph node metastasis. In an SSA/P series, endoscopic characteristics, including (semi)pedunculated morphology, double elevation, central depression, and reddishness, may help accurately diagnose SSA/Ps with advanced histology. Removal of SSA/Ps with dysplasia or invasive carcinoma was recommended. Endoscopic treatment such as endoscopic mucosal resection or endoscopic submucosal dissection is useful for those lesions. However, surgical resection with lymph node dissection might be indicated when SSA/Ps with invasive carcinoma are endoscopically suspected, because these have the high risk of lymph node metastasis. Greater awareness may promote further research into improving the detection, recognition, and complete resection rates of SSA/Ps with dysplasia or invasive carcinoma and reduce the interval cancer rates.
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Pólipos Adenomatosos/cirugía , Carcinoma/cirugía , Colectomía , Pólipos del Colon/cirugía , Colonoscopía , Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa , Pólipos Adenomatosos/patología , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma/patología , Colectomía/efectos adversos , Pólipos del Colon/patología , Colonoscopía/efectos adversos , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Resección Endoscópica de la Mucosa/efectos adversos , Femenino , Humanos , Escisión del Ganglio Linfático , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Resultado del TratamientoRESUMEN
BACKGROUND: Colorectal sessile serrated adenoma/polyps (SSA/Ps) are considered early precursor lesions in the serrated neoplasia pathway. Recent studies have shown associations of SSA/Ps with lost MLH1 expression, a CpG island methylator phenotype, and BRAF mutations. However, the molecular biological features of SSA/Ps with early neoplastic progression have not yet been fully elucidated, owing to the rarity of cases of SSA/P with advanced histology such as cytologic dysplasia or invasive carcinoma. In this study, we aimed to elucidate the molecular biological features of SSA/Ps with dysplasia/carcinoma, representing relatively early stages of the serrated neoplasia pathway. METHODS: We performed immunostaining for ß-catenin, MLH1, and mucins (e.g., MUC2, MUC5AC, MUC6, and CD10); targeted next-generation sequencing; and microsatellite instability (MSI) testing in 8 SSA/P lesions comprised of 4 SSA/Ps with high-grade dysplasia and 4 SSA/Ps with submucosal carcinoma. RESULTS: Lost MLH1 expression was found in 5 cases. All lesions studied were positive for nuclear ß-catenin expression. Regarding phenotypic mucin expression, all lesions were positive for MUC2, but negative for CD10. MUC5AC and MUC6 positivity was observed in 7 cases. Genetically, the most frequently mutated gene was BRAF (7 cases), and other mutations were detected in FBXW7 (3 cases); TP53 (2 cases), and KIT, PTEN, SMAD4, and SMARCB1 (1 case each). Furthermore, 4 of 8 lesions were MSI-high and the remaining 4 lesions were microsatellite-stable (MSS). Interestingly, all 4 MSI-high lesions displayed MLH1 loss, 3 of which harbored a FBXW7 mutation, but not a TP53 mutation. However, 2 MSS lesions harbored a TP53 mutation, although none harbored a FBXW7 mutation. CONCLUSIONS: SSA/Ps with dysplasia/carcinoma frequently harbored BRAF mutations. Activation of the WNT/ß-catenin signaling pathway may facilitate the development of dysplasia in SSA/Ps and progression to carcinoma. Furthermore, our results suggested that these lesions might be associated with both MSI-high and MSS colorectal cancer, which might be distinguished by distinct molecular biological features such as lost MLH1 expression, FBXW7 mutations, and TP53 mutations.
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Adenocarcinoma , Pólipos Adenomatosos , Biomarcadores de Tumor , Pólipos del Colon , Neoplasias Colorrectales , Análisis Mutacional de ADN/métodos , Secuenciación de Nucleótidos de Alto Rendimiento , Inmunohistoquímica , Inestabilidad de Microsatélites , Mutación , Adenocarcinoma/química , Adenocarcinoma/genética , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Pólipos Adenomatosos/química , Pólipos Adenomatosos/genética , Pólipos Adenomatosos/patología , Pólipos Adenomatosos/cirugía , Anciano , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Pólipos del Colon/química , Pólipos del Colon/genética , Pólipos del Colon/patología , Pólipos del Colon/cirugía , Neoplasias Colorrectales/química , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Femenino , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Fenotipo , Valor Predictivo de las PruebasRESUMEN
BACKGROUND There are 3 methods of treating T1 colorectal cancer (T1 CRC), which include endoscopic resection, endoscopic resection followed by additional colorectal resection, and surgical resection. In this retrospective study, changes in the management of T1 CRC after introduction of endoscopic submucosal dissection (ESD) were investigated by comparison with the 10-year period before introduction of ESD. MATERIAL AND METHODS During a 20-year period from 1996 to 2015, 835 patients with T1 CRC were treated, including 331 patients before introduction of ESD (Group A) and 504 patients after introduction of ESD (Group B). Clinicopathological findings and treatment methods were compared between these 2 groups. RESULTS As the initial treatment, endoscopic treatment was performed in 185 patients (55.9%) in Group A and 288 (57.1%) in Group B. In Group B, ESD was performed in 161 patients (55.9%), accounting for more than half of the T1 CRC patients receiving endoscopic treatment. In Groups A and B, observation after endoscopic resection was selected for 54.2% and 67.3% of T1a patients, respectively (p=0.04). A similar trend was noted for T1b patients, and there was no significant difference of the treatment approach. Among all T1 CRC patients, the percentage undergoing observation after endoscopic resection was significantly higher in Group B than in Group A (34.3% vs. 26.9%, p=0.02), and the percentage of patients undergoing additional colorectal resection was significantly lower in Group B (22.8% vs. 29.0%, p=0.04). CONCLUSIONS After introduction of ESD, it was performed in more than half of all patients with T1 CRC undergoing endoscopic treatment. The percentage of patients undergoing observation following endoscopic resection of T1 CRC increased after introduction of ESD.
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Neoplasias Colorrectales/cirugía , Resección Endoscópica de la Mucosa/métodos , Adenocarcinoma/patología , Adenocarcinoma/cirugía , Anciano , Anciano de 80 o más Años , Colonoscopía/métodos , Neoplasias Colorrectales/patología , Femenino , Humanos , Mucosa Intestinal/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/cirugía , Estadificación de Neoplasias , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Sessile serrated adenoma/polyps (SSA/Ps) are early precursor lesions in the serrated neoplasia pathway, which results in colorectal carcinomas with BRAF mutations, methylation for DNA repair genes, a CpG island methylator phenotype, and high levels of microsatellite instability. Some of these lesions can rapidly become dysplastic or invasive carcinomas that exhibit high lymphatic invasion and lymph node metastasis potentials. Detecting serrated lesions, including SSA/Ps with and without dysplasia/carcinoma, is critical, but SSA/Ps can be difficult to detect, are inconsistently identified by endoscopists and pathologists, and are often incompletely resected. Therefore, SSA/Ps are considered to be major contributors to "interval cancers". If colonoscopists can identify the specific endoscopic characteristics of SSA/Ps, their detection and the effectiveness of colonoscopy may improve. Here, the endoscopic features of SSA/Ps with and without dysplasia/carcinoma, including the characteristics determined using magnifying endoscopy, are reviewed in the context of previous reports. Endoscopically, these subtle polyps are like hyperplastic polyps, because they are slightly elevated and pale. Unlike hyperplastic polyps, SSA/Ps are usually larger than 5 mm, frequently covered by a thin layer called the ''mucus cap'', and are more commonly located in the proximal colon. Magnifying narrow-band imaging findings, which include dark spots inside the crypts and varicose microvascular vessels, in addition to the type II-open pit patterns detected using magnifying chromoendoscopy, effectively differentiate SSA/Ps from hyperplastic polyps. The lesions' endoscopic characteristics, which include their (semi)pedunculated morphologies, double elevations, central depressions, and reddishness, and the use of magnifying endoscopy, might help to detect dysplasia/carcinoma within SSA/Ps. Greater awareness may promote further research into improving the detection, identification, and complete resection rates of SSA/Ps with and without dysplasia/carcinoma and reduce the interval cancer rates.
Asunto(s)
Adenoma/diagnóstico por imagen , Pólipos del Colon/diagnóstico por imagen , Colonoscopía/métodos , Neoplasias Colorrectales/diagnóstico por imagen , Lesiones Precancerosas/diagnóstico por imagen , Adenoma/genética , Adenoma/patología , Colon/diagnóstico por imagen , Colon/patología , Pólipos del Colon/genética , Pólipos del Colon/patología , Colonoscopía/instrumentación , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Hiperplasia/diagnóstico , Hiperplasia/patología , Mutación , Imagen de Banda Estrecha/métodos , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas B-raf/genéticaRESUMEN
Ulcerative colitis (UC) is 1 of the 2 major phenotypes of chronic inflammatory bowel disease (IBD), which afflicts millions of individuals throughout the world with debilitating symptoms that impair function and quality of life. Further, IBD often affects women during childbearing age. Indeed, UC activity frequently increases during pregnancy, and the medications used to induce remission may adversely affect the health of the mother and the unborn child. We report successful induction of a remission in a UC case who experienced a flare-up in the first trimester of pregnancy. Upon relapse, she was treated with steroids and adsorptive granulomonocytapheresis (GMA) with the Adacolumn plus tacrolimus. This combination therapy induced a stable remission that was maintained during her entire pregnancy. She gave birth to a healthy child at 36 weeks of pregnancy with no maternal or fetal complications. Our experience indicates that GMA, as a non-drug therapeutic intervention with a favorable safety profile, plus tacrolimus might be a relevant treatment option for patients with active IBD during pregnancy. A future study of a large cohort of pregnant patients should strengthen our findings.