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We report a case of intraductal papillary neoplasms of the bile duct (IPNB) that metachronously developed twice in the downstream bile duct after radical resection. The first lesion was located in the left intrahepatic bile duct, the second lesion in the perihilar bile duct, and the third lesion in the distal bile duct. All lesions were IPNBs with associated invasive carcinoma (pancreatobiliary type). The depth of invasion was to the Glisson's capsule in the first lesion, to the subserosa in the second lesion, and to the fibromuscular layer in the third lesion, without lympho-vascular/perineural invasion and lymph-node metastasis. These were resected radically and had no biliary intraepithelial neoplasia and hyperplasia in the surrounding mucosa. In immunohistochemical examination, each lesion showed a different pattern. Although the downstream occurrence suggests intrabiliary dissemination, the mechanism of these metachronous developments may be multicentric. A literature review revealed that most metachronous cholangiocarcinomas have a grossly papillary appearance and tend to arise downstream. Our findings suggest that IPNB may develop metachronously in the residual bile duct after radical surgery, which may assist in early detection.
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Neoplasias dos Ductos Biliares , Carcinoma in Situ , Colangiocarcinoma , Humanos , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Ductos Biliares Intra-Hepáticos/patologia , Colangiocarcinoma/cirurgia , Carcinoma in Situ/patologiaRESUMO
BACKGROUND & AIMS: To date, no regional evidence of long-term colorectal cancer (CRC) risk reduction after endoscopic premalignant lesion removal has been established. We aimed to analyze this over a long-term follow-up evaluation. METHODS: This was a prospective cohort study of participants from the Japan Polyp Study conducted at 11 Japanese institutions. Participants underwent scheduled follow-up colonoscopies after a 2-round baseline colonoscopy process. The primary outcome was CRC incidence after randomization. The observed/expected ratio of CRC was calculated using data from the population-based Osaka Cancer Registry. Secondary outcomes were the incidence and characteristics of advanced neoplasia (AN). RESULTS: A total of 1895 participants were analyzed. The mean number of follow-up colonoscopies and the median follow-up period were 2.8 years (range, 1-15 y) and 6.1 years (range, 0.8-11.9 y; 11,559.5 person-years), respectively. Overall, 4 patients (all males) developed CRCs during the study period. The observed/expected ratios for CRC in all participants, males, and females, were as follows: 0.14 (86% reduction), 0.18, and 0, respectively, and 77 ANs were detected in 71 patients (6.1 per 1000 person-years). Of the 77 ANs detected, 31 lesions (40.3%) were laterally spreading tumors, nongranular type. Nonpolypoid colorectal neoplasms (NP-CRNs), including flat (<10 mm), depressed, and laterally spreading, accounted for 59.7% of all detected ANs. Furthermore, 2 of the 4 CRCs corresponded to T1 NP-CRNs. CONCLUSIONS: Endoscopic removal of premalignant lesions, including NP-CRNs, effectively reduced CRC risk. More than half of metachronous ANs removed by surveillance colonoscopy were NP-CRNs. The Japan Polyp Study: University Hospital Medical Information Network Clinical Trial Registry: University Hospital Medical Information Network Clinical Trial Registry, C000000058; cohort study: UMIN000040731.
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Pólipos do Colo , Neoplasias Colorretais , Pólipos , Feminino , Humanos , Masculino , Estudos de Coortes , Colonoscopia , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Japão/epidemiologia , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
OBJECTIVES: Most of the pancreatic cyst protrusions detected by B-mode endoscopic ultrasound (BM-EUS) are nonneoplastic and are not enhanced by contrast-enhanced EUS (CE-EUS) using ultrasound contrast agent (USCA). This study aimed to identify useful findings for distinguishing between neoplastic and nonneoplastic pancreatic cyst protrusions on BM-EUS to facilitate efficient USCA use. MATERIALS AND METHODS: A total of 151 pancreatic cyst protrusions in 119 consecutive patients who underwent CE-EUS were analyzed. We focused on the echo level (hyperechoic/isoechoic/hypoechoic/anechoic), base type (sessile without a basal waist/sessile with a basal waist/pedunculated), surface type (smooth/irregular), and the presence/absence of a hyperechoic surface layer. Enhanced and unenhanced protrusions on CE-EUS were interpreted as neoplastic and nonneoplastic, respectively. RESULTS: Forty-five and 106 protrusions were enhanced and unenhanced, respectively, on CE-EUS performed using USCA. In univariable analysis of predictors of nonneoplastic protrusion on BM-EUS, the following factors were found to be significant: echo level (hypoechoic/anechoic), base type (sessile with a basal waist/pedunculated), a smooth surface, and a hyperechoic surface layer. Of these, only a hyperechoic surface layer remained significant in the multivariable analysis ( P < 0.0001; odds ratio, 40.74; 95% confidence interval, 7.07-387.49). CONCLUSIONS: Pancreatic cyst protrusions with a hyperechoic surface layer on BM-EUS are suggestive of nonneoplastic disease.
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Cisto Pancreático , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Endossonografia , Cisto Pancreático/diagnóstico por imagem , Ultrassonografia , Meios de ContrasteRESUMO
BACKGROUND AND AIM: Endoscopic resection of the ileocecal valve lesions (ICVL) and peri-appendiceal orifice lesions (PAOL), is challenging. This study aimed to evaluate the feasibility of endoscopic submucosal dissection (ESD) for ICVLs and PAOLs compared with other cecal lesions (OCEL). METHODS: This was a multicenter, retrospective cohort study conducted at a cancer center hospital and two community hospitals. Non-pedunculated cecal lesions that were intended to be treated by ESD followed by at least one surveillance colonoscopy were included. The main outcome was curative resection defined as en-bloc resection and R0 resection without risk factors of metastases. The secondary outcome was co lon preservation. RESULTS: A total of 206 patients with 206 cecal lesions, including 37 ICVL, 27 PAOL, and 142 OCEL, who were to be treated with ESD were included in this study. Curative resection rates were 75.7% for ICVL, 70.4% for PAOL, and 77.5% for OCEL (P = 0.67). In the multivariate analysis of predictors of curative resection, tumor size (<40 mm) (odds ratio [OR] 2.40; 95% confidence intervals [CI], 1.14-5.04; P = 0.02) and a negative non-lifting sign (OR 6.12; 95% CI, 2.55-14.60; P < 0.01) were significant. Colon preservation was achieved for 91.9% of the ICVL, 92.6% of the PAOL, and 90.8% of the OCEL (P = 0.947). CONCLUSIONS: Based on curative resection and colon preservation rates, ESD was found to be feasible for ICVL and PAOL. Large tumor size (≥ 40 mm) and positive non-lifting signs were significant factors for non-curative resection.
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Neoplasias do Ceco , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Valva Ileocecal , Neoplasias do Ceco/etiologia , Neoplasias do Ceco/patologia , Neoplasias do Ceco/cirurgia , Colonoscopia , Neoplasias Colorretais/etiologia , Ressecção Endoscópica de Mucosa/efeitos adversos , Estudos de Viabilidade , Humanos , Valva Ileocecal/patologia , Valva Ileocecal/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND STUDY AIMS: Data from Japanese series show that surface morphology of laterally spreading tumors (LST) in the colon identifies lesions with different incidence and pattern of submucosal invasion. Such data from western countries are scarce. We compared clinical and histological features of LST in a western country and an eastern country, with special interest on mucosal invasiveness of LST, and investigated the effect of clinical factors on invasiveness in both countries. PATIENTS AND METHODS: Patients with LST lesions ≥20mm were included from a multicenter prospective registry in Spain and from a retrospective registry from the National Cancer Center Hospital East, Japan. The primary outcome was the presence of submucosal invasion in LST. The secondary outcome was the presence of high-risk histology, defined as high-grade dysplasia or submucosal invasion. RESULTS: We evaluated 1102 patients in Spain and 663 in Japan. Morphological and histological characteristics differed. The prevalence of submucosal invasion in Japan was six-fold the prevalence in Spain (Prevalence Ratio PR=5.66; 95%CI: 3.96, 8.08), and the prevalence of high-risk histology was 1.5 higher (PR=1.44; 95%CI: 1.31, 1.58). Compared to the granular homogeneous type and adjusted by clinical features, granular mixed, flat elevated, and pseudo-depressed types were associated with higher odds of submucosal invasion in Japan, whereas only the pseudo-depressed type showed higher risk in Spain. Regarding high-risk histology, both granular mixed and pseudo-depressed were associated with higher odds in Japan, compared with only the granular mixed type in Spain. CONCLUSION: This study reveals differences in location, morphology and invasiveness of LST in an eastern and a western cohort.
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Colonoscopia , Neoplasias Colorretais , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Humanos , Mucosa Intestinal/patologia , Invasividade Neoplásica/patologia , Estudos RetrospectivosRESUMO
This case revealed that branch pancreatic duct wall thickening by endoscopic ultrasonography represented periductal lymphoplasmacytic infiltrate as a characteristic histopathological finding of autoimmune pancreatitis, which may help in the diagnosis of autoimmune pancreatitis. An 80-year-old man was referred because fluorodeoxyglucose-positron emission tomography for lung cancer indicated abnormal uptake in the pancreatic head. Computed tomography showed an enhanced mass with cystic structures in the pancreatic head. Magnetic resonance cholangiopancreatography revealed mild dilatation of the main pancreatic duct in the pancreatic body with no strictures. Endoscopic ultrasonography demonstrated a lobulated heterogeneous hypoechoic mass in the pancreatic head. A branch pancreatic duct with wall thickening connected the mass to the main pancreatic duct. An intraductal neoplasm filling and spreading into the branch pancreatic duct was considered, and surgery was performed. Histopathologically, the mass consisted of marked inflammatory cell infiltration, storiform fibrosis, and obliterative phlebitis. The branch pancreatic duct with wall thickening revealed a band-like inflammatory cell infiltration with mainly lymphocytes and plasma cells beneath the normal pancreatic duct epithelium. Immunohistological staining revealed abundant IgG4-positive plasma cells (> 10 cells/HPF) in the inflammatory cell infiltration. The definite diagnosis was type 1 focal autoimmune pancreatitis.
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Doenças Autoimunes , Pancreatite Autoimune , Pancreatite , Idoso de 80 Anos ou mais , Doenças Autoimunes/diagnóstico por imagem , Humanos , Masculino , Pâncreas , Ductos Pancreáticos/diagnóstico por imagem , Pancreatite/diagnóstico por imagemRESUMO
BACKGROUND AND AIM: Accurate polyp size estimation is essential in deciding the therapeutic strategy of colorectal polyps and endoscopic surveillance intervals. However, many endoscopists frequently make incorrect size estimations without being aware of their errors. This cross-sectional study aimed to clarify the characteristics of endoscopists associated with inaccurate estimation. METHODS: We previously conducted a web trial involving 261 endoscopists in 51 institutions in Japan to assess their ability to estimate polyp size. Participants answered questions about polyp size using visual estimates in a test involving images of 30 polyps. Here, we investigated the relationships between inaccurate size estimation and the backgrounds of participants. The rates of overestimation and underestimation of polyp size were also compared to clarify any trends in the answers of participants with low accuracy (< 50%). RESULTS: Multivariable logistic regression analysis revealed that the number of colonoscopic procedures in the past year was the only factor associated with a low accuracy of polyp size estimation (odds ratio 0.750, 95% confidence interval 0.609-0.925; P = 0.007). Endoscopists with low accuracy had a greater tendency to overestimate polyp size (42.3% overestimation and 21.2% underestimation, P < 0.001) compared with other endoscopists (16.6% overestimation and 17.9% underestimation, P = 0.951). CONCLUSIONS: Endoscopists with limited experience of colonoscopy in the past year were more likely to make frequent errors in size estimation. Furthermore, endoscopists making inaccurate size estimations had a propensity to overestimate polyp size.
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Pólipos do Colo , Colonoscopia , Estudos Transversais , Humanos , Japão , Razão de ChancesRESUMO
During endoscopy, a light purple flat lesion suddenly appeared at the antrum and the lesion disappeared subsequently. This is an unusual reversible color change that is associated with blood flow, and that must be differentiated from neoplasia.
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BACKGROUND: Monopolar instruments are generally used in colorectal endoscopic mucosal resection (EMR). Bipolar instruments have previously been reported to be as safe as monopolar instruments. We sought to compare the safety of the monopolar and bipolar snare and hemostatic forceps in an animal model. METHODS: We created 5-mm, 10-mm, and 15-mm target lesions on an ex vivo porcine rectum. Two lesions of each size were resected via monopolar polypectomy (M-P), monopolar EMR (M-E), bipolar polypectomy (B-P), and bipolar EMR (B-E). We performed a pathological evaluation of the conditions of perforation and the effects of burning on the tissues. In addition, we burned the muscularis propria covered with submucosal layer using monopolar and bipolar hemostatic forceps and performed pathological evaluations. RESULTS: Polypectomy and EMR were performed in a total of 24 target lesions. A perforation was found on histology in one case of M-P and one case of M-E after removing target lesions of 15 mm in diameter. There were no perforations during endoscopic resection using the bipolar snare. The thermal denaturation in B-P did not reach the muscularis propria layer regardless of the size of the target lesion. Although thermal damage after using monopolar hemostatic forceps was extensive, thermal denaturation was only seen on the surface of the submucosal layer when bipolar hemostatic forceps were used. CONCLUSIONS: Bipolar instruments cause less damage to the tissue than monopolar instruments. Our results also suggest that bipolar instruments may be safer than monopolar instruments in endoscopic procedures for colorectal lesions.
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Colo/cirurgia , Colonoscopia/instrumentação , Ressecção Endoscópica de Mucosa/instrumentação , Segurança de Equipamentos , Reto/cirurgia , Animais , Neoplasias Colorretais , Modelos Animais , SuínosRESUMO
BACKGROUND AND STUDY AIMS: Visual assessment of laterally spreading tumors non-granular type (LST-NG) and depressed lesions by narrow band imaging (NBI) without magnification has not been studied. We investigated the role of non-magnifying NBI in detecting LST-NG and type IIc lesions on colonoscopy. PATIENTS AND METHODS: This retrospective study examined consecutive patients diagnosed as having LST-NG and/or type IIc lesions in our hospital between August 2011 and July 2013. These lesions were classified as "Brownish area (BA)," "Brown only in the margins (O-ring sign)," "Same color as the normal mucosa (SC)," and "Whitish area (WA)" based on their appearance on non-magnifying NBI, and their appearance were compared with their histopathological findings. RESULTS: A total of 18 type IIc and 180 LST-NG lesions were analyzed. Among the type IIc lesions, 5 (28â%), 12 (67â%), and 1 (5â%) were classified as BA, O-ring sign, and SC, respectively. Among the LST-NG lesions, 126 (70â%), 26 (14â%), and 28 lesions (16â%) were classified as BA, O-ring sign, and SC, respectively. The IIc lesions were found to have 1 lesion (20â%) with high-grade dysplasia (HGD) in the BA, and 2 lesions (17â%) with invasive cancer (IC) in the O-ring sign group.âAmong the LST-NG lesions, 27 (21â%) were found to have IC and 49 (39â%), HGD in the BA group; 8 lesions (31â%) had IC and 4 (15â%) had HGD in the O-ring sign group; and 1 lesion (4â%) had IC and 4 (14â%) had HGD in the SC group. CONCLUSIONS: Most flat and depressed colorectal lesions were seen on non-magnifying NBI as brown lesions with the exception of some flat lesions that were indistinguishable in color from the adjacent normal mucosa. Some of these flat lesions were also found to have HGD or IC.
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AIM: To identify the risk factors and clarify the subsequent clinical courses. METHODS: This study retrospectively analyzed consecutive patients with esophageal squamous cell carcinoma (ESCC) treated using endoscopic submucosal dissection (ESD) between April 2008 and October 2012. We divided the ESCC lesions into perforation cases and non-perforation cases, and compared characteristics and endoscopic findings between the two groups. "Intraoperative perforation" was defined as the detection of a perforation site during ESD and the presence of mediastinal emphysema. RESULTS: In total, 147 patients with 156 ESCC lesions were treated by ESD. Intraoperative perforation was recorded for nine lesions (5.8%) from nine patients. Multivariate analysis identified mucosal deficiency larger than 75% of the circumference of the esophagus as an independent risk factor for intraoperative perforation (OR = 7.37, 95%CI: 1.45-37.4, P = 0.016). The predominant site of perforation was the left wall [6/9 (67%)]. Six of nine perforation sites were successfully closed by clips during the procedures. Two of nine cases required drainage for pleural effusions; however, all nine cases recovered with conservative treatment and without surgical intervention. At the median follow up of 42 mo after ESD, no cases of local recurrence or distant organ metastasis had been observed. CONCLUSION: This study suggests that mucosal deficiency larger than 75% of the luminal circumference is a risk factor for intraoperative perforation during ESD for ESCC.
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Carcinoma de Células Escamosas/complicações , Ressecção Endoscópica de Mucosa/efeitos adversos , Neoplasias Esofágicas/complicações , Perfuração Esofágica/etiologia , Complicações Intraoperatórias/etiologia , Enfisema Mediastínico/etiologia , Mucosa/patologia , Recidiva Local de Neoplasia/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Drenagem , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Perfuração Esofágica/diagnóstico , Perfuração Esofágica/terapia , Carcinoma de Células Escamosas do Esôfago , Feminino , Seguimentos , Humanos , Complicações Intraoperatórias/terapia , Masculino , Pessoa de Meia-Idade , Derrame Pleural Maligno/terapia , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: A "skirt" is a slightly elevated flat lesion with wide pits occasionally observed at the margin of laterally spreading tumors (LSTs). However, the endoscopic treatment outcomes of LSTs with skirts have not been clarified. The aim of this study was to evaluate the endoscopic treatment outcomes of LSTs with skirts. METHODS: Between February 2006 and March 2014, 996 LSTs were retrospectively examined to assess the clinicopathologic characteristics, procedure time, en bloc resection rate, R0 resection rate, adverse events, and local recurrence rate of endoscopic submucosal dissection (ESD) and of endoscopic resection. RESULTS: Endoscopic treatment was performed in 35 cases of LSTs with skirts (ratio of ESD to endoscopic piecemeal mucosal resection [EPMR], 32:3) and 961 cases of LSTs without skirts (ratio of ESD to EMR to EPMR to polypectomy, 381:275:114:191). LSTs with a skirt were associated with a significantly higher recurrence rate (P < .01). In both ESD and EPMR, LSTs with a skirt were associated with a higher recurrence rate when compared with LSTs without a skirt (odds ratio, 12.7; P = .032, and odds ratio, 12.3; P = .061, respectively). Multivariate analysis demonstrated that the presence of the skirt and piecemeal resection were significant predictors of local recurrence. CONCLUSIONS: LSTs with skirts had a significantly higher local recurrence rate after endoscopic treatment compared with LSTs without skirts, especially after EPMR. Therefore, ESD should be recommended as an endoscopic treatment for LSTs with skirts to minimize local recurrence.
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Carcinoma/cirurgia , Colonoscopia/métodos , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/métodos , Recidiva Local de Neoplasia/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma/patologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Most studies have not reported an improvement in the detection of adenomas with the use of image-enhanced colonoscopy methods, possibly because of the darkness of the images. To overcome this limitation, a new-generation endoscopic system has been developed. This system has 2 blue-laser imaging (BLI) observation modes. The BLI observation was set to BLI-bright mode to detect lesions. We aimed to evaluate the efficacy of BLI in detecting lesions. METHODS: This study was designed as a randomized controlled trial with participants from 8 institutions. We enrolled patients aged ≥40 years. The participants were randomly assigned to 2 groups: observation by using white-light imaging (WLI) with a conventional xenon light source (WLI group) or observation by using BLI-bright mode with a laser light source (BLI group). All of the detected lesions were resected or had a biopsy taken for histopathologic analysis. The primary outcome was the mean number of adenomas per patient (MAP) that were detected per procedure. RESULTS: The WLI and BLI groups consisted of 474 and 489 patients, respectively. The MAP was significantly higher in the BLI group than in the WLI group (mean ± standard deviation [SD] WLI 1.01 ± 1.36, BLI 1.27 ± 1.73; P = .008). Adenoma detection rate in the BLI group was not significantly higher than in the WLI group. Observation times differed significantly, with BLI (9.48 minutes) being longer than WLI (8.42; P < .001). The mean (± SD) number of polyps per patient was significantly higher in the BLI group compared with the WLI group (WLI 1.43 ± 1.64, BLI 1.84 ± 2.09; P = .001). CONCLUSIONS: A newly developed system that uses BLI improves the detection of adenomatous lesions compared with WLI. (Clinical trial registration number: UMIN 000014555.).
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Adenoma/diagnóstico por imagem , Pólipos do Colo/diagnóstico por imagem , Colonoscopia/instrumentação , Neoplasias Colorretais/diagnóstico por imagem , Lasers , Adenoma/patologia , Adenoma/cirurgia , Idoso , Biópsia , Colonoscopia/métodos , Cor , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Background and study aims: One of the major complications after endoscopic resection (ER) for large superficial esophageal squamous cell carcinoma (ESCC) is benign esophageal stricture, which can reduce quality of life even if ESCC achieves a cure without organ resection. Recently, steroid administration has been reported as a prophylactic treatment to prevent esophageal strictures. This retrospective study evaluated the stricture rate according to the different width of mucosal defects due to ER and compared it to that seen with prophylactic steroid administration. Patients and methods: Between June 2007 and December 2013, we enrolled patients with ESCC who had 3/4 or larger circumferential mucosal defects due to ER. In December 2009, steroid injections (triamcinolone acetonide 50âmg) into the ulcer bed due to ER were introduced. Beginning in November 2012, we commenced oral steroid administration (prednisolone 30âmg/day, tapered gradually for 8 weeks) in addition to steroid injection. Patients were classified into 3 groups according to the width of mucosal defect after ER (Group A, ≥â3/4 and <â7/8; Group B, ≥â7/8 and less than the entire circumference; and Group C, the entire circumference). We retrospectively evaluated the stricture rate by comparing no treatment, steroid injection, or steroid injection followed by oral steroid according to the width of mucosal defect. Results: A total of 115 patients met the selection criteria. In Group B, no treatment had a significantly higher stricture rate (100â%, vs. steroid injection: 56â% Pâ=â0.015; vs steroid injection followed by oral steroid: 20â% Pâ<â0.001). Conversely, in Group C, the stricture rate was high, regardless of treatment (no treatment: 100â%; steroid injection: 100â%; steroid injection followed by oral steroid: 71â%). Conclusions: Although prophylactic steroid administration is effective to prevent strictures for 7/8 circumference or larger mucosal defects, it is ineffective for whole-circumference defects. Further investigation is required.
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This phase I study in Japanese patients evaluated the safety, pharmacokinetics, and preliminary efficacy of palbociclib, a highly selective and reversible oral cyclin-dependent kinase 4/6 inhibitor, as monotherapy for solid tumors (part 1) and combined with letrozole as first-line treatment of postmenopausal patients with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (part 2). Part 1 evaluated palbociclib 100 and 125 mg once daily (3 weeks on/1 week off; n = 6 each group) to determine the maximum tolerated dose. Part 2 evaluated palbociclib maximum tolerated dose (125 mg) plus letrozole 2.5 mg (n = 6). The most common treatment-related adverse event was neutropenia (all grades/grade 3/4): 100 mg, 83%/67%; 125 mg, 67%/33%; and palbociclib plus letrozole, 100%/83%. Heavier pretreatment with chemotherapy may have resulted in higher neutropenia rates observed with the 100-mg dose. Palbociclib exposure was higher with 125 vs 100 mg (mean area under the plasma concentration-time curve over dosing interval [τ]: 1322 vs 547.5 ng·h/mL [single dose], 2838 vs 1276 ng·h/mL [multiple dose]; mean maximum plasma concentration: 104.1 vs 41.4 ng/mL [single dose], 185.5 vs 77.4 ng/mL [multiple dose]). Half-life was 23-26 h. No drug-drug interactions between palbociclib and letrozole occurred. Four patients had stable disease (≥24 weeks in one patient with rectal cancer [100 mg] and one with esophageal cancer [125 mg]) in part 1; two patients had partial response and two had stable disease (both ≥24 weeks) in part 2. Palbociclib at the 125-mg dose (schedule 3/1) was tolerated and is the recommended dose for monotherapy and letrozole combination therapy in Japanese patients. The trials are registered with www.ClinicalTrials.gov: A5481010 and NCT01684215.
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Antineoplásicos/uso terapêutico , Quinase 4 Dependente de Ciclina/antagonistas & inibidores , Quinase 6 Dependente de Ciclina/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Neoplasias/enzimologia , Neoplasias/patologia , Neutrófilos/citologia , Piperazinas/administração & dosagem , Piperazinas/efeitos adversos , Piperazinas/farmacocinética , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Piridinas/farmacocinética , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND AND STUDY AIM: A slightly elevated flat lesion with wide pits has occasionally been observed at the margin of laterally spreading tumors (LSTs) and is known as a "skirt." The aim of this study was to evaluate the clinicopathological, endoscopic, and genetic characteristics of a skirt. PATIENTS AND METHODS: Consecutive LSTs were examined to evaluate the pathological, endoscopic, and genetic characteristics. Pathological characteristics, including the dimension of the cryptic opening (DCO), width of the individual gland (WIG), DCO to WIG ratio, and microvessel diameter were elucidated and compared with those of hyperplastic polyps, low grade dysplasia (LGD), and normal mucosa. The endoscopic findings of pit and microvascular patterns were assessed. Gene mutation analyses were performed for the KRAS, BRAF, NRAS, and PIK3CA genes. RESULTS: A skirt was identified in 35 of 1023 LSTs, and 80â% of lesions with a skirt had a component of either intramucosal or submucosal adenocarcinoma. The DCO, WIG, and DCO to WIG ratio of the skirt were significantly larger than those of other lesions. The microvessel diameters in skirts were significantly smaller than those in LGDs. Regarding the endoscopic findings, 30 skirts showed pits with a coral reef-like appearance, and all skirt regions were found to have a type I capillary pattern. KRAS mutation at codon 146 was found in the nodular part in one of five LSTs with a skirt. CONCLUSION: The skirt is a newly identified lesion distinct from hyperplastic polyps and LGDs, suggesting the presence of a novel pathway for rectal carcinogenesis from LSTs with a skirt.
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Pólipos do Colo/patologia , Colonoscopia/métodos , Neoplasias Colorretais/diagnóstico , Mucosa Intestinal , Adulto , Idoso , Carcinogênese/genética , Carcinogênese/patologia , Neoplasias Colorretais/genética , Feminino , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/diagnóstico por imagem , Mucosa Intestinal/patologia , Japão , Masculino , Microvasos/patologia , Pessoa de Meia-Idade , Mutação , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Fluxo Sanguíneo Regional , Estatística como AssuntoRESUMO
BACKGROUND: Endoscopic submucosal resection with a ligation device (ESMR-L) is effective for rectal neuroendocrine tumors (NETs); however, its effectiveness for duodenal NETs is unclear. This study evaluated the efficacy and safety of ESMR-L for duodenal NETs. METHODS: A total of 32 consecutive patients with duodenal NETs were treated in our hospital between December 2010 and August 2015. Among these 32 patients, we retrospectively analyzed the data of all patients who underwent ESMR-L for the treatment of duodenal NETs. ESMR-L was considered for patients in whom (1) the lesion size was ≤10 mm in diameter, (2) the lesion was located within the submucosal layer, and (3) no lymph node metastasis or distant metastasis was detected. RESULTS: Five patients underwent ESMR-L for the treatment of duodenal NETs. The en bloc complete resection rate was 100 %. The median procedure time for ESMR-L was 15 min (range 10-30 min). In all patients, perforation during and after the operation, and intraoperative bleeding were not observed; however, one patient experienced postoperative bleeding. During follow-up, no local recurrence or distant metastasis was noted in any of the patients. CONCLUSION: ESMR-L is feasible, effective, and safe for duodenal NETs measuring ≤10 mm in diameter that are confined to the submucosal layer without metastasis.