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OBJECTIVE: This study aimed to clarify the molecular mechanism of remnant pancreatic cancer (PC) development after primary PC resection. SUMMARY BACKGROUND DATA: Molecular mechanisms of the development of remnant PCs following primary PC resection are largely unknown. METHODS: Forty-three patients undergoing remnant PC resection after primary PC resection between 2001 and 2017 at 26 institutes were retrospectively analyzed. Clinicopathological features and molecular alterations detected by targeted amplicon sequencing of 36 PC-associated genes were evaluated. RESULTS: These patients showed significantly lower body mass indices and higher hemoglobin A1c values at remnant PC resection than at primary PC resection. A comparison of the molecular features between primary and remnant PCs indicated that remnant PCs were likely to develop via three different molecular pathways: successional, showing identical and accumulated alterations (n=14); phylogenic, showing identical and distinct alterations (n=26); and distinct, showing independent distinctive alterations (n=3). The similarity of gene alterations was associated with time to the remnant PC development (r=ï¼0.384, P=0.0173). Phylogenic pathways were significantly associated with the intraductal spread of carcinoma (P=0.007). Patient survival did not differ significantly depending on these molecular pathways. CONCLUSION: Molecular profiling uncovered three pathways for the development of remnant PCs, namely, successional, phylogenic, and distinct pathways. The vast majority of remnant PCs are likely to be molecularly associated with primary PCs either in the successional or phylogenic way. This information could impact the design of a strategy for monitoring and treating remnant PCs.
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BACKGROUND: S-1 has shown promising efficacy with a mild toxicity profile in patients with advanced biliary tract cancer. The aim of this study was to evaluate whether adjuvant S-1 improved overall survival compared with observation for resected biliary tract cancer. METHODS: This open-label, multicentre, randomised phase 3 trial was conducted in 38 Japanese hospitals. Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone no local residual tumour resection or microscopic residual tumour resection were randomly assigned (1:1) to undergo observation or to receive S-1 (ie, 40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice daily for 4 weeks, followed by 2 weeks of rest for four cycles). Randomisation was performed by the minimisation method, using institution, primary tumour site, and lymph node metastasis as adjustment factors. The primary endpoint was overall survival and was assessed for all randomly assigned patients on an intention-to-treat basis. Safety was assessed in all eligible patients. For the S-1 group, all patients who began the protocol treatment were eligible for a safety assessment. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry (UMIN000011688). FINDINGS: Between Sept 9, 2013, and June 22, 2018, 440 patients were enrolled (observation group n=222 and S-1 group n=218). The data cutoff date was June 23, 2021. Median duration of follow-up was 45·4 months. In the primary analysis, the 3-year overall survival was 67·6% (95% CI 61·0-73·3%) in the observation group compared with 77·1% (70·9-82·1%) in the S-1 group (adjusted hazard ratio [HR] 0·69, 95% CI 0·51-0·94; one-sided p=0·0080). The 3-year relapse-free survival was 50·9% (95% CI 44·1-57·2%) in the observation group compared with 62·4% (55·6-68·4%) in the S-1 group (HR 0·80, 95% CI 0·61-1·04; two-sided p=0·088). The main grade 3-4 adverse events in the S-1 group were decreased neutrophil count (29 [14%]) and biliary tract infection (15 [7%]). INTERPRETATION: Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients. FUNDING: The National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.
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Neoplasias do Sistema Biliar , Recidiva Local de Neoplasia , Humanos , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/etiologia , Quimioterapia Adjuvante/métodos , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/cirurgia , Modelos de Riscos Proporcionais , Adjuvantes Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
BACKGROUND & AIMS: Despite previously reported treatment strategies for nonfunctioning small (≤20 mm) pancreatic neuroendocrine neoplasms (pNENs), uncertainties persist. We aimed to evaluate the surgically resected cases of nonfunctioning small pNENs (NF-spNENs) in a large Japanese cohort to elucidate an optimal treatment strategy for NF-spNENs. METHODS: In this Japanese multicenter study, data were retrospectively collected from patients who underwent pancreatectomy between January 1996 and December 2019, were pathologically diagnosed with pNEN, and were treated according to the World Health Organization 2019 classification. Overall, 1490 patients met the eligibility criteria, and 1014 were included in the analysis cohort. RESULTS: In the analysis cohort, 606 patients (59.8%) had NF-spNENs, with 82% classified as grade 1 (NET-G1) and 18% as grade 2 (NET-G2) or higher. The incidence of lymph node metastasis (N1) by grade was significantly higher in NET-G2 (G1: 3.1% vs G2: 15.0%). Independent factors contributing to N1 were NET-G2 or higher and tumor diameter ≥15 mm. The predictive ability of tumor size for N1 was high. Independent factors contributing to recurrence included multiple lesions, NET-G2 or higher, tumor diameter ≥15 mm, and N1. However, the independent factor contributing to survival was tumor grade (NET-G2 or higher). The appropriate timing for surgical resection of NET-G1 and NET-G2 or higher was when tumors were >20 and >10 mm, respectively. For neoplasms with unknown preoperative grades, tumor size >15 mm was considered appropriate. CONCLUSIONS: NF-spNENs are heterogeneous with varying levels of malignancy. Therefore, treatment strategies based on tumor size alone can be unreliable; personalized treatment strategies that consider tumor grading are preferable.
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Pancreatectomia , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Japão/epidemiologia , Adulto , Tumores Neuroendócrinos/cirurgia , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/terapia , Tumores Neuroendócrinos/diagnóstico , Idoso de 80 Anos ou mais , Metástase Linfática , Gradação de Tumores , Carga TumoralRESUMO
BACKGROUND: Although accurate preoperative diagnosis of lymph node metastasis is essential for optimizing treatment strategies for low rectal cancer, the accuracy of present diagnostic modalities has room for improvement. OBJECTIVE: The study aimed to establish a high-precision diagnostic method for lymph node metastasis of low rectal cancer using artificial intelligence. DESIGN: A retrospective observational study. SETTINGS: A single cancer center and a college of engineering in Japan. PATIENTS: Patients with low rectal adenocarcinoma who underwent proctectomy, bilateral lateral pelvic lymph node dissection, and contrast-enhanced multidetector row CT (slice ≤1 mm) between July 2015 and August 2021 were included in the present study. All pelvic lymph nodes from the aortic bifurcation to the upper edge of the anal canal were extracted, regardless of whether within or beyond the total mesenteric excision area, and pathological diagnoses were annotated for training and validation. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: A total of 596 pathologically negative nodes and 43 positive nodes from 52 patients were extracted and annotated. Four diagnostic methods, with and without using super-resolution images and with and without using 3-dimensional shape data, were performed and compared. The super-resolution + 3-dimensional shape data method had the best diagnostic ability for the combination of sensitivity, negative predictive value, and accuracy (0.964, 0.966, and 0.968, respectively), whereas the super-resolution only method had the best diagnostic ability for the combination of specificity and positive predictive value (0.994 and 0.993, respectively). LIMITATIONS: Small number of patients at a single center and the lack of external validation. CONCLUSIONS: Our results enlightened the potential of artificial intelligence for the method to become another game changer in the diagnosis and treatment of low rectal cancer. See Video Abstract . DIAGNSTICO POR IMGENES CON INTELIGENCIA ARTIFICIAL MEDIANTE SUPERRESOLUCIN Y FORMA D PARA LA METSTASIS EN LOS GANGLIOS LINFTICOS DEL CNCER DE RECTO BAJO UN ESTUDIO PILOTO DE UN SOLO CENTRO: ANTECEDENTES:Aunque el diagnóstico preoperatorio preciso de metástasis en los ganglios linfáticos es esencial para optimizar las estrategias de tratamiento para el cáncer de recto bajo, la precisión de las modalidades de diagnóstico actuales tiene margen de mejora.OBJETIVO:Establecer un método de diagnóstico de alta precisión para las metástasis en los ganglios linfáticos del cáncer de recto bajo utilizando inteligencia artificial.DISEÑO:Un estudio observacional retrospectivo.AJUSTE:Un único centro oncológico y una facultad de ingeniería en Japón.PACIENTES:En el presente estudio se incluyeron pacientes con adenocarcinoma rectal bajo sometidos a proctectomía, disección bilateral de ganglios linfáticos pélvicos laterales y tomografía computarizada con múltiples detectores con contraste (corte ≤1 mm) entre julio de 2015 y agosto de 2021. Se resecaron todos los ganglios linfáticos pélvicos desde la bifurcación aórtica hasta el borde superior del canal anal, independientemente de si estaban dentro o más allá del área de escisión mesentérica total, y se registraron los diagnósticos patológicos para entrenamiento y validación.PRINCIPALES MEDIDAS DE RESULTADO:Sensibilidad, especificidad, valor predictivo positivo, valor predictivo negativo y precisión.RESULTADOS:Se extrajeron y registraron un total de 596 ganglios patológicamente negativos y 43 positivos de 52 pacientes. Se realizaron y compararon cuatro métodos de diagnóstico, con y sin imágenes de súper resolución y sin datos de imagen en 3D. El método de superresolución + datos de imagen en 3D tuvo la mejor capacidad de diagnóstico para la combinación de sensibilidad, valor predictivo negativo y precisión (0,964, 0,966 y 0,968, respectivamente), mientras que el método de súper resolución solo tuvo la mejor capacidad de diagnóstico para la combinación de especificidad y valor predictivo positivo (0,994 y 0,993, respectivamente).LIMITACIONES:Pequeño número de pacientes en un solo centro y falta de validación externa.CONCLUSIONES:Nuestros resultados iluminan el potencial de la inteligencia artificial para que el método se convierta en otro elemento de cambio en el diagnóstico y tratamiento del cáncer de recto bajo. (Traducción ---Dr. Fidel Ruiz Healy ).
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Adenocarcinoma , Inteligência Artificial , Linfonodos , Metástase Linfática , Neoplasias Retais , Humanos , Neoplasias Retais/patologia , Neoplasias Retais/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Metástase Linfática/patologia , Masculino , Feminino , Projetos Piloto , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Linfonodos/patologia , Linfonodos/diagnóstico por imagem , Adenocarcinoma/patologia , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/diagnóstico , Adenocarcinoma/secundário , Protectomia/métodos , Imageamento Tridimensional/métodos , Excisão de Linfonodo/métodos , Tomografia Computadorizada Multidetectores/métodos , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Pelve/diagnóstico por imagem , AdultoRESUMO
BACKGROUND: Although accurate preoperative diagnosis of lymph node metastasis is essential for optimizing treatment strategies for low rectal cancer, the accuracy of present diagnostic modalities has room for improvement. OBJECTIVE: To establish a high-precision diagnostic method for lymph node metastasis of low rectal cancer using artificial intelligence. DESIGN: A retrospective observational study. SETTINGS: A single cancer center and a college of engineering in Japan. PATIENTS: Patients with low rectal adenocarcinoma who underwent proctectomy, bilateral lateral pelvic lymph node dissection, and contrast-enhanced multi-detector row computed tomography (slice ≤1 mm) between July 2015 and August 2021 were included in the present study. All pelvic lymph nodes from the aortic bifurcation to the upper edge of the anal canal were extracted, regardless of whether within or beyond the total mesenteric excision area, and pathological diagnoses were annotated for training and validation. MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. RESULTS: A total of 596 pathologically negative and 43 positive nodes from 52 patients were extracted and annotated. Four diagnostic methods, with and without using super-resolution images and without using 3D shape data, were performed and compared. The super-resolution + 3D shape data method had the best diagnostic ability for the combination of sensitivity, negative predictive value, and accuracy (0.964, 0.966, and 0.968, respectively), while the super-resolution only method had the best diagnostic ability for the combination of specificity and positive predictive value (0.994 and 0.993, respectively). LIMITATIONS: Small number of patients at a single center and the lack of external validation. CONCLUSIONS: Our results enlightened the potential of artificial intelligence for the method to become another game changer in the diagnosis and treatment of low rectal cancer. See Video Abstract.
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BACKGROUND: Salvage esophagectomy for residual tumor and localized relapses after definitive chemoradiotherapy (dCRT) for patients with esophageal cancer is associated with a high rate of postoperative complications and in-hospital mortality. In addition, there are many controversial issues associated with salvage esophagectomy, such as the acceptability of minimally invasive surgery and the need for prophylactic dissection of mediastinal lymph nodes. The aim of this study was to evaluate the safety and usefulness of thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection. METHODS: The study included 31 patients who underwent thoracoscopic salvage esophagectomy with prophylactic mediastinal lymph node dissection after dCRT between 2013 and 2022 (salvage patients) and 610 nonsalvage patients who underwent conventional thoracoscopic esophagectomy during the same time period. RESULTS: Differences between the median ages and sexes of the 2 patient groups were not significant. The dominant location of tumors in the salvage patients was the upper thoracic esophagus. More salvage patients had clinical T4 disease. The salvage patients had a lower median number of retrieved mediastinal lymph nodes than the nonsalvage patients. The differences between the rates of R0, postoperative complications, and in-hospital deaths in the 2 patient groups were not significant. The 3-year overall survival (OS) rates for the salvage patients were 73%, with 3-year OS rates for R0 vs non-R0 of 81% vs 0%, p < 0.01 and pN0 vs pN1-3 of 89% vs 49%, p < 0.01. CONCLUSION: Regarding short-term outcomes, prophylactic mediastinal lymph node dissection for patients undergoing thoracoscopic salvage esophagectomy was as safe as prophylactic dissection for patients undergoing conventional thoracoscopic esophagectomy. R0 surgery and pN0 are important factors for long-term survival in patients undergoing thoracoscopic salvage esophagectomy.
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Quimiorradioterapia , Neoplasias Esofágicas , Esofagectomia , Excisão de Linfonodo , Mediastino , Terapia de Salvação , Toracoscopia , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/patologia , Esofagectomia/métodos , Masculino , Feminino , Terapia de Salvação/métodos , Excisão de Linfonodo/métodos , Toracoscopia/métodos , Pessoa de Meia-Idade , Idoso , Quimiorradioterapia/métodos , Estudos Retrospectivos , AdultoRESUMO
PURPOSE: Delay in initiating adjuvant chemotherapy (AC) after curative resection of colorectal cancer (CRC) has been reported to lead to poor prognosis, but few studies have looked at associated factors. This study aimed to identify risk factors for delay in initiating AC. METHODS: Data from 200 consecutive patients who underwent curative resection and AC for stage III CRC between 2013 and 2018 were retrospectively collected and analyzed. RESULTS: AC was initiated more than 8 weeks after surgery in 12.5% of patients (the delay group). Compared to those with no delay (the non-delay group), patients in the delay group had significantly higher rates of synchronous double cancers (2.3% vs. 16.0%, p = 0.001), preoperative bowel obstruction (10.3% vs. 32.0%, p = 0.003), laparotomy (56.0% vs. 80.0%, p = 0.02), concomitant resection (2.9% vs. 24.0%, p < 0.001), and postoperative complications (32.0% vs. 56.0%, p = 0.02), and a significantly longer length of hospital stay (median 12 vs. 30 days, p < 0.001). In multivariate analysis, synchronous double cancers (odds ratio 10.2, p = 0.008), preoperative bowel obstruction (odds ratio 4.6, p = 0.01), concomitant resection (odds ratio 5.2, p = 0.03), and postoperative complications of Clavien-Dindo grade ≥ IIIa (odds ratio 4.0, p = 0.03) were identified as independent risk factors for delay in initiating AC. CONCLUSION: Careful preoperative treatment planning for CRC patients with synchronous double cancers, preoperative bowel obstruction, and concomitant resection, and management for postoperative complication are necessary to avoid delay in initiating AC.
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Neoplasias Colorretais , Estadiamento de Neoplasias , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Masculino , Feminino , Quimioterapia Adjuvante , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Estudos Retrospectivos , Adulto , Complicações Pós-Operatórias , Idoso de 80 Anos ou mais , Tempo para o TratamentoRESUMO
BACKGROUND: Recurrent laryngeal nerve paralysis (RLNP) after esophagectomy can cause aspiration because of incomplete glottis closure, leading to pneumonia. However, patients with RLNP often have preserved swallowing function. This study investigated factors that determine swallowing function in patients with RLNP. METHODS: Patients with esophageal cancer who underwent esophagectomy and cervical esophagogastric anastomosis were enrolled between 2017 and 2020. Videofluoroscopic examination of swallowing study (VFSS) and acoustic voice analysis were performed on patients with suspected dysphagia including RLNP. Dysphagia in VFSS was defined as score ≥ 3 of the 8-point penetration-aspiration scale VFSS and acoustic analysis results related to dysphagia were compared between patients with and without RLNP. RESULTS: Among 312 patients who underwent esophagectomy, 74 developed RLNP. The incidence of late-onset pneumonia was significantly higher in the RLNP group than in the non-RLNP (18.9 vs. 8.0%, P = .008). Detailed swallowing function was assessed by VFSS in 84 patients, and patients with RLNP and dysphagia showed significantly shorter maximum diagonal hyoid bone elevation (10.62 vs. 16.75 mm; P = .003), which was a specific finding not seen in patients without RLNP. For acoustic voice analysis, the degree of hoarseness was not closely related to dysphagia. The length of oral intake rehabilitation for patients with and without RLNP was comparable if they did not present with dysphagia (8.5 vs. 9.0 days). CONCLUSIONS: Impaired hyoid bone elevation is a specific dysphagia factor in patients with RLNP, suggesting compensatory epiglottis inversion by hyoid bone elevation is important for incomplete glottis closure caused by RLNP.
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Transtornos de Deglutição , Pneumonia , Paralisia das Pregas Vocais , Humanos , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Deglutição/fisiologia , Esofagectomia/efeitos adversos , Nervo Laríngeo Recorrente , Paralisia das Pregas Vocais/epidemiologia , Paralisia das Pregas Vocais/etiologia , Aspiração RespiratóriaRESUMO
BACKGROUND: Based on the Japan Adjuvant Study Group of Pancreatic Cancer 01 study, the standard duration of adjuvant chemotherapy with S-1 (an oral 5-fluorouracil prodrug consisting of tegafur, gimeracil, and oteracil) in patients with resected pancreatic ductal adenocarcinoma (PDAC) was considered to be 6 months, but the impact of increasing its duration on postoperative survival was unknown. Here, the authors investigated this question by reviewing real-world data from a large cohort of patients with PDAC. METHODS: In total, 3949 patients who underwent surgery for PDAC during the study period followed by S-1 adjuvant chemotherapy in board-certified institutions were included. Based on the duration of S-1 chemotherapy, two subgroups were defined: a standard-duration group that included patients who were treated for 180 ± 30 days and a longer duration group that included patients who received treatment for >210 days. RESULTS: The median duration of S-1 chemotherapy was 167 days, with a mean ± standard deviation of 200 ± 193 days. After excluding patients who had a recurrence within 210 days after the initiation of adjuvant chemotherapy, postoperative recurrence-free survival (RFS) and overall survival (OS) in the standard-duration group (n = 1473) and the longer duration group (n = 975) were compared. RFS and OS did not differ significantly between the standard-duration and longer duration groups (5-year RFS: 37.8% vs. 36.2% respectively; p = .6186; 5-year OS: 52.8% vs. 53.4%, respectively; p = .5850). The insignificant difference was verified by multivariate analysis and propensity-score matching analysis. CONCLUSIONS: The current findings suggest that extending S-1 adjuvant chemotherapy beyond 6 months has no significant additional effect on survival in patients with PDAC. This could be useful in determining whether to extend S-1 chemotherapy in patients who have completed the standard 6-month treatment.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Tegafur/uso terapêutico , Ácido Oxônico/uso terapêutico , Japão/epidemiologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Quimioterapia Adjuvante , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Pâncreas/patologia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
BACKGROUND: According to some case series, patients with colorectal cancer (CRC) who underwent radical resection of synchronous peritoneal metastases (PM) with the primary tumor had better survival than patients who underwent non-surgical treatment. However, little evidence exists regarding the significance of radical resection for metachronous PM. OBJECTIVE: This study aimed to evaluate the clinical significance of surgical intervention for isolated PM from CRC, with a particular focus on time to PM. METHODS: A total of 74 consecutive patients with isolated PM from CRC, including 40 and 34 patients with synchronous and metachronous PM, respectively, treated between 2007 and 2018 were retrospectively analyzed. The primary outcome measure was overall survival (OS) from diagnosis, and the OS was compared between radical resection and palliative chemotherapy. RESULTS: Five-year OS was 39.7% for all patients. Patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy (62.8% vs. 11.0%; p < 0.0001). According to time to PM, patients with radical resection had significantly better 5-year OS compared with those with palliative chemotherapy for both synchronous PM (47.6% vs. 0%; p = 0.019) and metachronous PM (77.2% vs. 15.2%; p < 0.0001). Multivariable analysis stratified by time to PM revealed that surgical intervention is a significant favorable prognostic factor only in patients with metachronous PM (hazard ratio 0.117, 95% confidence interval 0.020-0.678; p = 0.017). CONCLUSIONS: Patients with radical resection of PM had good survival compared with those with chemotherapy alone, especially for metachronous PM. Surgical intervention should be considered for isolated metachronous PM when radical resection is feasible.
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Neoplasias Colorretais , Neoplasias Peritoneais , Humanos , Prognóstico , Neoplasias Peritoneais/terapia , Estudos Retrospectivos , Terapia Combinada , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Tranexamic acid (TXA) may reduce intraoperative blood loss, but it has not been investigated in pancreaticoduodenectomy (PD). METHODS: A pragmatic, multicentre, randomized, blinded, placebo-controlled trial was conducted. Adult patients undergoing planned PD for biliary, duodenal, or pancreatic diseases were randomly assigned to TXA or placebo groups. Patients in the TXA group were administered 1 g TXA before incision, followed by a maintenance infusion of 125 mg/h TXA. Patients in the placebo group were administered the same volume of saline as those in the placebo group. The primary outcome was blood loss during PD. The secondary outcomes included perioperative blood transfusions, operating time, morbidity, and mortality. RESULTS: Between September 2019 and May 2021, 218 patients were randomly assigned and underwent surgery (108 in the TXA group and 110 in the placebo group). Mean intraoperative blood loss was 659 ml in the TXA group and 701 ml in the placebo group (mean difference -42 ml, 95 per cent c.i. -191 to 106). Of the 218 patients, 202 received the intervention and underwent PD, and the mean blood loss during PD was 667 ml in the TXA group and 744 ml in the placebo group (mean difference -77 ml, 95 per cent c.i. -226 to 72). The secondary outcomes were comparable between the two groups. CONCLUSION: Perioperative TXA use did not reduce blood loss during PD. REGISTRATION NUMBER: jRCTs041190062 (https://jrct.niph.go.jp).
Removing part of the pancreas is an operation with a risk of major blood loss. Tranexamic acid is a drug thought to reduce blood loss. This study asked the question, 'Does tranexamic acid reduce blood loss during surgery on the pancreas?' Half of patients received tranexamic acid during surgery. The other half received only standard care. This study showed that tranexamic acid did not decrease the blood loss during the surgery and may have little effect in patients having a pancreaticoduodenectomy.
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Antifibrinolíticos , Ácido Tranexâmico , Adulto , Humanos , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Método Duplo-Cego , Resultado do TratamentoRESUMO
BACKGROUND/OBJECTIVES: The detection of malignancy is a major concern in the management of intraductal papillary mucinous neoplasm (IPMN). The height of the mural nodule (MN), estimated using endoscopic ultrasound (EUS) and computed tomography (CT), has been considered crucial for predicting malignant IPMN. Currently, whether surveillance using CT or EUS alone is sufficient for detecting MNs remains unclear. This study aimed to compare the ability of CT and EUS to detect MNs in IPMN. METHODS: This multicenter, retrospective observational study was conducted in 11 Japanese tertiary institutions. Patients who underwent surgical resection of IPMN with MN after CT and EUS examinations were eligible to participate. The MN detection rates between CT and EUS were examined. RESULTS: Two-hundred-and-forty patients who underwent preoperative EUS and CT had pathologically confirmed MNs. The MN detection rates of EUS and CT were 83% and 53%, respectively (p < 0.001). Additionally, the MN detection rate of EUS was significantly higher than that of CT regardless of morphological type (76% vs. 47% in branch-duct-type IPMN; 90% vs. 54% in mixed IPMN; 98% vs. 56% in main-duct-type IPMN; p < 0.001). Further, pathologically confirmed MNs ≥5 mm were more frequently observed on EUS than on CT (95% vs. 76%, p < 0.001). CONCLUSIONS: EUS was superior to CT for the detection of MN in IPMN. EUS surveillance is essential for the detection of MNs.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Carcinoma Ductal Pancreático/patologia , Japão , Adenocarcinoma Mucinoso/diagnóstico por imagem , Adenocarcinoma Mucinoso/cirurgia , Adenocarcinoma Mucinoso/patologia , Neoplasias Pancreáticas/patologia , Tomografia Computadorizada por Raios X , Estudos RetrospectivosRESUMO
BACKGROUND : There are several types of pancreatic mass, so it is important to distinguish between them before treatment. Artificial intelligence (AI) is a mathematical technique that automates learning and recognition of data patterns. This study aimed to investigate the efficacy of our AI model using endoscopic ultrasonography (EUS) images of multiple types of pancreatic mass (pancreatic ductal adenocarcinoma [PDAC], pancreatic adenosquamous carcinoma [PASC], acinar cell carcinoma [ACC], metastatic pancreatic tumor [MPT], neuroendocrine carcinoma [NEC], neuroendocrine tumor [NET], solid pseudopapillary neoplasm [SPN], chronic pancreatitis, and autoimmune pancreatitis [AIP]). METHODS : Patients who underwent EUS were included in this retrospective study. The included patients were divided into training, validation, and test cohorts. Using these cohorts, an AI model that can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions was developed using a deep-learning architecture and the diagnostic performance of the AI model was evaluated. RESULTS : 22â000 images were generated from 933 patients. The area under the curve, sensitivity, specificity, and accuracy (95â%CI) of the AI model for the diagnosis of pancreatic carcinomas in the test cohort were 0.90 (0.84-0.97), 0.94 (0.88-0.98), 0.82 (0.68-0.92), and 0.91 (0.85-0.95), respectively. The per-category sensitivities (95â%CI) of each disease were PDAC 0.96 (0.90-0.99), PASC 1.00 (0.05-1.00), ACC 1.00 (0.22-1.00), MPT 0.33 (0.01-0.91), NEC 1.00 (0.22-1.00), NET 0.93 (0.66-1.00), SPN 1.00 (0.22-1.00), chronic pancreatitis 0.78 (0.52-0.94), and AIP 0.73 (0.39-0.94). CONCLUSIONS : Our developed AI model can distinguish pancreatic carcinomas from noncarcinomatous pancreatic lesions, but external validation is needed.
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Carcinoma Ductal Pancreático , Aprendizado Profundo , Neoplasias Pancreáticas , Pancreatite Crônica , Humanos , Endossonografia/métodos , Diagnóstico Diferencial , Estudos Retrospectivos , Inteligência Artificial , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/diagnóstico , Pancreatite Crônica/diagnóstico por imagem , Neoplasias PancreáticasRESUMO
INTRODUCTION: Periostin, an extracellular matrix protein, plays an important role in osteogenesis and is also known to activate several signals that contribute to chondrogenesis. The absence of periostin in periostin knockout mice leads to several disorders such as craniosynostosis and periostitis. There are several splice variants with different roles in heart disease and myocardial infarction. However, little is known about each variant's role in chondrogenesis, followed by bone formation. Therefore, the aim of this study is to investigate the role of several variants in chondrogenesis differentiation and bone formation in the craniofacial region. Periostin splice variants included a full-length variant (Control), a variant lacking exon 17 (ΔEx17), a variant lacking exon 21 (ΔEx21), and another variant lacking both exon 17 and 21 ***(ΔEx17&21). MATERIALS AND METHODS: We used C56BL6/N mice (n = 6) for the wild type (Control)*** and the three variant type mice (n = 6 each) to identify the effect of each variant morphologically and histologically. Micro-computed tomography demonstrated a smaller craniofacial skeleton in ΔEx17s, ΔEx21s, and ΔEx17&21s compared to Controls, especially the mandibular bone. We, thus, focused on the mandibular condyle. RESULTS: The most distinctive histological observation was that each defected mouse appeared to have more hypertrophic chondrocytes than Controls. Real-time PCR demonstrated the differences among the group. Moreover, the lack of exon 17 or exon 21 in periostin leads to inadequate chondrocyte differentiation and presents in a diminutive craniofacial skeleton. DISCUSSION: Therefore, these findings suggested that each variant has a significant role in chondrocyte hypertrophy, leading to suppression of bone formation.
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Condrócitos , Condrogênese , Animais , Camundongos , Osso e Ossos , Diferenciação Celular/genética , Condrócitos/metabolismo , Condrogênese/genética , Hipertrofia/genética , Hipertrofia/metabolismo , Hipertrofia/patologia , Camundongos Knockout , Osteogênese/genética , Microtomografia por Raio-XRESUMO
BACKGROUND: Some patients with even T2 low rectal cancer are known to develop lateral pelvic lymph node metastasis. This study aimed to investigate real-world evidence regarding lateral nodal metastasis on T2 low rectal cancer treatment. METHODS: Consecutive patients with pathological T2 low rectal adenocarcinoma who underwent curative-intent surgery between January 2007 and December 2015 at two Japanese cancer centres dedicated to lateral pelvic lymph node dissection were identified and included in the analysis. Lateral pelvic lymph node metastasis was defined as pathologically confirmed metastatic lateral pelvic lymph node or lateral-local recurrence after primary surgery. RESULTS: A total of 215 consecutive patients, including 101 and 114 patients who did and did not undergo bilateral lateral pelvic lymph node dissection, were included in the analysis. Overall, 19 (8.8%) patients had lateral pelvic lymph node metastasis, including 13 with pathologically confirmed metastatic lateral pelvic lymph node and six with lateral-local recurrence. A total of 10 (4.7%) patients had local recurrence, including six with lateral-local recurrence, two with central-local recurrence and two with anastomotic recurrence. Five/7-year cumulative risks of lateral-local recurrence in patients with and without lateral pelvic lymph node dissection were 1.1/1.1% and 3.9/5.2%, respectively. CONCLUSION: The problem of the relatively high rate of lateral local recurrence remains in treating T2 low rectal cancer with only total mesorectal excision. The selection of high-risk patients of lateral pelvic lymph node metastasis and the indication of additional treatment in T2 low rectal cancer should be discussed further.
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Linfonodos , Neoplasias Retais , Humanos , Metástase Linfática/patologia , Linfonodos/cirurgia , Linfonodos/patologia , Excisão de Linfonodo , Neoplasias Retais/patologia , Pelve/patologia , Recidiva Local de Neoplasia/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Ingested alcohol is predominantly oxidized to acetaldehyde by alcohol dehydrogenase 1B (ADH1B), and acetaldehyde is further oxidized to acetate mainly by aldehyde dehydrogenase 2 (ALDH2). Although alcohol consumption is a convincing risk factor for oesophageal cancer, the role of ADH1B rs1229984 (His48Arg), the single-nucleotide polymorphism associated with slow alcohol metabolism, in oesophageal cancer development is unclear. Because this single-nucleotide polymorphism is associated with both increased risk of oesophageal cancer and drinking intensity, its association with oesophageal cancer might operate either through a direct pathway independently of drinking intensity, via an indirect pathway mediated by drinking intensity, or both. METHODS: To disentangle these different pathways, we applied a mediation analysis to an oesophageal cancer case-control study (600 cases and 865 controls) by defining the ADH1B Arg allele and alcohol consumption as exposure and mediator, respectively, and decomposed the total-effect odds ratio of the ADH1B Arg allele into direct- and indirect-effect odds ratio. RESULTS: The ADH1B Arg allele was associated with oesophageal cancer risk through pathways other than change in drinking intensity (direct-effect odds ratio, 2.03; 95% confidence interval, 1.41-2.92), in addition to the indirect pathway mediated by drinking intensity (indirect-effect odds ratio, 1.27; 95% confidence interval, 1.05-1.53). Further analyses by stratifying genotypes of ALDH2 rs671 (Glu504Lys), the functional single-nucleotide polymorphism that strongly attenuates the enzymatic activity, showed significant direct-effect odds ratio within each stratum. CONCLUSIONS: These results indicate that ADH1B Arg allele contributes to oesophageal cancer risk by slowing alcohol breakdown, in addition to its effect on the amount of alcohol consumed.
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Álcool Desidrogenase , Neoplasias Esofágicas , Humanos , Álcool Desidrogenase/genética , Aldeído-Desidrogenase Mitocondrial/genética , Consumo de Bebidas Alcoólicas/efeitos adversos , Estudos de Casos e Controles , Análise de Mediação , Polimorfismo de Nucleotídeo Único , Genótipo , Neoplasias Esofágicas/genética , Aldeído Desidrogenase/genéticaRESUMO
Dysphagia after esophagectomy is a major risk factor for aspiration pneumonia, thus preoperative assessment of swallowing function is important. The maximum phonation time (MPT) is a simple indicator of phonatory function and also correlates with muscle strength associated with swallowing. This study aimed to determine whether preoperative MPT can predict postoperative aspiration pneumonia. The study included 409 consecutive patients who underwent esophagectomy for esophageal cancer between 2017 and 2021. Pneumonia detected by routine computed tomography on postoperative days 5-6 was defined as early-onset pneumonia, and pneumonia that developed later (most often aspiration pneumonia) was defined as late-onset pneumonia. The correlation between late-onset pneumonia and preoperative MPT was investigated. Patients were classified into short MPT (<15 seconds for males and <10 seconds for females, n = 156) and normal MPT groups (≥15 seconds for males and ≥10 seconds for females, n = 253). The short MPT group was significantly older, had a lower serum albumin level and vital capacity, and had a significantly higher incidence of late-onset pneumonia (18.6 vs. 6.7%, P < 0.001). Multivariate analysis showed that short MPT was an independent risk factor for late-onset pneumonia (odds ratio: 2.26, P = 0.026). The incidence of late-onset pneumonia was significantly higher in the short MPT group (15.6 vs. 4.7%, P = 0.004), even after propensity score matching adjusted for clinical characteristics. MPT is a useful predictor for late-onset pneumonia after esophagectomy.
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Transtornos de Deglutição , Neoplasias Esofágicas , Pneumonia Aspirativa , Pneumonia , Masculino , Feminino , Humanos , Pneumonia/diagnóstico , Pneumonia/epidemiologia , Pneumonia/etiologia , Pneumonia Aspirativa/diagnóstico , Pneumonia Aspirativa/epidemiologia , Pneumonia Aspirativa/etiologia , Transtornos de Deglutição/diagnóstico , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Fonação/fisiologia , Neoplasias Esofágicas/complicações , Esofagectomia/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologiaRESUMO
A functional variant on ALDH2 rs671 (G>A) confers a protective effect against alcohol-induced carcinogenesis through an indirect pathway mediated by decreased alcohol consumption. Conversely, this variant also contributes to the accumulation of carcinogenic agents, resulting in a direct carcinogenic effect. This study aimed to separately quantify these two opposing effects of the rs671 A allele on pancreatic cancer risk and explore the impact of the rs671 A allele and alcohol consumption on pancreatic carcinogenesis. We included 426 cases and 1456 age- and sex-matched controls. Odds ratio (OR) and 95% confidence interval (CI) for alcohol consumption were estimated using a conditional logistic regression model. By defining rs671 A allele and alcohol consumption as exposure and mediator, respectively, we used mediation analysis to decompose the total-effect OR of the rs671 A allele into direct- and indirect-effect ORs. Alcohol consumption (10 g/d) was associated with pancreatic cancer risk (OR, 1.05; 95% CI, 1.01-1.10), but tests for interaction between the rs671 A allele and alcohol consumption were nonsignificant, indicating that the effect of alcohol consumption did not vary by genotype. Mediation analysis showed that the nonsignificant total effect (OR, 1.15; 95% CI, 0.92-1.44) can be decomposed into the carcinogenic direct (OR, 1.34; 95% CI, 1.04-1.72) and protective indirect effect (OR, 0.86; 95% CI, 0.77-0.95). This study supports the association between alcohol consumption and pancreatic cancer risk and indicates the potential contribution of the rs671 A allele to pancreatic carcinogenesis through impaired metabolism of known or unknown ALDH2 substrates.
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Análise de Mediação , Neoplasias Pancreáticas , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/genética , Aldeído-Desidrogenase Mitocondrial/genética , Carcinogênese/genética , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Modelos Logísticos , Neoplasias Pancreáticas/genética , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
OBJECTIVE: This study was performed to investigate the efficacy of the modified Collard (MC) technique for reducing anastomotic stricture after esophagectomy compared with the circular stapled (CS) technique. SUMMARY BACKGROUND DATA: The currently available techniques of anastomosis after esophagectomy are associated with a significant risk of anasto-motic complications. However, the optimal anastomotic technique after esophagectomy has not yet been established. METHODS: We randomly allocated patients to either the CS group or the MC group. The primary endpoint was the incidence of anastomotic stricture. The secondary endpoints included the incidence of postoperative complications (including anastomotic leakage) and quality of life (QoL). All anastomoses were performed after indocyanine green evaluation for objective homogeni-zation of blood flow to the gastric conduit between the 2 techniques. RESULTS: Among 100 randomized patients (CS group, n = 50; MC group, n = 50), anastomotic strictures were observed in 18 (42%) patients in the CS group and in no patients in the MC group. There were no significant between-group differences in anastomotic leakage (CS group, 7% vs MC group, 8%; P = 0.94). Quality of life domains of dysphagia and choking when swallowing at 3âmonths after surgery were significantly better in the MC group than in the CS group. CONCLUSIONS: The MC technique reduces the incidence of anastomotic stricture and improves postoperative quality of life. Furthermore, the incidence of anastomotic leakage is comparable between the 2 techniques based on accurate comparison under objective homogenization of the gastric conduit condition.
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Neoplasias Esofágicas , Esofagectomia , Anastomose Cirúrgica/métodos , Fístula Anastomótica/epidemiologia , Fístula Anastomótica/prevenção & controle , Constrição Patológica/epidemiologia , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Neoplasias Esofágicas/complicações , Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Humanos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Qualidade de Vida , Grampeamento Cirúrgico/efeitos adversos , Resultado do TratamentoRESUMO
OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and ß = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.