RESUMEN
BACKGROUND: A stapler is usually used for transection and closure of the pancreas in distal pancreatectomy (DP) or central pancreatectomy (CP). When the pancreas is transected to the right of the portal vein, it is difficult to use a stapler and clinically relevant postoperative pancreatic fistula (CR-POPF) frequently occurs. We report on the efficacy of pancreaticojejunostomy (PJ) of the pancreatic stump for patients in whom stapler use is difficult. METHODS: Patients who underwent DP or CP were enrolled in this study. The pancreas was usually transected by a stapler, and ultrasonic coagulating shears (UCS) were used depending on the tumor situation. When using UCS, hand-sewn closure or PJ was performed for the pancreatic stump. The relationship between clinicopathological factors and the methods of pancreatic transection and closure were investigated. RESULTS: In total, 164 patients underwent DP or CP, and the pancreas was transected with a stapler in 150 patients and UCS in 14 patients. The rate of CR-POPF was higher and the postoperative hospital stay was longer in the UCS group than in the stapler group. PJ of the pancreatic stump, which was performed for 7 patients, did not worsen intraoperative factors. CR-POPF was not seen in these 7 patients, which was significantly less than that with hand-sewn closure. CONCLUSIONS: PJ of the pancreatic stump during DP or CP reduces CR-POPF compared with hand-sewn closure and may be useful especially when the pancreas is transected to the right of the portal vein.
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Pancreatectomía , Fístula Pancreática , Neoplasias Pancreáticas , Pancreatoyeyunostomía , Humanos , Pancreatoyeyunostomía/métodos , Pancreatectomía/métodos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Fístula Pancreática/prevención & control , Fístula Pancreática/etiología , Neoplasias Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Adulto , Resultado del Tratamiento , Complicaciones Posoperatorias/prevención & control , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Anciano de 80 o más Años , Grapado Quirúrgico , Tiempo de Internación , Engrapadoras Quirúrgicas , Técnicas de SuturaRESUMEN
PURPOSE: Obesity is known to be associated with colorectal adenoma (CRA) and colorectal cancer (CRC); yet colonoscopy is not considered an essential preoperative evaluation before bariatric/metabolic surgery. The aim of this study was to clarify the clinical significance of preoperative colonoscopy for obese Japanese patients. METHODS: The subjects of this retrospective study were 114 patients who underwent screening colonoscopy before bariatric/metabolic surgery. Multivariate analyses were performed to evaluate the independent predictors of CRA/CRC among the characteristics identified as significant or nearly significant by univariate analyses. RESULTS: Colonoscopy revealed abnormal findings indicating the need for biopsy or polypectomy in 20 of the 114 patients (17.5%), and CRA was diagnosed in 13 patients (11.4%). Three patients (2.6%), who were all ≥ 56 years old, had a CRA ≥ 10 mm in diameter. The multivariate analysis showed that older age and male sex were significant predictors of CRA/CRC, which was identified in 46.2% of the male patients aged ≥ 46 years. CONCLUSION: Our findings suggest that older age and male sex may be risk factors for CRA/CRC in obese Japanese candidates for bariatric/metabolic surgery; thus, preoperative colonoscopy should be considered for these high-risk patients.
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Adenoma , Cirugía Bariátrica , Neoplasias Colorrectales , Laparoscopía , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Relevancia Clínica , Japón/epidemiología , Colonoscopía/efectos adversos , Factores de Riesgo , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/cirugía , Neoplasias Colorrectales/patología , Obesidad/complicaciones , Obesidad/epidemiología , Adenoma/diagnóstico , Adenoma/cirugía , Laparoscopía/efectos adversosRESUMEN
Constitutive activation of the mitogen-activated protein kinase (MAPK) signaling pathway is essential for tumorigenesis of pancreatic ductal adenocarcinoma (PDAC). To date, however, almost all clinical trials of inhibitor targeting this pathway have failed to improve the outcome of patients with PDAC. We found that implanted MIA Paca2, a human PDAC cell line sensitive to a MAPK inhibitor, PD0325901, became refractory within a week after treatment. By comparing the expression profiles of MIA Paca2 before and after acquisition of the refractoriness to PD0325901, we identified clusterin (CLU) as a candidate gene involved. CLU was shown to be induced immediately after treatment with PD0325901 or expressed primarily in more than half of PDAC cell lines, enhancing cell viability by escaping from apoptosis. A combination of PD0325901 and CLU downregulation was found to synergistically or additively reduce the proliferation of PDAC cells. In surgically resected PDAC tissues, overexpression of CLU in cancer cells was observed immunohistochemically in approximately half of the cases studied. Collectively, our findings highlight the mechanisms responsible for the rapid refractory response to MEK inhibitor in PDAC cells, suggesting a novel therapeutic strategy that could be applicable to patients with PDAC using inhibitor targeting the MAPK signaling pathway and CLU.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Clusterina/genética , Clusterina/metabolismo , Clusterina/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Quinasas de Proteína Quinasa Activadas por Mitógenos , Línea Celular Tumoral , Proliferación Celular , Neoplasias PancreáticasRESUMEN
BACKGROUND: The prognosis of distal cholangiocarcinoma (dCCA) remains poor; thus, the identification of new therapeutic targets is warranted. Phosphorylated S6 ribosomal protein indicates a mammalian target of rapamycin complex 1 (mTORC1) activity, and mTORC1 plays a central role in controlling cell growth and regulating glucose metabolism. We aimed to clarify the effect of S6 phosphorylation on tumor progression and the glucose metabolic pathway in dCCA. METHODS: Thirty-nine patients with dCCA who underwent curative resection were enrolled in this study. S6 phosphorylation and the expression of GLUT1 were evaluated by immunohistochemistry, and their relationship with clinical factors was investigated. The effect of S6 phosphorylation on glucose metabolism with PF-04691502 treatment, an inhibitor of S6 phosphorylation, was examined in cancer cell lines by Western blotting and metabolomics analysis. Cell proliferation assays were performed with PF-04691502. RESULTS: S6 phosphorylation and the expression of GLUT1 were significantly higher in patients with an advanced pathological stage. Significant correlations between GLUT1 expression, S6 phosphorylation, and SUV-max of FDG-PET were shown. In addition, cell lines with high S6 phosphorylation levels showed high GLUT1 levels, and the inhibition of S6 phosphorylation reduced the expression of GLUT1 on Western blotting. Metabolic analysis revealed that inhibition of S6 phosphorylation suppressed pathways of glycolysis and the TCA cycle in cell lines, and then, cell proliferation was effectively reduced by PF-04691502. CONCLUSION: Upregulation of glucose metabolism via phosphorylation of S6 ribosomal protein appeared to play a role in tumor progression in dCCA. mTORC1 may be a therapeutic target for dCCA.
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Colangiocarcinoma , Serina-Treonina Quinasas TOR , Humanos , Fosforilación , Serina-Treonina Quinasas TOR/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Proteínas Ribosómicas/metabolismo , Regulación hacia Arriba , Glucosa/metabolismo , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismoRESUMEN
BACKGROUND: Endoscopic tumor resection and intestinal defect repair are technically challenging leading to invasive surgery and colectomy performed for resection of benign polyps. In this study, we evaluated the use of an endoscopic overtube with bilateral tool channels for these procedures. METHODS: Using a fresh porcine colorectum in a 3D ex vivo model, 3 cm lesions at the posterior wall of the transverse colon were removed by two different techniques: standard endoscopic submucosal dissection (ESD) technique (STD, n = 12) and ESD using the overtube with an endoscopic snare and grasper through the bilateral channels (OT, n = 12). Procedure times and the number of muscular injuries were evaluated. Using the same model, 5-10 mm full-thickness perforations within a 3 cm mucosal defect at the posterior wall of the transverse colon were closed by two different techniques: standard endoscopic closure technique (STD, n = 12) and endoscopic closure using the overtube with two graspers (OT, n = 12). The outcomes measured included bursting pressure and the number of endoscopic clips used for closure. RESULTS: Endoscopic resection of lesions was performed by the OT group in a significantly shorter total procedure time (STD vs. OT = median 38.9 min vs. 17.3, p < 0.001) and with fewer muscular injuries (median 0 vs. 2, p = 0.002), compared with the STD group. After repair of intestinal defects, the OT group showed higher median bursting pressures (STD vs. OT = 11.2 mmHg vs. 57.1, p = 0.008) despite using fewer clips (median 13 vs. 10, p < 0.001). CONCLUSION: This study demonstrates a novel traction technique with an endoscopic overtube using multiple instruments to remove lesions and repair intestinal defects in the colon more effectively. This endoscopic platform could provide a safe alternative to invasive surgical treatment.
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Resección Endoscópica de la Mucosa , Animales , Colon/cirugía , Resección Endoscópica de la Mucosa/instrumentación , Resección Endoscópica de la Mucosa/métodos , Porcinos , Resultado del Tratamiento , Técnicas de Cierre de HeridasRESUMEN
BACKGROUND: The Critical View of Safety (CVS) was proposed in 1995 to prevent bile duct injury during laparoscopic cholecystectomy (LC). The achievement of CVS was evaluated subjectively. This study aimed to develop an artificial intelligence (AI) system to evaluate CVS scores in LC. MATERIALS AND METHODS: AI software was developed to evaluate the achievement of CVS using an algorithm for image classification based on a deep convolutional neural network. Short clips of hepatocystic triangle dissection were converted from 72 LC videos, and 23,793 images were labeled for training data. The learning models were examined using metrics commonly used in machine learning. RESULTS: The mean values of precision, recall, F-measure, specificity, and overall accuracy for all the criteria of the best model were 0.971, 0.737, 0.832, 0.966, and 0.834, respectively. It took approximately 6 fps to obtain scores for a single image. CONCLUSIONS: Using the AI system, we successfully evaluated the achievement of the CVS criteria using still images and videos of hepatocystic triangle dissection in LC. This encourages surgeons to be aware of CVS and is expected to improve surgical safety.
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Colecistectomía Laparoscópica , Cirujanos , Humanos , Colecistectomía Laparoscópica/métodos , Inteligencia Artificial , Grabación en Video , Grabación de Cinta de VideoRESUMEN
BACKGROUND: We have implemented Smart Endoscopic Surgery (SES), a surgical system that uses artificial intelligence (AI) to detect the anatomical landmarks that expert surgeons base on to perform certain surgical maneuvers. No report has verified the use of AI-based support systems for surgery in clinical practice, and no evaluation method has been established. To evaluate the detection performance of SES, we have developed and established a new evaluation method by conducting a clinical feasibility trial. METHODS: A single-center prospective clinical feasibility trial was conducted on 10 cases of LC performed at Oita University hospital. Subsequently, an external evaluation committee (EEC) evaluated the AI detection accuracy for each landmark using five-grade rubric evaluation and DICE coefficient. We defined LM-CBD as the expert surgeon's "judge" of the cystic bile duct in endoscopic images. RESULTS: The average detection accuracy on the rubric by the EEC was 4.2 ± 0.8 for the LM-CBD. The DICE coefficient between the AI detection area of the LM-CBD and the EEC members' evaluation was similar to the mean value of the DICE coefficient between the EEC members. The DICE coefficient was high score for the case that was highly evaluated by the EEC on a five-grade scale. CONCLUSION: This is the first feasible clinical trial of an AI system designed for intraoperative use and to evaluate the AI system using an EEC. In the future, this concept of evaluation for the AI system would contribute to the development of new AI navigation systems for surgery.
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Colecistectomía Laparoscópica , Humanos , Inteligencia Artificial , Conductos Biliares , Colecistectomía Laparoscópica/métodos , Estudios de Factibilidad , Estudios ProspectivosRESUMEN
BACKGROUND: Attention to anatomical landmarks in the appropriate surgical phase is important to prevent bile duct injury (BDI) during laparoscopic cholecystectomy (LC). Therefore, we created a cross-AI system that works with two different AI algorithms simultaneously, landmark detection and phase recognition. We assessed whether landmark detection was activated in the appropriate phase by phase recognition during LC and the potential contribution of the cross-AI system in preventing BDI through a clinical feasibility study (J-SUMMIT-C-02). METHODS: A prototype was designed to display landmarks during the preparation phase and Calot's triangle dissection. A prospective clinical feasibility study using the cross-AI system was performed in 20 LC cases. The primary endpoint of this study was the appropriateness of the detection timing of landmarks, which was assessed by an external evaluation committee (EEC). The secondary endpoint was the correctness of landmark detection and the contribution of cross-AI in preventing BDI, which were assessed based on the annotation and 4-point rubric questionnaire. RESULTS: Cross-AI-detected landmarks in 92% of the phases where the EEC considered landmarks necessary. In the questionnaire, each landmark detected by AI had high accuracy, especially the landmarks of the common bile duct and cystic duct, which were assessed at 3.78 and 3.67, respectively. In addition, the contribution to preventing BDI was relatively high at 3.65. CONCLUSIONS: The cross-AI system provided landmark detection at appropriate situations. The surgeons who previewed the model suggested that the landmark information provided by the cross-AI system may be effective in preventing BDI. Therefore, it is suggested that our system could help prevent BDI in practice. Trial registration University Hospital Medical Information Network Research Center Clinical Trial Registration System (UMIN000045731).
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Traumatismos Abdominales , Enfermedades de los Conductos Biliares , Colecistectomía Laparoscópica , Humanos , Inteligencia Artificial , Estudios Prospectivos , Conducto Cístico , Conductos Biliares/lesiones , Complicaciones Intraoperatorias/prevención & controlRESUMEN
BACKGROUND: Multidisciplinary therapy centered on antitumor drugs is indicated in patients with unresectable pancreatic neuroendocrine tumors (PanNET). However, the criteria for selection of optimal therapeutic agents is controversial. The aim of this study was to assess the malignancy of PanNET for optimal therapeutic drug selection. METHODS: Forty-seven patients with PanNET who underwent surgery were reviewed retrospectively, and immunohistochemical characteristics, including expression of GLUT1, SSTR2a, SSTR5, Survivin, X-chromosome-linked inhibitor of apoptosis protein (XIAP), and Caspase3 in the resected specimens, were investigated. Relapse-free survival (RFS) and overall survival (OS) were evaluated with regard to the characteristics using the Kaplan-Meier method and compared with the log-rank test. RESULTS: GLUT1 expression showed significant correlation with sex (p = 0.036) and mitotic rate (p = 0.048). Survivin and XIAP expression showed significant correlation with T-stage (p = 0.014 and 0.009), p-Stage (p = 0.028 and 0.045), and mitotic rate (p = 0.023 and 0.007). XIAP expression also significantly influenced OS (p = 0.044). CONCLUSIONS: Survivin and XIAP correlated with grade of malignancy, and expression of XIAP in particular was associated with a poor prognosis. Expression of these proteins may be a useful indicator to select optimal therapeutic agents in PanNET.
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Tumores Neuroendocrinos , Neoplasias Pancreáticas , Humanos , Survivin/metabolismo , Survivin/uso terapéutico , Proteínas Inhibidoras de la Apoptosis/metabolismo , Proteínas Inhibidoras de la Apoptosis/uso terapéutico , Estudios Retrospectivos , Transportador de Glucosa de Tipo 1 , Pronóstico , Recurrencia Local de Neoplasia , Proteína Inhibidora de la Apoptosis Ligada a X/metabolismo , Proteína Inhibidora de la Apoptosis Ligada a X/uso terapéutico , Apoptosis , Neoplasias Pancreáticas/patologíaRESUMEN
BACKGROUND: Laparoscopic repeat hepatectomy (LRH) has increased, but appropriate indications for LRH are unclear. This study aimed to clarify appropriate indications for LRH. METHODS: We retrospectively compared surgical outcomes between open RH (ORH) (n = 57) and LRH (n = 40) groups. To detect difficult cases of complete pure LRH, we examined patients with unplanned intraoperative hand-assisted laparoscopic surgery (HALS)/open conversion (n = 6). RESULTS: In the LRH versus ORH group, as previous hepatectomy, laparoscopic (75% vs. 12%, p < 0.001) and partial hepatectomy (Hr0) (73% vs. 37%, p = 0.002) were more frequently performed, and as RH procedure, partial hepatectomy (Hr0) (88% vs. 47%, p = 0.0002) was more frequently performed. S1 tumor cases were higher in ORH group (11% vs. 0%), but S2-6 cases were higher in LRH group (73% vs. 49%) (p = 0.02). In LRH group, compared to the pure LRH patients, HALS/open conversion patients underwent significantly more previous hepatectomy with more than lobectomy (Hr2-3) (33% vs. 2.9%, p = 0.033) and more RH procedures with segmentectomy (HrS) (33% vs. 2.9%, p = 0.03). All LRH requiring a repeat hepatic hilar approach were HALS conversions. CONCLUSION: Appropriate indications for LRH were previous hepatectomy was laparoscopic partial hepatectomy (Hr0), and RH procedure was partial hepatectomy (Hr0) for S2-6 tumor location. When RH is more than segmentectomy (HrS) requiring a repeat hepatic hilar approach, planned HALS or ORH may be a better approach than pure LRH.
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Laparoscopía , Neoplasias Hepáticas , Humanos , Hepatectomía/métodos , Neoplasias Hepáticas/cirugía , Estudios Retrospectivos , Laparoscopía/métodos , Tiempo de Internación , Resultado del TratamientoRESUMEN
BACKGROUND: Laparoscopic liver resection (LLR) is possible in many patients, but pure LLR is sometimes difficult to complete, and unplanned intraoperative hand-assisted laparoscopic surgery (HALS) or open conversion is sometimes necessary. However, appropriate indications and timing for conversion are unclear. This study aimed to clarify the indications for HALS and open conversion from pure LLR. METHODS: We collected data from 208 patients who underwent LLR from January 2010 to February 2021 in our department. We retrospectively examined these data between cases of unplanned intraoperative HALS conversion, open conversion, and pure LLR, and clarified risk factors and indications for HALS or open conversion. RESULTS: There were 191 pure LLRs, nine HALS conversions, and eight open conversions. In the HALS conversion group versus pure LLR group, body mass index (BMI) (27.0 vs. 23.7 kg/m2, p = 0.047), proportions of patients with history of upper abdominal surgery (78% vs. 33%; p = 0.006), repeat hepatectomy (56% vs. 15%; p = 0.002), S7 or S8 tumor location (67% vs. 35%; p = 0.049), and difficulty score (DS) ≥ 7 (56% vs. 19%; p = 0.008) were significantly higher, and surgical time (339 vs. 239 min; p = 0.031) was significantly longer. However, postoperative states were not significantly different between the two groups. The BMI cutoff value for risk of unplanned intraoperative conversion determined by receiver operating characteristic curve analysis was 25 kg/m2, and the proportion of patients with BMI ≥ 25 kg/m2 (89% vs. 31%, p < 0.001) was significantly higher in the HALS conversion versus pure LLR group. In the open conversion group, although there were no significant differences compared to the HALS group in clinicopathological factors except for sex, blood loss was greater (1425 vs. 367 mL; p < 0.001). CONCLUSION: Risk factors for considering HALS during LLR were patients with a history of upper abdominal surgery including repeat hepatectomy, BMI ≥ 25 kg/m2, S7 or S8 tumor location, DS ≥ 7, and prolonged surgical time. Furthermore, uncontrollable intraoperative bleeding was an indication for open conversion.
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Laparoscópía Mano-Asistida , Laparoscopía , Neoplasias Hepáticas , Neoplasias , Laparoscópía Mano-Asistida/efectos adversos , Hepatectomía/efectos adversos , Humanos , Laparoscopía/efectos adversos , Tiempo de Internación , Hígado/patología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/cirugía , Neoplasias/cirugía , Complicaciones Posoperatorias/etiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
PURPOSE: Postoperative weight loss is related to postoperative adherence to follow-up after bariatric/metabolic surgery, but many patients stop attending follow-up visits early. The aim of this study was to clarify predictors of early withdrawal from follow-up after laparoscopic sleeve gastrectomy (LSG) in a Japanese institution. METHODS: One hundred and fifty-three patients who underwent LSG were retrospectively included in this study. Multivariate analysis was performed to evaluate independent predictors of withdrawal from follow-up visits within 12 months after LSG among significant or nearly significant factors in the univariate analyses. The discrimination power of significant factors was estimated using area under the receiver operating characteristic curve (AUC). RESULTS: Within 12 months after LSG, 25 of the 153 patients withdrew from follow-up visits. The multivariate analysis showed that age was the only significant predictor of withdrawal. The AUC for age was 0.685, and the cut-off value was < 40 years. The younger patients (< 40 years old) had a significantly higher rate of withdrawal compared with the older patients (≥ 40 years) (27.0% vs. 8.9%). CONCLUSION: Older Japanese patients (≥ 40 years old) may be better candidates for LSG. We consider it significant to continue to emphasize the importance of follow-up visits in younger patients after LSG.
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Atención Ambulatoria/estadística & datos numéricos , Cirugía Bariátrica/métodos , Gastrectomía/métodos , Laparoscopía/métodos , Obesidad Mórbida/psicología , Obesidad Mórbida/cirugía , Cooperación del Paciente/estadística & datos numéricos , Pérdida de Peso , Privación de Tratamiento/estadística & datos numéricos , Adulto , Factores de Edad , Anciano , Femenino , Predicción , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Obesidad Mórbida/fisiopatología , Educación del Paciente como Asunto , Periodo Posoperatorio , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE: To compare the outcomes of laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) with those of open RAMPS (O-RAMPS) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS: We reviewed, retrospectively, the medical records of 50 patients who underwent RAMPS for PDAC without resection of major vessels and adjacent organs between 2007 and 2019, and analyzed the relationship between the operative method and surgical and oncological outcomes. RESULTS: Nineteen of the 50 patients underwent L-RAMPS and 31 patients underwent O-RAMPS. L-RAMPS was associated with significantly less blood loss (P = 0.034) but a longer operative time (P = 0.001) than O-RAMPS. There were no significant differences in patient characteristics, tumor factors, or postoperative course; or in the rates of recurrence-free survival (P = 0.084) or overall survival (P = 0.402) between the L-RAMPS and O-RAMPS groups. CONCLUSION: L-RAMPS for PDAC resulted in less blood loss but a longer operative time than O-RAMPS. Although L-RAMPS may be feasible, the operative time needs to be reduced by standardizing the procedure.
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Carcinoma Ductal Pancreático/cirugía , Laparoscopía/métodos , Pancreatectomía/métodos , Neoplasias Pancreáticas/cirugía , Esplenectomía/métodos , Anciano , Anciano de 80 o más Años , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Femenino , Humanos , Masculino , Tempo Operativo , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Mutations in RAS or BRAF are associated with poor prognosis and resistance to epidermal growth factor receptor (EGFR)-targeted therapy in colorectal cancer (CRC). Despite their common ability to activate downstream genes such as MEK and ERK, the therapeutic benefit of MEK inhibitors for patients with RAS/BRAF mutant CRC is limited, highlighting the need for biomarkers to predict the efficacy of MEK inhibition. Previously, we reported that a change in phosphorylation of ribosomal protein S6 (pS6) after MEK inhibition was significantly associated with sensitivity to MEK inhibition in gastric cancer cells. Here, we investigated the value of the response in pS6 for predicting the efficacy of trametinib, a MEK inhibitor, in patients with RAS/BRAF mutant CRC using patient-derived CRC organoids. We found that a subset of CRC cell lines and organoids were sensitive to trametinib. The change in phosphorylated ERK, a downstream molecule of the RAS/RAF/MEK pathway, was not significantly associated with trametinib sensitivity. On the other hand, only those with sensitivity showed a reduction of pS6 levels in response to trametinib. The change in pS6 after trametinib treatment was detectable by Western blotting, immunohistochemistry or immunocytochemistry. We also demonstrated an impact of MEK inhibition on pS6 in vivo using a xenograft model. Our data suggest that, in combination with patient-derived organoids, immunostaining-based detection of pS6 could be useful for prediction of trametinib sensitivity.
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Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Fosforilación/efectos de los fármacos , Piridonas/farmacología , Pirimidinonas/farmacología , Proteína S6 Ribosómica , Anciano , Anciano de 80 o más Años , Animales , Antineoplásicos/farmacología , Línea Celular Tumoral , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos NOD , Persona de Mediana Edad , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , Inhibidores de Proteínas Quinasas/farmacología , Proteína S6 Ribosómica/química , Proteína S6 Ribosómica/metabolismoRESUMEN
BACKGROUND: Progression of pancreatic intraepithelial neoplasia (PanIN) to invasive carcinoma is a critical factor impacting the prognosis of patients with pancreatic tumors. However, the molecular mechanisms involved are not fully understood. We have reported that the process frequently involves loss of chromosome 8p, causing downregulation of DUSP4, thus conferring invasive ability on cancer cells. Here, we focus on ZNF395, whose expression was also found to be decreased by 8p loss and was predicted to be a growth suppressor gene. METHODS: Pancreatic cancer cell lines inducibly expressing ZNF395 were established to assess the functional significance of ZNF395 in pancreatic carcinogenesis. Immunohistochemistry was also performed to analyze the expression levels of ZNF395 in pancreatic cancer tissues. RESULTS: Induction of ZNF395 in pancreatic cancer cells resulted in marked activation of JNK and suppression of their proliferation through a delay in cell cycle progression. Immunohistochemistry revealed that ZNF395 was expressed ubiquitously in both normal pancreatic ducts and PanINs but was significantly reduced in invasive cancers, especially those showing poor differentiation. CONCLUSION: ZNF395 acts as a novel tumor suppressor gene. Its downregulation caused by 8p loss in intraepithelial cells accelerates their proliferation through dysregulation of the cell cycle, leading to progression to invasive cancer.
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Carcinoma in Situ/genética , Carcinoma Ductal Pancreático/genética , Proteínas de Unión al ADN/genética , Progresión de la Enfermedad , Regulación hacia Abajo , Conductos Pancreáticos/patología , Factores de Transcripción/genética , Carcinoma Ductal Pancreático/fisiopatología , Línea Celular Tumoral , Humanos , Inmunohistoquímica/métodosRESUMEN
BACKGROUND: Endoscopic submucosal dissection (ESD) is a challenging procedure for the removal of colorectal tumors, especially tumors located in the right colon. The use of traction could make this procedure technically easier and reduce procedure times and complication rates. In this study, we demonstrated the feasibility and utility of a traction technique utilizing an endoscopic snare through an overtube, a double-balloon endolumenal interventional platform (DEIP) in a porcine colorectal model. METHODS: A total of 120 procedures were performed using three different techniques: standard ESD technique (STD), ESD with DEIP (DEIP alone), and ESD with DEIP and a snare (DEIP + Snare). The snare was passed inside the overtube and used as a grasper on the tissue to provide traction. Lesions 3 or 4 cm in diameter were removed with a 5 mm margin from the anterior and posterior walls of the proximal Transverse Colon, the Hepatic Flexure, and the posterior wall of the Cecum. The outcomes measured included procedure times and the number of muscularis propria injuries. RESULTS: The DEIP + Snare group showed significantly shorter total procedure and submucosal dissection times for lesions in all locations (median 28.1 min (DEIP + Snare, n = 32) vs 39.8 (STD, n = 32) vs 39.7 (DEIP alone, n = 32); 7.5 min vs 25.3 vs 25.1) and had fewer muscularis propria injuries (median 0 [range 0-2] vs 2 [0-7] vs 1 [0-6]) than the two other groups. Larger lesions (4 cm) were successfully removed by regrasping the tissue in DEIP + Snare group, which showed significantly shorter total procedure time [31.4 min (DEIP + Snare, n = 8) vs 40.1 (STD, n = 8) vs 45.6 (DEIP alone, n = 8)] and submucosal dissection time (12.3 min vs 27.6 vs 29.1) than the two other groups. CONCLUSIONS: ESD traction technique with an endolumenal platform and snare enables faster removal of large polyps in the right colon with fewer injuries than standard methods of ESD.
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Neoplasias Colorrectales , Resección Endoscópica de la Mucosa , Animales , Disección , Porcinos , Tracción , Resultado del TratamientoRESUMEN
BACKGROUND: The treatment strategy for pancreatic metastasis (PM) from renal cell carcinoma (RCC) is unclear due to its rarity. The aim of this study was to reveal the role of surgery for PM from RCC. METHODS: A systematic literature search was conducted using PubMed and the Cochrane Library. The effectiveness of surgery for PM was evaluated based on the primary outcome of overall survival (OS), which was investigated in relation to surgical procedures and metastatic sites via subgroup analyses. RESULTS: There was no significant difference in the rate of 2-year OS between the surgery and control group (OR 0.43, 95% CI 0.14-1.26, P = 0.12). However, the rate of 5-year OS was significantly higher in the surgery group than the control group (OR = 0.41, 95% CI 0.18-0.93, P = 0.03). The rates of the complications and OS were not significantly different between radical and conservative pancreatectomies. The rate of 5-year OS of the patients with PM was higher than that with other metastases (OR 0.38, 95% CI 0.20-0.74, P = 0.004). CONCLUSION: Surgical resection for PM from RCC is associated with good prognosis. Limited surgery may be a useful option depending on the location of the lesion.
Asunto(s)
Carcinoma de Células Renales , Neoplasias Renales , Neoplasias Pancreáticas , Carcinoma de Células Renales/cirugía , Humanos , Neoplasias Renales/cirugía , Pancreatectomía , Neoplasias Pancreáticas/cirugía , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a major complication of pancreatoduodenectomy (PD). A pancreatic stent is usually used for drainage of the pancreatic duct, but the best type of the stent remains unclear. The aim of this study was to investigate perioperative factors and their influence on the risk of CR-POPF following PD. METHODS: From 2006 to 2019, the records of 246 patients who underwent PD were retrospectively reviewed, and the relationship between perioperative factors including type of pancreatic stent and CR-POPF was investigated. External or internal pancreatic stents were used for drainage of the pancreatic duct, and the internal stent was inserted 1 cm into the jejunum to decrease stent obstruction. RESULTS: External and internal pancreatic stents were used in 137 and 109 patients, respectively. Multivariate analysis revealed that the diameter of the main pancreatic duct (odds ratio = 0.292, 95% confidence interval = 0.140-0.605, P = 0.001), diagnosis (odds ratio = 3.359, 95% confidence interval = 1.498-7.693, P = 0.003), and type of pancreatic stent (odds ratio = 0.435, 95% confidence interval = 0.203-0.934, P = 0.033) were independent factors related to CR-POPF after PD. Internal stent was associated with a low rate of CR-POPF (P < 0.001) and short postoperative hospital stay (P < 0.001) compared to external stent. CONCLUSION: A short pancreatic internal stent could decrease the incidence of CR-POPF.
Asunto(s)
Fístula Pancreática , Pancreaticoduodenectomía , Humanos , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Pancreaticoduodenectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/prevención & control , Estudios Retrospectivos , Factores de Riesgo , StentsRESUMEN
PURPOSE: Although the same distal pancreatectomy (DP) is performed regardless of the location of left-sided pancreatic ductal adenocarcinoma (PDAC), the clinicopathological features may differ depending on the tumor location. The present study investigated the relationship between the tumor location and clinicopathological features in patients with left-sided PDAC. METHODS: The records of 59 patients who underwent DP for PDAC were enrolled. The relationship between the tumor location and clinicopathological features was investigated. The tumor location was classified into three groups according to the 7th AJCC/UICC TNM classification: body (Pb), body and tail (Pbt), and tail (Pt). RESULTS: Tumors were located at the Pb in 26 patients, Pbt in 15, and Pt in 18. There was no metastasis to the lymph nodes around the common hepatic artery in Pt. The rate of peritoneal dissemination in the Pt was higher than that in the Pb (P = 0.034) or Pbt (P = 0.002). There were no significant differences in the overall survival among the three groups. CONCLUSION: There was no metastasis to the lymph nodes around the common hepatic artery, and peritoneal dissemination was the most common site of recurrence in Pt tumors.
Asunto(s)
Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Pancreatectomía/métodos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/clasificación , Femenino , Arteria Hepática , Humanos , Masculino , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Neoplasias Pancreáticas/clasificación , Peritoneo/patologíaRESUMEN
In Japan, the number of bariatric surgeries performed has remained low. Thus, concomitant laparoscopic cholecystectomy (LC) with laparoscopic sleeve gastrectomy (LSG) is still relatively uncommon, but is increasing. We developed new port-sharing techniques for LC and LSG, which we performed on 26 obese Japanese patients with gall bladder (GB) diseases, using the LSG trocar arrangement and one additional trocar. We performed LC first, and after exchanging a port for a liver retractor in the epigastrium, we then completed LSG. One patient with an anomalous extrahepatic bile duct required one additional port. The mean LC time was 55 min, and the transition to LSG just after LC was smooth in all the patients. One patient suffered postoperative intraperitoneal hemorrhage, which was managed conservatively. Concomitant LC with LSG using port-sharing techniques is feasible and safe for obese Japanese patients with GB diseases.