RESUMO
BACKGROUND: In patients with hepatic artery variation (HAV), feasibility and justification of robotic pancreatoduodenectomy (RPD) for periampullary lesions have been not been well established. METHODS: A total of 600 patients with periampullary lesions receiving RPD or open pancreaticoduodenectomy (OPD) were identified from our prospectively collected computer database. Surgical outcomes, oncological radicality, and survival outcomes after RPD in HAV ( +) and (-) patients were compared. RESULTS: The incidence of HAV was 16%, including 12.7% in patients with RPD and 23.0% in those with OPD. In the HAV ( +) group, vascular injury rate had no statistical difference between the RPD (3.7%) and OPD (9.1%) patients, P = 0.404. Among the RPD patients, those with HAV ( +) had longer operation time (8.5 ± 2.5 vs. 7.7 ± 2.0 h, P = 0.013) and higher vascular injury (3.8% vs. 0.6%, P = 0.024) when compared with the HAV (-) patients. There was no significant difference between the HAV ( +) and (-) patients with RPD regarding blood loss, open conversion, vascular resection, and surgical mortality and morbidity. There was no survival difference between the HAV ( +) and (-) patients with pancreatic head adenocarcinoma after RPD. There was no survival difference between RPD and OPD in the HAV ( +) group. CONCLUSIONS: When compared with OPD, RPD is feasible and justifiable without increasing vascular injury rate for patients with HAV ( +). Hepatic artery variation has no negative impact on surgical, oncological, and survival outcomes following an RPD, if it is accurately identified pre-operatively and appropriately managed intraoperatively.
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Artéria Hepática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/métodos , Artéria Hepática/cirurgia , Feminino , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias Pancreáticas/cirurgia , Idoso , Resultado do Tratamento , Duração da Cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: This study is to clarify the feasibility of and justification for robotic pancreaticoduodenectomy (RPD) in patients with pancreatic adenocarcinoma. METHODS: A 1-to-1 propensity score-matched comparison of RPD and open pancreaticoduodenectomy (OPD) was performed based on six covariates commonly used to predict the survival outcome for pancreatic adenocarcinoma. RESULTS: A total of 130 patients were enrolled, with 65 in each study group after propensity score matching. The median operating time was longer for RPD (8.3 h vs. 7.0 h, P = 0.002). However, RPD was associated with less blood loss, lower overall surgical complication rate, and lower incidence of delayed gastric emptying. The resection radicality was oncologically similar between these two groups, but the median lymph node yield was higher for RPD (18 vs. 16, P = 0.038). Before propensity score matching, the 5-year survival was better in RPD (27.0% vs. 17.6%, P = 0.006). After matching, there was still a trend towards improved overall survival in the RPD group; however, the difference in 5-year survival between RPD and OPD was not significant (24.5% vs. 19.7%, P = 0.088). CONCLUSION: RPD is not only technically feasible with no increase in surgical risk but also oncologically justifiable without compromising survival outcome. However, unlike randomized control trials, the limitations in this propensity score-matched analysis only accounted for 6 observed covariates commonly used to predict the survival outcome in patients with pancreatic adenocarcinoma, and confounders not included in this study could also affect our results.
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Adenocarcinoma , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Adenocarcinoma/cirurgia , Estudos de Viabilidade , Humanos , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pontuação de Propensão , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
BACKGROUND: To evaluate the surgical, oncological, and survival outcomes after pancreaticoduodenectomy (PD) with superior mesenteric vein (SMV)/portal vein (PV) resection by either robotic PD (RPD) or open PD (OPD). METHODS: Data of patients with periampullary lesions undergoing PD were retrieved from a prospectively collected computer database. Surgical risks as well as oncological and survival outcomes were compared between patients with (vein resection group) and without SMV/PV resection (without vein resection group). RESULTS: A total of 391 patients undergoing pancreaticoduodenectomy were enrolled, including 43 (11.0%) and 384 (89.0%) patients with and without vein resection, respectively. Eleven (25.6%) of PDs with vein resection were performed using the robotic approach. Operation time in the vein resection group was significantly longer (median of 8 vs. 7 h). Blood loss, curative resection (R0) rate, and harvested lymph node number were similar between these two groups. Surgical outcomes including postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), postpancreatectomy hemorrhage (PPH), chyle leakage, wound infection, and hospital stay were not significantly different between the two groups. There was no survival difference between these groups, with 1- and 3-year survival rates of 92.6% and 26.5%, respectively, for vein resection group, vs. 70.3% and 37.2%, respectively, for the without vein resection group. CONCLUSIONS: PD with vein resection is technically feasible by OPD and RPD in selected patients. Additional SMV/PV would not increase the surgical risks of PD and could achieve similar survival outcomes for pancreatic head adenocarcinoma when compared to PD without vein resection.
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Adenocarcinoma/cirurgia , Veias Mesentéricas/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/métodos , Veia Porta/cirurgia , Procedimentos Cirúrgicos Robóticos , Procedimentos Cirúrgicos Vasculares/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Pancreaticoduodenectomia/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Procedimentos Cirúrgicos Robóticos/mortalidade , Análise de Sobrevida , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/mortalidadeRESUMO
BACKGROUND: Gallbladder metastasis from renal cell carcinoma (RCC) is extremely rare. The purpose of this study is to clarify the characteristics of metastatic RCC to gallbladder. METHODS: The pooled data for analysis were collected from the case of metastatic RCC to gallbladder encountered by our institution along with sporadic cases reported in literature from 1991 to 2015. RESULTS: A total of 50 cases of metastatic RCC to gallbladder were recruited for study. Fifty-seven percentage of the primary RCC was from the right kidney and 43% from the left. The median interval between diagnoses of primary and metastatic RCC to gallbladder was 36 months, with the longest duration up to 324 months. Most (70%) were asymptomatic. The size of metastatic RCC to gallbladder ranged from 0.8 cm to 9 cm, with median of 2.6 cm. Majority (91%) of the metastatic RCCs presented as a polypoid mass with narrow stalk, and 82% were hypervascular lesion. The overall 1 year, 3 year and 5 year survival rate was 91.5%, 76.2% and 59.3% respectively, with a median of 26.5 months. Number of the metastatic site, timing of gallbladder metastasis, symptom, tumor size and operation type of cholecystectomy seemed to have no impact on survival. CONCLUSIONS: Metastatic RCC to the gallbladder should be taken into account for a gallbladder polypoid mass with narrow hypervascular stalk during the diagnosis and/or follow-up of primary RCC. Gallbladder metastasis from RCC is not necessarily to be an advanced stage with poor outcome, and cholecystectomy is recommended whenever possible.
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Carcinoma de Células Renais/patologia , Neoplasias da Vesícula Biliar/patologia , Pólipos/patologia , Carcinoma de Células Renais/diagnóstico , Feminino , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/secundário , Humanos , Masculino , Metástase NeoplásicaRESUMO
BACKGROUND: Polypoid lesions of the gallbladder (PLG) are common, and most are benign. Few lesions are found to be malignant, but are not preoperatively distinguished as such using common imaging modalities. Therefore, we compared characteristics of benign and malignant PLGs in depth. METHODS: We enrolled 1204 consecutive patients diagnosed with PLG at Taipei Veterans General Hospital between January 2004 and December 2013. Patients underwent either surgery or regular follow-up with various imaging modalities for at least 24 months. The mean follow-up duration was 72 ± 32 months. RESULTS: Of 1204 patients, 194 underwent surgical treatment and 1010, regular follow-up. In addition, 73 % patients were asymptomatic. The mean PLG size was 6.9 ± 7.7 (range 0.8-129) mm; the PLGs of 337 patients (28 %) grew during their follow-up periods. The majority of PLGs (90.4 %) were single lesions, and 10.5 % of patients had associated gallstones. The PLGs of 20.1 % of surgical patients were malignant. Malignant PLGs were found in 32.4 % of patients ≥50 years old and in 4.7 % of those <50 years old (p < 0.001). Right quadrant abdominal pain, epigastric pain, and body weight loss were the three most common symptoms associated with malignancy. Malignant PLGs were significantly larger than benign lesions (means: 27.5 ± 18.4 mm vs. 12.3 ± 12.3 mm, respectively, p < 0.001). Notably, the size of 5 % of malignant PLGs was 3-5 mm, and that of 8 % was 5-10 mm. The negative predictive value for gallbladder malignancy was 92.8 % based on a size ≥10 mm and 100 % based on a size ≥3 mm. CONCLUSIONS: Our study reassesses the PLG size that warrants more aggressive intervention. Cholecystectomy remains mandatory for PLGs > 10 mm, but should also be considered a definitive diagnostic and treatment modality for PLGs with diameters of 3-10 mm.
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Colecistectomia , Doenças da Vesícula Biliar/diagnóstico , Pólipos/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Feminino , Seguimentos , Doenças da Vesícula Biliar/patologia , Doenças da Vesícula Biliar/cirurgia , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/patologia , Neoplasias da Vesícula Biliar/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos/patologia , Pólipos/cirurgia , Valor Preditivo dos Testes , Estudos Retrospectivos , Carga Tumoral , Adulto JovemRESUMO
BACKGROUND: The aim of this study was to compare perioperative outcomes after Blumgart pancreaticojejunostomy (PJ) and pancreaticogastrostomy (PG) for pancreatic-enteric reconstruction following pancreaticoduodenectomy. METHODS: Data of patients undergoing Blumgart PJ and PG were retrieved from prospectively-collected database. Matched patients in each surgical groups were included based on the Callery risk scoring system for clinically relevant postoperative pancreatic fistula (CR-POPF) (grades B and C). Surgical parameters and risks were compared between these two groups. RESULTS: A total of 206 patients undergoing PD were included. Blumgart PJ was associated with shorter postoperative hospital stay (median (range) 25 (10-99) vs. 27 (10-97) days, P = 0.022). There was no surgical mortality in the Blumgart PJ group, but a 4.9% perioperative mortality in the PG, P = 0.030. The CR-POPF by Blumgrt PG is significantly lower than that by PG for overall patients (7% vs. 20%, P = 0.007), especially for those in intermediate fistula risk zone (6% vs. 21%, P =0.048) and high fistula risk zone (14% vs. 47%, P=0.038). CONCLUSIONS: Blumgart PJ is superior to PG in terms of pancreatic leakage and surgical mortality. Blumgart PJ can be recommended for pancreatic reconstruction after PD for all pancreatic remnant subtypes.
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Gastrostomia/métodos , Pancreaticoduodenectomia , Pancreaticojejunostomia , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Gastrostomia/efeitos adversos , Gastrostomia/mortalidade , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Pancreaticojejunostomia/efeitos adversos , Pancreaticojejunostomia/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Lymph node involvement is one of the well-demonstrated prognostic factors in ampullary carcinoma. The aim of this study is to clarify the role of lymph nodes in predicting the survival outcome of ampullary carcinoma. METHODS: A cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma from 1999 to 2014 was retrospectively analyzed. The effect of node-associated variables, including lymph node status, positive lymph node number, total harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using univariate and multivariate analyses for survival outcome prediction. RESULTS: In 194 evaluable patients, univariate analysis demonstrated that stage, cell differentiation, perineural invasion, and nodal status were significant conventional prognostic factors. Concerning the node-associated variables, positive nodal status, positive lymph node number≥2, THLN number<14, and LNR≥0.15 were significantly associated with poorer survival outcomes, with a 5-year survival rate of 20.3, 38.9, 25.4, and 18%, respectively. By multivariate analysis, nodal status and THLN number were two independent predictors of survival. The most favorable 5-year survival rate was 84.4% in patients with negative nodal involvement and THLN number≥14, compared with the poorest 5-year survival rate of 16.1% in those with positive nodal status and THLN number<14. CONCLUSIONS: Tumor biology reflected by lymph node status is the most important independent prognostic factor; nevertheless, surgical radicality based on THLN number also plays a significant role in the survival outcome for patients with ampullary carcinoma after curative pancreaticoduodenectomy.
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Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Linfonodos/patologia , Pancreaticoduodenectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/cirurgia , Diferenciação Celular , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/cirurgia , Feminino , Seguimentos , Humanos , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: Hepatoid carcinoma of the pancreas is extremely rare. This article tries to summarize the clinical features and outcomes of pancreatic hepatoid carcinoma. METHODS: The data pool for analysis includes the case we encountered with hepatoid carcinoma of the pancreas and the reported cases in the literature. RESULTS: Twenty-three cases of hepatoid carcinoma of the pancreas were analyzed. This tumor occurred more frequently in male than in female patients (69.6 vs. 30.4 %). Tumor sizes range from 0.5 to 11.0 cm with median of 6.0 cm. The most common symptom was epigastric pain (36.4 %). When the tumor locates at pancreatic head, nausea/vomiting (62.5 %) is more common, followed by jaundice and epigastric pain (50.0 %). For those at pancreatic body-tail, 42.9 % of the patients presented no symptom. Alpha-fetoprotein (AFP) was abnormally elevated in 60 % of the cases. Hepatoid carcinoma in the pancreas could be either pure form or mixed form with other malignancy (40.9 %), with the most common coexisted pathology of malignant neuroendocrine tumor (22.7 %). Metastasis occurred in 36.4 % of the cases at the diagnosis of this tumor, including liver metastasis in 31.8 % and lymph node metastasis in 21.1 %. The overall 1-year survival rate was 71.1 % and 5-year 40.4 %, with a median of 13.0 months. Unresectability, hepatic, and lymph node metastases are associated with negative impact on survival outcome. CONCLUSIONS: Elevation of serum AFP may be a clue leading to the diagnosis of pancreatic hepatoid carcinoma. This tumor could be mixed form with other malignancy. Surgical resection should be the treatment of choice whenever possible.
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Carcinoma Hepatocelular/patologia , Neoplasias Pancreáticas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/cirurgia , Adulto Jovem , alfa-Fetoproteínas/metabolismoRESUMO
BACKGROUND/OBJECTIVE: Robotic pancreaticoduodenectomy in ampullary cancer has never been studied. This study aimed to clarify the feasibility and justification of robotic pancreaticoduodenectomy in ampullary cancer in terms of surgical risks, and oncologic and survival outcomes. METHODS: A propensity score-matching comparison of robotic and open pancreaticoduodenectomy based on seven factors commonly used to predict the survival outcomes in ampullary cancer patients. RESULTS: A total of 147 patients were enrolled, of which 101 and 46 underwent robotic and open pancreaticoduodenectomies, respectively. After propensity score-matching with a 2:1 ratio, 88 and 44 patients in the robotic and open pancreaticoduodenectomy groups were included. The operation time was of no significant difference after matching. The median intraoperative blood loss was much less in those who underwent robotic pancreaticoduodenectomy, both before (median, 120 vs. 320 c.c. P < 0.001) and after (100 vs. 335 mL P < 0.001) score-matching. There were no significant differences in terms of surgical risks, including surgical mortality, surgical morbidity, Clavien-Dindo severity classification, postoperative pancreatic fistula, delayed gastric emptying, post-pancreatectomy hemorrhage, chyle leak, bile leak, and wound infection, both before or after score-matching. The survival outcomes were also similar between the two groups, regardless of matching. CONCLUSIONS: Robotic pancreaticoduodenectomy for ampullary cancer is not only technically feasible and safe without increasing surgical risks, but also oncologically justifiable without compromising surgical radicality and survival outcomes.
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Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Laparoscopia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Ampola Hepatopancreática/cirurgia , Pontuação de Propensão , Neoplasias do Ducto Colédoco/cirurgia , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgiaRESUMO
BACKGROUND: The role of the robotic approach for pancreaticoduodenectomy has not been well established with robust data. This study aimed to reappraise feasibility and justification of robotic pancreaticoduodenectomy (RPD) over time. METHODS: A total of 500 patients undergoing RPD were enrolled and divided into early (first 250 patients) and late (last 250 patients) groups for a comparative study. RESULTS: The conversion rate was 8.8% overall and was significantly lower in the late group (5.6% vs. 12.0%; p = .012). The overall median intraoperative blood loss was 130 mL. Radicality of resection was similar between early and late groups. The overall surgical mortality after RPD was 1.3%. The overall surgical morbidity and major complication was 44.1% and 13.2%, respectively, and similar between early and late groups. Chyle leakage was the most common complication after RPD (25.0%), followed by postoperative pancreatic fistula (POPF). The POPF rate was 8.6% overall, with 5.9% in the early group and 11.0% in the late group, p = .051. The overall delayed gastric emptying rate was 3.5%. The late group had better survival outcomes than those of the early group after RPD for ampullary adenocarcinoma (p = .027) but not for pancreatic head adenocarcinoma. CONCLUSIONS: Reappraisal of this study has confirmed that RPD is not only technically feasible without increasing surgical risks but also oncologically justified without compromising survival outcomes for both pancreatic head and other periampullary cancers over time. Moreover, RPD is associated with the benefits of low surgical mortality, blood loss, and delayed gastric emptying.
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Adenocarcinoma , Gastroparesia , Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Gastroparesia/complicações , Gastroparesia/cirurgia , Pâncreas/cirurgia , Fístula Pancreática/etiologia , Complicações Pós-Operatórias/cirurgia , Adenocarcinoma/cirurgia , Estudos RetrospectivosRESUMO
BACKGROUND: Duodenal adenocarcinoma is rare and its prognostic factors remain controversial. In our study, the role of cell-free deoxyribonucleic acid (cfDNA) as prognostic factor in duodenal adenocarcinoma was evaluated. METHODS: From June 2003 to July 2021, plasma samples were collected from 41 patients with duodenal adenocarcinoma. Plasma cfDNA was assessed in combination with clinicopathological and biochemical characteristics. Univariate and multivariate analyses were conducted to identify independent prognostic factors for overall survival with a Cox proportional hazards regression model. RESULTS: The 1- and 5-year survival rates of the patients with high plasma cfDNA level (>9288 copies/mL) group were 58.7% and 17.6%, respectively, which were much lower than patients with low cfDNA level (≤9288 copies/mL), with 95.2% and 64.6%. In univariate analysis, high cfDNA level, lymph node involvement, lymphovascular invasion, and tumor stage were associated with decreased survival. When subjected to multivariate analysis, only high cfDNA level showed significance in influencing the overall survival of duodenal cancer. CONCLUSION: cfDNA analysis is simple and noninvasive. High cfDNA level is a strong independent prognostic factor for decreased overall survival and it should be integrated into clinical care.
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Adenocarcinoma , Ácidos Nucleicos Livres , Neoplasias Duodenais , Humanos , Adenocarcinoma/genética , Modelos de Riscos Proporcionais , Biomarcadores Tumorais , PrognósticoRESUMO
BACKGROUND: Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. This study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection. METHODS: From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed. RESULTS: PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI < 45.2 best predicted overall survival (OS) (AUROC: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those higher postoperative values (median OS: 19.3 months vs. not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001). CONCLUSION: PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes.
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BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer type that urgently requires effective therapeutic strategies. Andrographolide, a labdane diterpenoid compound abundant in Andrographis paniculata, has anticancer effects against various cancer types, but its anticancer activity and mechanism against PDAC remain largely uncharacterized. PURPOSE: This study explores novel drug target(s) and underlying molecular mechanism of andrographolide against PDAC. STUDY DESIGN AND METHODS: The malignant phenotypes of PDAC cells, PANC-1 and MIA PaCa-2 cells, were measured using MTT, clonogenic assays, and Transwell migration assays. A PDAC xenograft animal model was used to evaluate tumor growth in vivo. Western blot, immunofluorescence and immunohistochemistry were used for measuring protein expression. The TCGA database was analyzed to evaluate promoter methylation status, gene expression, and their relationship with patient survival rates. RT-qPCR was used for detecting mRNA expression. Reporter assays were used for detecting signal transduction pathways. Promoter DNA methylation was determined by sodium bisulfite treatment and methylation-specific PCR (MSP). The biological function and role of specific genes involved in drug effects were measured through gene overexpression. RESULTS: Andrographolide treatment suppressed the proliferation and migration of PDAC cells and impaired tumor growth in vivo. Furthermore, andrographolide induced the mRNA and protein expression of zinc finger protein 382 (ZNF382) in PDAC cells. Overexpression of ZNF382 inhibited malignant phenotypes and cancer-associated signaling pathways (AP-1, NF-κB and ß-catenin) and oncogenes (ZEB-1, STAT-3, STAT-5, and HIF-1α). Overexpression of ZNF382 delayed growth of PANC-1 cells in vivo. ZNF382 mRNA and protein expression was lower in tumor tissues than in adjacent normal tissues of pancreatic cancer patients. Analysis of the TCGA database found the ZNF382 promoter is hypermethylated in primary pancreatic tumors which correlates with its low expression. Furthermore, andrographolide inhibited the expression of DNA methyltransferase 3 beta (DNMT3B) and increased the demethylation of the ZNF382 promoter in PDAC cells. Overexpression of DNMT3B attenuated the andrographolide-suppressed proliferation and migration of PDAC cells. CONCLUSION: Our finding revealed that ZNF382 acts as a tumor suppressor gene in pancreatic cancer and andrographolide restores ZNF382 expression to suppress pancreatic cancer, providing a novel molecular target and a promising therapeutic approach for treating pancreatic cancer.
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DNA (Citosina-5-)-Metiltransferases , Metilação de DNA , DNA Metiltransferase 3B , Diterpenos , Neoplasias Pancreáticas , Diterpenos/farmacologia , Humanos , Animais , Linhagem Celular Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Metilação de DNA/efeitos dos fármacos , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA (Citosina-5-)-Metiltransferases/genética , Camundongos Nus , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Camundongos , Regiões Promotoras Genéticas/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Antineoplásicos Fitogênicos/farmacologia , Transdução de Sinais/efeitos dos fármacos , MasculinoRESUMO
Background: With the rapid development of robotic surgery, especially for the abdominal surgery, robotic pancreatic surgery (RPS) has been applied increasingly around the world. However, evidence-based guidelines regarding its application, safety, and efficacy are still lacking. To harvest robust evidence and comprehensive clinical practice, this study aims to develop international guidelines on the use of RPS. Methods: World Health Organization (WHO) Handbook for Guideline Development, GRADE Grid method, Delphi vote, and the AGREE-II instrument were used to establish the Guideline Steering Group, Guideline Development Group, and Guideline Secretary Group, formulate 19 clinical questions, develop the recommendations, and draft the guidelines. Three online meetings were held on 04/12/2020, 30/11/2021, and 25/01/2022 to vote on the recommendations and get advice and suggestions from all involved experts. All the experts focusing on minimally invasive surgery from America, Europe and Oceania made great contributions to this consensus guideline. Results: After a systematic literature review 176 studies were included, 19 questions were addressed and 14 recommendations were developed through the expert assessment and comprehensive judgment of the quality and credibility of the evidence. Conclusions: The international RPS guidelines can guide current practice for surgeons, patients, medical societies, hospital administrators, and related social communities. Further randomized trials are required to determine the added value of RPS as compared to open and laparoscopic surgery.
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BACKGROUND: Robotic pancreatoduodenectomy is increasingly being implemented worldwide, with good results reported from individual expert centers. However, it is unclear to what extent outcomes will continue to improve during the learning curve, as large international studies are lacking. METHODS: An international retrospective multicenter case series, including consecutive patients after robotic pancreatoduodenectomy from 18 centers in 8 countries in Europe, Asia, and South America until December 31, 2019, was conducted. A cumulative sum analysis was performed to determine the inflection points for the feasibility (operative time and blood loss) and proficiency (postoperative pancreatic fistula grade B/C and major morbidity) learning curves. Outcomes were compared in 3 groups on the basis of the learning curve inflection points. RESULTS: Overall, 2,186 patients after robotic pancreatoduodenectomy were included. The feasibility learning curve was reached after 30-45 robotic pancreatoduodenectomy procedures and the proficiency learning curve after 90 robotic pancreatoduodenectomy procedures. These inflection points created 3 phases, which were associated with major morbidity (24.7%, 23.4%, and 12.3%, P < .001) but not 30-day mortality (2.1%, 2.0%, and 1.5%, P = .670). Other outcomes mostly continued to improve, including median operative time 432, 390, and 300 minutes (P < .0001), conversion 6.0%, 4.7%, and 2.7% (P = .002), bile leakage 7.2%, 4.1%, and 2.4% (P < .001), postpancreatectomy hemorrhage 6.5%, 6.1%, and 1.8% (n = 21) but not R0 resection (pancreatic ductal adenocarcinoma only) 78.5%, 73.9%, and 82.8% (P = .35), and 90-day mortality rate 3.1%, 3.5%, and 2.1% (P = .191). Centers performing >20 robotic pancreatoduodenectomies annually had lower rates of conversion, reoperation, and shorter median operative time as compared with centers performing 10-20 robotic pancreatoduodenectomies annually. CONCLUSION: This international multicenter study demonstrates that most outcomes of robotic pancreatoduodenectomy continued to improve during 3 learning curve phases without a negative effect on 90-day mortality. Randomized studies are needed in high-volume centers that have surpassed the first learning curves, to compare these outcomes with the open approach.
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OBJECTIVES: The aim of this study was to identify predictors for longterm survival following pancreaticoduodenectomy (PD) for pancreatic and other periampullary adenocarcinomas. METHODS: Clinicopathological factors were compared between short-term (<5 years) and longterm (≥ 5 years) survival groups. Rates of actual 5-year and actuarial 10-year survival were determined. RESULTS: There were 109 (21.8%) longterm survivors among a sample of 501 patients. Patients with ampullary adenocarcinoma represented 76.1% of the longterm survivors. Favourable factors for longterm survival included female gender, lack of jaundice, lower blood loss, classical PD, absence of postoperative bleeding or intra-abdominal abscess, non-pancreatic primary cancer, earlier tumour stage, smaller tumour size (≤ 2 cm), curative resection, negative lymph node involvement, well-differentiated tumours, and absence of perineural invasion. Independent factors associated with longterm survival were diagnosis of primary tumour, jaundice, intra-abdominal abscess, tumour stage, tumour size, radicality, lymph node status and cell differentiation. The prognosis was best for ampullary adenocarcinoma, for which the rate of actual 5-year survival was 32.8%, and poorest for pancreatic head adenocarcinoma, for which actual 5-year survival was only 6.5%. CONCLUSIONS: The majority of longterm survivors after PD for periampullary adenocarcinomas are patients with ampullary adenocarcinoma. The longterm prognosis in pancreatic head adenocarcinoma remains dismal.
Assuntos
Adenocarcinoma/cirurgia , Ampola Hepatopancreática/cirurgia , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia , Sobreviventes , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/mortalidade , Neoplasias do Ducto Colédoco/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/mortalidade , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Cell-free DNA (cfDNA) as an oncological biomarker has drawn much attention in recent years, but very limited effort has been made to investigate the prognostic values of cfDNA in distal common bile duct (CBD) cancer. METHODS: Plasma cfDNA was measured in 67 patients with resectable distal CBD cancer. Survival outcomes and the correlation of cfDNA with other conventional prognostic factors were determined. RESULTS: cfDNA levels were significantly higher in female patients, and those with poor tumor differentiation, abnormal serum carcinoembryonic antigen (CEA) level, and stage III cancer. The significant prognostic factors included a high cfDNA level (>8955 copies/mL), abnormal serum CEA level, stage III cancer, and positive resection margins. Compared with patients with high cfDNA level, those with lower cfDNA level (≤8955 copies/mL) had significantly better overall survival outcomes (74.4% vs 100% and 19.2% vs 52.6%, for 1- and 5-year survival rates, respectively, p = 0.001). The cfDNA level, perineural invasion, CEA level, and radicality were identified as independent prognostic factors for distal CBD cancer after multivariate analysis. CONCLUSION: Circulating cfDNA levels play a significant role in predicting the prognosis and survival outcome for resectable distal CBD cancer. Furthermore, acting as a promising liquid biopsy, cfDNA could serve as a prognostic and predictive biomarker in combination with current conventional markers to improve diagnostic and prognostic efficacy.
Assuntos
Ácidos Nucleicos Livres , Neoplasias , Humanos , Feminino , Prognóstico , Antígeno Carcinoembrionário , Biomarcadores Tumorais , Ducto ColédocoRESUMO
BACKGROUND: Central pancreatectomy (CP) is an ideal parenchyma-sparing procedure. The experience of r robotic central pancreatectomy (RCP) is very limited. MATERIALS AND METHODS: Patients undergoing CP were included. Comparisons were made between RCP and open central pancreatectomy (OCP) groups. RESULTS: The most common lesion in patients undergoing CP was serous cystadenoma (35.5%). The median operation time was 4.2 h for RCP versus 5.5 h for OCP. The median blood loss was significantly lower in RCP, 20 c.c. versus 170 c.c., p = 0.001. Postoperative pancreatic fistula occurred in 19.4% of all patients, with 22.1% in RCP and 15.4% in OCP. There was no significant difference regarding other surgical complications between the RCP and OCP groups. Only one patient in the OCP group developed de novo diabetes mellitus (DM), and no steatorrhoea/diarrhoea occurred after either RCP or OCP. CONCLUSIONS: RCP is feasible and safe without compromising surgical outcomes and pancreatic functions.
RESUMO
Aim: Whether to execute pancreaticoduodenectomy or not for older people could pose a dilemma. This study clarifies the safety and justification of robotic pancreaticoduodenectomy (RPD) for older individuals over 80. Methods: A total of 500 patients undergoing RPD were divided into group O (≥ 80 y/o) and group Y (< 80 y/o) for comparison. Results: There were 62 (12.4%) patients in group O. Surgical mortality was 1.6% for overall patients and higher in group O, 6.5% vs 0.9%; p = 0.001. The surgical complication was comparable between groups O and Y. Delayed gastric emptying and bile leakage were higher in group O, 9.7% vs 2.5%; p = 0.004, and 6.5% vs 0.9%; p = 0.001, respectively. Length of stay was also longer in group O, with a median of 26 vs 19 days; p = 0.001. Survival outcome after RPD was poorer in group O for overall periampullary adenocarcinomas, with a 5-year survival of 48.1% vs 51.2%; p = 0.025 and also for the subgroup of pancreatic head adenocarcinoma, with a 3-year survival of 27.4% vs 42.5%; p = 0.030. Conclusion: RPD is safe and justified for the selected octogenarians and even nonagenarians, whoever is fit for a major operation. Nevertheless, pancreatic head cancer and higher mortality risk for the aged over 80 with advanced ASA score ≥ 3 should be informed as part of counselling in offering RPD.