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Pancreatic adenocarcinoma is an aggressive disease marked by high rates of both local and distant failure. In the minority of patients with potentially resectable disease, multimodal treatment paradigms have allowed for prolonged survival in an increasingly larger pool of well-selected patients. Therefore, it is critical for surgical oncologists to be abreast of current guideline recommendations for both surgical management and multimodal therapy for pancreas cancer. We discuss these guidelines, as well as the underlying data supporting these positions, to offer surgical oncologists a framework for managing patients with pancreatic adenocarcinoma.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/cirurgia , Terapia Neoadjuvante , Terapia CombinadaRESUMO
INTRODUCTION: Patients with colorectal peritoneal metastases (CRPM) are increasingly treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Unfortunately, data identifying preoperative risk factors for poor oncologic outcomes after this procedure are limited. We aimed to determine the prognostic value of preoperative CEA, CA 125, and CA 19-9 on disease progression after CRS/HIPEC. METHODS: Patients with CRPM treated with curative intent CRS/HIPEC from 12 participating sites in the United States from 2000 to 2017 were identified. Progression-free survival (PFS), defined as disease progression or recurrence, was the primary outcome. RESULTS: In 279 patients who met inclusion criteria, the rate of disease progression was 63.8%, with a median PFS of 11 months (interquartile range [IQR] 5-20). Elevated CA 19-9 was associated with dismal PFS at 2 years (8.9% elevated vs. 30% not elevated, p < 0.01). In 113 patients who underwent upfront CRS/HIPEC, CA 19-9 emerged as the sole tumor marker independently predictive of worse PFS (hazard ratio [HR] 2.88, p = 0.048). In the subgroup of patients who had received neoadjuvant therapy (NAT), no variable was independently predictive of PFS. CA 19-9 levels over 37 U/ml were highly specific for accelerated disease progression after CRS/HIPEC. Lastly, there was no association between PFS and elevated CEA or CA 125. CONCLUSIONS: Elevated CA 19-9 is associated with decreased PFS in patients with CRPM. While traditionally CEA is the main tumor marker assessed in colon cancer, we found that CA 19-9 may better inform preoperative risk stratification for poor oncologic outcomes in patients with CRPM. However, prospective studies are required to confirm this association.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Neoplasias Peritoneais/secundário , Neoplasias Colorretais/patologia , Procedimentos Cirúrgicos de Citorredução , Quimioterapia do Câncer por Perfusão Regional , Progressão da Doença , Biomarcadores Tumorais , Terapia Combinada , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos RetrospectivosRESUMO
INTRODUCTION: Surgery followed by pathology-guided adjuvant therapy is standard treatment for colon cancer. Data from the FOxTROT clinical trial showed potential benefit of a 6-wk neoadjuvant chemotherapy (NACT) in T3/T4 patients. The present study evaluated real-world outcomes of neoadjuvant therapy in a national cohort of patients with resectable colon cancer. METHODS: 169,120 patients with clinical stage I, II, or III colon cancer from the National Cancer Database registry were included. Patients were categorized as having received neoadjuvant therapy followed by surgery (NACT), surgery then adjuvant chemotherapy (AC), or surgery alone. Factors associated with treatment sequencing and outcomes were assessed. RESULTS: Of identified patients, 1.4% received NACT including 0.5% of stage I, 1.8% of stage II, and 3.0% of stage III. For stage I, 5-y overall survival (OS) was 74.7% after AC, 62.2% after NACT, and 76.4% after SA. For stage II, 5-y OS was 73.2% after AC, 66.8% after NACT, and 64.3% after SA. For stage III, 5-y OS was 67.3% after AC, 67.7% after NACT, and 42.4% after SA. Cox proportional-hazards model suggested NACT had worse outcomes versus AC in clinical stages I (hazard ratio [HR] = 1.59, 95% confidence interval [CI] 1.39-1.85, P < 0.01) and II (HR = 1.37, 95% CI 1.23-1.52, P < 0.01). In stage III, there was no difference in OS between NACT and AC (HR = 1.1, 95% CI 0.99-1.22, P = 0.05). CONCLUSIONS: In a real-world national cohort of patients with resectable colon cancer, NACT had no OS benefit over AC. Future studies should examine which subset of patients might benefit from neoadjuvant approaches.
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INTRODUCTION: Grade-C postoperative pancreatic fistulas (POPFs) are dreaded complications following pancreaticoduodenectomy. The aim of this study was to quantify the incidence and risk factors associated with grade C POPF in a national database. METHODS: The National Surgical Quality Improvement Program targeted user files were queried for patients who underwent elective pancreaticoduodenectomy (2014-2020). Outcomes were compared between clinically relevant (CR) grade B POPF and grade C POPF. RESULTS: Twenty-six thousand five hundred fifty-two patients were included, of which 90.1% (n = 23,714) had No CR POPF, 8.7% (n = 2287) suffered grade B POPF, and 1.2% (n = 327) suffered grade C POPF. There was no change in the rate Grade-C fistula overtime (m = 0.06, P = 0.63), while the rate of Grade-B fistula significantly increased (m = +1.40, P < 0.01). Fistula Risk Scores were similar between grade B and C POPFs (high risk: 34.9% versus 31.2%, P = 0.21). Associated morbidity was increased with grade C POPF, including delayed gastric emptying, organ space infections, wound dehiscence, respiratory complications, renal complications, myocardial infarction, and bleeding. On multivariate logistic regression, diabetes mellitus (odds ratio: 1.41 95% confidence interval: 1.06-1.87, P = 0.02) was associated with grade C POPF. CONCLUSIONS: This study represents the largest contemporary series evaluating grade C POPFs. Of those suffering CR POPF, the presence of diabetes mellitus was associated with grade C POPF. While modern management has led to grade C POPF in 1% of cases, they remain associated with alarmingly high morbidity and mortality, requiring further mitigation strategies to improve outcomes.
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Diabetes Mellitus , Fístula Pancreática , Humanos , Fístula Pancreática/epidemiologia , Fístula Pancreática/etiologia , Fístula Pancreática/cirurgia , Pâncreas/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Fatores de Risco , Diabetes Mellitus/etiologia , Estudos RetrospectivosRESUMO
BACKGROUND: Robotic pancreaticoduodenectomy (RPD) is a safe and efficacious procedure in appropriately selected patients, though frequently with increased operative times compared to open pancreaticoduodenectomy (OPD). METHODS: From 2014 to 2019, patients who underwent elective, low-risk, RPDs and OPDs in the NSQIP database were isolated. The operative time threshold (OTT) for safety in RPD patients was estimated by identifying the operative time at which complication rates for RPD patients exceeded the complication rate of the benchmark OPD control. RESULTS: Of 6270 patients identified, 939 (15%) underwent RPD and 5331 (85%) underwent OPD. The incidence of major morbidity or mortality for the OPD cohort was 35.1%. The OTT was identified as 7.7 h. Patients whose RPDs were above the OTT experienced a higher incidence of major morbidity (42.5% vs. 35.0%, p < 0.01) and 30-day mortality (2.7% vs. 1.2%, p = 0.03) than the OPD cohort. Preoperative obstructive jaundice (OR: 1.47, [95% CI: 1.08-2.01]) and pancreatic duct size <3 mm (OR: 2.44, [95% CI: 1.47-4.06]) and 3-6 mm (OR: 2.15, [95% CI: 1.31-3.52]) were risk factors for prolonged RPDs on multivariable regression. CONCLUSION: The operative time threshold for safety, identified at 7.7 h, should be used to improve patient selection for RPDs and as a competency-based quality benchmark.
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Neoplasias Pancreáticas , Procedimentos Cirúrgicos Robóticos , Humanos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Duração da Cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Estudos RetrospectivosRESUMO
INTRODUCTION: The long-term prognosis of patients who undergo cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal surface malignancies (PSM) varies considerably on the basis of histological and operative factors. While overall survival (OS) estimates are used to inform adjuvant therapy and surveillance strategies, conditional survival may provide more clinically relevant estimates of prognosis by accounting for disease-free time elapsed. PATIENTS AND METHODS: All patients from 12 academic institutions who underwent CRS ± HIPEC for PSM from 2000 to 2017 were retrospectively analyzed. OS and disease-free survival (DFS) rates were calculated using the Kaplan-Meier method while conditional overall (COS) and conditional disease-free survival (CDFS) rates were calculated at 1, 2, or 3 years from surgery for different tumor histologies. RESULTS: Overall, 1610 patients underwent CRS ± HIPEC. Among patients with benign appendiceal mucinous tumors (N = 460), 5-year OS and COS at 3 years were 92.1% and 96.3% (Δ4.2%), respectively. For patients with well-differentiated appendiceal cancers (N = 400), 5-year OS and COS at 3 years were 76.3% and 88.3% (Δ12.0%), respectively. For patients with high-grade appendiceal cancers (N = 258), 5-year OS and COS at 3 years were 43.8% and 75.4% (Δ31.6%), respectively. For patients with colorectal cancers (N = 362), 5-year OS and COS at 3 years were 31.8% and 67.3% (Δ35.5%), respectively. For patients with peritoneal mesothelioma (N = 130), 5-year OS and COS at 3 years were 67.6% and 89.7% (Δ22.1%), respectively. Similar trends were observed for DFS/CDFS. CONCLUSION: The conditional survival of patients undergoing CRS ± HIPEC for PSM is associated with tumor histology. COS and CDFS provide a more accurate, dynamic estimate of survival than OS and DFS, especially for patients with more aggressive histologies.
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Neoplasias do Apêndice , Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/cirurgia , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/patologia , Terapia Combinada , Taxa de Sobrevida , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves survival in select patients with peritoneal metastases (PM), but the impact of social determinants of health on CRS/HIPEC outcomes remains unclear. PATIENTS AND METHODS: A retrospective review was conducted of a multi-institutional database of patients with PM who underwent CRS/HIPEC in the USA between 2000 and 2017. The area deprivation index (ADI) was linked to the patient's residential address. Patients were categorized as living in low (1-49) or high (50-100) ADI residences, with increasing scores indicating higher socioeconomic disadvantage. The primary outcome was overall survival (OS). Secondary outcomes included perioperative complications, hospital/intensive care unit (ICU) length of stay (LOS), and disease-free survival (DFS). RESULTS: Among 1675 patients 1061 (63.3%) resided in low ADI areas and 614 (36.7%) high ADI areas. Appendiceal tumors (n = 1102, 65.8%) and colon cancer (n = 322, 19.2%) were the most common histologies. On multivariate analysis, high ADI was not associated with increased perioperative complications, hospital/ICU LOS, or DFS. High ADI was associated with worse OS (median not reached versus 49 months; 5 year OS 61.0% versus 28.2%, P < 0.0001). On multivariate Cox-regression analysis, high ADI (HR, 2.26; 95% CI 1.13-4.50; P < 0.001), cancer recurrence (HR, 2.26; 95% CI 1.61-3.20; P < 0.0001), increases in peritoneal carcinomatosis index (HR, 1.03; 95% CI 1.01-1.05; P < 0.001), and incomplete cytoreduction (HR, 4.48; 95% CI 3.01-6.53; P < 0.0001) were associated with worse OS. CONCLUSIONS: Even after controlling for cancer-specific variables, adverse outcomes persisted in association with neighborhood-level socioeconomic disadvantage. The individual and structural-level factors leading to these cancer disparities warrant further investigation to improve outcomes for all patients with peritoneal malignancies.
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Neoplasias Colorretais , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias Peritoneais/secundário , Quimioterapia Intraperitoneal Hipertérmica , Procedimentos Cirúrgicos de Citorredução , Disparidades Socioeconômicas em Saúde , Hipertermia Induzida/efeitos adversos , Recidiva Local de Neoplasia/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Neoplasias Colorretais/patologiaRESUMO
BACKGROUND: The AJCC 8th edition stratifies stage IV disseminated appendiceal cancer (dAC) patients based on grade and pathology. This study was designed to externally validate the staging system and to identify predictors of long-term survival. METHODS: A 12-institution cohort of dAC patients treated with CRS ± HIPEC was retrospectively analyzed. Overall survival (OS) and recurrence-free survival (RFS) were analyzed by using Kaplan-Meier and log-rank tests. Univariate and multivariate cox-regression was performed to assess factors associated with OS and RFS. RESULTS: Among 1009 patients, 708 had stage IVA and 301 had stage IVB disease. Median OS (120.4 mo vs. 47.2 mo) and RFS (79.3 mo vs. 19.8 mo) was significantly higher in stage IVA compared with IVB patients (p < 0.0001). RFS was greater among IVA-M1a (acellular mucin only) than IV M1b/G1 (well-differentiated cellular dissemination) patients (NR vs. 64 mo, p = 0.0004). Survival significantly differed between mucinous and nonmucinous tumors (OS 106.1 mo vs. 41.0 mo; RFS 46.7 mo vs. 21.2 mo, p < 0.05), and OS differed between well, moderate, and poorly differentiated (120.4 mo vs. 56.3 mo vs. 32.9 mo, p < 0.05). Both stage and grade were independent predictors of OS and RFS on multivariate analysis. Acellular mucin and mucinous histology were associated with better OS and RFS on univariate analysis only. CONCLUSIONS: AJCC 8th edition performed well in predicting outcomes in this large cohort of dAC patients treated with CRS ± HIPEC. Separation of stage IVA patients based on the presence of acellular mucin improved prognostication, which may inform treatment and long-term, follow-up strategies.
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Neoplasias do Apêndice , Hipertermia Induzida , Neoplasias Peritoneais , Humanos , Neoplasias do Apêndice/patologia , Procedimentos Cirúrgicos de Citorredução , Estudos Retrospectivos , Neoplasias Peritoneais/patologia , Mucinas/uso terapêutico , Taxa de Sobrevida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estadiamento de NeoplasiasRESUMO
INTRODUCTION: Robotic-assisted minimally invasive esophagectomy (RAMIE) in clinical trials has demonstrated improved outcomes compared to open esophagectomy (OE). However, outcomes after national implementation remain unknown. The aim of this study was to evaluate postoperative outcomes after RAMIE. METHODS: Patients who underwent elective esophagectomy between 2016 and 2020 were identified from the American College of Surgeons-- National Surgical Quality Improvement Program esophageal targeted participant user files and categorized by operative approach, with patients who underwent hybrid procedures excluded. Outcomes were compared between OE and minimally invasive esophagectomy (MIE)/RAMIE, with subset analyses by minimally invasive operative approach. Primary outcomes included pulmonary complications, anastomotic leak requiring reintervention, all-cause morbidity, and 30-d mortality. RESULTS: In total 2786 patients were included, of which 58.3% underwent OE, 33.2% underwent MIE, and 8.4% underwent RAMIE. In the entire cohort, Ivor Lewis esophagectomy was the most common technique (64.6%), followed by transhiatal (22.0%), and a McKeown technique (13.4%). Comparing OE and MIE/RAMIE, pulmonary complications (21.5% versus 16.1%, P < 0.01) and all-cause morbidity (40.9% versus 32.3%, P < 0.01) were both reduced in the MIE/RAMIE group. When directly comparing MIE to RAMIE, there was no difference in the rate of pulmonary complications, anastomotic leak, all-cause morbidity, and mortality. However, RAMIE was associated with decreased all-cause morbidity compared to OE (40.9% versus 33.3%, P = 0.03). CONCLUSIONS: RAMIE was associated with decreased morbidity compared to OE, with similar outcomes to MIE. The national adoption of RAMIE in this select cohort appears safe.
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Neoplasias Esofágicas , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Esofagectomia/métodos , Fístula Anastomótica/cirurgia , Neoplasias Esofágicas/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Complicações Pós-Operatórias/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
BACKGROUND AND OBJECTIVES: Modern systemic therapy (immune checkpoint blockade [ICB], targeted therapy) has improved survival for patients with metastatic melanoma. The role of adrenal metastasectomy is not well characterized in this setting. METHODS: Consecutive patients treated with adrenalectomy 1/1/2007-1/1/2019 were retrospectively compared to patients treated with systemic therapy alone in the same time period. Overall survival and survival after adrenal metastasis were compared, prognostic factors associated with survival after adrenal metastasis development were evaluated. RESULTS: A total of 74 patients underwent adrenalectomy and were compared to 69 treated with systemic therapy alone. The most common indications for adrenalectomy were to render the patient disease-free in the setting of isolated adrenal metastasis (n = 32, 43.2%) or treatment of isolated progression in the setting of other stable/responding metastases (n = 32, 43.2%). Patients treated surgically had longer survival (116.9 vs. 11.0 months after adrenal metastasis diagnosis, p < 0.001). On multivariate analysis, receipt of ICB (hazard ratio [HR]: 0.62, 95% confidence interval [CI]: [0.40-0.95]) and selection for adrenalectomy (HR: 0.27, 95% CI: [0.17-0.42]) were the strongest factors associated with improved survival after adrenal metastasis diagnosis. CONCLUSIONS: Selective application of adrenal metastasectomy is associated with prolonged survival benefit and remains an important consideration in the multidisciplinary management of patients with metastatic melanoma.
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Neoplasias das Glândulas Suprarrenais , Melanoma , Humanos , Adrenalectomia , Estudos Retrospectivos , Neoplasias das Glândulas Suprarrenais/cirurgia , Melanoma/cirurgia , Melanoma/patologia , Glândulas SuprarrenaisRESUMO
BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is increasingly performed for peritoneal surface malignancies but remains associated with significant morbidity. Scant research is available regarding the impact of insurance status on postoperative outcomes. METHODS: Patients undergoing CRS/HIPEC between 2000 and 2017 at 12 participating sites in the US HIPEC Collaborative were identified. Univariate and multivariate analyses were used to compare the baseline characteristics, operative variables, and postoperative outcomes of patients with government, private, or no insurance. RESULTS: Among 2268 patients, 699 (30.8%) had government insurance, 1453 (64.0%) had private, and 116 (5.1%) were uninsured. Patients with government insurance were older, more likely to be non-white, and comorbid (p < 0.05). Patients with government (OR: 2.25, CI: 1.50-3.36, p < 0.001) and private (OR: 1.69, CI: 1.15-2.49, p = 0.008) insurance had an increased risk of complications on univariate analysis. There was no independent relationship on multivariate analysis. An American Society of Anesthesiologists score of 3 or 4, peritoneal carcinomatosis index score >15, completeness of cytoreduction score >1, and nonhome discharge were factors independently associated with a postoperative complication. CONCLUSION: While there were differences in postoperative outcomes between the three insurance groups on univariate analysis, there was no independent association between insurance status and postoperative complications after CRS/HIPEC.
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Hipertermia Induzida , Quimioterapia Intraperitoneal Hipertérmica , Humanos , Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Hipertermia Induzida/efeitos adversos , Quimioterapia do Câncer por Perfusão Regional/efeitos adversos , Estudos Retrospectivos , Cobertura do Seguro , Terapia Combinada , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Taxa de SobrevidaRESUMO
BACKGROUND: Feeding jejunostomy (JT) tubes are often utilized as an adjunct to optimize nutrition for successful esophagectomy; however, their utility has come into question. The aim of this study was to evaluate utilization and outcomes associated with JTs in a nationwide cohort of patients undergoing esophagectomy. METHODS: The NSQIP database was queried for patients who underwent elective esophagectomy. JT utilization was assessed between 2010 and 2019. Post-operative outcomes were compared between those with and without a JT on patients with esophagectomy-specific outcomes (2016-2019), with results validated using a propensity score-matched (PSM) analysis based on key clinicopathologic factors, including tumor stage. RESULTS: Of the 10,117 patients who underwent elective esophagectomy over the past decade, 53.0% had a JT placed concurrently and 47.0% did not. Utilization of JTs decreased over time, accounting for 60.0% of cases in 2010 compared to 41.7% in 2019 (m = - 2.14 95%CI: [- 1.49]-[- 2.80], p < 0.01). Patients who underwent JT had more composite wound complications (17.0% vs. 14.1%, p = 0.02) and a higher rate of all-cause morbidity (40.4% vs. 35.5%, p = 0.01). Following PSM, 1007 pairs were identified. Analysis of perioperative outcomes demonstrated a higher rate of superficial skin infections (6.1% vs. 3.5%, p = 0.01) in the JT group. However, length of stay, reoperation, readmission, anastomotic leak, composite wound complications, all-cause morbidity, and mortality rates were similar between groups. CONCLUSIONS: Among patients undergoing elective esophagectomy, feeding jejunostomy tubes were utilized less frequently over the past decade. Similar perioperative outcomes among matched patients support the safety of esophagectomy without an adjunct feeding jejunostomy tube.
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Neoplasias Esofágicas , Jejunostomia , Humanos , Jejunostomia/efeitos adversos , Jejunostomia/métodos , Nutrição Enteral/efeitos adversos , Nutrição Enteral/métodos , Estudos Retrospectivos , Esofagectomia/efeitos adversos , Esofagectomia/métodos , Intubação Gastrointestinal/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/etiologiaRESUMO
BACKGROUND: T2 intrahepatic cholangiocarcinoma (ICC) is defined as a solitary tumors with vascular invasion or multifocal tumors including satellite lesions, multiple lesions, and intrahepatic metastases. This study aimed to evaluate the prognosis associated with multifocal tumors. METHODS: The National Cancer Database was queried from 2004 to 2017 for patients with non-metastatic ICC. The patients were grouped based on T2 staging, multifocality, and lymph node involvement. RESULTS: The study enrolled and classified 4887 patients into clinical (c) stage groups as follows: 15.2% with solitary T2N0 (sT2N0) tumors, 21.3% with multifocal T2N0 (mT2N0) tumors, and 63.5% with node-positive (TxN1) disease. Patients with (c)sT2N0 tumors had higher rates of surgical resection than those with (c)mT2N0 or (c)TxN1 disease (33.5% vs 19.7% vs 15.0%; p < 0.01). Median overall survival (OS) was better for the patients with (c)sT2N0 tumors than for those with multifocal and node-positive disease (15.4 vs 10.4 vs 10.4 months; p < 0.01). On multivariate analysis, (c)sT2N0 tumors were associated with better OS than (c)mT2N0 tumors [hazard ratio (HR), 1.31; 95% confidence interval (CI), 1.17-1.46; p < 0.01] or (c)TxN1 disease (HR,1.41; 95% CI 1.28-1.56; p < 0.01). In a subset analysis based on pathologic (p) staging of patients who underwent surgical resection with regional lymphadenectomy, multivariate analysis demonstrated that (p)sT2N0 tumors were associated with better OS than (p)mT2N0 tumors (HR,1.40; 95% CI 1.03-1.92; p = 0.03) or (p)TxN1 disease (HR, 2.05; 95% CI 1.62-2.58; p < 0.01). CONCLUSIONS: Multifocal T2N0 ICC is associated with poor OS and has a disparate prognosis compared with solitary T2N0 disease, even among patients who undergo resection. Future staging criteria should account for the poor outcomes associated with multifocal ICC.
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Neoplasias dos Ductos Biliares , Colangiocarcinoma , Neoplasias dos Ductos Biliares/patologia , Ductos Biliares Intra-Hepáticos/patologia , Ductos Biliares Intra-Hepáticos/cirurgia , Colangiocarcinoma/patologia , Hepatectomia , Humanos , Excisão de Linfonodo , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: The role of systemic therapy for Stage IA pancreatic ductal adenocarcinoma (PDAC) is unclear. The aim of our study was to evaluate the impact of adjuvant chemotherapy (AC) on survival in patients with early stage disease. METHODS: The National Cancer Database was queried from 2006 to 2017 for resected pT1N0M0 (Stage 1A) PDAC. Exclusion criteria included neoadjuvant therapy, radiation, or those who suffered a 90-day mortality. RESULTS: Of the 1526 patients included in the study, 42.2% received AC and 57.8% underwent surgery alone. Patients who received AC were younger, had fewer comorbidities, and were more likely to have private insurance, compared with those treated with surgery alone. Patients who received AC had longer median overall survival (OS) compared with those who underwent surgery alone (105.7 months vs 72.0 months, p < 0.01). Subset analyses based on individual "good" prognostic features (size ≤ 1.0 cm, lymphovascular invasion negative, well/moderately differentiated, margin negative resection) demonstrated improved OS with AC. Following propensity score matching based on key clinicopathologic features, AC remained associated with improved median OS (83.7 months vs 59.8 months, p < 0.01). However, in the cohort with body/tail tumors (101.2 months vs 95.0 months, p = 0.19) and those with all "good" prognostic features (95.9 months vs 90.6 months, p = 0.15), AC was not associated with improved survival. CONCLUSIONS: In resected, Stage IA PDAC, AC is associated with improved overall survival in the vast majority of patients; however, in select cohorts the role of AC is unclear. Further study is needed to tailor treatment to individual patients with PDAC.
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BACKGROUND: Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even if they do, the impact of reduced dose density (DD) on survival is not known. PATIENTS AND METHODS: A single institutional prospective database was queried for patients with PDAC who underwent curative resection between 2009 and 2018. The primary outcome was DD, defined as the percentage of total planned chemotherapy actually received and associated survival. RESULTS: Of the 126 patients included, 38.9% underwent a neoadjuvant approach, which was associated with a greater median number of completed chemotherapy cycles (5 cycles versus 4 cycles, p < 0.01) and a higher median total DD (93.0% versus 65.0%, p < 0.01), compared with an adjuvant treatment approach. In both groups, adjuvant chemotherapy completion rates were low, with only 55 patients completing all adjuvant cycles. After sequential survival analysis, patients who received a DD ≥ 80% had improved median overall survival (OS) (27.1 months versus 18.6 months, p = 0.01), compared with patients who achieved a DD < 80%. On multivariate Cox proportional-hazards modeling, only the presence of lymphovascular invasion (HR: 1.77, 95% CI: 1.04-2.99, p = 0.04) and DD < 80% (HR: 1.91, 95% CI: 1.23-3.00, p = 0.01) were associated with decreased OS. CONCLUSIONS: In this cohort study, patients who received ≥ 80% DD had significantly better OS. DD should be considered an important prognostic metric in pancreatic cancer, and strategies are needed to improve chemotherapy tolerance to improve patient outcomes.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Terapia Combinada , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Neoplasias PancreáticasRESUMO
INTRODUCTION: The role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with extraperitoneal disease (EPD) is controversial. METHODS: Among patients with peritoneal metastases from appendiceal cancer (AC) and colorectal cancer (CRC) who underwent CRS-HIPEC, those with EPD (liver, lung, or retroperitoneal lymph nodes [RP LN]) were retrospectively compared to those without EPD. Overall (OS) and recurrence-free survival (RFS) analyses were performed before/after propensity score matching (PSM). RESULTS: Among 1341 patients with AC (64%) or CRC (36%) who underwent CRS ± HIPEC, 134 (10%) had EPD whereas 1207 (90%) did not. EPD was located in the lungs (47%), RP LN (28%), liver (18%), or multiple (6%). Patients with EPD experienced worse median OS (34 versus 63 mo; P = 0.002) and RFS (12 versus 19 mo; P < 0.001). On a multivariable analysis, EPD was associated with worse RFS (P = 0.003), but not OS (P = 0.071). After PSM, the association of EPD with OS (P = 0.204) and RFS (P = 0.056) was no longer significant. In the multivariable analysis of the PSM cohort, EPD was not associated with OS (P = 0.157) or RFS (P = 0.110). CONCLUSIONS: The findings of this large retrospective multi-institutional study suggest that EPD alone, while a negative prognostic indicator, should not be considered an absolute contraindication to CRS ± HIPEC for otherwise well-selected patients with peritoneal surface malignancies. Further research is needed to delineate whether location of EPD influences OS and RFS following CRS-HIPEC.
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Neoplasias do Apêndice , Neoplasias Colorretais , Hipertermia Induzida , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Apêndice/patologia , Neoplasias do Apêndice/terapia , Neoplasias Colorretais/patologia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução , Humanos , Quimioterapia Intraperitoneal Hipertérmica , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The aim of our study was to evaluate the rates of treatment for post-operative exocrine pancreatic insufficiency (EPI) and diabetes mellites (DM) between Duodenal Preserving Pancreatic Head Resections (DPPHR) and Pancreaticoduodenectomy (PD) from a prospectively maintained database of patients with chronic pancreatitis. METHODS: 104 patients were identified for inclusion, 62 of whom underwent DPPHR and 42 underwent PD. Study endpoints included changes in treatment for EPI and DM. RESULTS: In the DPPHR group, the vast majority (n = 55) received a Frey procedure, with a small minority of patients undergoing a Beger procedure (n = 4) or Berne modification (n = 3). Patients in the DPPHR group had a lower rate of new persistent treatment for EPI post-operatively compared to patients who underwent PD (28.0% vs. 76.5%, p = 0.002). There was no difference in the rate of new onset DM, with low rates of new insulin dependent diabetics in both groups. Both groups had equal efficacy in terms of pain control, with 67.7% of the DPPHR group and 61.9% of the PD group remaining opioid free at long-term follow-up (p = 0.539). CONCLUSION: In patients with head-predominant chronic pancreatitis, DPPHR was associated with reduced rates of new EPI treatment and similar endocrine function compared with PD.
Assuntos
Diabetes Mellitus , Insuficiência Pancreática Exócrina , Pancreatite Crônica , Insuficiência Pancreática Exócrina/diagnóstico , Insuficiência Pancreática Exócrina/etiologia , Humanos , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Pancreaticoduodenectomia/efeitos adversos , Pancreaticoduodenectomia/métodos , Pancreatite Crônica/diagnóstico , Pancreatite Crônica/cirurgia , Qualidade de VidaRESUMO
BACKGROUND: Total pancreatectomy and islet cell autotransplantation (TPIAT) offers an effective, lasting solution for the management of chronic pancreatitis up to 5-years post-operatively. Our aim was to assess durability of TPIAT at 10-years. METHODS: Patients undergoing TPIAT for chronic pancreatitis eligible for 10-year follow-up were included. Primary outcomes, including endocrine function and narcotic requirements, were reported at 5-, 7.5-, and 10-years post-operatively. RESULTS: Of the 231 patients who underwent TPIAT, 142 met inclusion criteria. All patients underwent successful TPIAT with an average of 5680.3 islet equivalents per body weight. While insulin independence tended to decrease over time (25.7% vs. 16.0% vs. 10.9%, p = 0.11) with an increase in HbA1C (7.6% vs. 8.2% vs. 8.4%, p = 0.09), partial islet function persisted (64.9% vs. 68.0% vs. 67.4%, p = 0.93). Opioid independence was achieved and remained durable in the majority (73.3% vs. 72.2% vs. 75.5%, p = 0.93). Quality of life improvements persisted, with 85% reporting improvement from baseline at 10-years. Estimated median overall survival was 202.7 months. CONCLUSION: This study represents one of the largest series reporting on long-term outcomes after TPIAT, demonstrating excellent long-term pain control and durable improvements in quality of life. Islet cell function declines over time however stable glycemic control is maintained.
Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Pancreatite Crônica , Humanos , Pancreatectomia/efeitos adversos , Transplante Autólogo , Transplante das Ilhotas Pancreáticas/efeitos adversos , Qualidade de Vida , Resultado do Tratamento , Pancreatite Crônica/cirurgia , Ilhotas Pancreáticas/cirurgiaRESUMO
Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS-CoV-2 spike (pp-VSV-SARS-CoV-2 spike) that served as a bona fide system mimicking SARS-CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS-CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV-SARS-CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.
Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Esfingosina/farmacologia , Glicoproteína da Espícula de Coronavírus/metabolismo , Animais , Células Cultivadas , Chlorocebus aethiops , Células HEK293 , Humanos , Mucosa Nasal/metabolismo , Mucosa Nasal/virologia , Ligação Proteica , SARS-CoV-2/patogenicidade , SARS-CoV-2/fisiologia , Células Vero , Internalização do Vírus/efeitos dos fármacosRESUMO
The surgical treatment of pancreas ductal adenocarcinoma (PDAC) is plagued by high rates of distant recurrences despite complete resection, highlighting the importance of systemic therapy. Historically, patients with PDAC have been treated with postoperative therapy, but this sequencing strategy can be associated with the inability to complete therapy due to perioperative complications and prolonged recovery. In addition, a subset of patients progress early, irrespective of whether surgery is performed, highlighting the systemic nature of this disease. Preoperative therapy has increasingly been utilized in clinical practice, but studies examining its benefits are limited. In this Landmark Series, we will review seminal studies for resectable and borderline resectable PDAC.