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OBJECTIVE: We integrate a new approach to chemosensitivity data for clinically-relevant regimen matching, and demonstrate the relationship with clinical outcomes in a large PDO biobank. SUMMARY BACKGROUND DATA: Pancreatic ductal adenocarcinoma (PDAC) usually recurs following potentially curative resection. Prior studies related patient-derived organoid (PDO) chemosensitivity with clinical responses. METHODS: PDOs were established from pre-treatment biopsies in a multi-institution clinical trial (n=21) and clinical specimens at a high-volume pancreatectomy center (n=74, of which 48 were pre-treated). PDO in vitro chemosensitivities to standard-of-care chemotherapeutics (pharmacotypes) were matched to potential clinically-relevant regimens by a weighted nearest-neighbors analysis. Clinical outcomes were then compared for patients who had well-matched versus poorly-matched treatment according to this metric. RESULTS: Our function matched 91% of PDOs to a standard-of-care regimen (9% pan-resistant). PDOs poorly-matched to the neoadjuvant regimen received would have matched to an alternative in 34% of cases. Patients receiving neoadjuvant chemotherapy well-matched to their pharmacotype experienced improved CA 19-9 response (60% decreased to normal when well-matched, 29% when poorly-matched, P<0.05) and lymph node down-staging (33% N0 after poorly-matched, 69% after well-matched, P<0.05). Patients receiving both well-matched neoadjuvant and adjuvant chemotherapy experienced improved recurrence-free- and overall survival (median RFS 8.5 mo poorly-matched, 15.9 mo well-matched, P<0.05; median OS 19.5 vs. 30.3 mo, P<0.05). CONCLUSION: In vitro PDO pharmacotyping can inform PDAC therapy selection. We demonstrate improved outcomes including survival for patients treated with regimens well-matched to their PDO chemosensitivities. A subsequent prospective study using PDO pharmacotype matching could improve oncologic outcomes and improve quality of life by avoiding therapies not expected to be effective.
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OBJECTIVES: The aim of the study was to assess the association of circulating tumor cells (CTCs) with survival as a biomarker in pancreatic ductal adenocarcinoma (PDAC) within the context of a delay in the initiation of adjuvant therapy. BACKGROUND: Outcomes in patients with PDAC remain poor and are driven by aggressive systemic disease. Although systemic therapies improve survival in resected patients, factors such as a delay in the initiation of adjuvant therapy are associated with worse outcomes. CTCs have previously been shown to be predictive of survival. METHODS: A retrospective study was performed on PDAC patients enrolled in the prospective CircuLating tUmor cellS in pancreaTic cancER trial (NCT02974764) on CTC-dynamics at the Johns Hopkins Hospital. CTCs were isolated based on size (isolation by size of epithelial tumor cells; Rarecells) and counted and characterized by subtype using immunofluorescence. The preoperative and postoperative blood samples were used to identify 2 CTC types: epithelial CTCs (eCTCs), expressing pancytokeratin, and transitional CTCs (trCTCs), expressing both pancytokeratin and vimentin. Patients who received adjuvant therapy were compared with those who did not. A delay in the receipt of adjuvant therapy was defined as the initiation of therapy ≥8 weeks after surgical resection. Clinicopathologic features, CTCs characteristics, and outcomes were analyzed. RESULTS: Of 101 patients included in the study, 43 (42.5%) experienced a delay in initiation and 20 (19.8%) did not receive adjuvant therapy. On multivariable analysis, the presence of trCTCs ( P =0.002) and the absence of adjuvant therapy ( P =0.032) were associated with worse recurrence-free survival (RFS). Postoperative trCTC were associated with poorer RFS, both in patients with a delay in initiation (12.4 vs 17.9 mo, P =0.004) or no administration of adjuvant chemotherapy (3.4 vs NR, P =0.016). However, it was not associated with RFS in patients with timely initiation of adjuvant chemotherapy ( P =0.293). CONCLUSIONS: Postoperative trCTCs positivity is associated with poorer RFS only in patients who either experience a delay in initiation or no receipt of adjuvant therapy. This study suggests that a delay in the initiation of adjuvant therapy could potentially provide residual systemic disease (trCTCs) a window of opportunity to recover from the surgical insult. Future studies are required to validate these findings and explore the underlying mechanisms involved.
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Carcinoma Ductal Pancreático , Células Neoplásicas Circulantes , Neoplasias Pancreáticas , Humanos , Estudios Retrospectivos , Células Neoplásicas Circulantes/patología , Estudios Prospectivos , Biomarcadores de Tumor , Neoplasias Pancreáticas/cirugía , Carcinoma Ductal Pancreático/cirugía , Pronóstico , Quimioterapia Adyuvante , Neoplasias PancreáticasRESUMEN
OBJECTIVE: To develop a predictive model of oncologic outcomes for patients with pancreatic ductal adenocarcinoma (PDAC) undergoing resection after neoadjuvant or induction chemotherapy use. BACKGROUND: Early recurrence following surgical resection for PDAC is common. The use of neoadjuvant chemotherapy prior to resection may increase the likelihood of long-term systemic disease control. Accurately characterizing an individual's likely oncologic outcome in the perioperative setting remains challenging. METHODS: Data from patients with PDAC who received chemotherapy prior to pancreatectomy at a single high-volume institution between 2007 and 2018 were captured in a prospectively collected database. Core clinicopathologic data were reviewed for accuracy and survival data were abstracted from the electronic medical record and national databases. Cox-proportional regressions were used to model outcomes and develop an interactive prognostic tool for clinical decision-making. RESULTS: A total of 581 patients were included with a median overall survival (OS) and recurrence-free survival (RFS) of 29.5 (26.5-32.5) and 16.6 (15.8-17.5) months, respectively. Multivariable analysis demonstrates OS and RFS were associated with type of chemotherapeutic used andthe number of chemotherapy cycles received preoperatively. Additional factors contributing to survival models included: tumor grade, histopathologic response to therapy, nodal status, and administration of adjuvant chemotherapy. The models were validated using an iterative bootstrap method and with randomized cohort splitting. The models were well calibrated with concordance indices of 0.68 and 0.65 for the final OS and RFS models, respectively. CONCLUSION: We developed an intuitive and dynamic decision-making tool that can be useful in estimating OS, RFS, and location-specific disease recurrence rates. This prognostic tool may add value to patient care in discussing the benefits associated with surgical resection for PDAC.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Terapia Neoadyuvante , Pancreatectomía/métodos , Carcinoma Ductal Pancreático/cirugía , Neoplasias Pancreáticas/cirugía , Pronóstico , Quimioterapia Adyuvante , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
OBJECTIVE: To define frequencies, pattern of progression (invasive vs noninvasive), and risk factors of progression of resected noninvasive intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: There is a risk of progression in the remnant pancreas after resection of IPMNs. METHODS: Four hundred forty-nine consecutive patients with resected IPMNs from 1995 to 2018 were included to the study. Patients with invasive carcinoma or with follow-up <6 months were excluded. Noninvasive progression was defined as a new IPMN, increased main pancreatic duct size, and increased size of an existing lesion (5 mm compared with preoperative imaging). Invasive progression was defined as development of invasive cancer in the remnant pancreas or metastatic disease. RESULTS: With a median follow-up of 48.9 months, progression was identified in 124 patients (27.6%); 108(24.1%) with noninvasive and 16(3.6%) with invasive progression. Median progression follow-up was longer for invasive progression (85.4 vs 55.9 months; P = 0.001). Five-and 10-year estimates for a cumulative incidence of invasive progression were 6.4% and 12.9% versus 26.9% and 41.5% for noninvasive progression. After risk adjustment, multifocality (HR 4.53, 95% CI 1.34-15.26; P = 0.02) and high-grade dysplasia (HGD) in the original resection (HR 3.60, 95% CI 1.13-11.48; P = 0.03) were associated with invasive progression. CONCLUSIONS: Progression to invasive carcinoma can occur years after the surgical resection of a noninvasive IPMN. HGD in the original resection is a risk factor for invasive progression but some cases of low-grade dysplasia also progressed to cancer. Patients with high-risk features such as HGD and multifocal cysts should be considered for more intensive surveillance and represent an important cohort for future trials such as anti-inflammatory or prophylactic immunotherapy.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductales Pancreáticas , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/cirugía , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Humanos , Pancreatectomía/métodos , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Intraductales Pancreáticas/cirugía , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: Prognosis in pancreatic ductal adenocarcinoma (PDAC) remains poor despite improved systemic therapies and surgical techniques. The identification of biomarkers to advance insight in tumor biology and achieve better individualized prognostication could help improve outcomes. Our aim was to elucidate the prognostic role of the four main driver mutations (KRAS, TP53, SMAD4, CDKN2A) and their combinations in resected PDAC. PATIENTS AND METHODS: A retrospective analysis was conducted utilizing the cBioPortal database and National Cancer Institute's Cancer Genomic Atlas (TCGA) on patients in whom next-generation sequencing was performed on upfront resected PDAC from 2012 to 2020. Multivariable Cox regression was implemented to elucidate risk-adjusted predictors of overall (OS) and recurrence-free survival (RFS). Results were validated employing a Johns Hopkins Hospital (JHH) cohort.' RESULTS: In the discovery cohort (n = 587), increased number of mutated driver genes was associated with worse OS (p = 0.047). Specifically, patients with mutations in ≥ 2 driver genes had worse OS than ≤ 1 mutated gene (18.2 versus 32.3 months, p = 0.033). Co-occurrence of mutant (mt)KRAS p.G12D with mtTP53 (median OS, 25.9 months) conferred better prognosis than co-occurrence of other mtKRAS variants (p.G12V/R/other) with mtTP53 (median OS, 16.9 months, p = 0.038). The findings were validated using a JHH cohort. Multivariable risk-adjustment found co-occurrence of mtKRAS p.G12D with mtTP53 to be an independent predictor of beneficial OS and RFS [HR (95% CI): 0.18 (0.03-0.81) and 0.31 (0.11-0.89) respectively]. CONCLUSION: In chemo-naïve resected PDAC, combinations of mutations in the four driver genes are associated with prognosis. In patients with combined mtKRAS and mtTP53, KRAS p.G12D variant confers a better OS and RFS.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Biomarcadores de Tumor/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Humanos , Mutación , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Proteínas Proto-Oncogénicas p21(ras)/genética , Estudios Retrospectivos , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Postoperative chemotherapy following pancreatic cancer resection is the standard of care. The utility of postoperative chemotherapy for patients who receive neoadjuvant therapy (NAT) is unclear. METHODS: Patients who underwent pancreatectomy after NAT with FOLFIRINOX or gemcitabine-based chemotherapy for non-metastatic pancreatic adenocarcinoma (2015-2019) were identified. Patients who received less than 2 months of neoadjuvant chemotherapy or died within 90 days from surgery were excluded. RESULTS: A total of 427 patients (resectable, 22.2%; borderline resectable, 37.9%; locally advanced, 39.8%) were identified with the majority (69.3%) receiving neoadjuvant FOLFIRINOX. Median duration of NAT was 4.1 months. Following resection, postoperative chemotherapy was associated with an improved median overall survival (OS) (28.7 vs. 20.4 months, P = 0.006). Risk-adjusted multivariable modeling showed negative nodal status (N0), favorable pathologic response (College of American Pathologists score 0 & 1), and receipt of postoperative chemotherapy to be independent predictors of improved OS. Regimen, duration, and number of cycles of NAT were not significant predictors. Thirty-four percent (60/176) of node-positive and 50.1% (126/251) of node-negative patients did not receive postoperative chemotherapy due to poor functional status, postoperative complications, and patient preference. Among patients with node-positive disease, postoperative chemotherapy was associated with improved median OS (27.2 vs. 10.5 months, P < 0.001). Among node-negative patients, postoperative chemotherapy was not associated with a survival benefit (median OS, 30.9 vs. 36.9 months; P = 0.406). CONCLUSION: Although there is no standard NAT regimen for patients with pancreatic cancer, postoperative chemotherapy following NAT and resection appears to be associated with improved OS for patients with node-positive disease.
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Adenocarcinoma , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/cirugía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/cirugía , Humanos , Terapia Neoadyuvante , Pancreatectomía , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/cirugía , Estudios Retrospectivos , Ácidos Urónicos , Neoplasias PancreáticasRESUMEN
BACKGROUND: Delayed bleeding after pancreaticoduodenectomy (PD) is a life-threatening complication. However, the optimal management remains unclear. We summarize our experience of the management of delayed bleeding after PD and define the outcomes associated with different types of management. METHODS: All patients who underwent a PD between January 1987 and June 2020 at Johns Hopkins University were retrospectively reviewed. Delayed bleeding was defined as bleeding on or after postoperative day 5 following PD. Incidence, outcomes, and trends were reported. RESULTS: Among the 6201 patients that underwent PD, delayed bleeding occurred in 130 (2.1%) at a median of 12 days (IQR: 9, 24) postoperation. The pattern of bleeding was classified as intraluminal (51.5%), extraluminal (40.8%), and mixed (7.7%). A clinically relevant postoperative pancreatic fistula and an intraabdominal abscess preceded the delayed bleeding in 43.1% and 31.5% of cases, respectively. Arterial pseudoaneurysm or bleeding from peripancreatic vessels was the most common reason (54.6%) with the gastroduodenal artery being the most common source (18.5%). Endoscopy, angiography, and reoperation were performed as a first-line approach in 35.4%, 52.3%, and 6.2% of patients, respectively. The overall mortality was 16.2% and decreased over the study period (p < 0.01). CONCLUSIONS: Delayed bleeding following PD remains a life-threatening complication. The most common location of delayed bleeding is from the gastroduodenal artery. Angiography with embolization should be the initial approach for urgent bleeding with surgical re-exploration reserved for unstable patients or failed control of bleeding after interventional angiography or endoscopy.
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Pancreaticoduodenectomía , Hemorragia Posoperatoria , Arteria Hepática , Humanos , Incidencia , Pancreaticoduodenectomía/efectos adversos , Hemorragia Posoperatoria/diagnóstico por imagen , Hemorragia Posoperatoria/epidemiología , Estudios RetrospectivosRESUMEN
BACKGROUND: Modern chemotherapeutics have led to improved systemic disease control for patients with locally advanced pancreatic cancer (LAPC). Surgical strategies such as distal pancreatectomy with celiac axis resection (DP-CAR) are increasingly entertained. Herein we review procedure-specific outcomes and assess biologic rationale for DP-CAR. METHODS: A prospectively maintained single-institution database of all pancreatectomies was queried for patients undergoing DP-CAR. We excluded all patients for whom complete data were not available and those who were not treated with contemporary multi-agent therapy. Data were supplemented with dedicated chart review and outreach for long-term oncologic outcomes. RESULTS: Fifty-four patients underwent DP-CAR between 2008 and 2018. The median age was 62.7 years. Ninety-eight percent received induction chemotherapy. Arterial reconstruction was performed in 17% and concomitant visceral resection in 30%. The R0 resection rate was 87%. Postoperative complications were common (43%) with chyle leak being the most frequent (17%). Length of stay was 8 days, readmission occurred in one-third, and 90-day mortality was 2%. Disease recurrence occurred in 74% during a median follow up of 17.4 months. Median recurrence-free (RFS) and overall survival (OS) were 9 and 25 months, respectively. CONCLUSIONS: Following modern induction paradigms, DP-CAR can be performed with low mortality, manageable morbidity, and excellent rates of margin-negative resection in high-volume settings. The profile of complications of DP-CAR is distinct from pancreaticoduodenectomy and simple distal pancreatectomy. OS and RFS are similar to those undergoing resection of borderline resectable and resectable disease. Improved systemic disease control will likely lead to increasing utilization of aggressive surgical approaches to LAPC.
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Pancreatectomía , Neoplasias Pancreáticas , Arteria Celíaca/cirugía , Humanos , Persona de Mediana Edad , Recurrencia Local de Neoplasia/cirugía , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
PURPOSE: The resection of retropancreatic nerve plexuses for pancreatic head cancer became standard of care during open pancreatoduodenectomy to minimize local recurrences. Since more surgical centers are progressing on the learning curve, robotically-assisted pancreatoduodenectomy is now increasingly performed with decreasing anatomic exclusion criteria. To achieve comparable and favorable oncologic outcomes, advanced surgical techniques should be transferred and implemented when performing robotic resections. METHODS: The nomenclature and anatomic principles of retropancreatic nerve plexuses and three different levels of dissections are utilized based on established definitions. RESULTS: The en bloc dissection in the "TRIANGLE" area (triangular-shaped retropancreatic space enclosed by the common hepatic artery, superior mesenteric artery, and superior mesenteric vein/portal vein) and the periadventitial dissection of arteries for non-tunica media-invading tumors were executed robotically. Both can be utilized to achieve a radical dorsal and medial margin. Video recordings are provided to illustrate varying TRIANGLE dissections. CONCLUSION: To accomplish oncologic non-inferiority, established principles from open pancreatic resections can be incorporated precisely and safely, overcoming the lack of haptic feedback while exploiting the technological advantages of the robotically-assisted platform.
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Neoplasias Pancreáticas , Procedimientos Quirúrgicos Robotizados , Disección , Humanos , Pancreatectomía , Neoplasias Pancreáticas/cirugía , PancreaticoduodenectomíaRESUMEN
BACKGROUND: Lymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy. METHODS: Data from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines. RESULTS: As ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage. CONCLUSION: This is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/patología , Carcinoma Ductal Pancreático/cirugía , Humanos , Escisión del Ganglio Linfático , Ganglios Linfáticos/patología , Ganglios Linfáticos/cirugía , Estadificación de Neoplasias , Páncreas/patología , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: The aim of this study was to determine the incidence of high-grade dysplasia (HGD) or invasive carcinoma in patients with small branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). METHODS: 923 patients who underwent surgical resection for an IPMN were identified. Sendai-negative patients were identified as those without history of pancreatitis or jaundice, main pancreatic duct size (MPD) <5 mm, cyst size <3 cm, no mural nodules, negative cyst fluid cytology for adenocarcinoma, or serum carbohydrate antigen 19-9 (CA 19-9) <37 U/L. RESULTS: BD-IPMN was identified in 388 (46.4%) patients and 89 (22.9%) were categorized as Sendai-negative. Overall, 68 (17.5%) of BD-IPMN had HGD and 62 (16.0%) had an associated invasive-carcinoma. Among the 89 Sendai-negative patients, 12 (13.5%) had IPMNs with HGD and only one patient (1.1%) had invasive-carcinoma. Of note, older age (OR 1.13, 95% CI 1.03-1.23; P = 0.008) and minimal dilation of MPD (OR 11.3, 95% CI 2.40-53.65; P = 0.002) were associated with high-risk disease in Sendai-negative patients after multivariable risk adjustment. CONCLUSION: The risk of harboring a high-risk disease remains low in small BD-IPMNs. However, Sendai-negative patients who are older than 65 years old and those with minimal dilation of MPD (3-5 mm) are at greater risk of high-risk lesions and should be given consideration to be included as a "worrisome feature" in a future guidelines update.
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Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Adenocarcinoma Mucinoso/diagnóstico por imagen , Adenocarcinoma Mucinoso/cirugía , Anciano , Carcinoma Ductal Pancreático/diagnóstico por imagen , Carcinoma Ductal Pancreático/cirugía , Dilatación , Humanos , Conductos Pancreáticos/diagnóstico por imagen , Conductos Pancreáticos/cirugía , Neoplasias Pancreáticas/diagnóstico por imagen , Neoplasias Pancreáticas/cirugía , Estudios RetrospectivosRESUMEN
Pancreatic ductal adenocarcinoma (PDAC) is increasing in incidence and is projected to become the second leading cause of cancer death in the United States. Despite significant advances in understanding the disease, there has been minimal increase in PDAC patient survival. PDAC tumors are unique in the fact that there is significant desmoplasia. This generates a large stromal compartment composed of immune cells, inflammatory cells, growth factors, extracellular matrix, and fibroblasts, comprising the tumor microenvironment (TME), which may represent anywhere from 15% to 85% of the tumor. It has become evident that the TME, including both the stroma and extracellular component, plays an important role in tumor progression and chemoresistance of PDAC. This review will discuss the multiple components of the TME, their specific impact on tumorigenesis, and the multiple therapeutic targets.
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Carcinoma Ductal Pancreático , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos , Neoplasias Pancreáticas , Microambiente Tumoral , Carcinoma Ductal Pancreático/tratamiento farmacológico , Carcinoma Ductal Pancreático/inmunología , Carcinoma Ductal Pancreático/patología , Progresión de la Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Resistencia a Antineoplásicos/inmunología , Humanos , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/patología , Microambiente Tumoral/efectos de los fármacos , Microambiente Tumoral/inmunologíaRESUMEN
INTRODUCTION: Pancreatic neuroendocrine tumors (p-NETS) are increasing in incidence, and prognostic factors continue to evolve. The benefit of lymphadenectomy for p-NETS ≤2 cm remains unclear. We sought to determine the significance of lymphovascular invasion (LVI) for small p-NETS. METHODS: The National Cancer Database was queried for patients with p-NETS ≤2 cm and with ≥1 evaluated lymph node (LN), years 2004-2015. Demographic, clinical, and treatment characteristics were analyzed. Multivariate logistic regression was performed to identify predictors of LN positivity. RESULTS: Among 2,499 patients identified, tumor location was delineated as the head (26%), body (18%), tail (38%), or unspecified (18%); 74% were well-differentiated versus 10% moderate, 2% poor, and 14% unknown. LVI occurred in 11%. A median of 9 LNs were evaluated; overall positivity was 18%. Mean survival was significantly longer in node-negative patients (115 vs. 95 months, log-rank p < 0.0001). LVI was the strongest predictor of node involvement (OR 10.4, p < 0.0001) when controlling for tumor size, grade, and location. Subset analysis of patients with known LVI status, grade, location, and mitoses found that LVI was more likely in the setting of moderate-to-high tumor grade, 1-2 cm size, pancreatic head location, and high mitotic rate. Among patients with ≥2 of these 4 factors, 25% were node-positive. CONCLUSIONS: Presence of LVI was the strongest predictor of node positivity. LVI on endoscopic biopsy should prompt resection and regional LN dissection to fully stage patients with small p-NETS. Patients with other high-risk factors should also be considered for resection and regional lymphadenectomy.
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Metástasis Linfática/diagnóstico , Metástasis Linfática/patología , Tumores Neuroendocrinos/diagnóstico , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Adolescente , Adulto , Anciano , Bases de Datos Factuales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Adulto JovenRESUMEN
BACKGROUND: Primary tumor location has emerged as an important surrogate for tumor biology in metastatic colorectal cancer treated with systemic chemotherapy. It is unclear if primary tumor location is associated with survival after cytoreductive surgery (CRS) with or without heated intraperitoneal chemotherapy (HIPEC) for colorectal carcinomatosis. METHODS: Study of a contemporary cohort merged data from the California Cancer Registry, 2004-2012, and the Office of Statewide Health Planning and Development inpatient database. For patients undergoing CRS/HIPEC, clinicopathologic variables, treatment characteristics, and survival were compared by right versus left colon primary site. Survival was analyzed by Cox proportional hazards. RESULTS: Of 272 patients identified, 128 (47.1%) had right-sided tumors. Left- and right-sided cohorts had similar patient, tumor, and treatment factors. Patients with left-sided primary tumors had significantly prolonged overall survival (mean 34 versus 15.5 mo, P = 0.0010). Factors independently associated with decreased overall survival included age >80 (HR 7.0, P < 0.0001), advanced T4 stage (HR 3.6, P = 0.0031), and positive lymph nodes (HR 2.2, P = 0.0004). Metachronous peritoneal involvement (HR 0.38, P < 0.0001) and left-sided primary tumors (HR 0.72, P = 0.041) were independently associated with improved overall survival. CONCLUSIONS: This study identifies location of primary tumor as an important determinant of long-term survival after CRS/HIPEC. Patients with left-sided tumors have a more favorable prognosis.
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Carcinoma/mortalidad , Colon/patología , Neoplasias Colorrectales/mortalidad , Procedimientos Quirúrgicos de Citorreducción , Adulto , Anciano , Anciano de 80 o más Años , California/epidemiología , Carcinoma/patología , Carcinoma/terapia , Quimioterapia del Cáncer por Perfusión Regional , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
BACKGROUND AND OBJECTIVES: Effective communication is essential to complex shared decision making and is associated with improved recovery and pain control. However, patients and surgeons often have disparate expectations of treatment efficacy and perceptions of cure for advanced malignancies. This study measures correlation of patient and surgeon expectations with perceptions of cure. METHODS: Our prospective study surveying surgeon-patient dyads before and after surgical consultation was performed for advanced abdominal malignancy between July and November 2017 at a single NCI designated cancer center using electronic questionnaires. RESULTS: Patients and surgeons' own opinions regarding surgical candidacy (Q1), chance at cure (Q2), and life expectancy (Q3) did not measurably change from pre- to postvisit survey as evidenced by unchanged response concordance (patients Q1 P = .82; Q2 P = .81; and Q3 P = .53; surgeon responses Q1: P = .17; Q2: P = .32; and Q3: P = .50). Patient and surgeon perception of likelihood of cure and of estimated life expectancy remained discordant in pre- and postvisit surveys (Q2: P = .006 and Q3: P = .03). CONCLUSIONS: These data highlight the stark differences between patient and surgeon perceptions of cure and prognosis of gastrointestinal cancers. These results prove that a larger scale study using this electronic questionnaire is feasible and important to better understand these differences and enhance shared decision making.
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Comunicación , Neoplasias Gastrointestinales/psicología , Neoplasias Gastrointestinales/cirugía , Relaciones Médico-Paciente , Cirujanos/psicología , Toma de Decisiones , Procedimientos Quirúrgicos del Sistema Digestivo/psicología , Estudios de Factibilidad , Humanos , Percepción , Pronóstico , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
BACKGROUND: Variations in care have been demonstrated both within and among institutions in many clinical settings. By standardizing perioperative practices, Enhanced Recovery After Surgery (ERAS) pathways reduce variation in perioperative care. We sought to characterize the variation in cytoreductive surgery (CRS)/heated intraperitoneal chemotherapy (HIPEC) perioperative practices among experienced US medical centers. METHODS: Data from the US HIPEC Collaborative represents a retrospective multi-institutional cohort study of CRS and CRS/HIPEC procedures performed from 12 major academic institutions. Patient characteristics and perioperative practices were reported and compared. Institutional variation was analyzed using hierarchical mixed-effects linear (continuous outcomes) or logistic (binary outcomes) regression models. RESULTS: A total of 2372 operations were included. CRS/HIPEC was performed most commonly for appendiceal histologies (64.2%). The rate of complications (overall 56.3%, range: 31.8-70.9) and readmissions (overall 20.6%, range: 8.9-33.3) varied by institution (P < .001). Institution-level variation in perioperative practice patterns existed among measured ERAS pathway process/outcomes (P < .001). The percentages of variation with each process/outcome measure attributable solely to institutional practices ranged from 0.6% to 66.6%. CONCLUSIONS: Significant variation exists in the perioperative care of patients undergoing CRS/HIPEC at major US academic institutions. These findings provide a strong rationale for the investigation of best practices in CRS/HIPEC patients.
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Procedimientos Quirúrgicos de Citorreducción/métodos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias/terapia , Estudios de Cohortes , Procedimientos Quirúrgicos de Citorreducción/normas , Procedimientos Quirúrgicos de Citorreducción/estadística & datos numéricos , Recuperación Mejorada Después de la Cirugía , Femenino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Older adults undergoing cancer surgery are at greater risk for poor postoperative outcomes. Caregivers also endure significant burden. Participation in perioperative physical activity may improve physical functioning and enhance overall well-being for both patients and caregivers. In this study, we assessed the feasibility of a personalized telehealth intervention to enhance physical activity for older (≥ 65 years) gastrointestinal (GI) and lung cancer surgery patients/caregivers. METHODS: Participants completed four telehealth sessions with physical therapy/occupational therapy (PT/OT) before surgery and up to 2 weeks post-discharge. Outcomes included preop geriatric assessment, functional measures, and validated measures for symptoms and psychological distress. Pre/post-intervention trends/trajectories for outcomes were explored. RESULTS: Thirty-four patient/caregiver dyads (16, GI; 18, lung) were included. Accrual rate was 76% over 8 months; retention rate was 88% over 2 months. Median for postop of a 6-min walk test, timed up and go, and short physical performance battery test scores improved from baseline to postop. Participant satisfaction scores were high. CONCLUSION: Our conceptually based, personalized, multimodal, telehealth perioperative physical activity intervention for older patient/caregiver dyads is feasible and acceptable. It offers an opportunity to improve postoperative outcomes by promoting functional recovery through telehealth, behavior change, and self-monitoring approaches. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03267524.
Asunto(s)
Cuidadores/psicología , Neoplasias/enfermería , Neoplasias/psicología , Periodo Posoperatorio , Calidad de Vida/psicología , Telemedicina/métodos , Anciano , Femenino , Humanos , Masculino , Proyectos PilotoRESUMEN
BACKGROUND: Given surgery's inherent risks, a patient should be able to make the most informed decisions possible in selecting surgical treatment. However, there is little information on what factors patients deem important when choosing a surgeon. We performed a systematic review of the literature focused on how patients select surgical care, focusing on identification of factors that influence patient choice as well as important sources of information used by patients. METHODS: A search of all available literature on factors associated with choice of surgeon/surgical care, as well as sources of information used by patients before undergoing surgery, was conducted using the MEDLINE/PubMed electronic database. RESULTS: Of the 2315 publications identified, 86 studies met inclusion criteria. Overall, patients draw upon a wide range of factors when choosing surgical care. Surgeon reputation and competency stood out as the most valued professional attributes. Patients also often selected surgeons based on their interpersonal skills. Many patients chose surgical care using hospital, rather than surgeon, characteristics. For these patients, hospital reputation and hospital distance were factors of primary importance. Importantly, most patients relied on word-of-mouth and physician referrals when choosing a surgeon. Patients also expressed interest in quality information on surgeons, indicating that these data would be useful in decision-making. CONCLUSIONS: Patients draw upon a myriad of factors when choosing a surgeon and the circumstances surrounding patients' decisions maybe differ based on sociodemographic, cultural, as well as other factors. Additional information on how patients choose surgeons or hospitals will help providers assist patients in finding their preferred caregivers.
Asunto(s)
Conducta de Elección , Toma de Decisiones , Hospitales , Prioridad del Paciente , Derivación y Consulta , Cirujanos , Humanos , Recursos HumanosRESUMEN
INTRODUCTION: Gallstone ileus is a mechanical bowel obstruction caused by a biliary calculus originating from a bilioenteric fistula. Because of the limited number of reported cases, the optimal surgical method of treatment has been the subject of ongoing debate. METHODS: A retrospective review of the Nationwide Inpatient Sample from 2004 to 2009 was performed for gallstone ileus cases treated surgically by enterotomy with stone extraction alone (ES), enterotomy and cholecystectomy with fistula closure (EF), bowel resection alone (BR), and bowel resection with fistula closure (BF). Patient demographics, hospital factors, comorbidities, and postoperative outcomes were reported. Multivariate analysis was performed comparing mortality, morbidity, length of stay, and total cost for the different procedure types. RESULTS: Of the estimated 3,452,536 cases of mechanical bowel obstruction from 2004 to 2009, 3268 (0.095%) were due to gallstone ileus-an incidence lower than previously reported. The majority of patients were elderly women (>70%). ES was the most commonly performed procedure (62% of patients) followed by EF (19% of cases). In 19%, a bowel resection was required. The most common complication was acute renal failure (30.44% of cases). In-hospital mortality was 6.67%. On multivariate analysis, EF and BR were independently associated with higher mortality than ES [(odds ratio [OR] = 2.86; confidence interval [CI]: 1.16-7.07) and (OR = 2.96; CI: 1.26-6.96) respectively]. BR was also associated with a higher complication rate, OR = 1.98 (CI: 1.13-3.46). CONCLUSIONS: Gallstone ileus is a rare surgical disease affecting mainly the elderly female population. Mortality rates appear to be lower than previously reported in the literature. Enterotomy with stone extraction alone appears to be associated with better outcomes than more invasive techniques.
Asunto(s)
Fístula Biliar/complicaciones , Procedimientos Quirúrgicos del Sistema Digestivo/tendencias , Cálculos Biliares/complicaciones , Fístula Intestinal/complicaciones , Obstrucción Intestinal/cirugía , Intestino Delgado/cirugía , Anciano , Anciano de 80 o más Años , Fístula Biliar/epidemiología , Fístula Biliar/mortalidad , Fístula Biliar/cirugía , Colecistectomía/estadística & datos numéricos , Colecistectomía/tendencias , Bases de Datos Factuales , Procedimientos Quirúrgicos del Sistema Digestivo/métodos , Procedimientos Quirúrgicos del Sistema Digestivo/estadística & datos numéricos , Femenino , Cálculos Biliares/epidemiología , Cálculos Biliares/mortalidad , Cálculos Biliares/cirugía , Mortalidad Hospitalaria , Humanos , Incidencia , Fístula Intestinal/epidemiología , Fístula Intestinal/mortalidad , Fístula Intestinal/cirugía , Obstrucción Intestinal/epidemiología , Obstrucción Intestinal/etiología , Obstrucción Intestinal/mortalidad , Modelos Logísticos , Masculino , Análisis Multivariante , Complicaciones Posoperatorias/epidemiología , Estudios Retrospectivos , Resultado del Tratamiento , Estados Unidos/epidemiologíaRESUMEN
The radiologic finding of focal stenosis of the main pancreatic duct is highly suggestive of pancreatic cancer. Even in the absence of a mass lesion, focal duct stenosis can lead to surgical resection of the affected portion of the pancreas. We present four patients with distinctive pathology associated with non-neoplastic focal stenosis of the main pancreatic duct. The pathology included stenosis of the pancreatic duct accompanied by wavy, acellular, serpentine-like fibrosis, chronic inflammation with foreign body-type giant cell reaction, and calcifications. In all cases, the pancreas toward the tail of the gland had obstructive changes including acinar drop-out and interlobular and intralobular fibrosis. Three of the four patients had a remote history of major motor vehicle accidents associated with severe abdominal trauma. These results emphasize that blunt trauma can injure the pancreas and that this injury can result in long-term complications, including focal stenosis of the main pancreatic duct. Pathologists should be aware of the distinct pathology associated with remote trauma and, when the pathology is present, should elicit the appropriate clinical history.