RESUMO
OBJECTIVE: Describe the utility of circulating tumor DNA in the post-operative surveillance of hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: Current biomarkers for HCC like Alpha-fetoprotein (AFP) are lacking. ctDNA has shown promise in colorectal and lung cancers, but its utility in HCC remains relatively unknown. METHODS: Patients with HCC undergoing curative-intent resection from 11/1/2020-7/1/2023 received ctDNA testing using the Guardant360 platform. TMB is calculated as the number of somatic mutations-per-megabase of genomic material identified. RESULTS: Forty seven patients had post-operative ctDNA testing. Mean follow-up was 27 months and maximum was 43.2 months. Twelve patients (26%) experienced recurrence. Most (n=41/47, 87.2%) had identifiable ctDNA post-operatively; 55.3%(n=26) were TMB-not detected versus 45.7% (n=21) TMB-detectable. Post-operative identifiable ctDNA was not associated with RFS (P=0.518). Detectable TMB was associated with reduced RFS (6.9 vs. 14.7months, P=0.049). There was a higher rate of recurrence in patients with TMB (n=9/21, 42.9%, vs. n=3/26, 11.5%, P=0.02). Area-Under the Curve (AUC) for TMB-prediction of recurrence was 0.752 versus 0.550 for AFP. ROC-analysis established a TMB cut-off of 4.8mut/mB for predicting post-operative recurrence (P=0.002) and RFS (P=0.025). AFP was not correlated with RFS using the lab-normal cut-off (<11 ng/mL, P=0.682) or the cut-off established by ROC-analysis (>4.6 ng/mL, P=0.494). TMB-high was associated with poorer RFS on cox-regression analysis (HR=5.386, 95%CI1.109-26.160, P=0.037) while micro-vascular invasion (P=0.853) and AFP (P=0.439) were not. CONCLUSIONS: Identifiable TMB on post-operative ctDNA predicts HCC recurrence, and outperformed AFP in this cohort. Perioperative ctDNA may be a useful surveillance tool following curative-intent hepatectomy. Larger-scale studies are needed to confirm this utility and investigate additional applications in HCC patients, including the potential for prophylactic treatment in patients with residual TMB after resection.
RESUMO
OBJECTIVE: Assess cost and complication outcomes after liver transplantation (LT) using normothermic machine perfusion (NMP). BACKGROUND: End-ischemic NMP is often used to aid logistics, yet its impact on outcomes after LT remains unclear, as does its true impact on costs associated with transplantation. METHODS: Deceased donor liver recipients at 2 centers (January 1, 2019, to June 30, 2023) were included. Retransplants, splits, and combined grafts were excluded. End-ischemic NMP (OrganOx-Metra) was implemented in October 2022 for extended-criteria donation after brain death (DBDs), all donations after circulatory deaths (DCDs), and logistics. NMP cases were matched 1:2 with static cold storage controls (SCS) using the Balance-of-Risk [donation after brain death (DBD)-grafts] and UK-DCD Score (DCD-grafts). RESULTS: Overall, 803 transplantations were included, 174 (21.7%) receiving NMP. Matching was achieved between 118 NMP-DBDs with 236 SCS; and 37 NMP-DCD with 74 corresponding SCS. For both graft types, median inpatient comprehensive complications index values were comparable between groups. DCD-NMP grafts experienced reduced cumulative 90-day comprehensive complications index (27.6 vs 41.9, P =0.028). NMP also reduced the need for early relaparotomy and renal replacement therapy, with subsequently less frequent major complications (Clavien-Dindo ≥IVa). This effect was more pronounced in DCD transplants. NMP had no protective effect on early biliary complications. Organ acquisition/preservation costs were higher with NMP, yet NMP-treated grafts had lower 90-day pretransplant costs in the context of shorter waiting list times. Overall costs were comparable for both cohorts. CONCLUSIONS: This is the first risk-adjusted outcome and cost analysis comparing NMP and SCS. In addition to logistical benefits, NMP was associated with a reduction in relaparotomy and bleeding in DBD grafts, and overall complications and post-LT renal replacement for DCDs. While organ acquisition/preservation was more costly with NMP, overall 90-day health care costs-per-transplantation were comparable.
Assuntos
Transplante de Fígado , Preservação de Órgãos , Perfusão , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Transplante de Fígado/economia , Pessoa de Meia-Idade , Perfusão/métodos , Preservação de Órgãos/métodos , Preservação de Órgãos/economia , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Adulto , Idoso , Sobrevivência de EnxertoRESUMO
We describe a novel pre-liver transplant (LT) approach in colorectal liver metastasis, allowing for improved monitoring of tumor biology and reduction of disease burden before committing a patient to transplantation. Patients undergoing LT for colorectal liver metastasis at Cleveland Clinic were included. The described protocol involves intensive locoregional therapy with systemic chemotherapy, aiming to reach minimal disease burden revealed by positron emission tomography scan and carcinoembryonic Ag. Patients with no detectable disease or irreversible treatment-induced liver injury undergo transplant. Nine patients received liver transplant out of 27 who were evaluated (33.3%). The median follow-up was 700 days. Seven patients (77.8%) received a living donor LT. Five had no detectable disease, and 4 had treatment-induced cirrhosis. Pretransplant management included chemotherapy (n = 9) +/- bevacizumab (n = 6) and/or anti-EGFR (n = 6). The median number of pre-LT cycles of chemotherapy was 16 (range 10-40). Liver-directed therapy included Yttrium-90 (n = 5), ablation (n = 4), resection (n = 4), and hepatic artery infusion pump (n = 3). Three patients recurred after LT. Actuarial 1- and 2-year recurrence-free survival were 75% (n = 6/8) and 60% (n = 3/5). Recurrence occurred in the lungs (n = 1), liver graft (n = 1), and lungs+para-aortic nodes (n = 1). Patients with pre-LT detectable disease had reduced RFS ( p = 0.04). All patients with recurrence had histologically viable tumors in the liver explant. Patients treated in our protocol (n = 16) demonstrated improved survival versus those who were not candidates (n = 11) regardless of transplant status ( p = 0.01). A protocol defined by aggressive pretransplant liver-directed treatment and transplant for patients with the undetectable disease or treatment-induced liver injury may help prevent tumor recurrence.
RESUMO
Ex situ normothermic machine perfusion (NMP) helps increase the use of extended criteria donor livers. However, the impact of an NMP program on waitlist times and mortality has not been evaluated. Adult patients listed for liver transplant (LT) at 2 academic centers from January 1, 2015, to September 1, 2023, were included (n=2773) to allow all patients ≥6 months follow-up from listing. Routine NMP was implemented on October 14, 2022. Waitlist outcomes were compared from pre-NMP pre-acuity circles (n=1460), pre-NMP with acuity circles (n=842), and with NMP (n=381). Median waitlist time was 79 days (IQR: 20-232 d) at baseline, 49 days (7-182) with acuity circles, and 14 days (5-56) with NMP ( p <0.001). The rate of transplant-per-100-person-years improved from 61-per-100-person-years to 99-per-100-person-years with acuity circles and 194-per-100-person-years with NMP ( p <0.001). Crude mortality without transplant decreased from 18.3% (n=268/1460) to 13.3% (n=112/843), to 6.3% (n=24/381) ( p <0.001) with NMP. The incidence of mortality without LT was 15-per-100-person-years before acuity circles, 19-per-100 with acuity circles, and 9-per-100-person-years after NMP ( p <0.001). Median Model for End-Stage Liver Disease at LT was lowest with NMP, but Model for End-Stage Liver Disease at listing was highest in this era ( p <0.0001). The median donor risk index of transplanted livers at baseline was 1.54 (1.27-1.82), 1.66 (1.42-2.16) with acuity circles, and 2.06 (1.63-2.46) with NMP ( p <0.001). Six-month post-LT survival was not different between eras ( p =0.322). The total cost of health care while waitlisted was lowest in the NMP era ($53,683 vs. $32,687 vs. $23,688, p <0.001); cost-per-day did not differ between eras ( p =0.152). The implementation of a routine NMP program was associated with reduced waitlist time and mortality without compromising short-term survival after liver transplant despite increased use of riskier grafts. Routine NMP use enables better waitlist management with reduced health care costs.
RESUMO
Colorectal cancer is the second most common cause of cancer-related death worldwide, and half of patients present with colorectal liver metastasis (CRLM). Liver transplant (LT) has emerged as a treatment modality for otherwise unresectable CRLM. Since the publication of the Lebeck-Lee systematic review in 2022, additional evidence has come to light supporting LT for CRLM in highly selected patients. This includes reports of >10-year follow-up with over 80% survival rates in low-risk patients. As these updated reports have significantly changed our collective knowledge, this article is intended to serve as an update to the 2022 systematic review to include the most up-to-date evidence on the subject.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais/patologia , Hepatectomia , Neoplasias Hepáticas/secundário , Revisões Sistemáticas como AssuntoRESUMO
BACKGROUND: Neoadjuvant systemic therapy (NAST) is a treatment option for intrahepatic cholangiocarcinoma (iCCA), though its impact on short-term oncologic outcomes and long-term survival remains relatively unknown. METHODS: The National Cancer Database (NCDB) between 2004 and 2019 was queried for patients with reportedly resectable (Stage I-IIIB) iCCA who received curative-intent resection with lymphadenectomy. Propensity matching was performed between groups based on the use of NAST and groups were compared for overall survival (OS) and oncologic outcomes, including nodal harvest, rate of node positivity, rate of positive margins, and administration of adjuvant therapy. RESULTS: Two thousand and five hundred ninety-six patients met inclusion criteria; 364 (14%) received NAST versus 1763 (68%) up-front resection. After matching, 332 pairs of patients were matched between NAST and no NAST. Patients receiving NAST had a greater nodal harvest (OR = 1.26 [1.09-1.88]; p < 0.001) and a lower rate of node positivity (OR = 0.67 [0.49-0.63]; p < 0.001). Patients without NAST were more likely to complete adjuvant systemic therapy (OR = 0.45 [0.33-0.62]; p < 0.001). However, patients receiving NAST had no OS benefit after resection compared to those who did not receive NAST (median OS 48.3 ± 5.3 vs. 38.8 ± 3.7 months; p = 0.160). Node-positive disease (OR = 2.10 [1.78-2.45]; p < 0.001) conferred the greatest risk for reduced OS followed by positive-margin resection (OR = 1.42 [1.21-1.47]; p < 0.001) and increasing T-stage (OR = 1.34 [1.21-1.47]; p < 0.001). CONCLUSION: NAST for iCCA was associated with improved quality of oncologic resection but did not confer an OS benefit versus up-front resection.
RESUMO
Secondary liver malignancies are a serious and challenging global health concern. Secondary metastasis to the liver is most commonly from colorectal cancer that has metastatically spread through splanchnic circulation. Metastatic diseases can portend poor prognosis due to the progressive nature typically found on detection. Improvements in detection of disease, monitoring therapy response, and monitoring for recurrence are crucial to the improvement in the management of secondary liver malignancies. Assessment of ctDNA in these patient populations poses an opportunity to impact the management of secondary liver malignancies. In this review, we aim to discuss ctDNA, the current literature, and future directions of this technology within secondary liver malignancies.
RESUMO
Primary liver malignancies are a serious and challenging global health concern. The most common primary tumors are hepatocellular carcinoma and cholangiocarcinoma. These diseases portend poor prognosis when presenting with progressive, extensive disease. There is a critical need for improved diagnosis, therapeutic intervention, and monitoring surveillance in liver-related malignancies. Liquid biopsy using ctDNA provides an opportunity for growth within these domains for liver-related malignancy. However, ctDNA is relatively understudied in this field compared with other solid tumor types, possibly due to the complex nature of the pathology. In this review, we aim to discuss ctDNA, the current literature, and future directions of this technology within primary liver malignancies.
RESUMO
INTRODUCTION: Colorectal cancer liver metastasis (CRLM) occurs in upto 50% of cases and drives patient outcomes. Up-front liver resection is the treatment of choice in resectable cases. There is no consensus yet established as to the safety of intraoperative autotransfusion in liver resection for CRLM. METHODS: Patients undergoing curative-intent hepatectomy for CRLM at a single quaternary-care institution from 1999 to 2016 were included. Demographics, surgical variables, Fong Clinical Risk Score (FCRS), use of intraoperative auto and/or allotransfusion, and survival data were analyzed. Propensity score matching (PSM) was performed accounting for allotransfusion, extent of hepatectomy, FCRS, and systemic treatment regimens. RESULTS: Three-hundred sixteen patients were included. The median follow-up was 10.4 years (7.8-14.1 years). The median recurrence-free survival (RFS) and overall survival (OS) in all patients were 1.6 years (interquartile range: 0.63-6.6 years) and 4.4 years (2.1-8.7), respectively. Before PSM, there was a significantly reduced RFS in the autotransfusion group (0.96 vs. 1.73 years, p = 0.20). There was no difference in OS (4.11 vs. 4.44 years, p = 0.118). Patients in groups of FCRS 0-2 and 3-5 both had reduced RFS when autotransfusion was used (p = 0.005). This reduction in RFS was further found when comparing autotransfusion versus no autotransfusion within the FCRS 0-2 group and within the FCRS 3-5 group (p = 0.027). On Cox-regression analysis, autotransfusion (hazard ratio = 1.423, 1.028-2.182, p = 0.015) remained predictive of RFS. After PSM, there were no differences in FCRS (p = 0.601), preoperative hemoglobin (p = 0.880), allotransfusion (p = 0.130), adjuvant chemotherapy (p = 1.000), immunotherapy (p = 0.172), tumor grade (p = 1.000), use of platinum-based chemotherapy (p = 0.548), or type of hepatic resection (p = 0.967). After matching, there was a higher rate of recurrence with autotransfusion (69.0% vs. 47.6%, p = 0.046). There was also a reduced time to recurrence in the autotransfusion group compared with the group without (p = 0.006). There was no difference in OS after PSM (p = 0.262). CONCLUSION: Autotransfusion may adversely affect recurrence in liver resection for CRLM. Until further studies clarify this risk profile, the use of intraoperative autotransfusion should be critically assessed on a case-by-case basis only when other resuscitation options are not available.
Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Seguimentos , Hepatectomia , Neoplasias Colorretais/patologia , Transfusão de Sangue Autóloga , Estudos Retrospectivos , Neoplasias Hepáticas/secundário , Recidiva Local de Neoplasia/patologia , PrognósticoRESUMO
Extraction of a residual root tip and implant placement can be challenging because of the complexity and invasiveness of the procedure. Improvised application of a guided implant surgery may avoid such challenges. This clinical report presents an innovative technique combining a 3-dimensionally printed surgical guide with conventional instrumentation for a residual root tip extraction in a minimally invasive and predictable way.
RESUMO
Haterumaimide J (hatJ) is reportedly the most cytotoxic member of the lissoclimide family of labdane diterpenoids. The unusual functional group arrangement of hatJ-C18 oxygenation and C2 chlorination-resisted our efforts at synthesis until we adopted an approach based on rarely studied terminal epoxide-based cation-π bicyclizations that is described herein. Using the C2-chlorine atom as a key stereocontrol element and a furan as a nucleophilic terminator, the key structural features of hatJ were rapidly constructed. The 18-step stereoselective synthesis features applications of chiral pool starting materials, and catalyst-, substrate-, and auxiliary-based stereocontrol. Access to hatJ and its acetylated congener hatK permitted their biological evaluation against aggressive human cancer cell lines.
Assuntos
Cloro/química , Diterpenos/síntese química , Diterpenos/toxicidade , Compostos de Epóxi/química , Ciclização , Modelos Moleculares , Estrutura MolecularRESUMO
Glyoxalase 1 (Glo1) is the first enzyme involved in glutathione-dependent detoxification of methylglyoxal, eventually generating d-lactate by the second enzyme glyoxalase 2 (Glo2). An accumulation of intracellular glyoxal and methylglyoxal leads to protein malfunction and mutation via formation of the advanced glycation end products (AGEs). Studies on mouse behavior suggest that methylglyoxal has anxiolytic properties. In this report, we generated and characterized a mouse knockout for Glo1. The knockout mice were viable without a pronounced phenotypic defect. Increased level of AGEs in Glo1 knockout mice was detected by immunoblotting with anti-MGH1 in liver homogenate, but not in brain. Alterations in behavior were observed in open field, light-dark transition, and tail suspension test. Open field data indicate increased exploration for novel environment and entry/stay in center zone in Glo1 knockout mice. In addition, increased light-dark transition and immobility was observed in the knockout mice. These data indicate that Glo1 knockout reduces anxiety-like behavior, but increases depression-like behavior.
Assuntos
Ansiedade/genética , Depressão/genética , Lactoilglutationa Liase/genética , Animais , Ansiedade/metabolismo , Depressão/metabolismo , Deleção de Genes , Glutationa/metabolismo , Produtos Finais de Glicação Avançada/metabolismo , Glioxal/metabolismo , Lactoilglutationa Liase/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Aldeído Pirúvico/metabolismoRESUMO
OBJECTIVES: The objective of this study was to evaluate whether surface chemistry-controlled TiO2 nanotube structures may serve as a local drug delivery system for zoledronic acid improving implant-bone support. METHODS: Twenty-four screw-shaped Ti implants with surface chemistry-controlled TiO2 nanotube structures were prepared and divided into a zoledronic acid-formatted test and a native control group. The implants were inserted into contra-lateral femoral condyles in 12 New Zealand White rabbits. Bone support was evaluated using resonance frequency analysis (RFA) and removal torque (RTQ), as well as histometric analysis following a 3-weeks healing interval. RESULTS: Zoledronic acid-formatted TiO2 nanotube test implants showed significantly improved implant stability and osseointegration measured using RFA and RTQ compared with control (p < 0.05), and showed significantly enhanced new bone formation within the root of the threads compared with control (p < 0.05). CONCLUSIONS: TiO2 nanotube implants may prove to be a significant delivery system for drugs or biologic agents aimed at supporting local bone formation. Additional study of candidate drugs/agents, optimized dosage and release kinetics is needed prior to evaluation in clinical settings.
Assuntos
Implantação Dentária Endóssea , Implantes Dentários , Difosfonatos/administração & dosagem , Sistemas de Liberação de Medicamentos , Imidazóis/administração & dosagem , Nanotubos , Titânio/farmacologia , Animais , Fêmur/cirurgia , Implantes Experimentais , Masculino , Microscopia Eletrônica de Varredura , Osseointegração/fisiologia , Coelhos , Análise de Frequência de Ressonância , Torque , Ácido ZoledrônicoRESUMO
Epithelioid hemangioendothelioma is a rare vascular sarcoma that arises from the lining (intima) of blood vessels. We report a case of a 43-year-old male patient, who presented with inferior vena cava (IVC) obstruction and acute bilateral lower extremity deep vein thrombosis. Mechanical thrombectomy was performed with an endovascular thrombectomy device, followed by stent placement in the IVC. The initial pathology on the retrieved specimen obtained from the thrombectomy device revealed an undifferentiated neoplasm, and definitive surgical resection of the retroperitoneal soft-tissue tumor of the IVC documented a rare case of epithelioid hemangioendothelioma.
Assuntos
Procedimentos Endovasculares/instrumentação , Hemangioendotelioma Epitelioide/patologia , Hemangioendotelioma Epitelioide/cirurgia , Neoplasias Retroperitoneais/patologia , Neoplasias Retroperitoneais/cirurgia , Trombectomia/instrumentação , Veia Cava Inferior/patologia , Veia Cava Inferior/cirurgia , Trombose Venosa/patologia , Trombose Venosa/cirurgia , Adulto , Biópsia , Diferenciação Celular , Desenho de Equipamento , Hemangioendotelioma Epitelioide/complicações , Humanos , Masculino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Neoplasias Retroperitoneais/complicações , Stents , Resultado do Tratamento , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Fluid administration practices may affect complication rates in some abdominal surgeries, but effects in patients undergoing pancreatectomy are not understood well. We sought to determine whether amount of intraoperative fluid administered to patients undergoing pancreatectomy is associated with postoperative complication rates and to determine whether hospitals vary in their fluid administration practices. METHODS: Data for 504 patients undergoing pancreatectomy at 38 hospitals between 2012 and 2015 were evaluated. The main exposure was intraoperative fluid administration (≤10, 10-15, >15 mL/kg/h). Mortality, complications, and length of stay were the main outcomes of interest. Patient-level associations between exposure and outcome were tested, with adjustment for potentially confounding patient and surgical factors, using random intercept, mixed-effects linear or logistic regression models. Hospitals were then categorized as having a restrictive, intermediate, or liberal resuscitation practice, and adjusted outcomes were compared. RESULTS: A total of 167 (33.1 %), 185 (36.7 %) and 152 (30.2 %) patients received restrictive, intermediate, or liberal fluid administration, respectively. Hospitals with more restrictive practices had significantly lower adjusted 30-day mortality than those with more liberal practices (2.7 vs. 6.6 %; P < 0.001). Hospitals with more restrictive practices had the lowest rates of severe (Grade 2 and 3) complications (15.4 % restrictive vs. 25.3 % intermediate vs. 44.3 % liberal; P < 0.001). More restrictive hospitals had decreased adjusted mean length of stay (9.5 days vs. 12.7 days intermediate vs. 11.6 days liberal; P < 0.001). CONCLUSIONS: More restrictive intraoperative resuscitation practices in pancreatectomy are associated with decreased hospital-level mortality, severe complications, and length of stay.
Assuntos
Hidratação/métodos , Cuidados Intraoperatórios , Pancreatectomia , Ressuscitação/métodos , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Michigan , Pessoa de Meia-Idade , Pancreatectomia/mortalidade , Complicações Pós-Operatórias , Resultado do TratamentoRESUMO
OBJECTIVES: Ablative therapies have been increasingly utilized in the treatment of locally advanced pancreatic cancer (LAPC). Irreversible electroporation (IRE) is an energy delivery system, effective in ablating tumors by inducing irreversible membrane destruction of cells. We aimed to demonstrate efficacy of treatment with IRE as part of multimodal treatment of LAPC. METHODS: From July 2010 to October 2014, patients with radiographic stage III LAPC were treated with IRE and monitored under a multicenter, prospective institutional review board-approved registry. Perioperative 90-day outcomes, local failure, and overall survival were recorded. RESULTS: A total of 200 patients with LAPC underwent IRE alone (n = 150) or pancreatic resection plus IRE for margin enhancement (n = 50). All patients underwent induction chemotherapy, and 52% received chemoradiation therapy as well for a median of 6 months (range, 5-13 months) before IRE. IRE was successfully performed in all patients. Thirty-seven percent of patients sustained complications, with a median grade of 2 (range, 1-5). Median length of stay was 6 days (range, 4-36 days). With a median follow-up of 29 months, 6 patients (3%) have experienced local recurrence. Median overall survival was 24.9 months (range: 4.9-85 months). CONCLUSIONS: For patients with LAPC (stage III), the addition of IRE to conventional chemotherapy and radiation therapy results in substantially prolonged survival compared with historical controls. These results suggest that ablative control of the primary tumor may prolong survival.
Assuntos
Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Eletroporação/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Ablação por Cateter/métodos , Quimiorradioterapia/métodos , Terapia Combinada , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/terapia , Segurança do Paciente , Sistema de Registros , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: A strong relationship between hospital caseload and adverse outcomes has been demonstrated for pancreatic resections. Participation in regional surgical collaboratives may mitigate this phenomenon. This study sought to investigate changes over time in adverse outcomes after pancreatectomy across hospitals with different caseloads in a statewide surgical collaborative. METHODS: The study investigated patients undergoing pancreatic resection from January 2008 to August 2013 at Michigan Surgical Quality Collaborative (MSQC) hospitals (1007 patients in 19 academic and community hospitals). Risk-adjusted rates of major complications, mortality, and failure to rescue were compared between hospitals based on caseloads (low, medium, and high) in early (2008-2010) and later (2011-2013) periods. Finally, the degree to which different complications explained changes in hospital outcome variation was assessed. RESULTS: Adjusted rates of major complications and mortality decreased over time, driven largely by improvements at low-caseload hospitals. In 2008-2010, risk-adjusted major complication rates were higher for low-caseload than for high-caseload hospitals (27.8 vs. 17.8 %; p = 0.02). However, these differences were attenuated in 2011-2013 (22.2 vs. 20.0 %; p = 0.74). Similarly, adjusted mortality rates were higher in low-caseload hospitals in 2008-2010 (6.2 vs. 0.8 %; p = 0.02), but these differences were attenuated in 2011-2013 (3.3 vs. 1.1 %; p = 0.18). Variation in major complications decreased, largely due to decreased variation in "medical" complication rates, with less change in surgical-site complications. CONCLUSION: Participation in regional quality collaboratives by lower-volume hospitals can attenuate the volume-outcome relationship for pancreatic surgery. Continued work in collaboratives with an emphasis on technical and intraoperative aspects of care may improve overall quality of care.
Assuntos
Comportamento Cooperativo , Hospitais com Alto Volume de Atendimentos/estatística & dados numéricos , Hospitais com Baixo Volume de Atendimentos/estatística & dados numéricos , Pancreatectomia/efeitos adversos , Pancreatectomia/mortalidade , Melhoria de Qualidade/tendências , Idoso , Falha da Terapia de Resgate/estatística & dados numéricos , Feminino , Hospitais com Alto Volume de Atendimentos/normas , Hospitais com Baixo Volume de Atendimentos/normas , Humanos , Masculino , Michigan , Pessoa de Meia-Idade , Pancreatectomia/normas , Programas Médicos Regionais , Sistema de RegistrosRESUMO
BACKGROUND: Surgical resection is underutilized for patients with colorectal liver metastases (CLM). Although the causes of underutilization are poorly understood, provider attitudes towards surgical referral may be contributory. We sought to understand medical oncologists' perspectives on referral for CLM. METHODS: Medical oncologists who treat colorectal cancer in the US state of Michigan were surveyed. We characterized respondents' attitudes regarding clinical and tumor-related contraindications to liver resection for CLM, as well as referral and treatment preferences using case-based scenarios. We then evaluated practice characteristics and treatment preferences between physicians. RESULTS: A total of 112 eligible responses were received (46 % response rate). Nearly 40 % of respondents reported having no liver surgeons in their practice area. Commonly perceived contraindications to liver resection included extrahepatic disease (80.3 %), poor performance status (77.7 %), the presence of >4 metastases (62.5 %), bilobar metastases (43.8 %), and metastasis size >5 cm (40.2 %). Compared with high-referring physicians, low-referring physicians were just as likely to refer a patient with very low recurrence risk (89.3 vs. 98.3 %; p = 0.099), but much less likely to refer a patient with moderate risk (0 vs. 82.8 %; p < 0.001). High-referring physicians were more likely to consider resection for scenarios consistent with higher recurrence risk (31.0 vs. 10.7 %; p = 0.05). CONCLUSIONS: We found wide variation in surgical referral patterns for CLM. Many felt that bilobar disease and tumor size were contraindications to liver-directed therapy despite a lack of supporting data. These findings suggest an urgent need to increase dissemination of evidence and guidance regarding management for CLM, perhaps through increased specialist participation in tumor boards.
Assuntos
Neoplasias Colorretais/cirurgia , Hepatectomia , Neoplasias Hepáticas/cirurgia , Recidiva Local de Neoplasia/cirurgia , Guias de Prática Clínica como Assunto/normas , Padrões de Prática Médica/normas , Encaminhamento e Consulta/estatística & dados numéricos , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/patologia , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/secundário , Michigan/epidemiologia , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Equipe de Assistência ao Paciente , Prognóstico , Encaminhamento e Consulta/normas , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Vascular endothelial growth factor (VEGF) is a critical pro-angiogenic factor, found in a number of cancers, and a target of therapy. It is typically assessed by immunohistochemistry (IHC) in clinical research. However, IHC is not a quantitative assay and is rarely reproducible. We compared VEGF levels in colon cancer by IHC and a quantitative immunoassay on proteins isolated from formalin fixed, paraffin embedded tissues. RESULTS: VEGF expression was studied by means of a well-based reverse phase protein array (RPPA) and immunohistochemistry in 69 colon cancer cases, and compared with various clinicopathologic factors. Protein lysates derived from formalin fixed, paraffin embedded tissue contained measurable immunoreactive VEGF molecules. The VEGF expression level of well differentiated colon cancer was significantly higher than those with moderately and poorly differentiated carcinomas by immunohistochemistry (P = 0.04) and well-based RPPA (P = 0.04). VEGF quantification by well-based RPPA also demonstrated an association with nodal metastasis status (P = 0.05). In addition, the normalized VEGF value by well-based RPPA correlated (r = 0.283, P = 0.018). Furthermore, subgroup analysis by histologic type revealed that adenocarcinoma cases showed significant correlation (r = 0.315, P = 0.031) between well-based RPPA and IHC. CONCLUSIONS: The well-based RPPA method is a high throughput and sensitive approach, is an excellent tool for quantification of marker proteins. Notably, this method may be helpful for more objective evaluation of protein expression in cancer patients.
RESUMO
The long-term follow-up findings of the phase I trial evaluating the efficacy of oncolytic adenovirus-mediated cytotoxic and interleukin-12 gene therapy in metastatic pancreatic cancer (mPC) seem very promising. The study employed a replication-competent Adenovector in combination with chemotherapy in a dose-escalation format. The trial demonstrated a clinically meaningful median overall survival (OS) benefit, with patients in the highest dose cohort exhibiting an impressive median OS of 18.4 months. This contrasts starkly with patients receiving lower doses who experienced a median OS of 4.8 and 3.5 months, respectively. Remarkably, subject number 10, who received the highest dose, demonstrated an extraordinary survival of 59.1 months, presenting a compelling case for further exploration. Additionally, this patient displayed complete responses in lung and liver metastases, a rare occurrence in mPC treatment. Statistical analyses supported the observed survival benefit. The unprecedented OS results emphasize the potential of this treatment strategy and pave the way for future investigations into this promising gene therapy approach.