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1.
CA Cancer J Clin ; 74(4): 359-367, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38685134

RESUMO

The American Joint Committee on Cancer (AJCC) staging system for all cancer sites, including gastroenteropancreatic neuroendocrine tumors (GEP-NETs), is meant to be dynamic, requiring periodic updates to optimize AJCC staging definitions. This entails the collaboration of experts charged with evaluating new evidence that supports changes to each staging system. GEP-NETs are the second most prevalent neoplasm of gastrointestinal origin after colorectal cancer. Since publication of the AJCC eighth edition, the World Health Organization has updated the classification and separates grade 3 GEP-NETs from poorly differentiated neuroendocrine carcinoma. In addition, because of major advancements in diagnostic and therapeutic technologies for GEP-NETs, AJCC version 9 advocates against the use of serum chromogranin A for the diagnosis and monitoring of GEP-NETs. Furthermore, AJCC version 9 recognizes the increasing role of endoscopy and endoscopic resection in the diagnosis and management of NETs, particularly in the stomach, duodenum, and colorectum. Finally, T1NXM0 has been added to stage I in these disease sites as well as in the appendix.


Assuntos
Neoplasias Intestinais , Estadiamento de Neoplasias , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Neoplasias Gástricas , Humanos , Tumores Neuroendócrinos/patologia , Tumores Neuroendócrinos/diagnóstico , Tumores Neuroendócrinos/terapia , Estadiamento de Neoplasias/métodos , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/diagnóstico , Neoplasias Intestinais/patologia , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/terapia , Estados Unidos
2.
Nature ; 618(7963): 144-150, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37165196

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is lethal in 88% of patients1, yet harbours mutation-derived T cell neoantigens that are suitable for vaccines 2,3. Here in a phase I trial of adjuvant autogene cevumeran, an individualized neoantigen vaccine based on uridine mRNA-lipoplex nanoparticles, we synthesized mRNA neoantigen vaccines in real time from surgically resected PDAC tumours. After surgery, we sequentially administered atezolizumab (an anti-PD-L1 immunotherapy), autogene cevumeran (a maximum of 20 neoantigens per patient) and a modified version of a four-drug chemotherapy regimen (mFOLFIRINOX, comprising folinic acid, fluorouracil, irinotecan and oxaliplatin). The end points included vaccine-induced neoantigen-specific T cells by high-threshold assays, 18-month recurrence-free survival and oncologic feasibility. We treated 16 patients with atezolizumab and autogene cevumeran, then 15 patients with mFOLFIRINOX. Autogene cevumeran was administered within 3 days of benchmarked times, was tolerable and induced de novo high-magnitude neoantigen-specific T cells in 8 out of 16 patients, with half targeting more than one vaccine neoantigen. Using a new mathematical strategy to track T cell clones (CloneTrack) and functional assays, we found that vaccine-expanded T cells comprised up to 10% of all blood T cells, re-expanded with a vaccine booster and included long-lived polyfunctional neoantigen-specific effector CD8+ T cells. At 18-month median follow-up, patients with vaccine-expanded T cells (responders) had a longer median recurrence-free survival (not reached) compared with patients without vaccine-expanded T cells (non-responders; 13.4 months, P = 0.003). Differences in the immune fitness of the patients did not confound this correlation, as responders and non-responders mounted equivalent immunity to a concurrent unrelated mRNA vaccine against SARS-CoV-2. Thus, adjuvant atezolizumab, autogene cevumeran and mFOLFIRINOX induces substantial T cell activity that may correlate with delayed PDAC recurrence.


Assuntos
Antígenos de Neoplasias , Vacinas Anticâncer , Carcinoma Ductal Pancreático , Ativação Linfocitária , Neoplasias Pancreáticas , Linfócitos T , Humanos , Adjuvantes Imunológicos/uso terapêutico , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/imunologia , Carcinoma Ductal Pancreático/terapia , Linfócitos T CD8-Positivos/citologia , Linfócitos T CD8-Positivos/imunologia , Imunoterapia , Ativação Linfocitária/imunologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Linfócitos T/citologia , Linfócitos T/imunologia , Vacinas de mRNA
3.
Ann Surg ; 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39355926

RESUMO

OBJECTIVE: To determine if cancer patients experience variability in incidence or management of emergency general surgery (EGS) conditions compared to non-cancer patients. BACKGROUND: The true frequency, and natural history of EGS conditions among cancer patients has not been characterized. METHODS: We utilized SEER-Medicare data from January 2006-December 2015 to compare patients with breast, prostate, and lung cancer to a non-cancer cohort. Patients were followed from date of cancer diagnosis, or an index date for non-cancer patients, to the development of an EGS condition, death or last follow up. We assessed the cumulative incidence of EGS conditions over time, and fit multivariable Cox proportional hazards models to evaluate the impact of time-dependent surgical intervention on mortality. RESULTS: We identified 322,756 patients with breast (N=82,147), lung (N=128,618), and prostate cancer (N=111,991) and 210,429 non-cancer patients.. Cancer patients had a higher incidence of an EGS condition within the first year after diagnosis (4.8% vs. 3.2%), with lung (6.8%) and breast cancer (4.0%) showing consistent rends. Cancer patients were less likely to undergo surgery for (13% vs. 14%, P=0.005), though this varied by cancer type and EGS conditions. Patients with breast (HR 1.27, 95%CI 1.17-1.39) and lung cancer (HR 3.27, 95%CI 3.07-3.48) were more likely to die within 30-days of an EGS diagnosis. CONCLUSIONS: Cancer patients experience a higher incidence of EGS conditions within the first year following diagnosis, but are less likely to undergo surgery. Future research is needed to explore the interplay between EGS conditions, their management, and receipt of intended oncologic therapy, and resulting outcomes.

4.
Ann Surg ; 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38939927

RESUMO

OBJECTIVE: To assess whether selective omission of operative drains after pancreaticoduodenectomy (PD) and distal pancreatectomy (DP) is associated with adverse perioperative outcomes. BACKGROUND: The routine use of operative drains after pancreatectomy is widely practiced; however, prospective randomized clinical trials and retrospective analyses have shown mixed results. METHODS: Patients who underwent PD or DP between November 2009 and May 2021 were reviewed and stratified by operative drain placement. Patient demographics, morbidity, the need for additional procedures, and mortality were compared between patients who did or did not develop a clinically relevant post-operative pancreatic fistula (CR-POPF). RESULTS: In total, 1,855 PD and 752 DP cases were analyzed. Among PD patients with a CR-POPF (N=259, 14%), 160 (62%) had an operative drain placed, of whom 141 (88%) required at least 1 additional procedure. Within this subgroup, grade ≥ 4 complications (7.5% vs. 11.1%, P=0.37), 90-day mortality (3.8% vs. 6.1%, P=0.54), length of stay (LOS) (median 12 vs. 13 d, P=0.19) and readmission rates (63.1% vs. 54.6%, P=0.19) were similar between drained and non-drained patients. Of note, drained PD patients without a CR-POPF had a longer hospital stay (8 vs. 7 d, respectively, P=0.004) and more thromboembolic events (2.4% vs. 1.1%, respectively, P=0.04) Among DP patients with a CR-POPF (n=129), 44 had an operative drain, with 37 (84%) requiring an additional procedure. Within this subgroup, grade ≥ 4 complications (4.6% vs. 5.9%, P>0.95), 90-day mortality (0%), LOS (median 7 d for both, P=0.88) and readmission rates (72.7% vs. 80%, P=0.38) were similar in drained and non-drained patients. CONCLUSION: This study confirms that selective omission of operative drains does not compromise perioperative outcomes, as initially reported in our prospective randomized trial.

5.
Ann Surg ; 279(1): 125-131, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37325926

RESUMO

BACKGROUND: Early-Onset (EO) pancreatic neuroendocrine tumor (PanNET) is a rare disease, but whether it is clinically different from late-onset (LO) PanNET is unknown. Our study aimed to evaluate clinical differences and disease outcomes between EO-PanNET and LO-PanNET and to compare sporadic EO-PanNET with those with a hereditary syndrome. METHODS: Patients with localized PanNET who underwent pancreatectomy at Memorial Sloan Kettering between 2000 and 2017 were identified. Those with metastatic disease and poorly differentiated tumors were excluded. EO-PanNET was defined as <50 and LO-PanNET >50 years of age at the time of diagnosis. Family history and clinical and pathology characteristics were recorded. RESULTS: Overall 383 patients were included, 107 (27.9%) with EO-PanNET. Compared with LO-PanNET, EO-PanNET were more likely to have a hereditary syndrome (2.2% vs. 16%, P <0.001) but had similar pathology features such as tumor grade ( P =0.6), size (2.2 Vs. 2.3 cm, P =0.5) and stageof disease ( P =0.8). Among patients with EO-PanNET, those with hereditary syndrome had more frequently a multifocal disease (65% vs. 3.3%, P <0.001). With a median follow-up of 70 months (range 0-238), the 5-year cumulative incidence of recurrence after curative surgery was 19% (95% CI 12%-28%) and 17% (95% CI 13%-23%), in EO-PanNET and LO-PanNET ( P =0.3). Five-year disease-specific survival was 99% (95% CI 98%-100%) with no difference with respect to PanNET onset time ( P =0.26). CONCLUSIONS: In this surgical cohort, we found that EO-PanNET is associated with hereditary syndromes but has pathologic characteristics and oncological outcomes similar to LO-PanNET. These findings suggest that patients with EO-PanNET can be managed similarly to those with LO-PanNET.


Assuntos
Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Estudos Retrospectivos , Pancreatectomia , Incidência
6.
Ann Surg ; 279(1): 119-124, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37212166

RESUMO

OBJECTIVE: To identify risk factors associated with the progression of pancreatic cysts in patients undergoing surveillance. BACKGROUND: Previous studies of intraductal papillary mucinous neoplasms (IPMNs) rely on surgical series to determine malignancy risk and have inconsistently identified characteristics associated with IPMN progression. METHODS: We conducted a retrospective review of 2197 patients presenting with imaging concerning for IPMN from 2010 to 2019 at a single institution. Cyst progression was defined as resection or pancreatic cancer development. RESULTS: The median follow-up time was 84 months from the presentation. The median age was 66 years, and 62% were female. Ten percent had a first-degree relative with pancreatic cancer, and 3.2% had a germline mutation or genetic syndrome associated with an increased risk of pancreatic ductal adenocarcinoma (PDAC). Cumulative incidence of progression was 17.8% and 20.0% at 12 and 60 months postpresentation, respectively. Surgical pathology for 417 resected cases showed noninvasive IPMN in 39% of cases and PDAC with or without associated IPMN in 20%. Only 18 patients developed PDAC after 6 months of surveillance (0.8%). On multivariable analysis, symptomatic disease [hazard ratio (HR)=1.58; 95% CI: 1.25-2.01], current smoker status (HR=1.58; 95% CI: 1.16-2.15), cyst size (HR=1.26; 95% CI: 1.20-1.33), main duct dilation (HR=3.17; 95% CI: 2.44-4.11), and solid components (HR=1.89; 95% CI: 1.34-2.66) were associated with progression. CONCLUSIONS: Worrisome features on imaging at presentation, current smoker status, and symptomatic presentation are associated with IPMN progression. Most patients progressed within the first year of presentation to Memorial Sloan Kettering Cancer Center (MSKCC). Further investigation is necessary to develop personalized cyst surveillance strategies.


Assuntos
Carcinoma Ductal Pancreático , Cisto Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Masculino , Neoplasias Intraductais Pancreáticas/patologia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/cirurgia , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/epidemiologia , Carcinoma Ductal Pancreático/cirurgia , Fatores de Risco , Cisto Pancreático/diagnóstico por imagem , Cisto Pancreático/cirurgia , Estudos Retrospectivos
7.
Oncologist ; 29(10): 894-903, 2024 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-38937977

RESUMO

INTRODUCTION: Immune checkpoint inhibitor (ICI) combinations extend overall survival (OS) while anti-PD-1/L1 monotherapy is non-inferior to sorafenib in treatment-naïve, patients with advanced hepatocellular carcinoma (HCC). Clinicogenomic features are posited to influence patient outcomes. METHODS: The primary objective of this retrospective study was to define the clinical, pathologic, and genomic factors associated with outcomes to ICI therapy in patients with HCC. Patients with histologically confirmed advanced HCC treated with ICI at Memorial Sloan Kettering Cancer Center from 2012 to 2022 were included. Association between clinical, pathological, and genomic characteristics were assessed with univariable and multivariable Cox regression model for progression-free survival (PFS) and OS. RESULTS: Two-hundred and forty-two patients were treated with ICI-based therapy. Patients were predominantly male (82%) with virally mediated HCC (53%) and Child Pugh A score (70%). Median follow-up was 28 months (0.5-78.4). Median PFS for those treated in 1st line, 2nd line and ≥ 3rd line was 4.9 (range: 2.9-6.2), 3.1 (2.3-4.0), and 2.5 (2.1-4.0) months, respectively. Median OS for those treated in 1st line, 2nd line, and ≥ 3rd line was 16 (11-22), 7.5 (6.4-11), and 6.4 (4.6-26) months, respectively. Poor liver function and performance status associated with worse PFS and OS, while viral hepatitis C was associated with favorable outcome. Genetic alterations were not associated with outcomes. CONCLUSION: Clinicopathologic factors were the major determinates of outcomes for patients with advanced HCC treated with ICI. Molecular profiling did not aid in stratification of ICI outcomes. Future studies should explore alternative biomarkers such as the level of immune activation or the pretreatment composition of the immune tumor microenvironment.


Assuntos
Carcinoma Hepatocelular , Inibidores de Checkpoint Imunológico , Imunoterapia , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Adulto , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Idoso de 80 Anos ou mais
8.
Ann Surg Oncol ; 31(10): 6551-6563, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39042229

RESUMO

BACKGROUND: Management of intrahepatic cholangiocarcinoma (IHC) has advanced in recent decades, including randomized trial evidence supporting systemic therapy in the palliative and adjuvant setting. Mounting observational evidence suggests resection of IHC with multifocal disease (IHC-MF) or lymph node metastasis (IHC-LNM) should be limited. It is unknown how real-world practice has evolved in light of research advances. This study characterizes trends in management and outcomes of IHC without distant metastasis. METHODS: We queried the National Cancer Database (NCDB) for patients treated for IHC without distant metastasis (M0) and identified subgroups with lymph node (cN1) or multifocal hepatic involvement (cT2b). Two-sided Cochran-Armitage tests evaluated trends in initial treating modality and perioperative chemotherapy. Logistic regression evaluated associations with choice of initial treating modality. Overall survival (OS) was evaluated by using Kaplan-Meier methods. RESULTS: Between 2004 and 2020, 11,368 patients were treated for IHC without extrahepatic metastasis. Forty-three percent underwent resection. Initial management shifted from resection towards radiation or systemic therapy in IHC-MF and IHC-LNM. Use of perioperative chemotherapy increased from 39% pre-2010 to 70% in 2018-2020 (p < 0.001), most often delivered postoperatively. Across the entire cohort, median OS improved from 16 (95% confidence interval [CI] 15-18) to 27 months (95% CI 26-29). More modest improvements were observed in IHC-MF and IHC-LNM. CONCLUSIONS: Use of perioperative chemotherapy has been widely adopted, predating randomized trial evidence in the adjuvant setting. Initial management of IHC-MF and IHC-LNM has shifted from resection to systemic and/or radiation therapy. While OS has improved overall, outcomes of IHC-MF and IHC-LNM remain poor, warranting further investigation.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Bases de Dados Factuais , Padrões de Prática Médica , Humanos , Colangiocarcinoma/terapia , Colangiocarcinoma/patologia , Colangiocarcinoma/cirurgia , Neoplasias dos Ductos Biliares/terapia , Neoplasias dos Ductos Biliares/patologia , Neoplasias dos Ductos Biliares/cirurgia , Masculino , Feminino , Taxa de Sobrevida , Padrões de Prática Médica/estatística & dados numéricos , Idoso , Pessoa de Meia-Idade , Hepatectomia , Prognóstico , Seguimentos , Gerenciamento Clínico , Terapia Combinada , Metástase Linfática
9.
Ann Surg Oncol ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39369120

RESUMO

OBJECTIVES: This study was designed to assess computed tomography (CT)-based radiomics of colorectal liver metastases (CRLM), extracted from posttreatment scans in estimating pathologic treatment response to neoadjuvant therapy, and to compare treatment response estimates between CT-based radiomics and radiological response assessment by using RECIST 1.1 and CT morphologic criteria. METHODS: Patients who underwent resection for CRLM from January 2003-December 2012 at a single institution were included. Patients who did not receive preoperative systemic chemotherapy, or without adequate imaging, were excluded. Imaging characteristics were evaluated based on RECIST 1.1 and CT morphologic criteria. A machine-learning model was designed with radiomic features extracted from manually segmented posttreatment CT tumoral and peritumoral regions to identify pathologic responders (≥ 50% response) versus nonresponders. Statistical analysis was performed at the tumor level. RESULTS: Eighty-five patients (median age, 62 years; 55 women) with 95 tumors were included. None of the subjectively evaluated imaging characteristics were associated with pathologic response (p > 0.05). Inter-reader agreement was substantial for RECIST categorical response assessment (K = 0.70) and moderate for CT morphological group response (K = 0.50). In the validation cohort, the machine learning model built with radiomic features obtained an area under the curve (AUC) of 0.87 and outperformed subjective RECIST assessment (AUC = 0.53, p = 0.01) and morphologic assessment (AUC = 0.56, p = 0.02). CONCLUSIONS: Radiologist assessment of oligometastatic CRLM after neoadjuvant therapy using RECIST 1.1 and CT morphologic criteria was not associated with pathologic response. In contrast, a machine-learning model based on radiomic features extracted from tumoral and peritumoral regions had high diagnostic performance in assessing responders versus nonresponders.

10.
Ann Surg Oncol ; 31(3): 1919-1932, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38170408

RESUMO

INTRODUCTION: About 25% of patients with localized pancreatic adenocarcinoma have non-elevated serum carbohydrate antigen (CA) 19-9 levels at baseline, hampering evaluation of response to preoperative treatment. Serum carcinoembryonic antigen (CEA) is a potential alternative. METHODS: This retrospective cohort study from five referral centers included consecutive patients with localized pancreatic adenocarcinoma (2012-2019), treated with one or more cycles of (m)FOLFIRINOX, and non-elevated CA19-9 levels (i.e., < 37 U/mL) at baseline. Cox regression analyses were performed to assess prognostic factors for overall survival (OS), including CEA level at baseline, restaging, and dynamics. RESULTS: Overall, 277 patients were included in this study. CEA at baseline was elevated (≥5 ng/mL) in 53 patients (33%) and normalized following preoperative therapy in 14 patients (26%). In patients with elevated CEA at baseline, median OS in patients with CEA normalization following preoperative therapy was 33 months versus 19 months in patients without CEA normalization (p = 0.088). At time of baseline, only elevated CEA was independently associated with (worse) OS (hazard ratio [HR] 1.44, 95% confidence interval [CI] 1.04-1.98). At time of restaging, elevated CEA at baseline was still the only independent predictor for (worse) OS (HR 1.44, 95% CI 1.04-1.98), whereas elevated CEA at restaging (HR 1.16, 95% CI 0.77-1.77) was not. CONCLUSIONS: Serum CEA was elevated in one-third of patients with localized pancreatic adenocarcinoma having non-elevated CA19-9 at baseline. At both time of baseline and time of restaging, elevated serum CEA measured at baseline was the only predictor for (worse) OS. Therefore, serum CEA may be a useful tool for decision making at both initial staging and time of restaging in patients with non-elevated CA19-9.


Assuntos
Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/cirurgia , Antígeno Carcinoembrionário , Antígeno CA-19-9 , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais , Prognóstico , Estudos Retrospectivos , Adenocarcinoma/cirurgia , Irinotecano , Oxaliplatina , Leucovorina , Fluoruracila
11.
Ann Surg Oncol ; 31(1): 58-65, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37833463

RESUMO

BACKGROUND: Comparative studies evaluating quality of care in different healthcare systems can guide reform initiatives. This study seeks to characterize best practices by comparing utilization and outcomes for patients with pancreatic cancer (PC) in the USA and Ontario, Canada. METHODS: Patients (age ≥ 66 years) with PC were identified from the Ontario Cancer Registry and SEER-Medicare databases from 2006 to 2015. Demographics and treatment (surgery, radiation, chemotherapy, or multimodality (surgery and chemotherapy)) were described. In resected patients, neoadjuvant therapy, readmission, and 30- and 90-day postoperative mortality rates were calculated. Survival was assessed using Kaplan-Meier curves. RESULTS: This study includes 38,858 and 11,512 patients with PC from the USA and Ontario, respectively. More female patients were identified in the USA (54.0%) versus Ontario (46.9%). In the entire cohort, US patients received more radiation in addition to other therapies (18.8% vs. 13.5% Ontario) and chemotherapy alone (34.3% vs. 19.0% Ontario). While rates of resection were similar (13.4% USA vs.12.5% Ontario), multimodality therapy was more common in the UAS (9.0% vs. 6.4%). Among resected patients, neoadjuvant chemotherapy was uncommon in both groups, although more frequent in the USA (12.0% vs. 3.2% Ontario). The 30- and 90-day postoperative mortality rates were lower in Ontario vs. the USA (30-day: 3.26% vs. 4.91%; 90-day: 7.08% vs. 10.96%), however, overall survival was similar between the USA and Ontario. CONCLUSIONS: We observed substantive differences in treatment and outcomes between PC patients in the USA and Ontario, which may reflect known differences in healthcare systems. Close evaluation of healthcare policies can inform initiatives to improve care quality.


Assuntos
Programas Nacionais de Saúde , Neoplasias Pancreáticas , Humanos , Feminino , Idoso , Ontário/epidemiologia , Terapia Combinada , Sistema de Registros , Neoplasias Pancreáticas/tratamento farmacológico , Terapia Neoadjuvante , Estudos Retrospectivos
12.
Ann Surg Oncol ; 31(1): 115-124, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37814188

RESUMO

BACKGROUND: A post-hoc analysis of ABC trials included 34 patients with liver-confined unresectable intrahepatic cholangiocarcinoma (iCCA) who received systemic chemotherapy with gemcitabine and cisplatin (gem-cis). The median overall survival (OS) was 16.7 months and the 3-year OS was 2.8%. The aim of this study was to compare patients treated with systemic gem-cis versus hepatic arterial infusion pump (HAIP) chemotherapy for liver-confined unresectable iCCA. METHODS: We retrospectively collected consecutive patients with liver-confined unresectable iCCA who received gem-cis in two centers in the Netherlands to compare with consecutive patients who received HAIP chemotherapy with or without systemic chemotherapy in Memorial Sloan Kettering Cancer Center. RESULTS: In total, 268 patients with liver-confined unresectable iCCA were included; 76 received gem-cis and 192 received HAIP chemotherapy. In the gem-cis group 42 patients (55.3%) had multifocal disease compared with 141 patients (73.4%) in the HAIP group (p = 0.023). Median OS for gem-cis was 11.8 months versus 27.7 months for HAIP chemotherapy (p < 0.001). OS at 3 years was 3.5% (95% confidence interval [CI] 0.0-13.6%) in the gem-cis group versus 34.3% (95% CI 28.1-41.8%) in the HAIP chemotherapy group. After adjusting for male gender, performance status, baseline hepatobiliary disease, and multifocal disease, the hazard ratio (HR) for HAIP chemotherapy was 0.27 (95% CI 0.19-0.39). CONCLUSIONS: This study confirmed the results from the ABC trials that survival beyond 3 years is rare for patients with liver-confined unresectable iCCA treated with palliative gem-cis alone. With HAIP chemotherapy, one in three patients was alive at 3 years.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Masculino , Gencitabina , Cisplatino , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica , Colangiocarcinoma/tratamento farmacológico , Desoxicitidina , Fígado , Ductos Biliares Intra-Hepáticos , Bombas de Infusão , Resultado do Tratamento
13.
Br J Surg ; 111(3)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38456678

RESUMO

BACKGROUND: Surgery in selected patients with locally advanced pancreatic cancer after induction chemotherapy may have drawbacks related to surgical risks and breaks or delays in oncological treatment, in particular when curative intent resection is not possible (that is non-therapeutic laparotomy). The aim of this study was to assess the incidence and oncological impact of a non-therapeutic laparotomy in patients with locally advanced pancreatic cancer treated with induction (m)FOLFIRINOX chemotherapy. METHODS: This was a retrospective international multicentre study including patients diagnosed with pathology-proven locally advanced pancreatic cancer treated with at least one cycle of (m)FOLFIRINOX (2012-2019). Patients undergoing a non-therapeutic laparotomy (group A) were compared with those not undergoing surgery (group B) and those undergoing resection (group C). RESULTS: Overall, 663 patients with locally advanced pancreatic cancer were included (67 patients (10.1%) in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C). A non-therapeutic laparotomy occurred in 28.2% of all explorations (67 of 238), with occult metastases in 30 patients (30 of 67, 44.8%) and a 90-day mortality rate of 3.0% (2 of 67). Administration of palliative therapy (65.9% versus 73.1%; P = 0.307) and median overall survival (20.4 [95% c.i. 15.9 to 27.3] versus 20.2 [95% c.i. 19.1 to 22.7] months; P = 0.752) did not differ between group A and group B respectively. The median overall survival in group C was 36.1 (95% c.i. 30.5 to 41.2) months. The 5-year overall survival rates were 11.4%, 8.7%, and 24.7% in group A, group B, and group C, respectively. Compared with group B, non-therapeutic laparotomy (group A) was not associated with reduced overall survival (HR = 0.88 [95% c.i. 0.61 to 1.27]). CONCLUSION: More than a quarter of surgically explored patients with locally advanced pancreatic cancer after induction (m)FOLFIRINOX did not undergo a resection. Such non-therapeutic laparotomy does not appear to substantially impact oncological outcomes.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Laparotomia , Estudos Retrospectivos , Fluoruracila , Leucovorina/uso terapêutico , Terapia Neoadjuvante , Irinotecano , Oxaliplatina
14.
Pancreatology ; 24(4): 608-615, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38749803

RESUMO

BACKGROUND: Acute cholangitis (AC) is a common complication of pancreatic ductal adenocarcinoma (PDAC). Herein, we evaluated outcomes after the first AC episode and predictors of mortality and AC recurrence in patients with stage IV PDAC. METHODS: We conducted a single-center, retrospective observational study using institutional databases. Clinical data and outcomes for patients with stage IV PDAC and at least one documented episode of AC, were assessed. Overall survival (OS) was estimated using the Kaplan-Meier method, and Cox regression model was employed to identify predictors of AC recurrence and mortality. RESULTS: One hundred and twenty-four patients with stage IV PDAC and AC identified between January 01, 2014 and October 31, 2020 were included. Median OS after first episode of AC was 4.1 months (95 % CI, 4.0-5.5), and 30-day, 6, and 12-month survival was 86.2 % (95 % CI, 80.3-92.5), 37 % (95 % CI, 29.3-46.6 %) and 18.9 % (95 % CI, 13.1-27.3 %), respectively. Primary tumor in pancreatic body/tail (HR 2.29, 95 % CI: 1.26 to 4.18, p = 0.011), concomitant metastases to liver and other sites (HR 1.96, 95 % CI: 1.16 to 3.31, p = 0.003) and grade 3 AC (HR 2.26, 95 % CI: 1.45 to 3.52, p < 0.001), predicted worse outcomes. Intensive care unit admission, sepsis, systemic therapy, treatment regimen, and time to intervention did not predict survival or risk of recurrence of AC. CONCLUSIONS: AC confers significant morbidity and mortality in advanced PDAC. Worse outcomes are associated with higher grade AC, primary tumor location in pancreatic body/tail, and metastases to liver and other sites.


Assuntos
Colangite , Neoplasias Pancreáticas , Humanos , Colangite/complicações , Colangite/mortalidade , Masculino , Feminino , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/patologia , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Prognóstico , Estadiamento de Neoplasias , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/complicações , Carcinoma Ductal Pancreático/patologia , Idoso de 80 Anos ou mais , Adenocarcinoma/mortalidade , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Doença Aguda , Fatores de Risco
15.
AJR Am J Roentgenol ; 2024 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-39166726

RESUMO

Background: A Society of Abdominal Radiology (SAR) Pancreatic Ductal Adenocarcinoma (PDAC) Disease-Focused Panel (DFP) consensus statement described findings suspicious for local recurrence (LR) on surveillance imaging after PDAC resection. Objective: To evaluate the interreader agreement and predictive utility of potential imaging findings of LR on serial surveillance CT examinations after Whipple procedure for PDAC, using the SAR PDAC DFP consensus statement. Methods: This retrospective study included 126 patients (mean age, 68.5±10.3 years; 72 men, 54 women) who underwent Whipple surgery for PDAC between January 2009 and December 2014. Three radiologists independently reviewed baseline and subsequent postoperative contrast-enhanced abdominopelvic CT examinations performed within 2 years postoperatively, evaluating features in the SAR PDAC DFP consensus statement relating to surgical bed stranding, surgical bed soft tissue, vessel encasement, main pancreatic duct dilatation, and ascites. Interreader agreement was calculated. The reference standard for LR development within 2 years postoperatively incorporated all available information. Imaging features' frequencies were calculated for recurrence examinations (i.e., first surveillance examinations indicating LR). For baseline postoperative examinations, features associations' with eventual LR development were assessed by multivariable logistic regression analysis. Results: LR developed within 2 years postoperatively in 81/126 patients. For both baseline and subsequent examinations, agreement for stranding and soft tissue morphology were poor, for vessel encasement was fair, for soft tissue and ascites were moderate, and for main pancreatic duct dilatation was substantial. On recurrence examinations, across readers, new or increased stranding was present in 27-77%; new or increased soft tissue, 80-86%; soft tissue with vessel encasement and luminal narrowing, 36-59%; new or increased main pancreatic duct dilatation, 25-26%; and new or increased ascites, 20-23%. On baseline postoperative examinations, independent predictors of eventual LR were soft tissue for all three readers (OR=2.78-6.85) and stranding for reader 1 (OR=3.59); main pancreatic duct dilatation and ascites were not independent predictors of LR for any reader. Conclusion: This study highlights the role of soft tissue, particularly when associated with vessel encasement and luminal narrowing, in raising suspicion for LR after PDAC resection. Clinical Impact: This study supports the SAR PDAC DFP consensus statement, while highlighting opportunities for continued optimization.

16.
Surg Endosc ; 38(8): 4365-4373, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38886227

RESUMO

BACKGROUND: Although minimally invasive hepato-pancreato-biliary (MIS HPB) surgery can be performed with good outcomes, there are currently no standardized requirements for centers or surgeons who wish to implement MIS HPB surgery. The aim of this study was to create a consensus statement regarding safe dissemination and implementation of MIS HPB surgical programs. METHODS: Sixteen key questions regarding safety in MIS HPB surgery were generated after a focused literature search and iterative review by three field experts. Participants for the working group were then selected using sequential purposive sampling and snowball techniques. Review of the 16 questions took place over a single 2-h meeting. The senior author facilitated the session, and a modified nominal group technique was used. RESULTS: Twenty three surgeons were in attendance. All participants agreed or strongly agreed that formal guidelines should exist for both institutions and individual surgeons interested in implementing MIS HPB surgery and that routine monitoring and reporting of institutional and surgeon technical outcomes should be performed. Regarding volume cutoffs, most participants (91%) agreed or strongly agreed that a minimum annual institutional volume cutoff for complex MIS HPB surgery, such as major hepatectomy or pancreaticoduodenectomy, should exist. A smaller proportion (74%) agreed or strongly agreed that a minimum annual surgeon volume requirement should exist. The majority of participants agreed or strongly agreed that surgeons were responsible for defining (100%) and enforcing (78%) guidelines to ensure the overall safety of MIS HPB programs. Finally, formal MIS HPB training, minimum case volume requirements, institutional support and infrastructure, and mandatory collection of outcomes data were all recognized as important aspects of safe implementation of MIS HPB surgery. CONCLUSIONS: Safe implementation of MIS HPB surgery requires a thoughtful process that incorporates structured training, sufficient volume and expertise, a proper institutional ecosystem, and monitoring of outcomes.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos Minimamente Invasivos/normas , Segurança do Paciente/normas , Procedimentos Cirúrgicos do Sistema Biliar/métodos , Hepatectomia/métodos , Hepatectomia/normas , Hepatectomia/efeitos adversos , Consenso
17.
Surg Endosc ; 38(10): 5643-5650, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39117957

RESUMO

BACKGROUND: Despite a growing body of literature supporting the safety of robotic hepatopancreatobiliary (HPB) procedures, the adoption of minimally invasive techniques in HPB surgery has been slow compared to other specialties. We aimed to identify barriers to implementing robotic assisted surgery (RAS) in HPB and present a framework that highlights opportunities to improve adoption. METHODS: A modified nominal group technique guided by a 13-question framework was utilized. The meeting session was guided by senior authors, and field notes were also collected. Results were reviewed and free text responses were analyzed for major themes. A follow-up priority setting survey was distributed to all participants based on meeting results. RESULTS: Twenty three surgeons with varying robotic HPB experience from different practice settings participated in the discussion. The majority of surgeons identified operating room efficiency, having a dedicated operating room team, and the overall hospital culture and openness to innovation as important facilitators of implementing a RAS program. In contrast, cost, capacity building, disparities/risk of regionalization, lack of evidence, and time/effort were identified as the most significant barriers. When asked to prioritize the most important issues to be addressed, participants noted access and availability of the robot as the most important issue, followed by institutional support, cost, quality of supporting evidence, and need for robotic training. CONCLUSIONS: This study reports surgeons' perceptions of major barriers to equitable access and increased implementation of robotic HPB surgery. To overcome such barriers, defining key resources, adopting innovative solutions, and developing better methods of collecting long term data should be the top priorities.


Assuntos
Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Procedimentos Cirúrgicos do Sistema Digestório/métodos , Acessibilidade aos Serviços de Saúde , Procedimentos Cirúrgicos do Sistema Biliar/métodos
18.
JAMA ; 332(13): 1080-1089, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39158894

RESUMO

Importance: Tranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear. Objective: To determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection. Design, Setting, and Participants: Multicenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization. Interventions: Tranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia. Main Outcomes and Measures: The primary outcome was receipt of red blood cell transfusion within 7 days of surgery. Results: The primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, -2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08). Conclusions and Relevance: Among patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications. Trial Registration: ClinicalTrials.gov Identifier: NCT02261415.


Assuntos
Antifibrinolíticos , Hepatectomia , Neoplasias Hepáticas , Complicações Pós-Operatórias , Ácido Tranexâmico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Método Duplo-Cego , Transfusão de Eritrócitos/estatística & dados numéricos , Hepatectomia/efeitos adversos , Hepatectomia/estatística & dados numéricos , Neoplasias Hepáticas/cirurgia , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Período Perioperatório/estatística & dados numéricos
19.
HPB (Oxford) ; 2024 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-39289133

RESUMO

BACKGROUND: Adoption of robotic pancreatoduodenectomy (RPD) is growing, although there are challenges for safe introduction of this technique, including limitations in on-site expert proctoring. We developed and implemented a structured approach for safe introduction of a new RPD program using virtual collaboration. METHODS: A structured framework for introducing a RPD program was designed; key steps included obtaining additional training, identifying required resources, establishing a dedicated team, and patient safety considerations. Virtual collaboration with a proctor for bidirectional communication was utilized for remote operative guidance. In the initial cohort, perioperative data and postoperative outcomes were extracted from a prospectively maintained database. RESULTS: From August 2020 to December 2023, 68 patients underwent RPD. The median operative time was 407 min with an estimated blood loss of 150 mL. Median length of stay was 8 days. Negative margins were obtained in 90% of resections. Operative time was significantly shorter in the second half of cases compared to the first (380min vs 441min, p < 0.01) and rate of conversion decreased (6% vs 21%). CONCLUSION: The safe initiation of a structured RPD program is feasible through virtual expert collaboration. With careful consideration and an appropriate environment, excellent perioperative outcomes are achievable even for initial cases.

20.
Ann Surg ; 278(5): e1073-e1079, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37796751

RESUMO

OBJECTIVES: We aimed to determine whether surgeon variation in management of intraductal papillary mucinous neoplasm (IPMN) is driven by differences in risk perception and quantify surgeons' risk threshold for changing their recommendations. BACKGROUND: Surgeons vary widely in management of IPMN. METHODS: We conducted a survey of members of the Americas HepatoPancreatoBiliary Association, presented participants with 2 detailed clinical vignettes and asked them to choose between surgical resection and surveillance. We also asked them to judge the likelihood that the IPMN harbors cancer and that the patient would have a serious complication if surgery was performed. Finally, we asked surgeons to rate the level of cancer risk at which they would change their treatment recommendation. We examined the association between surgeons' treatment recommendations and their risk perception and risk threshold. RESULTS: One hundred fifty surgeons participated in the study. Surgeons varied in their recommendations for surgery [19% for vignette 1 (V1) and 12% for V2] and in their perception of the cancer risk (interquartile range: 2%-10% for V1 and V2) and risk of surgical complications (V1 interquartile range: 10%-20%, V2 20-30%). After adjusting for surgeon characteristics, surgeons who were above the median in cancer risk perception were 22 percentage points (27% vs 5%) more likely to recommend resection than those who were below the median (95% CI: 11%-4%; P <0.001). The median risk threshold at which surgeons would change their recommendation was 15% (V1 and V2). Surgeons who recommended surgery had a lower risk threshold for changing their recommendation than those who recommended surveillance (V1: 10.0 vs 15.0, P =0.06; V2: 7.0 vs 15.0, P =0.05). CONCLUSIONS: The treatment that patients receive for IPMNs depends greatly on how their surgeons perceive the risk of cancer in the lesion. Efforts to improve cancer risk prediction for IPMNs may lead to decreased variations in care.


Assuntos
Adenocarcinoma Mucinoso , Carcinoma Ductal Pancreático , Neoplasias Intraductais Pancreáticas , Neoplasias Pancreáticas , Cirurgiões , Humanos , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Adenocarcinoma Mucinoso/cirurgia , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia
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