Publications by authors named "Daniel Nussbaum"

Background: Hepatic arterial infusion (HAI) is an established treatment for patients with unresectable colorectal liver metastases (uCRLM). Until recently, HAI was only performed at a limited number of centers. We previously reported early outcomes suggesting that implementation of a new HAI program is safe and feasible.

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Purpose: Intraductal papillary mucinous neoplasms (IPMN) occur in 5-10% of the population, but only a small minority progress to pancreatic ductal adenocarcinoma (PDAC). The lack of accurate predictors of high-risk disease leads both to unnecessary operations for indolent neoplasms as well as missed diagnoses of PDAC. Digital spatial RNA profiling (DSP-RNA) provides an opportunity to define and associate transcriptomic states with cancer risk.

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Approximately 50% of colorectal cancer patients develop liver metastases. Hepatic metastases represent the most common cause of colorectal cancer-related mortality. Metastasectomy, if possible, represents the most effective treatment strategy; 20% of patients will be cured and more than 50% survive at least 5 years.

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Article Synopsis
  • Ampullary adenocarcinoma (AA) shows clinical and genetic diversity, and a new genomic classifier may improve patient classification beyond traditional methods, but it needs validation before being widely used.
  • A study involving 192 patients with AA assessed the accuracy of this genomic classifier against standard histology to see if it could predict survival outcomes.
  • Results indicated a 55% agreement between genomic and histological classifications; however, while histological subtypes did not predict survival, the genomic scores did correlate with survival probabilities, suggesting the genomic approach might be more effective.
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  • Desmoid tumors (DTs) are uncommon, non-metastasizing growths that can behave aggressively locally, with a shift in management from traditional surgery to active surveillance.
  • A review of 103 patients showed a significant decrease in surgical resection rates over time, indicating a preference for monitoring rather than immediate intervention.
  • The study highlights improved treatment-free survival for those under active surveillance, aligning with updated guidelines from expert panels advocating for this approach.
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Objective: To determine the interobserver variability for complications of pancreatoduodenectomy as defined by the International Study Group for Pancreatic Surgery (ISGPS) and others.

Background: Good interobserver variability for the definitions of surgical complications is of major importance in comparing surgical outcomes between and within centers. However, data on interobserver variability for pancreatoduodenectomy-specific complications are lacking.

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Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs.

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Background: Liver transplantation (LT) has been shown to be superior to resection in highly selected patients with perihilar cholangiocarcinoma (CCA), yet has traditionally been contraindicated for intrahepatic CCA (iCCA). Herein, we aimed to examine contemporary trends and outcomes for surgical resection and LT for iCCA.

Methods: The National Cancer Database was queried for patients presenting with stage I-III iCCA between 2010 and 2018 who underwent resection or LT.

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Objective: We sought to comprehensively profile tissue and cyst fluid in patients with benign, precancerous, and cancerous conditions of the pancreas to characterize the intrinsic pancreatic microbiome.

Summary Background Data: Small studies in pancreatic ductal adenocarcinoma (PDAC) and intraductal papillary mucinous neoplasm (IPMN) have suggested that intra-pancreatic microbial dysbiosis may drive malignant transformation.

Methods: Pancreatic samples were collected at the time of resection from 109 patients.

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Background: Radical cholecystectomy is recommended for T1B and greater gallbladder cancer, however, there are conflicting reports on the utility of extended resection for T1B disease. Herein, we characterize outcomes following simple and radical cholecystectomy for pathologic stage T1B gallbladder cancer.

Methods: The National Cancer Database (NCDB) was queried for patients with pathologic T1B gallbladder cancer diagnosed from 2004 to 2018.

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Background: This meta-analysis investigated the effects of enhanced recovery after surgery (ERAS) protocols compared to conventional care on postoperative outcomes in patients aged 70 years or older undergoing pancreatoduodenectomy (PD).

Methods: Five databases were systematically searched. Comparative studies with available individual patient data (IPD) were included.

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ABSTRACT: BACKGROUND: Pancreatic adenocarcinoma (PDAC) is highly lethal with up to 80% of resected patients experiencing disease recurrence within 2 years (Watanabe, Nakamura, Kimura et al in Int J Mol Sci 23(19):11521, 2022). Cross-sectional imaging and serum tumor markers are used for monitoring post-operative recurrence; however, both have significant limitations (Edland, Tjensvoll, Oltedal et al in Mol Oncol 17:1857-1870, 2023). Circulating tumor DNA (ctDNA) has emerged as a valuable prognostic tool to measure molecular residual disease (MRD) and predict recurrence in solid tumors (Watanabe, Nakamura, Kimura et al in Int J Mol Sci 23(19):11521, 2022).

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Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs.

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Objectives: We performed a retrospective analysis within a national cancer registry on outcomes following resection or ablation for intrahepatic cholangiocarcinoma (iCCA).

Methods: The National Cancer Database was queried for patients with clinical stage I-III iCCA diagnosed during 2010-2018, who underwent resection or ablation. Overall survival (OS) was compared with Kaplan-Meier and multivariable Cox proportional hazards methods.

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Background: Hepatectomy is the cornerstone of curative-intent treatment for intrahepatic cholangiocarcinoma (ICC). However, in patients unable to be resected, data comparing efficacy of alternatives including thermal ablation and radiation therapy (RT) remain limited. Herein, we compared survival between resection and other liver-directed therapies for small ICC within a national cancer registry.

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Background: Society guidelines remain inconsistent on the role of endoscopic and radiographic surveillance as an alternative to surgical resection of small gastric gastrointestinal stromal tumors (GISTs). Herein, we aimed to assess survival among patients with gastric GISTs undergoing observation versus surgical resection, stratified by tumor size.

Methods: The National Cancer Database (NCDB) was queried for gastric GISTs < 2 cm diagnosed from 2010-2017.

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Article Synopsis
  • Resection is the main treatment for biliary tract cancers, but recent studies suggest adjuvant chemotherapy (AC) could play a role in improving outcomes.
  • The analysis of 7,039 patients from the National Cancer Database revealed that AC usage increased from 23% in 2010 to 41% in 2018, influenced by factors like gender, insurance type, and disease stage.
  • While AC overall didn't show a survival benefit, it significantly reduced mortality for patients with extrahepatic cholangiocarcinoma, highlighting the need for guidelines that target at-risk groups for better outcomes.
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  • Patients with unresectable colorectal liver metastases often undergo systemic chemotherapy to make their condition operable, but many do not achieve this after first-line treatment.
  • Despite limited success with second- and third-line therapies, there’s renewed interest in combining hepatic artery infusion chemotherapy with systemic treatments as a way to improve outcomes.
  • Recent studies show promising results for this combined approach, even among patients who are resistant to traditional chemotherapy, leading to wider adoption across North America and beyond.
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Background: Disparities in healthcare exist, yet few data are available on racial differences in time from admission to surgery. This study aimed to compare time from admission to laparoscopic cholecystectomy for acute cholecystitis between non-Hispanic Black and non-Hispanic White patients.

Methods: Patients who underwent laparoscopic cholecystectomy for acute cholecystitis from 2010 to 2020 were identified using NSQIP.

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Background: Multimodal therapy has improved survival outcomes for rectal cancer (RC) significantly with an exemption for older patients. We sought to assess whether older non-comorbid patients receive substandard oncological treatment for localized RC referring to the National Comprehensive Cancer Network (NCCN) guidelines and whether it affects survival outcomes.

Methods: This is a retrospective study using patient data from the National Cancer Data Base (NCDB) for histologically confirmed RC from 2002 to 2014.

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The histopathologic heterogeneity of intraductal papillary mucinous neoplasms (IPMN) complicates the prediction of pancreatic ductal adenocarcinoma (PDAC) risk. Intratumoral regions of pancreaticobiliary (PB), intestinal (INT), and gastric foveolar (GF) epithelium may occur with either low-grade dysplasia (LGD) or high-grade dysplasia (HGD). We used digital spatial RNA profiling of dysplastic epithelium (83 regions) from surgically resected IPMN tissues (12 patients) to differentiate subtypes and predict genes associated with malignancy.

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Background: Management of clinical stage II or III esophageal cancer requires multidisciplinary care. Multi-institutional care has been associated with worse survival in other malignant diseases. This study aimed to determine the impact of multi-institutional care on survival in patients with stage II or III esophageal cancer.

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Background: Intraductal papillary mucinous neoplasms (IPMN) are the only radiographically identifiable precursor to pancreatic adenocarcinoma, yet little is known about how these lesions progress to cancer. Inflammation has been associated with dysplastic progression; however, the cause and composition of this inflammation remains poorly characterized. We sought to comprehensively profile immune cell infiltration using parallel spatial transcriptomic and flow cytometric techniques.

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