Publications by authors named "Giorgos C Karakousis"

Background: Merkel cell carcinoma (MCC) is a radiosensitive aggressive skin cancer that spreads via the lymphatics. There is uncertainty regarding the optimal management of the nodal basin for patients with MCC with clinically positive nodes. We study the efficacy of single node excision (SNE) as an alternative to a therapeutic lymph node dissection (TLND) in patients with limited nodal disease.

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Background: Metastasectomy is a useful adjunct in the management of metastatic cancer. Widespread adoption of novel targeted and immunotherapies has improved the survival profiles of multiple malignancies, which has potentially altered the role of metastasectomy. This study aimed to characterize trends in metastasectomy across five primary cancers eligible for these therapies.

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Introduction: We examined trends in major morbidity and mortality following total gastrectomy for malignancy in a national cohort.

Methods: The National Surgical Quality Improvement Program was used to identify patients who underwent total gastrectomy for malignancy from 2007 to 2021. Joinpoint regression was used to determine annual percent changes (APCs) in thirty-day postoperative major morbidity, mortality, and length of stay (LOS).

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Background And Objectives: The impact of neoadjuvant immunotherapy (NIT) on overall survival (OS) in patients with resectable stage III melanoma remains unknown. We sought to identify factors associated with receipt of NIT and survival outcomes in patients with clinical stage III melanoma undergoing surgery.

Methods: The National Cancer Database (2016-2020) was used to identify patients with clinical stage III melanoma who underwent surgery and received either NIT or adjuvant immunotherapy (AIT) only.

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Article Synopsis
  • A new subset of macrophages called iron-rich tumor-associated macrophages (iTAMs) was identified, marked by high levels of intracellular iron and involvement in angiogenesis and immunosuppression in tumors.
  • Two types of iTAMs were characterized based on their location and gene expression: perivascular (pviTAM) and stromal (stiTAM).
  • The endothelin receptor type B (Ednrb) was identified as a specific marker for iTAMs, and its deletion reduced tumor growth, while the transcription factor Bach1 was found to regulate iTAM functions by inhibiting Ednrb expression.
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Purpose: Neoadjuvant anti-PD-1 therapy in melanoma may increase tumor-infiltrating lymphocytes (TIL), and more TIL are associated with better treatment response. A major pathologic response (MPR) in melanoma after neoadjuvant anti-PD-1 therapy usually comprises tumor necrosis and fibrosis. The role of TIL in necrotic tumor necrosis (nTIL) has not been explored.

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Combination checkpoint blockade with anti-PD-1 and anti-CTLA-4 antibodies has shown promising efficacy in melanoma. However, the underlying mechanism in humans remains unclear. Here, we perform paired single-cell RNA and T cell receptor (TCR) sequencing across time in 36 patients with stage IV melanoma treated with anti-PD-1, anti-CTLA-4, or combination therapy.

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Melanoma is the fifth most common cancer in the United States and accounts for the majority of all skin cancer-related deaths, making it the most lethal cutaneous malignancy. Systemic adjuvant therapy for stage IIB-IV melanoma is now approved for patients who have undergone surgical resection, given the appreciable risk of recurrence and mortality in this patient population. Despite the lower stage, high-risk stage II melanoma (stage IIB/IIC) can often exhibit an even more aggressive course when compared to stage IIIA/IIIB disease, thus justifying consideration of adjuvant therapy in these patients.

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Background: Longer time to surgery (TTS) is associated with worse survival in patients with breast cancer. Whether this association has encouraged more prompt care delivery remains unknown.

Methods: The National Cancer Database was used to identify patients ≥18 years of age diagnosed with clinical stage 0-III breast cancer between 2006 and 2019 for whom surgery was the first mode of treatment.

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Background: A concerning increase in early-onset colorectal cancer led to guideline changes in 2018 by the American Cancer Society to lower the age for initial colorectal cancer screening from 50 to 45 years of age. Although this would be expected to result in increased screening rates and subsequent earlier detection of colorectal cancer, the effect of this guideline change at a national level is not yet fully understood.

Methods: Using the National Cancer Database, we identified patients newly targeted for screening (age 45-49 years) diagnosed with colon cancer in either 2017 (early cohort) or 2019 (late cohort).

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Article Synopsis
  • - The study evaluated the effectiveness of pegsitacianine, a fluorescent imaging agent, in detecting residual disease after cytoreductive surgery (CRS) in patients with peritoneal carcinomatosis, which could enhance long-term survival chances.
  • - In a phase II trial, 50 patients received pegsitacianine before surgery, and after CRS, 50% of evaluable patients showed residual disease during examination under near-infrared light.
  • - Pegsitacianine was found to be well tolerated, with no serious side effects reported, and helped improve the detection of occult residual disease, indicating its potential utility in surgical procedures.
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The standard of care for patients with resectable stage III/IV melanoma classically included upfront resection with adjuvant therapy. However, in more recent years, the amount of systemic therapies available for neoadjuvant use for these patients has increased. This article reviewed clinical trials investigating neoadjuvant therapy for patients with resectable stage III/IV melanoma.

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Macrophages play a pivotal role in tumor immunity. We report that reprogramming of macrophages to tumor-associated macrophages (TAMs) promotes the secretion of exosomes. Mechanistically, increased exosome secretion is driven by MADD, which is phosphorylated by Akt upon TAM induction and activates Rab27a.

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Background: Clinically localized Merkel cell carcinoma (MCC) is commonly treated with surgical excision and radiotherapy. The relationship between time to adjuvant radiotherapy and overall survival (OS) remains understudied.

Methods: This retrospective study used data from the National Cancer Database (2006-2019).

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Background: Although historic studies of state registries have demonstrated decreased radiation therapy use for patients with breast cancer living further away from radiation facilities, the association between travel distance and breast cancer treatment in a modern national cohort remains unknown.

Methods: Female patients with estrogen receptor/progesterone receptor positive and human epidermal growth factor receptor 2 negative pathologic stages I to II breast cancer were identified from the National Cancer Database (2018-2020) and dichotomized by distance ≤20 miles or >20 miles (75th percentile) from the treatment facility. The association between travel distance and type of surgery and treatment administered was analyzed by univariate and multivariate logistic regression and after 1:1 propensity matching.

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Introduction: Management of retroperitoneal sarcoma (RPS) remains controversial, with the mainstay of treatment being surgery. While neoadjuvant radiation demonstrated no improvement in recurrence-free survival in a prospective randomized trial (STRASS), the role of neoadjuvant chemotherapy (NCT) remains unknown and is the subject of ongoing study (STRASS2).

Methods: Patients who underwent surgical resection of high-grade RP leiomyosarcoma (LMS) or dedifferentiated liposarcoma (DDLS) were identified from the National Cancer Database (2006-2019).

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Background: Disparities have been previously described in the presentation, management, and outcomes of other thyroid cancer subtypes; however, it is unclear whether such disparities exist in anaplastic thyroid cancer (ATC).

Methods: We identified patients with ATC from the National Cancer Database (2004-2020). The primary outcomes were receipt of surgery, chemotherapy, and radiation.

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