L G Koniaris

Johns Hopkins University, Baltimore, MD, United States

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Publications (56)128.95 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: This large-volume, single-institution review examines factors influencing long-term survival after resection in patients with adenocarcinoma of the head, neck, uncinate process, body, or tail of the pancreas. Between January 1984 and July 1999 inclusive, 616 patients with adenocarcinoma of the pancreas underwent surgical resection. A retrospective analysis of a prospectively collected database was performed. Both univariate and multivariate models were used to determine the factors influencing survival. Of the 616 patients, 526 (85%) underwent pancreaticoduodenectomy for adenocarcinoma of the head, neck, or uncinate process of the pancreas, 52 (9%) underwent distal pancreatectomy for adenocarcinoma of the body or tail, and 38 (6%) underwent total pancreatectomy for adenocarcinoma extensively involving the gland. The mean age of the patients was 64.3 years, with 54% being male and 91% being white. The overall perioperative mortality rate was 2.3%, whereas the incidence of postoperative complications was 30%. The median postoperative length of stay was 11 days. The mean tumor diameter was 3.2 cm, with 72% of patients having positive lymph nodes, 30% having positive resection margins, and 36% having poorly differentiated tumors. Patients undergoing distal pancreatectomy for left-sided lesions had larger tumors (4.7 vs. 3.1 cm, P < 0.0001), but fewer node-positive resections (59% vs. 73%, P = 0.03) and fewer poorly differentiated tumors (29% vs. 36%, P < 0.001), as compared to those undergoing pancreaticoduodenectomy for right-sided lesions. The overall survival of the entire cohort was 63% at 1 year and 17% at 5 years, with a median survival of 17 months. For right-sided lesions the 1- and 5-year survival rates were 64% and 17%, respectively, compared to 50% and 15% for left-sided lesions. Factors shown to have favorable independent prognostic significance by multivariate analysis were negative resection margins (hazard ratio [HR] = 0.64, confidence interval [CI] = 0.50 to 0.82, P = 0.0004), tumor diameter less than 3 cm (HR = 0.72, CI = 0.57 to 0.90, P = 0.004), estimated blood loss less than 750 ml (HR = 0.75, CI = 0.58 to 0.96, P = 0.02), well/moderate tumor differentiation (HR = 0.71, CI = 0.56 to 0.90, P = 0.005), and postoperative chemoradiation (HR = 0.50, CI = 0.39 to 0.64, P < 0.0001). Tumor location in head, neck, or uncinate process approached significance in the final multivariate model (HR = 0.60, CI = 0.35 to 1.0, P = 0.06). Pancreatic resection remains the only hope for long-term survival in patients with adenocarcinoma of the pancreas. Completeness of resection and tumor characteristics including tumor size and degree of differentiation are important independent prognostic indicators. Adjuvant chemoradiation is a strong predictor of outcome and likely decreases the independent significance of tumor location and nodal status.
    Journal of Gastrointestinal Surgery 04/2012; 4(6):567-79. · 2.36 Impact Factor
  • L G Koniaris, A K Mandal, T Genuit, J L Cameron
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    ABSTRACT: A case of a gunshot wound to the head of the pancreas and superior mesenteric vein requiring pancreaticoduodenectomy is discussed. Managing such an injury is challenging, first because of the ongoing hemorrhage and second because of the technical difficulty in working with a normal pancreas and bile duct. In the case presented herein, enteric reconstruction was performed 72 hours after the initial surgery. A delay in reconstruction resulted in tissue changes that facilitated enteric reconstruction A two-stage pancreaticoduodenectomy may be considered if the surgeon is faced with an unstable patient.
    Journal of Gastrointestinal Surgery 04/2012; 4(4):366-9. · 2.36 Impact Factor
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    ABSTRACT: NOV-002 (a formulation of disodium glutathione disulfide) modulates signaling pathways involved in tumor cell proliferation and metastasis and enhances anti-tumor immune responsiveness in tumor models. The addition of NOV-002 to chemotherapy has been shown to increase anti-tumor efficacy in animal models and some early phase oncology trials. We evaluated the clinical effects of NOV-002 in primary breast cancer, whether adding NOV-002 to standard preoperative chemotherapy increased pathologic complete response rates (pCR) at surgery, and determined whether NOV-002 mitigated hematologic toxicities of chemotherapy and whether levels of myeloid derived suppressor cells (MDSC) were predictive of response. Forty-one women with newly diagnosed stages II-IIIc HER-2 negative breast cancer received doxorubicin-cyclophosphamide followed by docetaxel (AC → T) every 3 weeks and concurrent daily NOV-002 injections. The trial was powered to detect a doubling of pCR rate from 16 to 32% with NOV-002 plus AC → T (α = 0.05, β = 80%). Weekly complete blood counts were obtained as well as circulating MDSC levels on day 1 of each cycle were quantified. Of 39 patients with 40 evaluable tumors, 15 achieved a pCR (38%), meeting the primary endpoint of the trial. Concurrent NOV-002 resulted in pCR rates for AC → T chemotherapy higher than previously reported. Patients with lower levels of circulating MDSCs at baseline and on the last cycle of chemotherapy had significantly higher probability of a pCR (P = 0.02). Further evaluation of NOV-002 in a randomized study is warranted.
    Breast Cancer Research and Treatment 12/2011; 132(1):215-23. · 4.47 Impact Factor
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    ABSTRACT: We assessed differences in locoregional outcome based on receptor status combinations in a cohort of stage II-III breast cancer patients treated with modern trimodality therapy. Medical records of 582 consecutively treated patients receiving post-mastectomy radiation (PMRT) between 1/1999 and 12/2009 were reviewed. Rate of local regional recurrence (LRR) was estimated by the method of cumulative incidence allowing for competing risks. The effect of prognostic factors was examined by Gray's test and by Fine and Gray's modeling approach. Median follow-up was 44.7 months. Five-year progression-free survival (PFS) was 73.9% and overall survival (OS) was 84%. The cumulative 5-year incidence of LRR as first site of failure was 6.2% (95% CI 4.2-8.7). Five-year cumulative incidence of LRR was 8.6 versus 4.4% for estrogen receptor (ER) negative versus ER positive (P = 0.017), 8.5 versus 3.4% for progesterone receptor (PR) negative versus PR positive (P = 0.011), and 1.7 versus 7.5% for HER2 positive (86% received trastuzamab) versus HER2 negative (P = 0.032). Five-year cumulative incidence of LRR was 11.8% for the triple negative subtype and 3.9% for other receptor combinations (P < 0.001). Among patients whose disease is ER positive, 5-year LRR rate was 7.8 versus 3.4% for PR negative versus PR positive (P = 0.130). The prognostic value of the triple negative and HER2 negative subtypes was maintained on multivariate analysis. In the era of HER-2 targeted therapy, tumors that are HER-2 over expressing and are treated with trastuzumab have a very low rate of LRR. ER negative, PR negative, and triple negative status are associated with increased risk of LRR.
    Breast Cancer Research and Treatment 04/2011; 128(3):899-906. · 4.47 Impact Factor
  • Fuel and Energy Abstracts 01/2011; 81(2).
  • Journal of Surgical Research - J SURG RES. 01/2011; 165(2):337-337.
  • Journal of Surgical Research 02/2010; 158(2):280. · 2.02 Impact Factor
  • M C Cheung, R Yang, Y Zhuge, L G Koniaris, J E Sola
    Journal of Surgical Research 02/2010; 158(2):273. · 2.02 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):367. · 2.02 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):281. · 2.02 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):282. · 2.02 Impact Factor
  • Journal of Surgical Research 02/2010; 158(2):280-1. · 2.02 Impact Factor
  • Fuel and Energy Abstracts 01/2010; 78(3).
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    ABSTRACT: Using a population-based registry, we evaluated the impact of neoadjuvant radiotherapy and lymphadenectomy on survival of patients undergoing curative-intent surgery for esophageal adenocarcinoma (EAC). Surveillance, Epidemiology, and End Results (SEER) data for patients with esophageal adenocarcinoma from 1988 to 2005 were queried. Patients undergoing curative operations were included. Treatment was stratified between no radiotherapy, neoadjuvant versus adjuvant radiotherapy, and adequate (> or = 18 lymph nodes) versus inadequate (<18 lymph nodes) lymphadenectomy. Univariate and multivariate analysis were performed to determine median survival (MST) and cause-specific survival (CSS). Overall, 4,224 patients underwent surgical extirpation with curative intent for EAC in the study period. MST and CSS for the entire cohort were 25 and 31 months, respectively. Multivariate analysis showed age <65 years, well-differentiated tumor, local disease, negative lymph node status, adequate lymphadenectomy, and neoadjuvant radiotherapy to be independent predictors of improved survival. In node-positive patients, the greatest survival benefit was seen in patients who received both neoadjuvant radiotherapy and adequate lymphadenectomy (MST = 32 months, CSS = 34 months). The lymph node ratio (LNR) for adequately dissected patients treated with neoadjuvant radiotherapy was 0.17, which is <0.2, the established LNR cutoff that is an independent predictor of improved survival. The survival benefit of neoadjuvant treatment is additive to that of adequate lymphadenectomy. There is a cooperative survival benefit for neoadjuvant radiation and adequate lymphadenectomy in patients with node-positive EAC. Both are independent predictors of improved survival. Patients who have clinically node-positive disease should undergo both neoadjuvant radiation and adequate lymphadenectomy to ensure optimal outcome.
    Annals of Surgical Oncology 12/2009; 17(3):791-803. · 4.12 Impact Factor
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    ABSTRACT: To use a population-based registry to evaluate the effect of chemotherapy or radiation on survival for patients undergoing curative-intent surgery for adenocarcinoma of the esophagus or stomach. A linked data set between the Florida Cancer Data System and the Florida Agency for Health Care Administration from 1998 to 2003 was queried. Overall, 3,378 patients underwent surgical extirpation with curative intent, 636 patients had esophageal adenocarcinoma (EAC), and 2,742 patients had gastric adenocarcinoma (GAC). Outcomes were adjusted for patient comorbidities and hospital teaching status. Overall, no benefit was observed for adjuvant therapies for EAC patients. A small improvement in survival was observed with adjuvant therapies for GAC. For localized EAC or GAC there was no additional survival benefit associated with adjuvant therapies. For patients with regional EAC, chemotherapy (20.0 vs. 13.0 months, P < .001) and radiation (18.6 vs. 13.5 months, P = .007) were associated with a statistically significant survival benefit. In multivariate analysis, independent predictors of improved survival for regional EAC include chemotherapy (hazard ratio [HR] .535, P < .001) and radiotherapy (HR .656, P = .01). For GAC, patients with regional disease showed an improved median survival with chemotherapy (21.1 vs. 11.2 months, P < .001) and radiotherapy (22.6 vs. 12.3 months, P < .001). In multivariate analysis, independent predictors of improved survival for regional GAC include chemotherapy (HR .629, P < .001) and radiation (HR .603, P < .001). Patients with regional adenocarcinoma of the esophagus or stomach, but not those with localized disease, derive a statistically significant survival benefit from the addition of chemotherapy and radiation to surgical resection.
    Annals of Surgical Oncology 09/2009; 17(1):98-108. · 4.12 Impact Factor
  • Teresa A Zimmers, Juan C Gutierrez, Leonidas G Koniaris
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    ABSTRACT: Growth-differentiation factor (GDF)-15, a member of the TGF-beta superfamily, is potently induced in the intestine following mechanical injury, genotoxic insult and following non-steroidal anti-inflammatory drugs (NSAIDs) exposure. GDF-15 expression correlates with apoptosis in intestinal cells and has been implicated in the pathogenesis of colorectal cancer formation and the anti-tumor effects of NSAIDs. We sought to determine the effect of loss of Gdf15 on animal tumor models of hereditary colon cancer and in the NSAID-mediated prevention of heritable colorectal cancer. GDF-15 null (Gdf15 (-/-)) mice and mice with the genetic mutation found in hereditary poliposis coli, Apc ( min/+ ) were bred. Gdf15 ( -/- ), Apc ( min/+ ) and Gdf15 ( +/+ ), Apc ( min/+ ) mice were generated. In Gdf15 ( -/- ), Apc ( min/+ ) mice, intestinal neoplasia formation rate and size were indistinguishable from that in Gdf15 ( +/+ ), Apc ( min/+ ) mice. Sulindac chemoprotection activity although potent in Gdf15 ( +/+ ), Apc ( min/+ ) mice was abolished in Gdf15 ( -/- ), Apc ( min/+ ) mice. These results demonstrate in a murine model that GDF-15 does not significantly regulate heritable in vivo intestinal carcinogenesis but does mediate sulindac chemoprevention in heritable colon cancer. These data suggest that the use of GDF-15 activated signaling pathways may allow improved chemoprevention and therapies for colorectal cancer.
    Journal of Cancer Research and Clinical Oncology 09/2009; 136(4):571-6. · 2.91 Impact Factor
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    ABSTRACT: Inflammatory breast cancer (IBC) remains the breast malignancy with the worst prognosis. We sought to determine the effects of race, socioeconomic status and treatment on outcomes for women with IBC. Study design The Florida cancer registry, inpatient and ambulatory data were queried for patients diagnosed from 1998 to 2002. A total of 935 patients with IBC were identified (1.5% of all breast cancers). Overall, 83.1% were Caucasian, 13.9% African American (AA), and 15.7% Hispanic. The mean age of diagnosis was 57 years old. AA patients presented at a younger age, with higher tumor grade, and were less likely to undergo surgical therapy than their Caucasian counterparts. Median survival time (MST) for the entire cohort was 32 months, while MST for AA patients was 20 months. Patients who received chemotherapy before surgery, surgery without chemotherapy, and surgery before chemotherapy demonstrated an independent, significantly improved outcome in comparison to patients who underwent chemotherapy without surgical extirpation. The administration of radiation therapy did not demonstrate an improvement in survival. By multivariate analysis, AA race (HR = 2.19) and failure to provide surgery (HR = 2.3) were independent predictors of worse prognosis. No effect of poverty or ethnicity on outcome was observed. IBC carries a poor prognosis for all patients with significantly worse outcomes for AA women. Multimodality therapy provided the best survival rates.
    Breast Cancer Research and Treatment 02/2009; 117(3):631-41. · 4.47 Impact Factor
  • M. C. Cheung, N. Housri, L. G. Koniaris
    Journal of Surgical Research - J SURG RES. 01/2009; 151(2):297-297.
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):290-290.
  • Journal of Surgical Research - J SURG RES. 01/2009; 151(2):284-284.

Publication Stats

1k Citations
128.95 Total Impact Points

Institutions

  • 2000–2012
    • Johns Hopkins University
      • Department of Surgery
      Baltimore, MD, United States
  • 2011
    • Thomas Jefferson University Hospitals
      Philadelphia, Pennsylvania, United States
  • 2008–2010
    • University of Miami Miller School of Medicine
      • Division of Surgical Oncology
      Miami, Florida, United States
  • 2001–2004
    • University of Rochester
      • Department of Surgery
      Rochester, NY, United States