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1.
PLoS One ; 17(8): e0272910, 2022.
Article in English | MEDLINE | ID: mdl-35976968

ABSTRACT

BACKGROUND: Fifteen percent of US adults have chronic kidney disease (CKD). The effect of CKD on the development of different malignancies is unknown. Understanding the effect of CKD on the risk of development of cancer could have important implications for screening and early detection of cancer in these patients. METHODS: Adult CKD patients [estimated GFR (eGFR) <60ml/min/1.73m2] between January 2001 and December 2020 were identified in this single institution study. Patients were divided into four stages of CKD by eGFR. The incidence of cancer and time to development of the first cancer were identified. Multivariable models were used to compare the overall cancer incidence while considering death as a competing risk event and adjusting for relevant covariates (sex, race, diabetes, hypertension, CAD, smoking or not, BMI, and CKD stages). Separate multivariable models of the incidence of cancers were conducted in each age group. Multivariable Cox models were used to fit the overall death adjusting for relevant covariates. Patients were censored at the conclusion of the study period (December 31, 2020). Statistical analysis was performed with SAS software (version 9.4). RESULTS: Of the 13,750 patients with a diagnosis of CKD in this cohort, 2,758 (20.1%) developed a malignancy. The median time to development of cancer following a diagnosis of CKD was 8.5 years. Factors associated with the risk of developing cancer in CKD patients included increasing age, male sex and worsening chronic kidney disease, while diabetes was associated with a lower risk of malignancy. On multivariate analysis, the factors associated with increased mortality in patients who developed cancer included increasing age, diabetes and lower eGFR. CONCLUSION: CKD is an increased risk factor for the development of various malignancies. Age appropriate cancer screening should be aggressively pursued in those with progressive CKD.


Subject(s)
Diabetes Mellitus , Neoplasms , Renal Insufficiency, Chronic , Adult , Cohort Studies , Diabetes Mellitus/epidemiology , Glomerular Filtration Rate , Humans , Male , Neoplasms/complications , Neoplasms/epidemiology , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology , Risk Factors
2.
Infect Dis Rep ; 13(4): 1036-1042, 2021 Dec 06.
Article in English | MEDLINE | ID: mdl-34940404

ABSTRACT

Hepatitis B vaccination is recommended in all patients with end-stage kidney disease (ESKD). However, only 50-60% of these patients achieve protective antibody levels if immunized after starting dialysis. Strategies to overcome this low seroconversion rate include a 6-month vaccination schedule starting earlier [chronic kidney disease (CKD) stage 4 and 5] to ensure immunity when patients progress to ESKD. We conducted a quality improvement program to immunize pre-dialysis patients. Patients who were found to have a negative baseline serology with a negative hepatitis B surface antibody level (HBsAb) were offered vaccination on a 6-month schedule (0, 1 and 6 months) with one of two available vaccines within the VA system (Recombivax™ or Engerix™). HBsAb titers were checked 3-4 months later, and titers ≥ 12 mIU/mL were indicative of immunity at VA. Patients who did not seroconvert were offered a repeat schedule of three more doses. We screened 198 patients (187 males and 11 females) with CKD 4 and 5 [glomerular filtration rate (GFR) < 29 mL/min/1.73 m2]. The median age of this cohort was 72 years (range 38-92 years). During the study period of 5 years (2015-2020), 10 patients were excluded since their GFR had improved to more than 30 mL/min/1.73 m2, 24 others had baseline immunity and 2 refused vaccination. The hepatitis B vaccination series was not started on 106 patients. Of the remaining 56, 12 patients progressed to ESKD and started dialysis before completion of the vaccination schedule, 6 expired and 1 did not come to clinic in 2020 due to the pandemic. Of the 37 patients who completed the vaccination schedule, 16 achieved seroconversion with adequate HBsAb titers, 10 did not develop immunity despite a second hepatitis B vaccination series, while 11 did not get a second series. Given the low seroconversion rate, albeit in a small cohort, vaccination should be considered in patients with earlier stages of CKD. Other options include studies on FDA approved vaccines of shorter duration. We plan to increase awareness among nephrologists, patients and nursing staff about the importance of achieving immunity against hepatitis B.

3.
Clin Transplant ; 32(3): e13204, 2018 03.
Article in English | MEDLINE | ID: mdl-29345387

ABSTRACT

BACKGROUND: All living kidney donors are counseled about the possible surgical and medical risks associated with donation. Only a minority of transplant centers discuss the potential benefit of discovering undiagnosed medical conditions in the donor during evaluation, as part of their consent process. METHODS: We retrospectively investigated all potential living kidney donors evaluated over a 10-year period at a single center to characterize incidentally diagnosed serious medical conditions. RESULTS: Sixty-five of the 762 potential donors (8.5%) were not approved for donation because of a newly diagnosed serious medical condition discovered during their evaluation. This included six patients diagnosed with malignancies, five of which required operative intervention, six patients diagnosed with transmittable diseases requiring follow-up and treatment, four patients were found to have bilateral renal stones with significant stone burden, and two patients diagnosed with IgA nephropathy. Additionally, four patients were diagnosed with significant heart disease, and one of those patients subsequently required a coronary artery bypass surgery. CONCLUSIONS: The evaluation process can diagnose serious medical conditions in a significant minority of donors that would have otherwise been unrecognized. The benefit associated with the donor evaluation should be considered an important part of the consent process.


Subject(s)
Donor Selection/standards , Kidney Transplantation/methods , Kidney/physiopathology , Living Donors/statistics & numerical data , Risk Assessment/methods , Severity of Illness Index , Tissue and Organ Harvesting/standards , Adult , Evaluation Studies as Topic , Female , Follow-Up Studies , Humans , Informed Consent , Male , Middle Aged , Prognosis , Retrospective Studies
5.
Clin Appl Thromb Hemost ; 22(1): 12-20, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26239316

ABSTRACT

Hematopoietic stem cell transplant-associated thrombotic microangiopathy (TA-TMA) is a fatal, multifactorial disorder, which may present with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. The pathogenesis of TA-TMA is complex and includes multiple risk factors such as certain conditioning regimens, calcineurin inhibitors (CNIs), graft-versus-host disease (GVHD), human leukocyte antigen mismatch, and opportunistic infections. The end result of these insults is endothelial injury in the kidney and other organs. Recent studies also indicate a role of complement activation in tissue damage. The lack of sensitive and specific diagnostic tests for TA-TMA often results in delayed diagnosis. Biopsy is not always possible for diagnosis because of the risk of complications such as bleeding. Recently, an emerging role of renal-centered screening approach has been demonstrated, which utilize the monitoring of blood pressure, urine protein, serum lactate dehydrogenase and hemogram for early detection. Therapeutic options are limited, and plasma exchange plays a minor role. Withdrawal of offending agent such as CNIs and the use of rituximab can be effective in some patients. However, the current treatment strategy is suboptimal and associated with high mortality rate. Recently, eculizumab has been utilized in a few patients with good outcomes. Patients, who develop TA-TMA, are also at an increased risk of GVHD, infection, renal, cardiovascular, and other complications, which can contribute to high mortality. Better understanding of molecular pathogenesis, improvement in posttransplant management, leading to early diagnosis, and management of TA-TMA are required to improve outcomes of this fatal entity.


Subject(s)
Hematopoietic Stem Cell Transplantation/adverse effects , Plasma Exchange , Rituximab/therapeutic use , Thrombotic Microangiopathies , Female , Graft vs Host Disease/diagnosis , Graft vs Host Disease/etiology , Graft vs Host Disease/pathology , Graft vs Host Disease/therapy , Humans , Male , Risk Factors , Thrombotic Microangiopathies/diagnosis , Thrombotic Microangiopathies/etiology , Thrombotic Microangiopathies/pathology , Thrombotic Microangiopathies/therapy , Transplantation Conditioning
6.
Target Oncol ; 10(4): 487-99, 2015 Dec.
Article in English | MEDLINE | ID: mdl-25922090

ABSTRACT

With the incorporation of targeted therapies in routine cancer therapy, it is imperative that the array of toxicities associated with these agents be well-recognized and managed, especially since these toxicities are distinct from those seen with conventional cytotoxic agents. This review will focus on these renal toxicities from commonly used targeted agents. This review discusses the mechanisms of these side effects and management strategies. Anti-vascular endothelial growth factor (VEGF) agents including the monoclonal antibody bevacizumab, aflibercept (VEGF trap), and anti-VEGF receptor (VEGFR) tyrosine kinase inhibitors (TKIs) all cause hypertension, whereas some of them result in proteinuria. Monoclonal antibodies against the human epidermal growth factor receptor (HER) family of receptors, such as cetuximab and panitumumab, cause electrolyte imbalances including hypomagnesemia and hypokalemia due to the direct nephrotoxic effect of the drug on renal tubules. Cetuximab may also result in renal tubular acidosis. The TKIs, imatinib and dasatinib, can result in acute or chronic renal failure. Rituximab, an anti-CD20 monoclonal antibody, can cause acute renal failure following initiation of therapy because of the onset of acute tumor lysis syndrome. Everolimus, a mammalian target of rapamycin (mTOR) inhibitor, can result in proteinuria. Discerning the renal adverse effects resulting from these agents is essential for safe treatment strategies, particularly in those with pre-existing renal disease.


Subject(s)
Antineoplastic Agents/adverse effects , Kidney Diseases/chemically induced , Molecular Targeted Therapy/adverse effects , Vascular Endothelial Growth Factor A/antagonists & inhibitors , Animals , Antineoplastic Agents/therapeutic use , Humans , Kidney Neoplasms/drug therapy , Kidney Neoplasms/pathology
7.
J Natl Compr Canc Netw ; 12(8): 1077-81, 2014 Aug.
Article in English | MEDLINE | ID: mdl-25099440

ABSTRACT

Ipilimumab, a monoclonal antibody that blocks cytotoxic T-lymphocyte-associated antigen-4, leading to enhanced T-cell activation and proliferation, is associated with improved overall survival in melanoma. Its use can result in immune-related adverse events, the most common of which are skin rash, diarrhea, and colitis. Ipilimumab-induced hypophysitis is uncommon, mostly involves anterior pituitary, and is associated with abnormalities in pituitary MRI, whereas uveitis has been rarely reported. These immune-related adverse events occur during therapy. This report describes a patient who developed uveitis and hypophysitis involving both anterior and posterior pituitary, without MRI findings more than 3 weeks after the fourth dose of ipilimumab. This case illustrates the unusual presentation of and diagnostic challenges associated with ipilimumab-induced immune-related adverse events.


Subject(s)
Antibodies, Monoclonal/adverse effects , Drug-Related Side Effects and Adverse Reactions/pathology , Exanthema/pathology , Melanoma/drug therapy , Antibodies, Monoclonal/administration & dosage , CTLA-4 Antigen/antagonists & inhibitors , CTLA-4 Antigen/immunology , Drug-Related Side Effects and Adverse Reactions/immunology , Exanthema/chemically induced , Exanthema/immunology , Humans , Ipilimumab , Male , Melanoma/complications , Melanoma/pathology , Middle Aged , Pituitary Diseases/chemically induced , Pituitary Diseases/pathology , Uveitis/chemically induced , Uveitis/pathology
8.
J Prim Care Community Health ; 2(3): 157-62, 2011 Jul 01.
Article in English | MEDLINE | ID: mdl-23804795

ABSTRACT

CONTEXT: The Kidney Disease Outcomes and Quality Initiative guidelines are the most widely disseminated guidelines regarding the clinical evaluation and management of chronic kidney disease (CKD). PURPOSE: Assess the prevalence of diagnosis and staging of CKD by primary care providers (PCPs). METHODS: For the purpose of this assessment, stage 3 CKD was defined as an estimated glomerular filtration rate (eGFR) between 30 and 59 mL/min/1.73 m(2) for at least 3 months. Eligible individuals were 1447 white, nondiabetic patients 40-74 years of age. RESULTS: Information on a random sample of 110 patients was analyzed. Chronic kidney disease was reported in 22% of the patients, whereas only 7% of patients had both CKD and stage 3 reported in their medical record. PCPs were significantly more likely to record CKD in male than in female patients (79% vs 34%; P < .001). Patients who had CKD recorded were significantly more likely to be referred to a nephrologist (46% vs 3%; P < .001). Even among patients who had a diagnosis of coronary artery disease, were older, or had lower eGFR, a diagnosis of CKD was less likely to be recorded. Only 22% had their serum phosphorus, 12% their parathyroid hormone, and 64% a urinalysis recorded. CONCLUSIONS: This study found that the prevalence of recording CKD and staging by PCPs was low. Primary care providers were more likely to record CKD in male than in female patients. Finally, testing for bone disease is underperformed. There is a need to identify mechanisms to improve evaluation and management of CKD by PCPs.

9.
J Clin Oncol ; 24(1): 59-63, 2006 Jan 01.
Article in English | MEDLINE | ID: mdl-16314616

ABSTRACT

PURPOSE: Lung cancer is the leading cause of cancer-related death in women. Hormone replacement therapy (HRT) is frequently prescribed to postmenopausal women, but there is little data on its effect on lung cancer. Hence, we conducted a retrospective study to examine the impact of HRT on the natural history of lung cancer. METHODS: We conducted a retrospective chart review of women diagnosed with lung cancer between January 1994 and December 1999. Data collected included age, stage, past history of cancer, smoking history, family history of cancer, HRT use, treatment, and overall survival. The effects of various clinical features on survival were examined using Cox proportional hazards regression models. RESULTS: Four hundred ninety-eight women (median age, 67 years; range, 31 to 93 years) with lung cancer were included. A history of smoking was present in 429 women (86%), whereas 86 women (17%) had taken HRT. Women with lung cancer who received HRT were younger than women with lung cancer who never received HRT (63 v 68 years old, respectively; P < .0001). Overall survival was significantly higher in patients with no HRT compared with patients who received HRT (79 v 39 months, respectively; hazard ratio = 1.97; 95% CI, 1.14 to 3.39). This effect seemed to be more pronounced in women with a smoking history. CONCLUSION: HRT may affect outcomes from lung cancer adversely. Further studies examining the role of HRT use on outcomes from lung cancer, especially in women with a history of smoking, are urgently needed to clarify this important problem.


Subject(s)
Estrogen Replacement Therapy/adverse effects , Lung Neoplasms/mortality , Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Receptors, Estrogen/analysis , Retrospective Studies , Smoking/adverse effects
10.
Am J Clin Oncol ; 27(5): 452-6, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15596909

ABSTRACT

Prediction of outcome in patients with meningiomas remains a significant problem to date. We have evaluated the role of symptoms at presentation and overexpression of her-2/neu overexpression as independent prognostic factors in meningiomas. In a retrospective study on patients with biopsy-proven diagnosis of meningioma, her-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of > or =2+ was considered positive for overexpression. Two hundred thirty-seven patients thus identified between January 1986 and December 1999 included 149 females and 88 males, with a mean age of 63.44 years. Survival was estimated using the Kaplan-Meier method. Incidence of meningiomas in females (62.8%) was significantly greater than in males. Focal neurodeficits, headache, and seizures (39.66%) were the most common presenting complaints and were not related to tumor behavior/outcome. Syncope at presentation was associated with a decreased survival, but this symptom constituted only 2.53% of the total, so reliable conclusions could not be drawn. Only 6 (2.53%) specimens revealed HER-2/neu overexpression by IHC. HER-2/neu overexpression is not a predictor of tumor behavior and has no role as a prognostic factor in meningiomas. Syncope as the clinical presentation at diagnosis may predict a poor outcome, but needs further investigation.


Subject(s)
Meningeal Neoplasms/metabolism , Meningioma/metabolism , Receptor, ErbB-2/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Meningeal Neoplasms/diagnosis , Meningeal Neoplasms/mortality , Meningioma/diagnosis , Meningioma/mortality , Middle Aged , Prognosis , Retrospective Studies , Survival Analysis , Syncope/etiology
11.
Anticancer Res ; 24(1): 333-7, 2004.
Article in English | MEDLINE | ID: mdl-15015617

ABSTRACT

PURPOSE: The aim of this study was to determine the incidence of HER-2/neu, VEGF and CD117 overexpression in soft tissue sarcomas (STS) and to study the effect of this overexpression, if present, on survival in patients with specific histological subtypes of STS. MATERIALS AND METHODS: We conducted a retrospective observational study on patients diagnosed with STS during the period of 1986-2001. HER-2/neu overexpression was measured in these patients by immunohistochemistry (IHC) using the Hercep test developed by DAKO. VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). Immunohistochemical staining for c-kit was performed using a 1:250 dilution of the rabbit polyclonal antibody A4502 (IMPATH, CA) with the EnVision detection system. RESULTS: Two hundred and seventy three patients were diagnosed as having STS between 1986 and 2001, however of these patients, only 90 (51 females and 49 males) had enough sample available for testing. Patients who overexpressed VEGF had a significantly shorter survival (23 vs. 52 months; p=0.01). There was no effect of overexpression of either CD117 or HER-2/neu on survival. Studying the individual histological subtypes we found that, in malignant fibrous histiocytoma, overexpression of either VEGF or CD117 increased survival (41.3 vs. 19.5 months, p=0.01; and 84.5 vs. 17 months, p=0.006 respectively). In leiomyosarcoma, VEGF overexpression significantly decreased survival (7.5 vs. 76 months, p=0.03), while CD117 overexpression significantly increased survival (70.9 vs. 46.3 months, p=0.03). CONCLUSION: VEGF overexpression is associated with an adverse outcome in STS. Whether this is true of any particular histological subtype is unclear and needs further investigation. Also, site-specific agents targeting these three bio-markers (alone or with conventional therapy) may have a therapeutic role and need to be elaborated in future clinical trials.


Subject(s)
Proto-Oncogene Proteins c-kit/biosynthesis , Receptor, ErbB-2/biosynthesis , Sarcoma/metabolism , Soft Tissue Neoplasms/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Humans , Infant , Male , Middle Aged , Retrospective Studies , Survival Rate
12.
J Cancer Res Clin Oncol ; 130(2): 80-6, 2004 Feb.
Article in English | MEDLINE | ID: mdl-14634801

ABSTRACT

PURPOSE: To determine the prevalence and evaluate the possible prognostic value of the molecular targets in malignant melanoma, we studied the overexpression of HER-2/neu, c-Kit, and vascular endothelial growth factor (VEGF) in this patient population. MATERIALS AND METHODS: Overexpression of HER-2/neu, c-Kit, and VEGF was evaluated using immunohistochemical assays in 202 archival tissue specimens. RESULTS: Only two patients (0.9%) revealed HER-2/neu overexpression, whereas 46 (22.8%) revealed c-Kit and 42 (20.8%) specimens showed VEGF overexpression. Multivariate analysis performed did not show a significant difference in survival between c-Kit-positive and c-Kit-negative groups (P = 0.36) and VEGF-positive and VEGF-negative groups (P = 0.25). Interestingly, c-Kit was more likely to be overexpressed in the superficial spreading type and VEGF was overexpressed preferentially in the amelanotic melanoma type. CONCLUSIONS: HER-2/neu has no role in melanogenesis. Both c-Kit (expressed in superficial spreading disease) and VEGF (expressed in amelanotic melanoma) may have significant therapeutic implications as molecular targets, which warrants further investigation.


Subject(s)
Biomarkers, Tumor/analysis , Melanoma/chemistry , Proto-Oncogene Proteins c-kit/analysis , Receptor, ErbB-2/analysis , Vascular Endothelial Growth Factor A/analysis , Biopsy , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , Male , Medical Records , Melanoma/diagnosis , Middle Aged , Retrospective Studies , Survival Analysis , Up-Regulation
13.
J Cancer Res Clin Oncol ; 130(1): 52-6, 2004 Jan.
Article in English | MEDLINE | ID: mdl-14600832

ABSTRACT

PURPOSE: To evaluate the prevalence and role of vascular endothelial growth factor (VEGF) overexpression in soft tissue sarcoma (STS). PATIENTS AND METHODS: VEGF expression was detected by the avidin-biotin-complex method using Santa Cruz biotechnology (SC 7629). The expression of VEGF was assessed according to the percentage of immunoreactive cells: more than 10% of the cells staining were graded as positive. No detectable staining or <10% (of cells) staining was graded as negative. RESULTS: Two hundred and seventy-three patients (164 females and 109 males) with a mean age of 56 years (range: 1-93 years) were included in the study. Sixty-eight of the 273 (24.91%) patients diagnosed with STS between 1986 and 2001 revealed VEGF overexpression. VEGF overexpression was predominantly seen in 30% (15/50) of patients with malignant fibrous histiocytoma (MFH), 20.45% (9/44) of dermatofibrosarcomas (DFS), 25% (9/36) of leiomyosarcomas (LMS), and 30% (6/20) of patients with carcinosarcomas (CS). Despite overexpression being seen in about a quarter of patients with STS, VEGF overexpression was of prognostic value in only those patients with the LMS histologic type, as VEGF overexpression was associated with a shorter survival in this subgroup( P=0.01, by log-rank sum test). CONCLUSION: Twenty-four point nine percent of STS overexpress VEGF and interestingly there is diversity seen in VEGF expression amongst the various histologic subtypes of STS. LMS, CS, and MFH are more likely to reveal overexpression of VEGF than the other histologic subtypes. There was no relationship between survival and VEGF status in any subtype of STS, except LMS. There is an urgent need for larger studies to validate our findings. In addition, randomized clinical trials evaluating the efficacy of angiogenesis inhibitors in soft tissue sarcomas, especially LMS, are warranted.


Subject(s)
Biomarkers, Tumor/analysis , Leiomyosarcoma/chemistry , Sarcoma/chemistry , Vascular Endothelial Growth Factor A/analysis , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Female , Gene Expression Regulation, Neoplastic , Humans , Infant , Male , Middle Aged , Up-Regulation
14.
Anticancer Res ; 23(5A): 4023-6, 2003.
Article in English | MEDLINE | ID: mdl-14666713

ABSTRACT

BACKGROUND: Molecular changes associated with the transition of melanoma cells from radial to vertical growth phase are not defined. To evaluate the role of VEGF in melanogenesis and determine its possible diagnostic and prognostic implications, we analyzed overexpression of VEGF in 202 cases of melanoma. MATERIALS AND METHODS: Overexpression of VEGF was evaluated in 202 archival paraffin-embedded tissue specimens using an avidin-biotin immunohistochemical (IHC) assay. RESULTS: Of the 202 melanoma specimens, 42 (20.8%) showed evidence of VEGF overexpression on IHC testing. Multivariate analysis performed using Cox proportional hazards method did not show a statistically significant survival difference between the VEGF-positive and negative groups (p = 0.25). CONCLUSION: Although of no significant prognostic value, VEGF may have critical therapeutic implications as a molecular target since it is expressed in about 20% of melanomas. The role of target-specific therapies against VEGF in malignant melanoma warrants further investigations.


Subject(s)
Melanoma/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Male , Melanoma/pathology , Middle Aged , Prognosis , Proportional Hazards Models , Retrospective Studies , Sex Factors , Survival Rate
15.
In Vivo ; 17(5): 389-92, 2003.
Article in English | MEDLINE | ID: mdl-14598600

ABSTRACT

The examination of Prussian-blue-stained bone marrow aspirates for the presence or absence of histiocytic iron granules has been considered the gold standard in evaluating iron-depeleted states. We performed this study to evaluate the predictive accuracy of absent stainable bone marrow iron for iron deficiency anemia (IDA). A retrospective study was performed on an unselected series of 53 consecutive bone marrow biopsy specimens. Only those patients who had totally depleted iron stores and who had iron studies done within 6 months of bone marrow biopsy were included in the study. Based on these criteria, 12 patients were found eligible. After complete evaluation to determine the cause of the patient's illness, the final diagnosis was IDA in only 6 patients (50%). There was no significant difference between the two groups as regards hemoglobin level, reticulocyte count, serum iron levels, total iron binding capacity, red blood cell mean corpuscular volume, ferritin and the transferrin saturation levels. The finding of absent bone marrow iron stores is not necessarily predictive of iron deficiency anemia. The finding of absent stores of iron in the bone marrow needs to be taken in conjunction with other laboratory findings and the clinical scenario while making a diagnosis of IDA, since certain other hematological diseases may co-exist.


Subject(s)
Anemia, Iron-Deficiency/diagnosis , Bone Marrow/pathology , Iron/metabolism , Anemia, Iron-Deficiency/blood , Bone Marrow/metabolism , Bone Marrow Examination , Female , Humans , Male , Predictive Value of Tests , Prussian Blue Reaction , Reproducibility of Results
16.
Anticancer Res ; 23(3B): 2671-4, 2003.
Article in English | MEDLINE | ID: mdl-12894556

ABSTRACT

BACKGROUND: Hepatocellular carcinoma has an overall 5-year survival of less than 5%. Similarly, pancreatic cancer has a mortality: incidence ratio of 0.99. The aim of this study was to determine the prevalence of HER-2/neu and c-kit (CD117) overexpression and to identify a possible predictive role in patients with these two malignancies. MATERIALS AND METHODS: We performed a retrospective study on archival specimens of subjects with hepatocellular and pancreatic carcinoma. HER-2/neu and CD117 overexpression were evaluated by immunohistochemistry. RESULTS: Thirty-three patients with pancreatic carcinoma and 25 patients with hepatocellular carcinoma were identified. The mean age was 71.7 years for patients with pancreatic carcinoma and 66 years for patients with hepatocellular carcinoma. Two patients with hepatocellular carcinoma and none with pancreatic cancer overexpressed HER-2/neu, while 2 patients with pancreatic carcinoma and 1 patient with hepatocellular carcinoma overexpressed CD117. CONCLUSION: HER-2/neu and CD117 are not significantly overexpressed in either cancer. There appears to be no role for the use of trastuzumab in either malignancy. Similarly, while there appears to be no role for tyrosine kinase inhibitors in the treatment of hepatocellular carcinoma, further larger studies are necessary in pancreatic adenocarcinoma.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Liver Neoplasms/metabolism , Pancreatic Neoplasms/metabolism , Receptor, ErbB-2/biosynthesis , Adult , Aged , Aged, 80 and over , Female , Humans , Immunohistochemistry , Infant , Male , Middle Aged , Retrospective Studies
17.
Am J Clin Oncol ; 26(2): 188-91, 2003 Apr.
Article in English | MEDLINE | ID: mdl-12714894

ABSTRACT

Sarcomas currently represent 1% of adult malignancies and 15% of pediatric malignancies. To determine the prevalence of HER-2/neu overexpression by the histologic type and to identify a possible predictive role in patients with sarcoma, we performed a retrospective study on subjects with a biopsy-proven diagnosis of a soft tissue sarcoma. HER-2/neu overexpression was evaluated using immunohistochemistry (IHC) performed on paraffin-embedded specimens. An IHC score of 2+ or greater was considered positive for overexpression. Two hundred seventy-three patients with soft tissue sarcoma were identified (164 females, 109 males) with a mean age of 56 (range: 1-93). The most common tumors identified were malignant fibrous histiocytoma (MFH) (18.3%), dermatofibrosarcoma (DFS) (16.1%), leiomyosarcoma (13.2%) and carcinosarcomas (CS) (7.3%). Of the 273 specimens, 29 (10.6%) revealed HER-2/neu overexpression. CS, MFH, and DFS specimens showed the highest incidence of HER-2/neu overexpression (40%, 26%, and 18.2%, respectively). The incidence of HER-2/neu overexpression was found to be significantly higher in patients with a survival of less than 8 months (p = 0.035). This demonstrates that HER-2/neu overexpression is preferentially seen in certain soft tissue sarcomas, and when present is associated with a poorer prognosis in patients with sarcoma. Further studies would delineate whether HER-2/neu overexpression renders sarcomas chemoresistant and thus adversely affects outcome. In addition, there may be a role for Herceptin (trastuzumab) alone, or in combination with conventional therapy, in patients with CS, MHF, and DFS.


Subject(s)
Receptor, ErbB-2/metabolism , Sarcoma/metabolism , Adolescent , Adult , Aged , Aged, 80 and over , Carcinosarcoma/metabolism , Child , Child, Preschool , Dermatofibrosarcoma/metabolism , Female , Histiocytoma, Benign Fibrous/metabolism , Humans , Immunohistochemistry , Infant , Leiomyosarcoma/metabolism , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Retrospective Studies , Sarcoma/pathology , Survival Analysis
18.
Int J Cardiol ; 88(1): 1-9, 2003 Mar.
Article in English | MEDLINE | ID: mdl-12659977

ABSTRACT

The endothelium is a dynamic organ and responds to various physical and humoral conditions. The endothelium secretes several biologically active substances, both vasoconstrictors and vasodilators, which control these processes. Endothelial function is most commonly assessed as the vasodilatory response to stimuli. Several endothelium-dependent agonists have been identified, each of which acts through a membrane receptor. Nitric oxide which is continuously synthesized by the endothelium has a wide range of biological properties that maintain vascular homeostasis. It is a potent vasodilator and inhibitor of platelet aggregation and thus has an important protective role. Endothelial dysfunction in hypercholesterolemic patients is in large part due to a reduced bioavailability of NO. Traditional coronary risk factors, especially hypercholesterolemia, produce endothelial dysfunction even in patients with normal blood vessels. The underlying mechanisms involve a local inflammatory response, release of cytokines and growth factors, activation of oxidation-sensitive mechanisms in the arterial wall, modulation of intracellular signaling pathways, increased oxidation of low-density lipoprotein cholesterol, and quenching of nitric oxide. Clinical studies have shown a significant improvement in endothelial dysfunction following lowering of serum cholesterol levels, infusion of nitric oxide donors like L-arginine and exercise training. Clinical trials are underway examining the role of endothelin-1 receptor antagonists like bosentan in the prevention of graft atherosclerosis.


Subject(s)
Cardiovascular Diseases/metabolism , Cardiovascular Diseases/physiopathology , Endothelium, Vascular/metabolism , Endothelium, Vascular/physiopathology , Lipid Metabolism , Lipids/physiology , Cardiovascular Diseases/drug therapy , Endothelium, Vascular/drug effects , Humans , Nitric Oxide/pharmacology , Nitric Oxide/therapeutic use , Vasodilator Agents/pharmacology , Vasodilator Agents/therapeutic use
19.
Med Oncol ; 19(4): 233-7, 2002.
Article in English | MEDLINE | ID: mdl-12512917

ABSTRACT

Pancreatic cancer is the fourth leading cause of cancer death in both men and women with a mortality incidence ratio of 0.99. In an effort to describe the role of clinical features at initial presentation, we conducted a retrospective observational study in patients with a biopsy-proven diagnosis of adenocarcinoma of the pancreas. Between 1986 and 2001, 308 patients (160 males, 148 females) were diagnosed with pancreatic adenocarcinoma. The mean age at diagnosis was 70.1 yr (range: 34-96 yr). The mean survival was 7.6 mo (range: 0-97 mo). Statistical analysis was performed using log-rank tests and analysis of variance. As expected, age at diagnosis was a significant factor affecting survival, with older patients doing relatively poorly (p < 0.05). Patients with a good performance status performed significantly better than those with a poor performance status (p < 0.01). In addition, the presence of the tumor in the head of the pancreas was a predictor for improved survival (p < 0.01). Although smoking increased the chances of detection at an earlier age, neither diabetes mellitus nor a positive smoking history had a statistically significant effect on the survival. Pancreatic adenocarcinoma is a disease of the elderly associated with a poorer outcome. Knowledge of possible clinical predictors of survival may lead to better patient counseling regarding prognosis.


Subject(s)
Adenocarcinoma/etiology , Pancreatic Neoplasms/etiology , Adenocarcinoma/complications , Adenocarcinoma/therapy , Adult , Aged , Aged, 80 and over , Diabetes Complications , Female , Humans , Male , Middle Aged , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/therapy , Retrospective Studies , Risk Factors , Sex Factors , Smoking/adverse effects
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