Orbital Pheochromocytoma Metastasis in 2 Patients With Known Pheochromocytoma.

Two patients with previously diagnosed pheochromocytoma presented with facial pain and ptosis. Imaging revealed orbital lesions. Both patients were referred for surgical evaluation of the orbital mass. Surgical excision was performed for both. Pathology confirmed metastatic pheochromocytoma. Pheochromocytomas commonly metastasize to bone, liver, and other tissues. Five cases of metastasis to orbital bone have been previously described. These 2 cases are unique in that the metastases were not hormonally active, presented soon after initial diagnosis, and were treated palliatively with surgical excision. Previous treatment of orbital bony metastasis used radiotherapy. These cases demonstrate that surgical resection is a viable treatment option in these situations. Orbital metastasis of pheochromocytomas should be considered with the appropriate clinical presentation. These are the first documented cases of intraorbital metastasis, separate from the bony walls. Previously, orbital bony wall metastases were treated with radiation. Surgical excision is a viable option for treatment of such metastases.Orbital involvement should be considered in patients with systemic disease presenting with new ocular findings.

A phase II trial of bevacizumab and everolimus as treatment for patients with refractory, progressive intracranial meningioma.

Meningiomas that progress after standard therapies are challenging with limited effective chemotherapy options. This phase II trial evaluated the efficacy of everolimus plus bevacizumab in patients with recurrent, progressive meningioma after treatment with surgical resection and local radiotherapy when appropriate. Patients with recurrent meningioma (WHO grade I, II, or III) following standard treatments with surgical resection and radiotherapy received bevacizumab (10 mg/kg IV days 1 and 15) and everolimus (10 mg PO daily) each 28 day cycle. Evaluation of response occurred every 2 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response rate, overall survival and safety. Seventeen patients with a median age of 59 years (29-84) received study treatment. WHO grades at study entry included: I, 5 (29 %); II, 7 (41 %); III, 4 (24 %); unknown, 1 (6 %). Patients received a median of 8 cycles (1-37); all patients are off study treatment. A best response of SD was observed in 15 patients (88 %), and 6 patients had SD for >12 months. Overall median PFS was 22 months (95 % CI 4.5-26.8) and was greater for patients with WHO grade II and III compared to grade I tumors (22.0 months vs 17.5 months). Four patients discontinued treatment due to toxicity (proteinuria, 2; colitis, 1, thrombocytopenia, 1). However, other grade 3 toxicity was uncommon, and no patient had grade 4 toxicity. The combination of everolimus and bevacizumab was well-tolerated, and produced stable disease in 88 % of patients; the median duration of disease stabilization of 10 months (2-29). The median PFS from this prospective trial was similar to previous retrospective reports of bevacizumab in the treatment of recurrent meningioma.

Hepatitis C and neutropenia.

PURPOSE OF REVIEW: This review describes the pathogenesis and therapeutic implications of neutropenia in patients with hepatitis C. RECENT FINDINGS: Mild-to-moderate neutropenia is increasingly recognized as the hepatitis C population has caused increased cirrhosis. Multiple mechanisms for the neutropenia have been postulated, with recent evidence pointing toward a combination of hypersplenism, autoimmunity, and direct viral infection of bone marrow cells. Advances in antiviral therapy are associated with worsened neutropenia and dose modification. Severe neutropenia is underreported and is generally not associated with increased rates of infection. SUMMARY: Although neutropenia is common in hepatitis C patients it generally has a benign course and may not prohibit antiviral therapy.

Senior adult oncology, version 2.2014: clinical practice guidelines in oncology .

Cancer is the leading cause of death in older adults aged 60 to 79 years. The biology of certain cancers and responsiveness to therapy changes with the patient's age. Advanced age alone should not preclude the use of effective treatment that could improve quality of life or extend meaningful survival. The challenge of managing older patients with cancer is to assess whether the expected benefits of treatment are superior to the risk in a population with decreased life expectancy and decreased tolerance to stress. These guidelines provide an approach to decision-making in older cancer patients based on comprehensive geriatric assessment and also include disease specific issues related to age in the management of some cancer types in older adults.

Severe neutropenia in patients with chronic hepatitis C: a benign condition.

BACKGROUND/AIMS: Patients with chronic hepatitis C virus (HCV) infection may develop neutropenia, which can delay or prevent treatment. Severe neutropenia, absolute neutrophil counts (ANC) ≤0.500 × 10(9)/l, is a rare finding, with only two isolated reports published in the literature. The aim of this study was to evaluate the incidence and natural history of severe neutropenia in hepatitis C patients. METHODS: The records of 685 patients with active HCV were reviewed to identify those with severe neutropenia. The laboratory parameters and clinical history data of patients with severe neutropenia were then compared to a cohort of patients with HCV patients who had the more common minor neutropenia (ANC = 1.000-1.500 10(9)/l). RESULTS: There was no significant difference in race, MELD (Model for End Stage Liver Disease) scores, portal hypertension, splenomegaly, viral load, viral type, or hemoglobin or platelet levels. Neither group suffered serious systemic infections. CONCLUSIONS: Severe neutropenia in HCV patients is underreported and not associated with serious HCV complications such as elevated MELD score or cirrhosis. Serious infection is rare and patients respond well to granulocyte colony-stimulating factor. Severely neutropenic patients with HCV appear to have a benign course and may be candidates for antiviral therapy.

Evaluation of a method to improve the consent process: improved data retention with stagnant comprehension.

Our study explored whether a simple, cost-effective intervention directed only at physicians could improve patient comprehension with informed consent process. In our medical university oncology clinic, we performed a baseline survey on 69 patients receiving new therapy, testing for comprehension of the important components of the informed consent process. We then instituted a three-part intervention, including (1) physician education, (2) an available toxicity list, and (3) a checklist to ensure physician compliance. We repeated the survey on 54 consecutive patients who consented for treatment, evaluating four outcomes. The intervention produced a 38 % improvement in patients' listing of toxicities (p = 0.0003) and no significant improvements in the understanding of therapeutic goals, likelihood of achieving those goals, and confidence in their understanding of treatment. Our three-part intervention, directed solely at physicians, improved patients' recall of toxicity data but did not influence the other important areas of patient comprehension within the informed consent process.

Treatment of non-small cell lung cancer in the older patient.

Lung cancer is a disease of the elderly, with a median age at diagnosis of 70 years. However, there is a dearth of good quality evidence to guide treatment in this population and most of the data are extrapolated from younger patients. Current research is directed toward establishing simplified instruments to quantify fitness of older patients for various forms of therapy. Although current evidence suggests that outcomes after standard therapy are similar to those seen in younger patients, older patients have an increased incidence of adverse events. Until better predictive markers are available to guide treatment, therapy should be individualized using available instruments, including a comprehensive geriatric assessment. If an older patient is deemed to be fit, it is reasonable to use the treatment options recommended for younger individuals. This article summarizes the available data on the treatment of non-small cell lung cancer in the older patient.

Cancer- and chemotherapy-induced anemia.

Anemia is prevalent in 30% to 90% of patients with cancer. Anemia can be corrected through either treating the underlying cause or providing supportive care through transfusion with packed red blood cells or administration of erythropoiesis-stimulating agents (ESAs), with or without iron supplementation. Recent studies showing detrimental health effects of ESAs sparked a series of FDA label revisions and a sea change in the perception of these once commonly used agents. In light of this, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Cancer- and Chemotherapy-Induced Anemia underwent substantial revisions this year. The purpose of these NCCN Guidelines is twofold: 1) to operationalize the evaluation and treatment of anemia in adult cancer patients, with an emphasis on those who are receiving concomitant chemotherapy, and 2) to enable patients and clinicians to individualize anemia treatment options based on patient condition.

The Effect of Race on Outcomes in Veterans With Hepatocellular Carcinoma at a Single Center.

Background: Black patients have a higher incidence and mortality associated with hepatocellular carcinoma (HCC) compared with that of White patients in many retrospective analyses. This study sought to determine whether veterans treated for HCC at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee showed similar disparities in terms of stage at diagnosis, type of therapy received, and overall survival (OS). Methods: A retrospective review evaluated 132 White and 95 Black patients treated for HCC between 2009 and 2021. We evaluated the impact on OS of age, sex, comorbidities, tumor stage, α-fetoprotein level, method of diagnosis, first-line treatment, systemic treatment, and surgical options offered. Kaplan-Meier analysis was used to investigate differences in OS and cumulative hazard ratio for death. Cox regression multivariate analysis evaluated discrepancies among investigated variables. Results: The study found no significant difference in OS between Black and White veterans with HCC. Significant differences were found in who received surgical treatment and systemic therapy. More White veterans received any form of treatment compared with Black veterans (P < .001), and White veterans were more likely to undergo surgical resection and transplant (P = .052). There was no significant difference between age or stage at diagnosis, receipt of systemic therapy, alcohol, tobacco or drug use, HIV coinfection, or cirrhosis. Conclusions: Black veterans with HCC at the Memphis VAMC were less likely to receive any form of treatment, surgical resection, or transplant compared with White veterans, but this did not have a statistically significant effect on OS.

Chronic idiopathic neutrophilia: experience and recommendations.

OBJECTIVES: To distinguish chronic idiopathic neutrophilia (CIN) in a cost-effective manner from neutrophilia caused by important underlying illnesses. METHODS: This was a retrospective review of patients visiting a Veterans Affairs Medical Center over the last 10 years with a diagnosis of leukocytosis or myeloproliferative disorder. Of this group, fifty-seven patients from 1999 to 2008 were identified with CIN. Clinical and laboratory parameters were examined to identify CIN and establish its course. Eighty-one patients who presented from 2005 to 2010 with myeloproliferative disorders were also studied at time of diagnosis to determine any possible confusion with CIN. RESULTS: The patients with CIN were followed for a mean of ≥ 7.3 years without progression to other serious disorders. Compared to non-CIN patients evaluated for neutrophilia, in multiple logistic regression analyses, smoking (P = .001) and increased BMI (P = .004) were significantly associated with CIN. No CIN patient developed a clinically apparent myeloproliferative disorder other than chronic myeloid leukemia (CML). Of the patients with myeloproliferative neoplasms reviewed at the time of their initial diagnosis, only CML occasionally presented with a picture consistent with CIN. For nonsmokers, the BMI of CIN patients was significantly higher than the average VA population (P < .001). CONCLUSION: Cigarette smoking and obesity are confirmed as factors associated with CIN and may be causative. CIN is unlikely to develop into a clinically recognizable myeloproliferative neoplasm other than CML. Cost-effective guidelines for the diagnostic evaluation of neutrophilia in otherwise healthy patients are presented.

Antiviral Therapy Improves Hepatocellular Cancer Survival.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is a common risk factor for hepatocellular cancer (HCC). Patients with HCV infection are at a higher risk of developing HCC because the virus induces fibrosis in the liver, which may lead to cirrhosis. Early treatment of HCV and achieving a sustained virologic response (SVR) may lead to decreased incidence and mortality associated with HCC. METHODS: We performed a retrospective review of patients at the Memphis Veterans Affairs Medical Center (VAMC) in Tennessee from November 2008 to March 2019 to determine whether treatment of HCV infection makes a difference in overall survival (OS) among patients who develop HCC. Patients were treated with an interferon-based regimen or direct-acting antiviral agents (DAAs). Among the patients with HCV infection who were treated, we identified those who did achieve or did not achieve SVR. RESULTS: We identified 111 patients with HCV and HCC; 68 were treated for HCV infection. Forty-eight patients received DAA and 20 patients received an interferon-based regimen and 51 achieved SVR. In a multivariate analysis accounting for severity of liver disease, treated patients had an improved 5-year OS rate, median 1338 days (95% CI, 966-3202) when compared with untreated patients whose median OS was 452 days (95% CI, 242-853) (P = .0005). The treatment group had a longer median progression-free survival (PFS) than did the nontreatment group (460 days [95% CI, 294-726] vs 286 days [95% CI, 205-405], P = .04). Patients with SVR had an increased 5-year OS compared with patients without SVR (median 1973 days [95% CI, 1222-NA] vs 470 days [95% CI, 242-853], P < .001). HCV treatment type (interferon vs DAA) was not found to be associated with either OS or PFS, regardless of time period. Advanced liver disease stage as characterized by a high model for end-stage liver disease (MELD) score (> 10) or high Child-Pugh score (B or C) was associated with worse survival outcome. CONCLUSIONS: A retrospective analysis of patients with HCV infection and HCC confirms that treatment of HCV infection leads to OS benefit among patients with HCC. We further demonstrate that patients with HCV infection who achieve SVR have an OS benefit over patients unable to achieve SVR. The type of treatment, DAA vs an interferon-based regimen, did not show a significant survival benefit.

Managing Massive Splenic Hematoma: Exploratory Laparotomy or Active Surveillance?

Splenic hematoma is a known complication of blunt force abdominal trauma. Traditional management of splenic hematomas has been primarily surgical. However, more recently, spleen-sparing management has been favored over surgical management for cases that meet certain criteria, with surgery now reserved for patients with complications. In this report, we present a case of a massive splenic hematoma that was managed conservatively and analyze the challenges faced in clinical decision making.

CIN or not: An approach to the evaluation and management of chronic idiopathic neutrophilia.

Neutrophilia refers to an increase in the number of circulating neutrophils in the peripheral blood. Some common etiologies include infection, inflammatory conditions, myeloproliferative disorders, malignancies, endocrinopathies, drugs, and anemia. Rare disorders such as leukocyte adhesion deficiency can also cause neutrophilia. In many cases, there is an elevation of neutrophil count that persists for months or even years with no clear underlying cause in an otherwise asymptomatic patient. This is referred to as chronic idiopathic neutrophilia (CIN). Despite being a condition encountered by many physicians, there is a paucity of literature addressing CIN. Certain conditions such as stress, exercise, smoking, obesity, and obstructive sleep apnea have been associated with CIN and may provide explanations for neutrophilia previously thought to be idiopathic. Herein, we present a review of the literature on CIN and propose a systematic approach to this commonly encountered clinical condition.

Rapid Response in a Patient with Relapsed/Refractory Multiple Myeloma Treated with BRAF/MEK Inhibitors.

Patients with relapsed and refractory multiple myeloma have a poor prognosis. The mitogen-activated protein kinase (MAPK) pathway has been implicated in the pathogenesis of multiple myeloma. Several mutations in this pathway can lead to its constitutive activation leading to oncogenesis. One such mutation is BRAFV600E which is a therapeutic target in the treatment of melanoma, lung cancer, colon cancer, thyroid cancer, and hairy cell leukemia. BRAFV600E-directed therapy currently does not have approval in multiple myeloma. It has been proposed that this mutation leads to proteasome inhibitor resistance. About 4-10% of multiple myeloma cases harbor the BRAFV600E mutation. Herein, we report a case of a patient with relapsed and refractory multiple myeloma who had a progression-free survival (PFS) of 8.5 months on BRAF-targeted therapy.

Liver Imaging Reporting and Data System in Patients at High Risk for Hepatocellular Carcinoma in the Memphis Veterans Affairs Population.

Although hepatocellular carcinoma can be difficult to detect, use of the LI-RADS algorithm could lead to earlier identification in at-risk patients.

ICU Deaths in Patients With Advanced Cancer.

BACKGROUND: A significant number of advanced cancer admissions to the intensive care unit (ICU) are inappropriate in that they do not result in prolonged survival. No clear consensus criteria for reasonable admissions of advanced cancer patients have been developed. METHOD: We established four criteria for reasonable admissions to ICU in patients who suffered from advanced, incurable cancer: post procedure complication, recent notification of cancer, ECOG performance status of 0-1, and life expectancy of more than 6 months. Based on these criteria, we reviewed the charts of all patients who died in the ICU at the University of Tennessee Health Science Center (UTHSC) affiliated Veteran's Affairs Medical Center between 10/2005 and 10/2010. We identified patients with advanced, incurable cancer and performed an in depth review of their charts. RESULTS: In the 421 charts of patients who died in our ICU between October 2005 and October 2010 we identified 52 patients admitted to the ICU with advanced, incurable cancer. 14 patients were diagnosed with cancer one month or less prior to admission. 21 patients had ECOG performance status of 0-1. 14 patients had life expectancy of more than 6 months and 8 patients were admitted for post procedure complication. 47% of patients who did not satisfy any of our reasonable admission criteria had APDs. CONCLUSIONS: Incorporating proposed admission criteria in ICU admission guidelines may prevent 37% of inappropriate, advanced cancer admissions to the ICU. A simple increase in numbers of APDs would not likely change significantly the numbers of inappropriate ICU admissions.

Investigating the prognostic value of KOC (K homology domain containing protein overexpressed in cancer) overexpression after curative intent resection of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic adenocarcinoma (PDAC) is now the third leading cause of cancer mortality in the United States. More than 80% of patients present with distant metastasis precluding surgical eligibility. Even among patients with localized disease deemed eligible for surgical resection, the median survival is only 22.8 months due to high recurrence rates. Identification of a biomarker correlated with patient specific prognosis upon initial diagnosis can serve as a way to individualize treatment options. METHODS: We performed a retrospective cohort study analyzing pathology of patients who underwent curative intent surgery for PDAC at Geisinger Medical Center from 1998-2011 to identify whether the expression of KOC can be predictive of patient specific prognosis. Tissue microarrays of specimens were assessed by immunohistochemistry. RESULTS: A total of 62 patients are included. Comparisons between groups on overall survival (OS) and progression free survival (PFS) are estimated using the Kaplan-Meier method and the log-rank test. Each biomarker was represented as low and high expression by categorizing the expression score at <4+ or >4+, based on intensity and extent of cells stained. 40 deaths occurred in the sample. Distant metastasis and differentiation (well/moderate vs. poor) were related to OS (P=0.0120, P=0.0086). Twenty-nine patients progressed in their disease. High/low KOC expression were significantly related to PFS (P=0.0556). Patients with a high KOC expression were more than 2 times more likely to progress compared to those with a low KOC expression (HR =2.04; 95% CI: 0.97, 4.29). CONCLUSIONS: Our data is suggestive of KOC being a useful prognostic biomarker for identifying those patients with PDAC who have a high risk for early progression and distant metastasis. Larger studies are needed to determine whether KOC can be a therapeutic target in the treatment of pancreatic cancer. Furthermore, considering high KOC expressers had a worse PFS than their counterparts, investigation regarding the use of KOC expression as a biomarker to preselect patients who may benefit most from neoadjuvant chemotherapy is warranted.

Modulation of the Fas signaling pathway by IFN-gamma in therapy of colon cancer: phase I trial and correlative studies of IFN-gamma, 5-fluorouracil, and leucovorin.

Potentiation of 5-fluorouracil/leucovorin (FUra/LV) cytotoxicity by IFN-gamma in colon carcinoma cells is dependent on FUra-induced DNA damage, the Fas death receptor, and independent of p53 and RNA-mediated FUra toxicity, which occurs in normal gastrointestinal tissues. This provides a rationale for enhancing the selective action of FUra/LV by IFN-gamma in the treatment of colorectal carcinoma. Based on results from our preclinical studies we designed a Phase I trial combining FUra (370 mg/m2) and LV (200 mg/m2), i.v. bolus daily x 5 days, with escalating doses of IFN-gamma (10-100 micro g/m2) s.c. on days 1, 3, and 5, every 28 days. Twenty-five patients with carcinomas were enrolled; 6 patients received IFN-gamma on days 1 and 3 only. The dose-limiting toxicity, stomatitis, occurred most frequently at 100 micro g/m2 IFN-gamma. Minor response or SD was observed in 2 of 9 patients and in 4 of 12 patients at dose levels of < or =50 micro g/m2 and > or =75 micro g/m2 IFN-gamma, respectively. Three evaluable chemonaive patients demonstrated partial response (2) or complete response (1). Serial plasma samples revealed peak FUra concentrations of >100 micro M; at 100 micro g/m2 IFN-gamma plasma concentrations >5 units/ml persisted for 6.5 h and >1 unit/ml for 28.5 h. The pharmacokinetic parameters of IFN-gamma correlated with a 2-3-fold up-regulation of Fas expression at 24 h in CD15+ cells in peripheral blood samples. Furthermore, clinically relevant IFN-gamma concentrations up-regulated Fas expression and sensitized HT29 colon carcinoma cells in vitro to FUra/LV cytotoxicity. On the basis of the modulation of Fas signaling, FUra/LV combined with IFN-gamma has shown activity in a Phase I trial in colorectal carcinoma and warrants additional evaluation in Phase II.