The objectives of the study are to assess the impact of HIV status on the outcome of patients wit... more The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced...
Developments in HIV-related medicine have significant implications for the practice of oncology. ... more Developments in HIV-related medicine have significant implications for the practice of oncology. Although HIV is a relatively new discipline within medicine, the identification and therapeutic targeting of HIV has been rapid. Furthermore, political lobbying has sculpted scientific research and patient care. Rational drug design has reduced morbidity and mortality to such an extent that the development of predictive surrogate endpoints has been necessary to enable randomised assessments of new protocols to continue. These studies now include the routine detection of resistance to tailor specific therapies to the patient. The involvement of affected communities in dynamically modelled studies have shown the efficacy of new, preventive strategies and debates about such approaches have improved the standard of care. In this review, we discuss what oncologists can learn from the HIV epidemic.
Non-AIDS-defining cancers are an important problem in HIV-infected patients. The occurrence of ne... more Non-AIDS-defining cancers are an important problem in HIV-infected patients. The occurrence of neuroendocrine (NE) tumors in sites other than the lung and skin has not been well characterized in the setting of concurrent HIV infection. HIV-positive patients with biopsy-confirmed NE tumors localized to the gastrointestinal tract were identified based on the personal archives of the authors. A retrospective chart review was performed, and data regarding demographics, HIV status, presenting symptoms and signs, diagnostic work-up, therapeutic interventions, and outcome were extracted. We identified 4 adult patients, mean age 42 years (range: 37-47) infected with HIV, who developed NE tumors originating in their gastrointestinal tact. They had only moderate immunosuppression with a median CD4 count of 497 cells/mm (range: 182-1100) and chronic HIV infection (2-15 years duration). Symptoms at presentation were nonspecific, including abdominal pain, diarrhea, weight loss, and rectal bleeding. A specialized diagnostic work-up was required, including serum chromogranin and urinary 5-hydroxyindoleacetic acid levels, colonoscopy, radioactive isotope scans, and the demonstration of NE differentiation in procured pathologic material. The spectrum of tumors ranged from benign (typical carcinoid) to highly aggressive neoplasms (NE carcinoma). Treatment with octreotide, surgical resection, or systemic chemotherapy provided effective symptomatic relief and was associated with a favorable outcome, despite metastases in 2 patients. These cases serve to broaden the spectrum of neoplasms that may be encountered in the current HIV era, and illustrate the difficulty in establishing the diagnosis of NE tumors in the context of HIV infection.
We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bro... more We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bronchoscopy and in whom Pneumocystis carinii pneumonia (PCP) and/or cytomegalovirus (CMV) were identified in bronchoalveolar fluid (BAL). CMV was identified by detection of early antigen fluorescent foci (DEAFF) testing in cell cultures of BAL fluid. The short- and long-term survival of all patients was similar regardless of whether PCP, CMV or both were detected at bronchoscopy. Ten out of 14 patients with CMV alone and 13 out of 26 with both CMV and PCP were treated with anti-CMV therapy, but the short- and long-term mortality was similar to that in patients who had no specific antiviral therapy. Extrapulmonary recurrence of CMV (retinitis or gastrointestinal disease) occurred in 22% of patients with evidence of CMV in BAL compared with 16% of those with PCP alone, but this difference was not statistically significant and this recurrence rate was independent of anti-CMV therapy. Detection of CMV shedding from more than one site (BAL, urine, throat or blood) was associated with a worse prognosis at 3 months than in patients in whom CMV was detected in BAL alone. It does not appear that finding CMV shedding is a guide to the cause of pneumonia or an indication for treatment in AIDS patients.
Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence ... more Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence in men with HIV infection. We performed a matched case-control study comparing outcomes in HIV-positive men and the general population with GCT, using three age and stage matched controls for each case. There was no difference in the 5-year GCT-free survival between cases and controls. However, overall survival was significantly decreased in the cases (log rank P=0.03). HIV was responsible for 70% of this mortality. The relapse-free survival for stage I patients treated with orchidectomy and surveillance was not affected by HIV status (log rank P=0.68). There was no difference in disease free survival in patients with metastatic disease (log rank P=0.78). The overall survival has not improved since the introduction of highly active antiretroviral therapy (log rank P=0.4). Thus, HIV-related GCT is not more aggressive than GCT in the general population.
Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is ass... more Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is associated with leucopenia; however, its effects on specific immune cell subsets are unclear. Alterations in immune cell subsets may contribute to tumour progression. Lymphocyte subsets (CD3, 4, 8, 19 and 56) were measured in 43 untreated MCRC patients who received sunitinib. The protocol included a structured treatment interruption of 5 weeks. Cell populations were measured at specific time points during sunitinib treatment and the treatment break. Sunitinib was associated with significant declines in total leucocyte (-48%), neutrophil (-62%), CD3 total T cell (-31%) and CD4 counts (32%; p < 0.05). There was no significant change in CD19 B lymphocyte, CD8 or CD56 natural killer cells. During the sunitinib-free interval, all parameters recovered to baseline. No patients developed opportunistic infections or neutropenic sepsis. The level of specific immune subsets at presentation or occurrence of a fall in specific counts had an effect on progression-free survival (p > 0.05). Sunitinib is associated with reversible inhibition of specific lymphocyte subsets which has implications for the immunological control of MCRC and its use in combination with other agents. Despite suppressive effects, there was no evidence of predisposition to immune suppressive-related infection.
The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conduc... more The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization.
AIDS-associated Kaposi&am... more AIDS-associated Kaposi's sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi's sarcoma. Of 5873 individuals with HIV-1 infection, 326 (6%) developed Kaposi's sarcoma; for 262 (80%) this was their first AIDS-defining illness. We did univariate and multivariate Cox regression analyses to identify covariates predictive of overall survival and validated our model with an independent data set of 446 patients with Kaposi's sarcoma. In the primary model, we developed a prognostic score from 0 to 15 starting at 10. Having Kaposi's sarcoma as the AIDS-defining illness (-3 points) and increasing CD4 count (-1 point for every complete 100 cells per mm3) improved prognosis; age of 50 years or older (2 points) and having another AIDS-associated illness at the same time (3 points) conveyed a poorer prognosis. In individuals with prognostic scores of 0, 5, 10, and 15, probability of survival at 1-year was 0.993, 0.967, 0.834, and 0.378, and at 5 years was 0.984, 0.918, 0.631, and 0.084, respectively. Increasing prognostic score by 1 increased 1-year death hazard ratio by 40% (95% CI 28-53%; bootstrapped hazard ratio 1.39, 1.25-1.51). The index had concordance of 76.8% (71.7-82.3). We identified four prognostic factors that can be used to obtain an accurate prognostic index at diagnosis of AIDS-associated Kaposi's sarcoma. This index is widely applicable and can be used to guide therapeutic options.
ABSTRACT In order to evaluate the negative predictive value of a low prostate-specific antigen (P... more ABSTRACT In order to evaluate the negative predictive value of a low prostate-specific antigen (PSA) for a positive bone scan, we performed a retrospective study in a patient material from the Umea region in Northern Sweden. We also evaluated whether different tumour grades could influence this predictive value. Four-hundred-and-forty-six patients of newly diagnosed prostate cancer were reviewed. We analysed different levels of PSA, tumour grade, tumour stage and combinations of these parameters for their use in making a positive bone scintigraphy (BS) prediction. Among 214 patients with PSA <20 ng/ml, 9 showed a positive BS. When tumours of grades 2 and 3 were excluded, the number of positive BS predictions decreased to 6. For 350 of these 446 patients, a classification according to TNM was available; 162 of these 350 had a PSA value <20 ng/ml, and when this group comprised only small and well-differentiated tumours (T1-2, G1), only one of the remaining 81 patients had a positive BS result. We conclude that in most patients with small and well-differentiated tumours (T1-2, G1) and PSA <20, BS staging need not be carried out.
JNCI Journal of the National Cancer Institute, 2006
From a cohort of 9621 human immunodeficiency virus type 1-infected individuals, we identified 61 ... more From a cohort of 9621 human immunodeficiency virus type 1-infected individuals, we identified 61 patients with primary central nervous system lymphoma (PCL) who had a median survival of 1.3 months. We compared clinicopathologic variables of patients who were treated in the pre-highly active antiretroviral therapy (HAART) and HAART eras and investigated whether exposure to antiretroviral agents with differing cerebrospinal fluid penetrations was associated with risk for PCL. All statistical tests were two-sided. Incidence of PCL was lower in the HAART era (1.2 cases per 1000 patient-years, 95% confidence interval [CI] = 0.8 to 1.9) than in the pre-HAART era (three cases per 1000 years, 95% CI = 2.1 to 4.0; P<.001), and overall survival was longer (median survival = 32 days, range = 5-315 days, versus 48 days, range = 15-1136 days; log rank P = .03). In the HAART era, fewer patients had prior acquired immunodeficiency syndrome-defining illnesses than in the pre-HAART era (64% versus 90%; P = .013), and patients were more likely to have the diagnosis of PCL confirmed histologically or by polymerase chain reaction (77% versus 26%; P<.001). Exposure to specific antiretroviral agents was not associated with risk for PCL.
A prognostic index for AIDS-associated Kaposi&amp... more A prognostic index for AIDS-associated Kaposi's sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) was based on routine clinical and laboratory characteristics. Because immune subset measurement is often performed in HIV-positive individuals, we examined whether these were predictive of mortality independently of the prognostic index, or could predict time to progression of KS. We performed univariate and multivariate Cox regression analyses on a data set of 326 individuals with AIDS-associated KS to identify immune subset covariates predictive of overall survival and time to progression. Adaptive (CD8 T cell and CD19 B cell) and innate (CD16/56 natural-killer cell) immune parameters were studied by flow cytometry. In univariate analyses, all three immune subsets had significant effects on overall survival (P < .025). In multivariate analyses including the prognostic index, only CD8 counts remained significant (P = .026), although its effect on the overall prognostic index is small. An increase of 100 cells/mm3 in the CD8 count confers a 5% improvement in overall survival. Individuals with a higher CD8 count did not have an increased time to progression. Patients who were already on HAART at the time of KS diagnosis did not have a shorter time to progression than those who were antiretroviral naïve at KS diagnosis. The CD8 count appears to provide independent prognostic information in individuals with AIDS-associated KS. Measurement of the CD8 count is clinically useful in patients with KS.
The use of transient elastography to assess liver stiffness measurement (LSM) has now become wide... more The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and cirrhosis (F4). A total of 22 studies were selected comprising 4,430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.
The objectives of the study are to assess the impact of HIV status on the outcome of patients wit... more The objectives of the study are to assess the impact of HIV status on the outcome of patients with non-small-cell lung cancer (NSCLC) in the era of highly active antiretroviral therapy (HAART). Patients diagnosed with HIV-related NSCLC in the HAART era (since January 1996) were identified from a prospective single-centre lung cancer database. The clinicopathological characteristics and outcome of each HIV-positive patient were compared to three age- and stage-matched HIV-negative controls with NSCLC who were diagnosed over the same time period and treated in an identical manner. The results showed that the two groups had similar disease characteristics and received a similar amount of chemotherapy. The median overall survival of the two groups was the same (4 months, log rank P=0.55). None of the HIV-positive patients developed an AIDS defining illness or died of HIV during treatment or follow-up. In conclusion, in this cohort, HIV status does not influence the prognosis of advanced...
Developments in HIV-related medicine have significant implications for the practice of oncology. ... more Developments in HIV-related medicine have significant implications for the practice of oncology. Although HIV is a relatively new discipline within medicine, the identification and therapeutic targeting of HIV has been rapid. Furthermore, political lobbying has sculpted scientific research and patient care. Rational drug design has reduced morbidity and mortality to such an extent that the development of predictive surrogate endpoints has been necessary to enable randomised assessments of new protocols to continue. These studies now include the routine detection of resistance to tailor specific therapies to the patient. The involvement of affected communities in dynamically modelled studies have shown the efficacy of new, preventive strategies and debates about such approaches have improved the standard of care. In this review, we discuss what oncologists can learn from the HIV epidemic.
Non-AIDS-defining cancers are an important problem in HIV-infected patients. The occurrence of ne... more Non-AIDS-defining cancers are an important problem in HIV-infected patients. The occurrence of neuroendocrine (NE) tumors in sites other than the lung and skin has not been well characterized in the setting of concurrent HIV infection. HIV-positive patients with biopsy-confirmed NE tumors localized to the gastrointestinal tract were identified based on the personal archives of the authors. A retrospective chart review was performed, and data regarding demographics, HIV status, presenting symptoms and signs, diagnostic work-up, therapeutic interventions, and outcome were extracted. We identified 4 adult patients, mean age 42 years (range: 37-47) infected with HIV, who developed NE tumors originating in their gastrointestinal tact. They had only moderate immunosuppression with a median CD4 count of 497 cells/mm (range: 182-1100) and chronic HIV infection (2-15 years duration). Symptoms at presentation were nonspecific, including abdominal pain, diarrhea, weight loss, and rectal bleeding. A specialized diagnostic work-up was required, including serum chromogranin and urinary 5-hydroxyindoleacetic acid levels, colonoscopy, radioactive isotope scans, and the demonstration of NE differentiation in procured pathologic material. The spectrum of tumors ranged from benign (typical carcinoid) to highly aggressive neoplasms (NE carcinoma). Treatment with octreotide, surgical resection, or systemic chemotherapy provided effective symptomatic relief and was associated with a favorable outcome, despite metastases in 2 patients. These cases serve to broaden the spectrum of neoplasms that may be encountered in the current HIV era, and illustrate the difficulty in establishing the diagnosis of NE tumors in the context of HIV infection.
We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bro... more We performed a retrospective study on 112 patients with AIDS-related pneumonias who underwent bronchoscopy and in whom Pneumocystis carinii pneumonia (PCP) and/or cytomegalovirus (CMV) were identified in bronchoalveolar fluid (BAL). CMV was identified by detection of early antigen fluorescent foci (DEAFF) testing in cell cultures of BAL fluid. The short- and long-term survival of all patients was similar regardless of whether PCP, CMV or both were detected at bronchoscopy. Ten out of 14 patients with CMV alone and 13 out of 26 with both CMV and PCP were treated with anti-CMV therapy, but the short- and long-term mortality was similar to that in patients who had no specific antiviral therapy. Extrapulmonary recurrence of CMV (retinitis or gastrointestinal disease) occurred in 22% of patients with evidence of CMV in BAL compared with 16% of those with PCP alone, but this difference was not statistically significant and this recurrence rate was independent of anti-CMV therapy. Detection of CMV shedding from more than one site (BAL, urine, throat or blood) was associated with a worse prognosis at 3 months than in patients in whom CMV was detected in BAL alone. It does not appear that finding CMV shedding is a guide to the cause of pneumonia or an indication for treatment in AIDS patients.
Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence ... more Testicular germ cell tumour (GCT) is not an AIDS-defining illness despite an increased incidence in men with HIV infection. We performed a matched case-control study comparing outcomes in HIV-positive men and the general population with GCT, using three age and stage matched controls for each case. There was no difference in the 5-year GCT-free survival between cases and controls. However, overall survival was significantly decreased in the cases (log rank P=0.03). HIV was responsible for 70% of this mortality. The relapse-free survival for stage I patients treated with orchidectomy and surveillance was not affected by HIV status (log rank P=0.68). There was no difference in disease free survival in patients with metastatic disease (log rank P=0.78). The overall survival has not improved since the introduction of highly active antiretroviral therapy (log rank P=0.4). Thus, HIV-related GCT is not more aggressive than GCT in the general population.
Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is ass... more Sunitinib is standard first-line therapy for metastatic clear cell renal cancer (MCRC). It is associated with leucopenia; however, its effects on specific immune cell subsets are unclear. Alterations in immune cell subsets may contribute to tumour progression. Lymphocyte subsets (CD3, 4, 8, 19 and 56) were measured in 43 untreated MCRC patients who received sunitinib. The protocol included a structured treatment interruption of 5 weeks. Cell populations were measured at specific time points during sunitinib treatment and the treatment break. Sunitinib was associated with significant declines in total leucocyte (-48%), neutrophil (-62%), CD3 total T cell (-31%) and CD4 counts (32%; p < 0.05). There was no significant change in CD19 B lymphocyte, CD8 or CD56 natural killer cells. During the sunitinib-free interval, all parameters recovered to baseline. No patients developed opportunistic infections or neutropenic sepsis. The level of specific immune subsets at presentation or occurrence of a fall in specific counts had an effect on progression-free survival (p > 0.05). Sunitinib is associated with reversible inhibition of specific lymphocyte subsets which has implications for the immunological control of MCRC and its use in combination with other agents. Despite suppressive effects, there was no evidence of predisposition to immune suppressive-related infection.
The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conduc... more The role of prophylactic antibacterial agents after chemotherapy remains controversial. We conducted a randomized, double-blind, placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary, severe neutropenia (fewer than 500 neutrophils per cubic millimeter). Patients were randomly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period. The primary outcome was the incidence of clinically documented febrile episodes (temperature of more than 38 degrees C) attributed to infection. Secondary outcomes included the incidence of all probable infections, severe infections, and hospitalization but did not include a systematic evaluation of antibacterial resistance. A total of 1565 patients underwent randomization (784 to placebo and 781 to levofloxacin). The tumors included breast cancer (35.4 percent), lung cancer (22.5 percent), testicular cancer (14.4 percent), and lymphoma (12.8 percent). During the first cycle of chemotherapy, 3.5 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 7.9 percent in the placebo group (P<0.001). During the entire chemotherapy course, 10.8 percent of patients in the levofloxacin group had at least one febrile episode, as compared with 15.2 percent of patients in the placebo group (P=0.01); the respective rates of probable infection were 34.2 percent and 41.5 percent (P=0.004). Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group (P=0.004). The respective rate of severe infection was 1.0 percent and 2.0 percent (P=0.15), with four infection-related deaths in each group. An organism was isolated in 9.2 percent of probable infections. Among patients receiving chemotherapy for solid tumors or lymphoma, the prophylactic use of levofloxacin reduces the incidence of fever, probable infection, and hospitalization.
AIDS-associated Kaposi&am... more AIDS-associated Kaposi's sarcoma remains common in individuals with HIV-1 infection in the era of highly active antiretroviral therapy (HAART). We developed a simple model for predicting mortality on the basis of clinical characteristics present at the time of diagnosis of Kaposi's sarcoma. Of 5873 individuals with HIV-1 infection, 326 (6%) developed Kaposi's sarcoma; for 262 (80%) this was their first AIDS-defining illness. We did univariate and multivariate Cox regression analyses to identify covariates predictive of overall survival and validated our model with an independent data set of 446 patients with Kaposi's sarcoma. In the primary model, we developed a prognostic score from 0 to 15 starting at 10. Having Kaposi's sarcoma as the AIDS-defining illness (-3 points) and increasing CD4 count (-1 point for every complete 100 cells per mm3) improved prognosis; age of 50 years or older (2 points) and having another AIDS-associated illness at the same time (3 points) conveyed a poorer prognosis. In individuals with prognostic scores of 0, 5, 10, and 15, probability of survival at 1-year was 0.993, 0.967, 0.834, and 0.378, and at 5 years was 0.984, 0.918, 0.631, and 0.084, respectively. Increasing prognostic score by 1 increased 1-year death hazard ratio by 40% (95% CI 28-53%; bootstrapped hazard ratio 1.39, 1.25-1.51). The index had concordance of 76.8% (71.7-82.3). We identified four prognostic factors that can be used to obtain an accurate prognostic index at diagnosis of AIDS-associated Kaposi's sarcoma. This index is widely applicable and can be used to guide therapeutic options.
ABSTRACT In order to evaluate the negative predictive value of a low prostate-specific antigen (P... more ABSTRACT In order to evaluate the negative predictive value of a low prostate-specific antigen (PSA) for a positive bone scan, we performed a retrospective study in a patient material from the Umea region in Northern Sweden. We also evaluated whether different tumour grades could influence this predictive value. Four-hundred-and-forty-six patients of newly diagnosed prostate cancer were reviewed. We analysed different levels of PSA, tumour grade, tumour stage and combinations of these parameters for their use in making a positive bone scintigraphy (BS) prediction. Among 214 patients with PSA <20 ng/ml, 9 showed a positive BS. When tumours of grades 2 and 3 were excluded, the number of positive BS predictions decreased to 6. For 350 of these 446 patients, a classification according to TNM was available; 162 of these 350 had a PSA value <20 ng/ml, and when this group comprised only small and well-differentiated tumours (T1-2, G1), only one of the remaining 81 patients had a positive BS result. We conclude that in most patients with small and well-differentiated tumours (T1-2, G1) and PSA <20, BS staging need not be carried out.
JNCI Journal of the National Cancer Institute, 2006
From a cohort of 9621 human immunodeficiency virus type 1-infected individuals, we identified 61 ... more From a cohort of 9621 human immunodeficiency virus type 1-infected individuals, we identified 61 patients with primary central nervous system lymphoma (PCL) who had a median survival of 1.3 months. We compared clinicopathologic variables of patients who were treated in the pre-highly active antiretroviral therapy (HAART) and HAART eras and investigated whether exposure to antiretroviral agents with differing cerebrospinal fluid penetrations was associated with risk for PCL. All statistical tests were two-sided. Incidence of PCL was lower in the HAART era (1.2 cases per 1000 patient-years, 95% confidence interval [CI] = 0.8 to 1.9) than in the pre-HAART era (three cases per 1000 years, 95% CI = 2.1 to 4.0; P<.001), and overall survival was longer (median survival = 32 days, range = 5-315 days, versus 48 days, range = 15-1136 days; log rank P = .03). In the HAART era, fewer patients had prior acquired immunodeficiency syndrome-defining illnesses than in the pre-HAART era (64% versus 90%; P = .013), and patients were more likely to have the diagnosis of PCL confirmed histologically or by polymerase chain reaction (77% versus 26%; P<.001). Exposure to specific antiretroviral agents was not associated with risk for PCL.
A prognostic index for AIDS-associated Kaposi&amp... more A prognostic index for AIDS-associated Kaposi's sarcoma (KS) diagnosed in the era of highly active antiretroviral therapy (HAART) was based on routine clinical and laboratory characteristics. Because immune subset measurement is often performed in HIV-positive individuals, we examined whether these were predictive of mortality independently of the prognostic index, or could predict time to progression of KS. We performed univariate and multivariate Cox regression analyses on a data set of 326 individuals with AIDS-associated KS to identify immune subset covariates predictive of overall survival and time to progression. Adaptive (CD8 T cell and CD19 B cell) and innate (CD16/56 natural-killer cell) immune parameters were studied by flow cytometry. In univariate analyses, all three immune subsets had significant effects on overall survival (P < .025). In multivariate analyses including the prognostic index, only CD8 counts remained significant (P = .026), although its effect on the overall prognostic index is small. An increase of 100 cells/mm3 in the CD8 count confers a 5% improvement in overall survival. Individuals with a higher CD8 count did not have an increased time to progression. Patients who were already on HAART at the time of KS diagnosis did not have a shorter time to progression than those who were antiretroviral naïve at KS diagnosis. The CD8 count appears to provide independent prognostic information in individuals with AIDS-associated KS. Measurement of the CD8 count is clinically useful in patients with KS.
The use of transient elastography to assess liver stiffness measurement (LSM) has now become wide... more The use of transient elastography to assess liver stiffness measurement (LSM) has now become widely available for the diagnosis of liver fibrosis as a rapid, noninvasive test (it is still not approved for use in the United States). It has previously been showed as an accurate method of representing the state of liver fibrosis with concomitant evaluation of liver biopsy and the histologic scoring system METAVIR. We performed a meta-analysis to further assess its use in comparison with liver biopsy. Studies from the literature were analyzed with a median liver stiffness value in kilopascal given for fibrosis stages according to histopathologic findings on biopsy and best discriminant cutoff levels in kilopascals for significant fibrosis (>or=F2) and cirrhosis (F4). A total of 22 studies were selected comprising 4,430 patients; chronic hepatitis C infection was the most common etiology of fibrosis. The pooled estimates for significant fibrosis (>or=F2) measured 7.71 kPa (LSM cutoff value) with a sensitivity of 71.9% [95% confidence interval (CI): 71.4%-72.4%] and specificity of 82.4% (95% CI: 81.9-82.9%), whereas for cirrhosis (F4) the results showed a cutoff of 15.08 kPa with a sensitivity of 84.45% (95% CI: 84.2-84.7%) and specificity of 94.69% (95% CI: 94.3%-95%). Further evaluation of transient elastography to assess LSM is required in prospective studies to potentially increase the sensitivity and establish its clinical utility.
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Papers by Mark Bower