Evaluation of chest computed tomography in the staging of patients with potentially resectable liver metastases from colorectal carcinoma.

BACKGROUND: Chest computed tomography (CT) often is used to rule out lung metastases in patients with potentially resectable liver metastases from colorectal carcinoma. In the current study the authors evaluated whether CT of the chest was necessary in patients with a negative chest radiograph. METHODS: The authors performed a retrospective analysis of 202 patients with negative initial chest X-rays who were undergoing evaluation for potentially resectable liver metastases from colorectal carcinoma. Patients with highly suspicious pulmonary lesions on the initial chest CT scan underwent a thoracoscopy and biopsy. All patients were monitored for the development of pulmonary metastases. RESULTS: Sixty patients (30%) had a positive initial chest CT scan. Two patients were found to have metastases by comparison with prior CT scans. Seventeen patients had highly suspicious lesions that were biopsied, but only 2 were found to have pulmonary metastases; the other lesions were benign. An additional 13 of these 60 patients developed lung metastases during follow-up, 6 of whom were diagnosed in retrospect. Of the 142 patients with a negative initial CT scan, 33 (23%) developed pulmonary metastases. The rate of pulmonary metastases in both groups was not significantly different, regardless of whether the CT scans were positive or negative. CONCLUSIONS: During routine preoperative workup for liver resection, the majority of lesions appearing on chest CT scans of patients with negative chest radiographs were not malignant. The positive yield of CT-guided workup was only 10 of 202 patients (5%). Based on this review the authors question the use of chest CT scans in this setting.

HIV-related non-Hodgkin's lymphoma: CHOP induction therapy and interferon-alpha-2b/zidovudine maintenance therapy.

In a prospective multicenter study 68 out of 158 patients with HIV infection and malignant lymphoma were assigned to a risk-adapted induction therapy using the following algorithm: High-risk patients fulfilled 2 of 3 criteria: T4 lymphocytes <50/microL; WHO activity index 3 or 4; pre-existing AIDS-defining opportunistic infection. Normal-risk patients received 4 to 6 cycles of CHOP chemotherapy; those that achieved complete remission (CR) received zidovudine (500 mg/d) and interferon-alpha maintenance therapy (5 million units three times a week) for one year. High-risk patients received low-dose CHOP or vincristine/prednisone chemotherapy. Supportive care was performed with pentamidine inhalation and G-CSF. Intrathecal (it) methotrexate was given for CNS prophylaxis. The median survival was 634 days for 38 patients of the normal-risk group and 129 days for 30 patients of the high-risk group. 18 high-risk patients treated with low-dose CHOP had better survival (156 days) than 12 patients treated with vincristine/prednisone (72 days p=0.044). 68% of the patients in the normal-risk group achieved complete remission. 5 out of 18 high-risk patients treated with low-dose CHOP achieved complete remission. Three normal-risk patients developed fatal opportunistic infections during chemotherapy. Immune parameters deteriorated after CHOP induction and partially recovered with maintenance treatment. We conclude that the normal-risk patients survived longer than reported in most published studies. Toxicity was low. Low-dose CHOP seems to be superior to vincristine/prednisone therapy in high-risk patients.

Should a platelet limit of 600 x 10(9)/l be used as a diagnostic criterion in essential thrombocythaemia? An analysis of the natural course including early stages.

In order to evaluate the natural history of essential thrombocythaemia (ET), clinical data and prognostic factors of 143 patients with ET were retrospectively analysed (mean observation time 6.1 +/- 4.6 years). In 42 patients the early phase of the disease with initial platelet counts between 250 and 600 x 10(9)/l was assessed. In most early cases, ET was suggested by clinical symptoms (79%) and increased megakaryopoiesis (95%) with abnormal megakaryocytes in bone marrow histology (n = 34) and cytology (n = 5). Other myeloproliferative disorders and reactive thrombocytosis were excluded according to the diagnostic criteria of the Polycythemia Vera Study Group. During follow-up of the 38 early cases not treated cytoreductively at diagnosis, the platelet counts increased to >600 x 10(9)/l in 28 patients (74%) and remained between 450 and 600 x 10(9)/l in 10 patients (26%). In primarily asymptomatic patients (n = 46) with initial platelet counts above (n = 37) and below 600 x 10(9)/l (n = 9) the rates of increase of symptomatic patients were similar at about 7% per year. No influence of the initial platelet count on survival was seen in multivariate analysis of prognostic factors which included all 143 cases. Survival was mainly influenced by the rate of ET-related complications during follow-up (P = 0.002). Analysing the influence of cytoreductive therapy on symptom-free survival, platelet reduction benefited patients under 60 years (19 cytoreductively treated v 65 untreated patients, P = 0.075). The results demonstrate the possible clinical relevance of the early stages of ET and suggest that the features of pathologic megakaryopoiesis in the bone marrow are a more reliable diagnostic criterion than a definite platelet limit. Therefore, further therapeutic studies should include all stages of the disease and all age groups.

Neutropenic enterocolitis in a patient with colorectal carcinoma: unusual course after treatment with 5-fluorouracil and leucovorin--a case report.

BACKGROUND: Neutropenic enterocolitis is observed in approximately 25% of patients with acute leukemia, but has been reported rarely in patients with solid tumors. If treatment is not initiated promptly, the mortality is high. The incidence of this disease is rising in patients with hematologic malignancies. Increasing numbers of patients with solid tumors are subject to high dose chemotherapy regimens or new drugs known to cause severe neutropenia. Therefore, the frequency of this disease can be expected to increase. METHODS: The authors report a patient with colorectal carcinoma who developed neutropenic enterocolitis after treatment with 5-fluorouracil and leucovorin. RESULTS: The patient developed the typical clinical picture of abdominal pain, diarrhea, and neutropenia. The course was complicated by a recurrence of symptoms after initially successful antibiotic therapy without the patient receiving further chemotherapy. CONCLUSIONS: This case indicates that neutropenic enterocolitis may occur in patients with colorectal carcinoma receiving 5-fluorouracil and leucovorin.

[Ocular microangiopathy syndrome in patients with AIDS is associated with increased plasma levels of the vasoconstrictor endothelin-1]. / Das okuläre Mikroangiopathie-Syndrom bei Patienten mit AIDS ist mit erhöhten Plasma-Spiegeln des Vasokonstriktors Endothelin-1 assoziiert.

OBJECTIVE: Ocular microangiopathic syndrome is the most frequent ophthalmic finding in patients suffering from the acquired immunodeficiency syndrome (AIDS). Ocular microvascular changes including cotton-wool spots are closely associated with neuroretinal and cognitive deficits in patients infected with the human immunodeficiency virus type 1 (HIV-1). Endothelin-1 is a recently identified cytokine with potent vasoconstrictor activity which is associated with various diseases involving vascular structures. METHODS: We studied 29 patients with AIDS by indirect ophthalmoscopy and by slit lamp biomicroscopy, and endothelin-1 immunoreactivity (IR) was measured in plasma by radioimmunoassay. Cotton-wool spots were counted as indicator of retinal microvasculopathy. Conjunctival bloodflow sludging in conjunctival vessels was measured by a standardized rating scale as indicator of conjunctival microvasculopathy. Parameters of immunosystemic damage were determined as covariates. RESULTS: Endothelin-1 IR was closely associated with the number of cotton-wool spots (Spearman r = 0.53, p < 0.01) and with the extent of conjunctival blood-flow sludging (r = 0.61, p < 0.001). The level of significance became stronger applying analysis of covariance with Endothelin-1 IR as dependent variable and number of cotton-wool spots (p < 0.0001) or extent of conjunctival blood-flow sludging (p < 0.0001) as independent variables. CONCLUSION: Our data are consistent with the hypothesis that the vasoconstrictor endothelin-1 has an important role in the pathogenesis of HIV-1-related ocular microangiopathic syndrome. As HIV-1-related ocular microangiopathic syndrome is associated with neuroretinal and cognitive deficits in patients with HIV-1 disease the therapeutic use of endothelin antagonists currently under investigation should be discussed.

HIV-related ocular microangiopathic syndrome and color contrast sensitivity.

PURPOSE: Color vision deficits in patients with acquired immunodeficiency syndrome (AIDS) or human immunodeficiency virus (HIV) disease were reported, and a retinal pathogenic mechanism was proposed. The purpose of this study was to evaluate the association of color vision deficits with HIV-related retinal microangiopathy. METHODS: A computer graphics system was used to measure protan, deutan, and tritan color contrast sensitivity (CCS) thresholds in 60 HIV-infected patients. Retinal microangiopathy was measured by counting the number of cotton-wool spots, and conjunctival blood-flow sludging was determined. Additional predictors were CD4+ count, age, time on aerosolized pentamidine, time on zidovudine, and Walter Reed staging. The relative influence of each predictor was calculated by stepwise multiple regression analysis (inclusion criterion; incremental P value = < 0.05) using data for the right eyes (RE). The results were validated by using data for the left eyes (LE) and both eyes (BE). RESULTS: The only included predictors in multiple regression analyses for the RE were number of cotton-wool spots (tritan: R = .70; deutan: R = .46; and protan: R = .58; P < .0001 for all axes) and age (tritan: increment of R [Ri] = .05, P = .002; deutan: Ri = .10, P = .004; and protan: Ri = .05, P = .002). The predictors time on zidovudine (Ri = .05, P = .002) and Walter Reed staging (Ri = .03, P = .01) were additionally included in multiple regression analysis for tritan LE. The results for deutan LE were comparable to those for the RE. In the analysis for protan LE, the only included predictor was number of cotton-wool spots. In the analyses for BE, no further predictors were included. The predictors Walter Reed staging and CD4+ count showed a significant association with all three criteria in univariate analysis. Additionally, tritan CCS was significantly associated with conjunctival blood-flow sludging. CONCLUSION: CCS deficits in patients with HIV disease are primarily associated with the number of cotton-wool spots. Results of this study are in accordance with the hypothesis that CCS deficits are in a relevant part caused by neuroretinal damage secondary to HIV-related microangiopathy.

Liposomal doxorubicin in the treatment of advanced AIDS-related Kaposi sarcoma.

Neither single-agent therapy nor any combination treatment has been satisfactory enough to be regarded as standard in systemic advanced Kaposi sarcoma. In an attempt to achieve high efficacy in combination with low toxicity, we used a new liposomal formulation of doxorubicin. Pharmacologic data had established a long plasma half-life, an increased accumulation in tumor tissue, and a decrease in uptake by tissues such as liver, spleen, and bone marrow. In a phase I/II open-label, dose-escalating trial 40 male AIDS patients with advanced Kaposi sarcoma were enrolled to receive intravenous "stealth" liposomal doxorubicin biweekly at doses of 10 mg/m2 (n = 10), 20 mg/m2 (n = 27), and 40 mg/m2 (n = 3). The median CD4 count at baseline was 25/microL. After six cycles (12 weeks), 39 patients were evaluable. Three patients (7.5%) showed a complete response, which was histologically confirmed. A partial response was documented in 33 patients (85%). Stable disease was observed in three patients (7.5%). During a median treatment duration of 25 weeks, four patients developed stomatitis (10%), and four patients (10%) experienced alopecia. The most frequent hematologic toxicity was neutropenia. Grade 4 neutropenia was seen in 42.5%, and grade 3 toxicity was seen in 30%. Toxicity was dose-dependent and more frequent in the 40 mg/m2 stratum. During a median observation period of 25 weeks, opportunistic infections occurred in 57.5% of the patient population. We conclude that liposomal doxorubicin at dose levels of 10 and 20 mg/m2 is safe and effective for treatment of advanced Kaposi sarcoma in AIDS. A controlled trial comparing liposomal doxorubicin to conventional combination therapy is underway.

Impairment of colour contrast sensitivity and neuroretinal dysfunction in patients with symptomatic HIV infection or AIDS.

Ophthalmic and neurological complications are frequent findings in patients with AIDS. Little is known about neuroretinal dysfunction in patients with HIV infection. The purpose of this study was to measure and evaluate colour vision in patients with HIV infection or AIDS. Colour contrast sensitivity tests were performed on 75 patients (150 eyes) in different stages of HIV infection. A highly sensitive computer graphics system was used to measure tritan, deutan, and protan colour contrast thresholds. Patients were classified into three clinical groups: (a) asymptomatic HIV infection, (b) lymphadenopathy syndrome or AIDS-related complex, and (c) AIDS. Overall, tritan (p < 0.0001), deutan (p = 0.003), and protan (p = 0.009) colour contrast sensitivities were significantly impaired in patients with HIV infection compared with normal controls. Colour thresholds in patients with asymptomatic HIV infection (mean tritan threshold: 4.33; deutan: 4.41; protan: 3.97) were not impaired compared with normal controls. Colour vision was slightly impaired in patients with lymphadenopathy syndrome or AIDS-related complex (tritan: 6.25 (p < 0.0001); deutan: 4.99 (p = 0.02); protan: 4.45 (p = 0.05)). In patients with AIDS the impairment was even more marked (tritan: 7.66 (p < 0.0001); deutan: 5.15 (p < 0.0009); protan: 4.63 (p = 0.004)). Analysis of covariance controlling for age demonstrated a close association between impairment of tritan colour contrast sensitivity and progression of HIV disease (p < 0.0001). Following Köllner's rule, our study suggests that neuroretinal dysfunction occurs in patients with symptomatic HIV infection or AIDS. This is emphasised by the finding that the relative impairment in tritan vision compared with deutan/protan vision might reflect the difference in the number of cones or receptive fields. Measurement of tritan colour contrast sensitivity appears to be an appropriate and easily applicable method to detect early neuroretinal dysfunction in patients with HIV disease.

[Acute kidney failure caused by sulfadiazine stones. A complication of the therapy of toxoplasmosis in AIDS]. / Akute Niereninsuffizienz durch Sulfadiazinsteine. Komplikation der Therapie einer Toxoplasmose bei AIDS.

A 45-year-old man with AIDS was treated for a recurrence of cerebral toxoplasmosis with sulphadiazine, 4 g, and pyrimethamine, 75 mg, daily. Owing to a lack of appetite and dysphagia he drank rather little water during the first week of treatment. On the 13th day after starting the drugs he had bilateral renal colics and renal failure was diagnosed (serum creatinine 3.8 mg/dl). Ultrasound examination demonstrated multiple stones with bilateral urinary retention. After parenteral fluid replacement, alkalization of the urine with sodium-potassium-hydrogen citrate and N-butylcopolamine a stone, consisting of sulphadiazine and acetylsulphadiazine, was passed after two days. Three days later the creatinine concentration was within normal limits, and in further two days the ultrasound picture was normal. It is pointed out that diarrhoea, fever or dysphagia often prevent sufficient fluid intake in AIDS patients. Satisfactory oral fluid intake and alkalization of urine is thus of great importance for avoiding complications during sulphadiazine treatment.

Ultrasound as a tool to evaluate remission of cutaneous Kaposi's sarcoma.

OBJECTIVE: To evaluate ultrasound measurement of Kaposi's sarcoma (KS) tumour volume for follow-up during therapy. Two-dimensional evaluation of size and description of gross alteration (for example, colour, nodularity, resolution) was used to assess treatment of KS. Flattening of palpable cutaneous KS lesions during anti-KS therapy has not been quantified objectively by a reliable method. METHODS: In six patients with advanced AIDS and KS, a total of 17 cutaneous lesions were evaluated prospectively by ultrasound and surface measurements. KS lesions were examined histologically before and after 12 weeks of chemotherapy with liposomal doxorubicin. RESULTS: In comparison with size reduction, volume measurement showed a more pronounced reduction of tumour volume. The mean tumour volume was reduced by 94% from 451 mm3 +/- 655 mm3 to 66 mm3 +/- 165 mm3 at week 12 (P < 0.001). Histological evaluation of lesions no longer detectable by ultrasound after therapy showed abundant siderophages but no increase in spindle cells and no mitoses. CONCLUSIONS: Our findings suggest that ultrasound is a useful method with which to follow growth and remission of cutaneous KS. In contrast, pigmentation due to iron deposition is unaffected by chemotherapy because, despite histological remission, pigmentation can persist. Though ultrasound cannot replace histologic evaluation for complete response, we suggest the use of ultrasound assessment, thus introducing a more objective criterion than subjective rating of nodularity.

HIV-related ocular microangiopathic syndrome and cognitive functioning.

Ocular microangiopathic syndrome is found frequently in patients with AIDS or severe HIV infection. Symptoms of this microvascular syndrome can include cotton-wool spots, hemorrhages, and Roth's spots. The clinical and functional significance of HIV-related ocular microangiopathic syndrome has not been clarified as yet. The objective of this study was to evaluate a possible association between HIV-related ocular microangiopathic syndrome and cognitive functioning. Thirty-seven patients infected with HIV (24 with AIDS) underwent ophthalmological and neuropsychological examination. HIV-related ocular microangiopathic syndrome was measured by counting the number of cotton-wool spots in both eyes. Neuropsychological examination included five standardized tests, with the first three primarily measuring function of short-term memory; these tests were as follows: the Auditory-Verbal Learning Test, the Benton Test, the Stroop Colour Word Test, the Trail-Making Part B test, and the Vocabulary for Measuring Premorbid Intelligence test. HIV-related ocular microangiopathic syndrome was found in 15 patients with AIDS (62.5%), and in one patient, staged Walter Reed 5. In 10 patients, one eye was affected (mean count of cotton-wool spots 1.5). In six patients, both eyes were affected (mean count of cotton-wool spots 7.0). Univariate correlations between the number of cotton-wool spots in both eyes and test scores were as follows: Auditory-Verbal Learning Test: 0.56 (p < 0.001); Benton Test: 0.51 (p < 0.001); Stroop Colour and Word: 0.50 (p < 0.001); Trail-Making Part B: 0.15 (not significant); Vocabulary for Measuring Premorbid Intelligence: -0.05 (not significant). Multiple correlation between the test scores and the number of cotton-wool spots was 0.70 (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Low incidence of Pneumocystis carinii pneumonia in HIV patients receiving 300 mg pentamidine aerosol every 2 weeks.

The optimal dosage of pentamidine for prophylaxis of Pneumocystis carinii pneumonia (PcP) is unknown. We assessed the effects of 300 mg pentamidine inhaled every 2 weeks. Salbutamol was added for prevention of bronchoconstriction. A total of 128 consecutive HIV patients were enrolled, 21 of whom were excluded within 8 weeks; the remaining 107 patients, 66 on primary and 41 on secondary prophylaxis, were treated for 39 weeks (median; range 8-133). Two patients developed PcP. Side effects occurred in only 14 of 5082 inhalations. Three patients developed hypoglycemia after inhalations. Blood glucose levels determined in 34 patients before and after inhalation revealed a decline from 89 +/- 23 mg/dl to 79 +/- 23 mg/dl (P < 0.005). A randomized prospective trial is necessary to evaluate the efficacy of 300 mg pentamidine inhaled every 4 or 2 weeks.

[Differences in detectability of human immunodeficiency virus type 1 in tears and blood lymphocytes]. / Unterschiede in der Nachweisbarkeit von Humanem Immunschwäche Virus Typ 1 in Tränenflüssigkeit und Blutlymphozyten.

Reported data on the isolation of the human immunodeficiency virus type 1 (HIV-1) from tears are controversial. The purpose of the study was to try to isolate HIV-1 from tears in a large sample of HIV-1-positive patients at different stages of infection. 53 tear samples were obtained from 50 patients. Additionally isolation of HIV-1 from peripheral blood lymphocytes (PBL) was attempted. HIV-1 was isolated from none (= 0%) of the 53 tear samples. Isolation from PBL was successful depending on absolute CD4+ lymphocyte count and Walter Reed staging (Walter Reed stage 6: 83%; stage 2 to 5: 11%; p less than 0.0001). Treatment with zidovudine was not related to the frequency of HIV-1 isolation. These results suggest that tears of patients infected with HIV-1 contain low or no quantities of tissue-culture-infectious units of HIV-1. Nosocomial infection with HIV-1 from tears appears to be unlikely. The known precautions for the prevention of spread of viral disease in ophthalmological practice are sufficient and should be strictly followed.

Expansion of neopterin and beta 2-microglobulin in cerebrospinal fluid reaches maximum levels early and late in the course of human immunodeficiency virus infection.

Elevated cerebrospinal fluid (CSF) levels of neopterin and beta 2-microglobulin (beta 2MG) reflect activation of the cellular immune response in the central nervous system (CNS). In 118 consecutive subjects [15 controls and 103 patients with human immunodeficiency virus (HIV) infection classified according to the Walter Reed staging system (WR)], neopterin and beta 2MG were determined in paired samples of CSF and serum. The permeability of the blood-CSF barrier and local release of neopterin and beta 2MG were taken into account: The molecular weight and diameter were used to determine filtration at the blood-CSF barrier. CSF neopterin levels were increased in all stages of HIV infection. beta 2MG levels were elevated in WR2 and later stages. Neopterin, beta 2MG, and cell counts similarly showed peaks in WR2, as did neopterin and beta 2MG also in the later stages WR5 and WR6. Neurologically asymptomatic patients exhibited higher neopterin CSF levels than did controls (12.67 +/- 11.6 vs. 2.34 +/- 1.05 nmol/l, P less than 0.001) and higher CSF beta 2MG (2.12 +/- 1.25 vs. 1.3 +/- 0.37 mg/l, P = 0.001). Patients with HIV encephalopathy had higher levels of beta 2MG (3.75 +/- 1.83 mg/l) than asymptomatic patients (P less than 0.01). CSF levels of neopterin were markedly different in patients with HIV encephalopathy and toxoplasmosis (P less than 0.01). A high quantity of local release of the markers neopterin and beta 2MG may reflect HIV infection of the CNS in early and late stages and additional release upon opportunistic infections.