[Acquired alpha-thalassemia in an 86-year-old patient with myelodysplastic syndrome]. / Une alpha thalassémie acquise chez un patient de 86 ans avec un syndrome myélodysplasique.

BACKGROUND: Alpha thalassemia-myelodysplastic syndrome (ATMDS) is one of the possible complications related to the genetic instability typical of clonal hemopoietic disorders such as myelodysplastic syndromes (MDS). Hemoglobin H acquisition, which is hemoglobin without alpha chains and with 4 beta chains is the hallmark of this disease. OBSERVATION: An 86-year-old male with chronic, microcytic anemia was referred due to a fall in his hemoglobin level. The blood smear was remarkable for intense anisocytoses and poikilocytosis. Bone marrow analysis was followed by a diagnosis of MDS with a good prognostic score. Peripheral blood coloration with brilliant cresyl blue showed "golf ball-like" erythrocytes. Hemoglobin electrophoresis is notable for the presence of H hemoglobin. The new generation sequencing confirmed the diagnosis of ATMDS showing a non-sense mutation in the gene ATRX. CONCLUSION: The diagnosis of ATMDS should be considered in the presence of the association of MDS, microcytic anemia and marked blood smear abnormalities such as anisocytosis and poikilocytosis. A little less than 10% of all MDS are complicated by ATMDS.

Recurrent mutations refine prognosis in chronic lymphocytic leukemia.

Through the European Research Initiative on chronic lymphocytic leukemia (CLL) (ERIC), we screened 3490 patients with CLL for mutations within the NOTCH1 (n=3334), SF3B1 (n=2322), TP53 (n=2309), MYD88 (n=1080) and BIRC3 (n=919) genes, mainly at diagnosis (75%) and before treatment (>90%). BIRC3 mutations (2.5%) were associated with unmutated IGHV genes (U-CLL), del(11q) and trisomy 12, whereas MYD88 mutations (2.2%) were exclusively found among M-CLL. NOTCH1, SF3B1 and TP53 exhibited variable frequencies and were mostly enriched within clinically aggressive cases. Interestingly, as the timespan between diagnosis and mutational screening increased, so too did the incidence of SF3B1 mutations; no such increase was observed for NOTCH1 mutations. Regarding the clinical impact, NOTCH1 mutations, SF3B1 mutations and TP53 aberrations (deletion/mutation, TP53ab) correlated with shorter time-to-first-treatment (P<0.0001) in 889 treatment-naive Binet stage A cases. In multivariate analysis (n=774), SF3B1 mutations and TP53ab along with del(11q) and U-CLL, but not NOTCH1 mutations, retained independent significance. Importantly, TP53ab and SF3B1 mutations had an adverse impact even in U-CLL. In conclusion, we support the clinical relevance of novel recurrent mutations in CLL, highlighting the adverse impact of SF3B1 and TP53 mutations, even independent of IGHV mutational status, thus underscoring the need for urgent standardization/harmonization of the detection methods.

Distinct patterns of novel gene mutations in poor-prognostic stereotyped subsets of chronic lymphocytic leukemia: the case of SF3B1 and subset #2.

Recent studies have revealed recurrent mutations of the NOTCH1, SF3B1 and BIRC3 genes in chronic lymphocytic leukemia (CLL), especially among aggressive, chemorefractory cases. Nevertheless, it is currently unknown whether their presence may differ in subsets of patients carrying stereotyped B-cell receptors and also exhibiting distinct prognoses. Here, we analyzed the mutation status of NOTCH1, SF3B1 and BIRC3 in three subsets with particularly poor prognosis, that is, subset #1, #2 and #8, aiming to explore links between genetic aberrations and immune signaling. A remarkably higher frequency of SF3B1 mutations was revealed in subset #2 (44%) versus subset #1 and #8 (4.6% and 0%, respectively; P<0.001). In contrast, the frequency of NOTCH1 mutations in subset #2 was only 8%, lower than the frequency observed in either subset #1 or #8 (19% and 14%, respectively; P=0.04 for subset #1 versus #2). No associations were found for BIRC3 mutations that overall were rare. The apparent non-random association of certain mutations with stereotyped CLL subsets alludes to subset-biased acquisition of genomic aberrations, perhaps consistent with particular antigen/antibody interactions. These novel findings assist in unraveling specific mechanisms underlying clinical aggressiveness in poor-prognostic stereotyped subsets, with far-reaching implications for understanding their clonal evolution and implementing biologically oriented therapy.

Multiple lung abscesses due to Ochroconis gallopavum, a dematiaceous fungus, in a nonimmunocompromised wood pulp worker.

An occurrence of multiple chronic lung abscesses managed by lobectomy is described. These abscesses were present for 13 years in the patient, a nonimmunocompromised wood pulp worker. The patient had hemoptysis at presentation. The organism isolated was Ochroconis gallopavum, a dematiaceous fungus known to cause disease in immunocompromised patients and epidemic encephalitis in poultry. The fungus is typically found in warm environments and in decaying compost; for this reason, we postulate that his illness was occupationally acquired.

Photodynamic therapy for early stage squamous cell carcinoma of the lung.

OBJECTIVE: To study the effectiveness of photodynamic therapy (PDT) as a therapeutic strategy in roentgenographically occult squamous cell carcinoma of the lung. MATERIAL AND METHODS: A carefully selected group of 21 patients (with 23 cancers) who had early stage squamous cell carcinoma of the lung and were eligible for surgical treatment were offered PDT as an alternative to resection. Patients underwent close follow-up with bronchoscopic surveillance and were offered resection if cancer persisted after no more than two sessions of PDT. RESULTS: A complete response was identified in 15 patients (16 cancers) after an initial PDT session. A complete response that lasted longer than 12 months was noted in 11 patients (52%). After PDT, the minimal follow-up period was 24 months. A subsequent primary lung cancer developed in 5 of the 21 patients (24%). Ten patients ultimately had surgical treatment, in 3 (30%) of whom N1 disease was identified at the time of resection. Two patients refused a surgical procedure and received alternative therapy. Therefore, nine patients (43%) were spared an operation (95% confidence interval, 21.8 to 66.6%). The mean duration of follow-up for these nine patients was 68 months (range, 24 to 116). CONCLUSION: On the basis of this investigation, we can conclude with 95% confidence that at least 22% of patients with early stage squamous cell lung cancer who are candidates for PDT can be spared surgical resection.

An unusual case of carcinoma polyarthritis with associated vasculitis.

This report describes a patient who presented with an unusual polyarthritis syndrome. After extensive evaluation, squamous cell carcinoma of the lung was diagnosed. During the course of the illness, the patient developed vasculitic features and "rheumatoid-like" nodules. Two months after the administration of combined-modality therapy for stage IIIA non-small cell lung carcinoma, the signs and symptoms of polyarthritis and vasculitis had disappeared completely. Ten months later, the patient remains in clinical remission. This is the first published report of simultaneous vasculitic and polyarticular manifestations in a patient with carcinoma polyarthritis.

Photodynamic therapy. Its use in the management of bronchogenic carcinoma.

Photodynamic therapy is an investigational treatment of various types of carcinoma. It involves a photosensitizing agent which, when exposed to light of the proper wavelength, forms toxic oxygen radicals that result in cell death. This article describes its current use in the management of bronchogenic carcinoma.

Ancillary therapies in the management of lung cancer: photodynamic therapy, laser therapy, and endobronchial prosthetic devices.

Endoscopic therapy for cancer that involves the tracheobronchial tree is currently available for two distinct types of lesions: radiographically occult superficial squamous cell carcinoma and advanced malignant tumors that cause severe airway obstruction. Photodynamic therapy, which uses a photosensitizing agent, is effective for managing early superficial squamous cell carcinoma. Neodymium:yttrium-aluminum-garnet laser therapy has been effective in the palliative management of patients with advanced or recurrent malignant obstructive airway lesions, either alone or in combination with intraluminal radiation therapy. Most recently, endobronchial prosthetic devices (stents) have been used in patients with advanced airway obstruction. The use of each of these modalities in the management of lung cancer is reviewed.

Photodynamic therapy in the management of early superficial squamous cell carcinoma as an alternative to surgical resection.

Photodynamic therapy has been used since 1980 at our institution for the management of cancer of the tracheobronchial tree. We identified 13 patients (14 cancers) who were thought to be surgical candidates but who elected to have photodynamic therapy. Thirteen cancers (93 percent) had a complete response to hematoporphyrin-derivative phototherapy. Ten cancers (71 percent) showed a complete response after single treatment, and three (21 percent) required a second course of therapy to achieve a complete response. Ten (77 percent) of 13 cancers have shown no local recurrence. Three patients with persistent cancer underwent surgical resection and were found not to have nodal involvement. We concluded that photodynamic therapy is an alternative to surgical resection in the management of early superficial squamous cell carcinoma.

A prospective study of pulmonary function and gas exchange following liver transplantation.

Pulmonary function and gas exchange were prospectively studied in 95 patients before and 9 to 15 months following liver transplantation. Pretransplant, the most common PF abnormality was impaired efficiency of gas exchange as measured by Dss. As a group, the mean Dss was 78.0 +/- 16.6 percent predicted and was found to be less than 80 percent predicted in 50 patients. As a group, patients with the most severe liver diseases clinically (Child's C classification) had the lowest mean Dss pretransplant. Posttransplant, three findings were of clinical importance: PaCO2 significantly improved posttransplantation, suggesting a resolution of pretransplant respiratory alkalosis. Expiratory airflow obstruction, measured by a change in the FEV1/FVC, was extremely uncommon posttransplant. Mean Dss improved significantly in patients with Child's C severity of liver disease. The most frequent deteriorations in Dss statistically were associated with posttransplant thoracotomy, ARDS, nonspecific pneumonitis, significant pleural effusions and hepatic retransplantation.

Solitary pulmonary nodule: CT evaluation of enhancement with iodinated contrast material--a preliminary report.

The authors hypothesized that the degree of contrast material enhancement of a pulmonary nodule, measured with computed tomography (CT), may indicate the likelihood of malignancy. Fifty-two patients with uncalcified solitary pulmonary nodules (diameter, 6-30 mm) were studied. Five single serial thin-section CT scans were obtained at 1-minute intervals after injection of 100 mL of nonionic contrast material. Twenty-two patients were excluded because the diagnosis was not clearly established: The observation period was less than 2 years, or the examination was technically inadequate. Malignant nodules were identified in 23 of the 30 remaining patients, and benign nodules were identified in seven. Within the first 2 minutes after the injection, all the malignant nodules had enhanced by 20 HU or greater (only one benign nodule had that degree of enhancement). The authors conclude that the degree of contrast material enhancement of pulmonary nodules as measured with CT may indicate the likelihood of malignancy.

Primary biliary cirrhosis: relation between hepatic function and pulmonary function in patients who never smoked.

We studied the relationship between selected variables of hepatic and pulmonary function in 47 patients with primary biliary cirrhosis, who were participating in a prospective study to assess sequential pulmonary function at yearly intervals. An additional 20 patients with primary biliary cirrhosis, who were liver transplant candidates awaiting transplantation, were studied. None of the 67 patients ever smoked cigarettes. Severity of primary biliary cirrhosis was characterized by histological stage and the Mayo risk score derived from a Cox regression model that used the following variables: serum bilirubin and serum albumin levels, age, prothrombin time and clinical severity of edema. Pulmonary function assessment included key variables describing expiratory airflow (forced expiratory volume in 1 sec divided by forced vital capacity) and efficiency of gas exchange (steady-state diffusing capacity for carbon monoxide). We found a significant relationship between histological stage of primary biliary cirrhosis and steady-state diffusing capacity (p = 0.02) and between the Mayo risk score for disease severity and steady-state diffusing capacity (p = 0.03). Progressive deterioration of steady-state diffusing capacity was associated with increasing severity of primary biliary cirrhosis. No relationship existed between pulmonary function and the presence of sicca complex or Sjögren's syndrome or the clinical manifestations of portal hypertension (e.g., esophageal varices, ascites and splenomegaly). No significant relationship existed between expiratory airflow and severity of primary biliary cirrhosis. We conclude that in patients with primary biliary cirrhosis who have never smoked, a statistically significant relationship exists between the severity of the liver disease and the efficiency of gas exchange measured by steady-state diffusing capacity.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of bleomycin on hematoporphyrin derivative phototherapy of solid tumors.

Hematoporphyrin derivative phototherapy (HpD-PT) has been successfully used to localize and treat superficial squamous cell cancers. Bleomycin sulfate is a glycopeptide antibiotic that has antineoplastic properties against squamous cell cancers. Because both HpD-PT and bleomycin chemotherapy are accepted forms of treatment for squamous cell cancer and their cytotoxicity is mediated by singlet oxygen and oxygen radicals, we studied the possibility of enhancing the response of solid tumors to HpD-PT by combining this modality with systemic bleomycin chemotherapy in a murine tumor model. Bleomycin did not enhance HpD-PT significantly. Also, we are not confident that HpD-PT alone or in combination with other agents can eradicate solid tumors; it certainly did not in this syngeneic murine tumor model.

A prospective pilot study evaluating the effectiveness of secretory IgA measurements in bronchoalveolar lavage to detect non-small cell lung cancer.

Previous studies have described significant elevations in the concentrations of secretory immunoglobulin A (sIgA) in bronchial washings obtained from cancerous lungs. To date, there have been no prospective investigations examining the predictive value of sIgA measurements in clinically relevant settings. Our goal was to determine if measurement of sIgA in bronchoalveolar lavage (BAL) at the time of bronchoscopic evaluation of potentially malignant lung nodules might prospectively predict the presence of cancer. We observed no significant increase in the sIgA obtained from eight BALs obtained from cancerous lungs as compared with BALs taken from these same patients' contralateral cancer-free lungs. We also saw no significant difference in BAL (sIgA) obtained from patients eventually found to have cancer (N = 8) as compared with those found to have noncancer diagnoses (N = 6). In light of these findings, we think it unlikely that measurement of sIgA will be clinically useful in the diagnosis of pulmonary malignant neoplasms.

Localization of hematoporphyrin. Derivative to human colorectal cancer.

This study documents the affinity of hematoporphyrin derivative (HpD) for human colorectal cancer by analysis of surface fluorescence. Ten patients undergoing elective surgery for primary colorectal cancer received intravenous HpD (2-5 mg/kg) either 3 or 72 hours preoperatively. Fluorescent photographs were taken of freshly resected specimens and analyzed using a computerized videodensitometric technique. This technique subtracted contaminating non-HpD fluorescence and facilitated estimation of HpD tissue levels. The HpD-specific fluorescence localized to tumors in all cases, and the mean HpD concentration was six-fold greater in malignant tissue than in surrounding normal mucosa (0.6 microgram/g versus 0.1 microgram/g, P less than 0.001). The authors conclude that HpD preferentially localizes to human colorectal cancer and this is relevant to the photodetection and phototherapy of colorectal neoplasia.