Granulocytic sarcoma (chloroma): rare extramedullary tumors associated with acute non-lymphoblastic leukemia

The authors report 5 new cases of pediatric granulocytic sarcomas. These rare extramedullary tumors are composed of immature granulocytic cells, usually associated with an acute non lymphoblastic leukemia, but may appear several months before. Their characteristics are exposed (epidemiology, clinical features, cytology and cytogenetics), and therapeutic rules are discussed, especially for the granulocytic sarcomas without evidence of bone marrow involvement. The prognosis is known to be poor.     

A seroepidemiological study of toxocariasis and risk factors for infection in children in Sri Lanka

A seroepidemiology study using TES-ELISA was carried out in 1,020 children aged 1-12 years in the Hindagala Community Health Project, Sri Lanka. Toxocariasis seroprevalence was 43% with 16.6% showing high antibody levels. Unconditional logistic regression analysis showed 7-9 year olds to be at the highest risk (OR 3.0820; CI = 1.95-4.87). Dog ownership, especially puppies (OR 29.28; CI = 7.40-116.0), and geophagia-pica (OR 6.3732; CI = 3.87-10.50), were significant risk factors. Family clustering of toxocariasis was significant (chi2 = 88.000; p = 0.0001). Abdominal pain (45%), cough (30%), limb pain (23%) and skin rashes (20%) were significantly associated with seropositivity indicating that toxocariasis causes covert morbidity. These findings are, overall, applicable to other areas in Sri Lanka. However, in the dry zone, survival of infective eggs in the soil could be affected by the climate while more importantly, in agricultural areas with a high buffalo population, Toxocara vitulorum could account for human toxocariasis. Using a species specific double sandwich ELISA based on 57 kDa protein of T. canis ES antigen, it is demonstrated that 91% of the seropositives were due to T. canis. Thus along with rabies and dirofilariasis, toxocariasis is an important zoonotic health hazard from dogs in Sri Lanka and prevention is indicated.     

Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung

Frequent losses of chromosome 19p have recently been observed in sporadic lung adenocarcinomas, targeting the location of a critical tumor suppressor gene. Here we performed fine mapping of the short arm of chromosome 19 and found that the LKB1/STK11 gene mapped in the minimal-deleted region. Because germ-line mutations at LKB1/STK11 result in the Peutz-Jeghers syndrome and an increased risk of cancer, we performed a detailed genetic screen of the LKB1/STK11 gene in lung tumors. We detected a high frequency of somatic alterations (mainly nonsense mutations) in primary lung adenocarcinomas and in lung cancer cell lines. Thus, our findings demonstrate for the first time that LKB1/STK11 inactivation is a very common event and may be integrally involved in the development of sporadic lung adenocarcinoma.     

Epidermal growth factor receptor is a predictor of tumor response in locally advanced rectal cancer patients treated with preoperative radiotherapy

Epidermal growth factor receptor (EGFR) expression is observed in 50%–70% of colorectal carcinomas and is associated with poor prognosis. The aim of this study was to determine the EGFR expression rate in locally advanced rectal cancer and to analyze whether EGFR expression predicts tumor response to preoperative radiotherapy.

Between December 1997 and October 2000, 45 patients were included. Treatment consisted of preoperative pelvic radiotherapy and, in 21 patients, 2 courses of 5-fluorouracil leucovorin. Surgical resection was performed 4–8 weeks later. Immunohistochemistry for EGFR was determined at the preradiation diagnostic biopsy and in the resected specimens. Immunostaining was performed using EGFR monoclonal antibody (Biogenex, MU 207-UC). Immunohistochemical staining was evaluated according to extension and intensity. We defined positive staining (EGFR+) as extension of 5% or more.

Preoperative treatment resulted in pathologic complete remission in 7 patients (15%), downstaging in 13 patients (29%), and no response in 25 patients (56%). EGFR+ was observed in 29 of 45 tumors (64%) and was associated with neither clinical tumor stage nor clinical nodal stage. The overall response rate was 34% in EGFR+ patients vs. 62% in those who were EGFR− (p = 0.07). Only 1 of the 7 pathologic complete remission patients was EGFR+ (p = 0.003).

EGFR is expressed in a significant number of locally advanced rectal tumors. EGFR expression is an indicator for poor response to preoperative radiotherapy in advanced rectal carcinoma.     

Cosmetic outcome of breast conservative treatment for early stage breast cancer

Purpose To evaluate the cosmetic outcome of breast conservative therapy and to examine the degree of agreement between the patients’ and oncologists’ ratings. We also analyze the influence of several factors on cosmesis. Methods and materials We retrospectively evaluated 145 patients with primary breast cancer treated by local excision and radiotherapy between January 2000 and May 2001. Cosmetic outcome was evaluated by doctors and patients and was scored as excellent, good, fair or poor. Results 73% of patients rated cosmesis as excellent or good while the percentage was 71% when rated by radiation oncologists. The degree of cosmesis concordance evaluated by oncologists and patients was low (kappa=0.3). In our study the variables which significantly influence on the cosmetic outcome were concomitant adjuvant chemotherapy (p=0.04) and radiation therapy boost, either by electron beam or brachytherapy (p=0.013). Conclusion The cosmetic outcome of breast conserving therapy was good. There was a similar rating by the patient and radiation oncologist, but the level of concordance between patients and doctors was low. Factors that significantly influence the cosmesis appear to be concomitant adjuvant chemotherapy and radiation therapy boost.     

Clonidine premedication and isoflurane anesthesia to reduce bleeding in otologic surgery]

Seventy-seven ASA 1 patients scheduled for ear surgery were premedicated orally, 90 min before anaesthesia. They were randomly assigned to two groups, according to the drug used: hydroxyzine alone (group T, n = 39) or combined with clonidine (4.9 +/- 0.3 micrograms.kg-1) (group C, n = 38). Anaesthesia was induced with midazolam (0.3 mg.kg-1) and alfentanil (30 micrograms.kg-1). Ventilation was controlled with a 50/50 v/v mixture of oxygen and nitrous oxide (FETCO2 = 4 to 4.5%), and anaesthesia was maintained with repeated injections of alfentanil (15 micrograms.kg-1 at the start of surgery, and then every 15 min) and with isoflurane (mean end-expiratory concentration 0.6 +/- 0.3 vol %). Surgical bleeding was assessed every ten minutes on a numerical scale with four values. A bloodless surgical field was obtained by adjusting the isoflurane concentration up to 2 MAC, and by using a trinitrine infusion as required. Cardiovascular monitoring included an electrocardioscope and automatic blood pressure measurements. Before induction of anaesthesia, the blood pressure was lower in group C (84.7 +/- 11.2 vs. 95.9 +/- 106 mmHg) (p less than 0.001); the difference in heart rate was not significant (65 +/- 15 vs. 70.6 +/- 14 b.min-1). Moderate stable intraoperative hypotension was obtained in both groups. However, mean arterial blood pressure (C:65.8 +/- 7.8 mmHg; T: 73 +/- 9.4 mmHg) and heart rate (C: 53.4 +/- 6.8 b.min-1; T: 60.4 +/- 8 b.min-1) were significantly lower in the patients premedicated with clonidine (p less than 0.001). There were more periods of sinus bradycardia (heart rate less than or equal to 50 b.min-1), mostly seen before the beginning of surgery, in group C patients (p less than 0.01); atropine was also required more often (when the heart rate was less than or equal to 40 b.min-1) in this group of patients (NS). The comparative assessment of surgical field quality was in favour of group C (no troublesome bleeding) as opposed to the control group (16% troublesome bleeding); there were also more bloodless surgical fields in the former group (73.7% vs. 48.7% in group T, p less than 0.05). This study therefore demonstrated that clonidine premedication before anaesthesia with isoflurane was helpful in decreasing bleeding during ear surgery.     

Fine-needle aspiration cytology of intraductal papillary mucinous tumors of the pancreas

BACKGROUND: Intraductal papillary mucinous tumors (IPMT) account for 5% of pancreatic neoplasms. Preoperative identification is important because of their frequent multifocal or diffuse involvement in pancreatic ducts, which makes extensive surgery necessary even in benign cases. To the authors' knowledge, the cytologic features of this entity in fine-needle aspiration biopsy (FNAB) specimens have seldom been described and are poorly standardized. METHODS: Eleven consecutive cases of surgically proven IPMT with previous endoscopic ultrasonography (EUS)-guided FNAB were collected for retrospective analysis. EUS-FNAB had been performed with on-site attendance of a cytopathologist in all cases. Macroscopic and microscopic appearance of mucin, cellular type and arrangement, presence of nuclear grooves, and degree of nuclear atypia were recorded. RESULTS: Final diagnosis was benign IPMT (B) in four cases, borderline IPMT (Bo) in two cases, malignant IPMT (M) in one case, and IPMT associated with invasive carcinoma (Ca) in four. Retrospective analysis found moderate to high levels of extracellular mucin in 10 of the 11 cases. The other case (one Ca) showed a small amount of thick mucin. In all cases, epithelial cells were identified, although cellularity was very low in four cases (three B and one Bo). Atypia was absent in two cases (two B) slight in two cases (two B), moderate in three cases (one Bo and two Ca), and severe in four cases (one Bo, one M, and two Ca). Mucinous epithelium was found in nine cases and nonmucinous epithelium in five cases (one Bo and four Ca). Papillary structures were observed in five cases (two Bo and three Ca), sheets in eight cases (four B, one Bo, one M, and two Ca), single atypical cells in five cases (one Bo and four Ca), irregular clusters in three cases (one Bo and two Ca), and nuclear grooves in two cases (one B and one Bo). CONCLUSIONS: The most common features of IPMT were extracellular mucin and sheets of mucinous epithelium. Papillae and nuclear grooves were not consistently found. Nonmucinous epithelium, severe atypia, single atypical cells, and irregular clusters indicated a high probability of malignant transformation. Even in the absence of atypia, a clinically significant diagnostic orientation can be established in most cases on the basis of the characteristic cytologic picture.     

Platelet function profiles in patients with type 2 diabetes and coronary artery disease on combined aspirin and clopidogrel treatment

To assess platelet function profiles in diabetic and nondiabetic patients on aspirin and clopidogrel therapy, two patient populations were included to investigate the 1) acute effects of a 300-mg clopidogrel loading dose (group 1, n = 52) and 2) long-term effects of clopidogrel (group 2, n = 120) on platelet function in diabetic compared with nondiabetic patients already on aspirin treatment. Patients were stratified according to the presence of type 2 diabetes. Platelet aggregation was assessed using light transmittance aggregometry (groups 1 and 2). Platelet activation (P-selectin expression and PAC-1 binding) was determined using whole-blood flow cytometry (group 2). Clopidogrel response was also assessed. In group 1, platelet aggregation was significantly increased in diabetic (n = 16) compared with nondiabetic (n = 36) patients at baseline and up to 24 h following a 300-mg loading dose (P = 0.005). In group 2, platelet aggregation and activation were increased in diabetic (n = 60) compared with nondiabetic (n = 60) subjects (P < 0.05 for all platelet function assays). Diabetic subjects had a higher number of clopidogrel nonresponders (P = 0.04). Diabetic patients have increased platelet reactivity compared with nondiabetic subjects on combined aspirin and clopidogrel treatment. Reduced sensitivity to antiplatelet drugs may contribute to the increased atherothombotic risk in diabetic patients.