Apoptosis and p53 in inverting papilloma of the sinonasal tract

The objective of this study was to identify apoptotic bodies and p53 positivity in inverting papilloma lesions to study these two as biomarkers in premalignant lesions. Archival specimens of 15 patients with inverting papilloma between the years 1992 and 1995 were retrieved. In situ end labeling technique was used to identify apoptotic bodies. Immunohistochemistry was used to detect p53 in the same specimens. The clinical course was evaluated conducting a retrospective chart review in these patients. Compared to normal epithelium, inverting papilloma lesions had a greater proportion of apoptotic bodies, which was nearly statistically significant (average 0.506/100 cells for inverting papilloma compared with 0.1/100 cells for the normal surrounding tissue). Four cases of inverting papilloma were p53 positive. There was, however, no association between p53 positive staining and the apoptotic rate. The minimum follow-up for patients was 2 years. All had a uniformly good clinical outcome with only one patient who was p53 positive showing concurrent squamous cell carcinoma. We concluded that inverting papilloma contained a higher average number of apoptotic bodies compared with normal surrounding sinonasal tissue. This showed a trend toward a positive between the apoptotic rate and premalignancy, suggesting both increased cellular proliferation and increased cell death may occur in such lesions. In this study p53 did not show a positive association with the apoptotic rate, suggesting that p53 may not be directly involved in the apoptotic regulatory pathway in inverting papillomas.     

RNA interference targeting of A1 receptor-overexpressing breast carcinoma cells leads to diminished rates of cell proliferation and induction of apoptosis

To determine if A1 adenosine receptors mediate breast tumorigenesis, we evaluated A1 receptor expression in human tumor cell lines and human primary breast tumor tissues using both quantitative RT-PCR and Western blot analysis. A1 receptor mRNA expression is upregulated in all breast tumor cell lines examined (n=7) compared to normal mammary epithelial cells/cell lines (n=3) as determined by quantitative RT-PCR analysis. Western blot analysis indicates that protein expression of A1 adenosine receptor is higher in 15 (62.5%) of 24 human primary breast tumor tissues than in matched normal breast tissue. To explore its cellular function, the A1 adenosine receptor was depleted by small interfering RNA (siRNA) in MDA-MB-468 human breast tumor cells. Depletion of A1 receptors in MDA-MB-468 breast tumor cells attenuated both cell growth and cell proliferation as measured by cell number counts and [(14)C]-thymidine incorporation, respectively. Cell cycle analysis indicated that depletion of A1 receptors by siRNA impairs G(1) checkpoint, leading to marked accumulation of cells in G(2)/M phase, in agreement with the inhibitory effect on cell proliferation. Further supporting this finding, synchronization studies of Hela cells in various cell cycle phases suggest that A1 receptor expression is suppressed in G(2)/M cells and depletion of A1 receptor expression by siRNA produced differential expression of several key cell cycle regulators, i.e., accumulation of the cyclin-dependent kinase inhibitor p27 with concomitant reduction of CDK4 and cyclin E proteins. In addition to the impact on cell cycle progression, depletion of A1 receptors by siRNA results in substantial cell death and apoptosis as determined by FACS analysis and annexin V staining method. Together these findings suggest that the A1 adenosine receptor may contribute to tumor cell growth and survival in breast tumor cells.     

Predictors of systemic recurrence and disease-specific survival after ipsilateral breast tumor recurrence

BACKGROUND: In patients with breast carcinoma, ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is an independent predictor of systemic recurrence and disease-specific survival (DSS). However, only a subgroup of patients with IBTR develop systemic recurrences. Therefore, the management of isolated IBTR remains controversial. The objective of the current study was to identify determinants of systemic recurrence and DSS after IBTR. METHODS: The medical records of 120 women who underwent BCT for Stage 0-III breast carcinoma between 1971 and 1996 and who subsequently developed isolated IBTR were reviewed. Clinicopathologic factors were studied using univariate and multivariate analyses for their association with DSS and the development of systemic recurrence after IBTR. RESULTS: The median time to IBTR was 59 months. At a median follow-up of 80 months after IBTR, 45 patients (37.5%) had a systemic recurrence. Initial lymph node status was the strongest predictor of systemic recurrence according to the a univariate analysis (P = 0.001). Other significant factors included lymphovascular invasion (LVI) in the primary tumor, time to IBTR < or = 48 months, clinical and pathologic IBTR tumor size > 1 cm, LVI in the recurrent tumor, and skin involvement at IBTR. In a multivariate logistic regression analysis, initially positive lymph node status (relative risk [RR], 5.3; 95% confidence interval [95% CI], 1.4-20.1; P = 0.015) and skin involvement at IBTR (RR, 15.1; 95% CI, 1.5-153.8; P = 0.022) remained independent predictors of systemic recurrence. The 5-year and 10-year DSS rates after IBTR were 78% and 68%, respectively. In a multivariate Cox proportional hazards model analysis, only LVI in the recurrent tumor was found to be an independent predictor of DSS (RR, 4.6; 95% CI, 1.5-14.1; P = 0.008). CONCLUSIONS: Patients who initially had lymph node-positive disease or skin involvement or LVI at IBTR represented especially high-risk groups that warranted consideration for aggressive, systemic treatment and novel, targeted therapies after IBTR. Determinants of prognosis after IBTR should be taken into account when evaluating the need for further systemic therapy and designing risk-stratified clinical trials.     

Improving local control with breast-conserving therapy: a 27-year single-institution experience

BACKGROUND: The risk of ipsilateral breast tumor recurrence (IBTR) after breast-conserving therapy (BCT) is associated with treatment and tumor-related variables, such as surgical margin status and the use of systemic therapy, and these variables have changed over time. Correspondingly, the authors of the current study hypothesized that the contemporary multidisciplinary management of breast carcinoma would lead to an improvement in IBTR rates after BCT. METHODS: Between 1970 and 1996, 1355 patients with pathologic Stage I-II invasive breast carcinoma underwent BCT (breast-conserving surgery and adjuvant radiation therapy) at The University of Texas M. D. Anderson Cancer Center. Contemporary methods of analyzing surgical margins were in routine use by 1994. To analyze the effect of this variable and others, patient and tumor characteristics and IBTR rates in patients treated during 1994-1996 were compared with those in patients treated from 1970 to 1993. RESULTS: Characteristics were similar in patients treated during 1994-1996 (n = 381) and those treated before 1994 (n = 974) except for patients aged >50 years (63.3% vs. 51.7%, P < 0.001), and patients who had a family history of breast carcinoma (37.9% vs. 30.8%, P = 0.017). Patients treated after 1994 were less likely to have positive or unknown margins (2.9 % vs. 24.1 %, P = 0.0001), more likely to receive chemotherapy (40.5% vs. 26%, P < 0.001), and more likely to receive hormonal therapy (33.3% vs. 19.4%, P < 0.001), but less likely to receive radiation boosts to the primary tumor bed (59.8% vs. 89%, P < 0.001). The 5-year cumulative IBTR rate was significantly lower among patients treated in 1994-1996 than among patients treated before 1994 (1.3% vs. 5.7%, P = 0.001) largely because of the drop in IBTR rates among patients aged < or = 50 years (1.4 % vs. 9.1 %, P = 0.0001). On multivariate analysis, age > 50 (hazards ratio [HR] = 0.401; P = 0.0001), presence of negative surgical margins (HR = 0.574; P = 0.017), and use of adjuvant hormonal therapy (HR = 0.402; P = 0.05) were independent predictors of improved 5-year IBTR-free survival. On subgroup analysis, use of chemotherapy was associated with increased IBTR-free survival among women aged < or = 50 years (HR = 0.383; P = 0.001). Although 5-year cumulative IBTR rates were lower among women aged > 50 years than among younger women before 1994 (2.6 % vs. 9.1%, P < 0.0001), no such difference was found in the group treated in 1994-1996 (1.2 % for age > 50 yrs vs. 1.4 % for < or = 50 yrs, P = 0.999). CONCLUSIONS: The IBTR rate after BCT appears to be declining, especially among patients < 50 years of age. However, long-term follow-up is necessary to confirm this finding. This finding may reflect changes in surgical approaches and pathologic evaluation as well as an increased use of systemic therapy. The current low incidence of IBTR with multidisciplinary management of breast carcinoma may result in more patients choosing BCT over mastectomy.     

Management of suspected scaphoid fractures in accident and emergency departments--time for new guidelines

INTRODUCTION: The objectives of this work were to assess the clinical knowledge of clinicians in the accident and emergency (A&E) departments in England & Wales and evaluate the current trend for the acute management of radiologically normal, but clinically suspected, fractures of the scaphoid. SUBJECTS AND METHODS: We conducted a telephone survey on 146 A&E senior house officers (SHOs) in 50 different hospitals. This survey assessed the clinicians'' experience, their clinical and radiological diagnostic methods, and their initial treatment of suspected scaphoid fractures. RESULTS: The majority (55.8%) of SHOs performed only one clinical test to diagnose suspected scaphoid fractures. Overall, 41% were unable to cite the number of the radiographic views taken and only 10% of departments have direct access to further radiological investigation. There is wide variation in the early treatment of this injury, with the scaphoid cast used most commonly (46%). The majority of SHOs (89%) were unable to describe the features of immobilisation. The mean follow-up period was 10 days, and 53% of cases were followed-up by the senior staff in A&E. Of SHOs, 54% were not aware of any local guidelines for the management of suspected scaphoid fractures in their departments, and 92% were not aware of the existence of the 1992 British Association for Accident and Emergency Medicine (BAEM) guidelines. CONCLUSIONS: The clinical knowledge and the management of suspected scaphoid fractures in A&E are unsatisfactory. We, therefore, suggest that the dissemination of up-to-date guidelines could help to educate clinicians to provide better care to the patients.     

Management of simultaneously ingested and aspirated foreign bodies in an infant

This report describes the management of a 7-month-old baby who aspirated one and ingested two paper pins at a time. Bronchoscopic removal was done for aspirated pin and ingested pins were observed for spontaneous passage in stool, which occurred in 48 hours without any untoward incidence.     

Fungal keratitis due to fusarium solani

A young man presented with swelling, congestion and lacrimation of right eye for one week. On examination, he had corneal ulcer. Corneal scrapings on lactophenol cotton blue stain revealed fungal hyphae. Culture on Sabouraud agar yielded Fusarium solani after 48 hours. Patient was treated with ketoconazole and miconazole and responded well.     

Sirenomelia (Mermaid baby)

Sirenomelia is a rare anomaly that rarely occurs as an isolated lesion. Several theories have been proposed regarding the etiopathogenesis. In this communication, we report a case of sirenomelia. Our patient was referred to hospital at the age of four hours. On examination, fusion of both lower limbs with hook shaped appendage, attached distally, absent genitalia and absent anal orifice was found. Spine was deficient in sacral region. Upper torso looked normal. Baby also had frothing from mouth. Abdomen was non-distended. Feeding tube no.10 was tried to pass through mouth, which got obstructed at the level of upper esophagus that suggested oesophageal atresia. The skeletogram revealed absence of pelvic bones, sacral agenesis, absent fibulae and fracture of both femora. The patient died at the age of 12 hours.     

Recombinant coagulation factor VIIa in major liver resection: a randomized, placebo-controlled, double-blind clinical trial

BACKGROUND: Prevention of bleeding episodes in noncirrhotic patients undergoing partial hepatectomy remains unsatisfactory in spite of improved surgical techniques. The authors conducted a randomized, placebo-controlled, double-blind trial to evaluate the hemostatic effect and safety of recombinant factor VIIa (rFVIIa) in major partial hepatectomy. METHODS: Two hundred four noncirrhotic patients were equally randomized to receive either 20 or 80 microg/kg rFVIIa or placebo. Partial hepatectomy was performed according to local practice at the participating centers. Patients were monitored for 7 days after surgery. Key efficacy parameters were perioperative erythrocyte requirements (using hematocrit as the transfusion trigger) and blood loss. Safety assessments included monitoring of coagulation-related parameters and Doppler examination of hepatic vessels and lower extremities. RESULTS: The proportion of patients who required perioperative red blood cell transfusion (the primary endpoint) was 37% (23 of 63) in the placebo group, 41% (26 of 63) in the 20-microg/kg group, and 25% (15 of 59) in the 80-microg/kg dose group (logistic regression model; P = 0.09). Mean erythrocyte requirements for patients receiving erythrocytes were 1,024 ml with placebo, 1,354 ml with 20 microg/kg rFVIIa, and 1,036 ml with 80 microg/kg rFVIIa (P = 0.78). Mean intraoperative blood loss was 1,422 ml with placebo, 1,372 ml with 20 microg/kg rFVIIa, and 1,073 ml with 80 microg/kg rFVIIa (P = 0.07). The reduction in hematocrit during surgery was smallest in the 80-microg/kg group, with a significant overall effect of treatment (P = 0.04). CONCLUSIONS: Recombinant factor VIIa dosing did not result in a statistically significant reduction in either the number of patients transfused or the volume of blood products administered. No safety issues were identified.