Increased adhesion to endothelial cells of erythrocytes from patients with polycythemia vera is mediated by laminin alpha5 chain and Lu/BCAM

Patients with polycythemia vera (PV) have a JAK2 (a cytosolic tyrosine kinase) mutation and an increased risk of vascular thrombosis related to red blood cell (RBC) mass and platelet activation. We investigated functional RBC abnormalities that could be involved in thrombosis. RBC adhesion to human umbilical vein endothelial cells (HUVECs) was measured by a radiometric technique and in a flow system by video microscopy, and adhesion molecule expression was determined using specific antibodies (against CD36, CD49d, ICAM-4, Lu/BCAM, CD147, and CD47) and flow cytometry in a group of 38 patients with PV and a group of 36 healthy volunteers. Adhesion of PV RBCs was 3.7-fold higher than that of normal RBCs (P < .001). Adhesion was inhibited when PV RBCs were incubated with anti-Lutheran blood group/basal cell adhesion molecule (Lu/BCAM) or when HUVECs were treated with anti-laminin alpha(5) and to a lesser extent with anti-alpha(3) integrin. Lu/BCAM was constitutively phosphorylated in PV RBCs. Transfection of K562 cells with JAK2 617V>F resulted in increased expression and phosphorylation of Lu/BCAM. Phosphorylation of Lu/BCAM increases RBC adhesion. Our results indicate that JAK2 mutation might be linked to Lu/BCAM modification and increased RBC adhesiveness, which may be a factor favoring thrombosis in PV.     

Surgical management of growing teratoma syndrome: the M. D. Anderson cancer center experience

PURPOSE: We defined the growth rate and reviewed our experience in the surgical management of growing teratoma syndrome in patients with nonseminomatous germ cell tumors. MATERIALS AND METHODS: Nine patients were clinically diagnosed with growing teratoma syndrome at our center from 1980 to 2003. The defining criteria of growing teratoma syndrome were growing metastatic mass in the retroperitoneum or other site consisting entirely of mature teratoma detected on serial abdominal/pelvic imaging during chemotherapy, and a significant decrease in or normalization of tumor markers. RESULTS: Precise serial abdominal/pelvic radiological measurements of the retroperitoneal masses were available for 7 of 9 patients. The median growth rate of growing teratoma syndrome measured as the increase in diameter during chemotherapy was 0.7 cm per month. The median growth rate measured as the increase in tumor volume was 12.9 cc per month. Median time from the start of chemotherapy to retroperitoneal lymph node dissection was 5.4 months (range 2.7 to 21.6). Pathological evaluation of the retroperitoneal lymph node dissection specimen revealed teratoma with no viable tumor in all 9 cases. There were 2 intraoperative complications (1 aortic and 1 ureteral injury) and 4 postoperative complications (2 ileus, 1 acute pancreatitis and 1 chylous ascites). At a median followup of 2 years 7 patients were alive without disease, 1 died of postoperative sepsis and 1 died of an unknown cause. CONCLUSIONS: The growth rate of growing teratoma syndrome can vary significantly, which must be taken into account when evaluating cases. Retroperitoneal lymph node dissection is an effective treatment for growing teratoma syndrome, providing excellent local control and a low risk of progression.     

P0 stage at radical cystectomy for bladder cancer is associated with improved outcome independent of traditional clinical risk factors

OBJECTIVES: Final pathologic specimen free of detectable disease (P0) is not uncommon in patients undergoing cystectomy for bladder cancer, especially in the era of neoadjuvant chemotherapy. To improve our understanding of its significance in a contemporary series, we performed an outcomes analysis of this cohort of patients. METHODS: Over the last 15 yr, 1104 patients with bladder cancer underwent radical cystectomy at our institution. Of these, 120 (11%) were pT0N0M0 (P0) in the surgical specimen and form the basis of this report. Survival data were estimated by method of Kaplan and Meier, with Cox proportional hazards regression model used to evaluate associations between survival and variables studied. RESULTS: Clinical stages were cT1, 21 patients; cT2, 65; cT3b, 20; cT4a, 11; and cT4b, 3. The 5-yr estimates of overall (OS), disease-specific (DSS), and recurrence-free survival (RFS) rates were 84%, 88%, and 84%, respectively. With mean follow-up of 43 mo, 11 patients developed recurrences, 9 of whom died of disease. Median time to recurrence was 7.7 mo (range: 2.2-45 mo). On multivariate analysis, presence of lymphovascular invasion and concomitant carcinoma in situ on the transurethral resection of the bladder tumor specimen were the only significant prognostic factors associated with shorter OS (p = 0.04) and RFS (p = 0.049), respectively. Notably, patients who received preoperative chemotherapy (n = 77) had 5-yr survival rates similar to those of patients who did not. CONCLUSION: Although patients who are P0 at cystectomy have a good prognosis, not all can be considered cured. The favorable prognosis conferred by a P0 state appears to be independent of whether this is achieved by neoadjuvant chemotherapy or by thorough transurethral resection before cystectomy.     

Hypercalcaemia and acute renal failure after major burns: An under-diagnosed condition

Background

Hypercalcaemia has been shown to occur in about 20% of patients with major burns requiring prolonged intensive care unit (ICU) treatment, and it may be associated with renal failure. Having observed the early onset of hypercalcaemia, the study aimed to determine the frequency and timing of this condition in a European patient cohort.

Methods

A retrospective cohort study on a prospectively collected, computerised database of the 225 burn-injury ICU admissions between 2001 and 2007 was undertaken. The inclusion criteria included: burns >20% of the body surface area (BSA) or in-hospital stay >20 days. Hypercalcaemia was defined as an ionised plasma calcium (Ca²⁺) concentration >1.32 mmol l⁻¹ (or total corrected calcium = [Ca]c > 2.55 mmol l⁻¹). Four emblematic cases are reported in this article.

Results

A total of 73 patients met the inclusion criteria (age: 13–88 years, burns: 12–85% BSA): of these, 22 (30%) developed hypercalcaemia. The median time to the first hypercalcaemia value was 21 days. Only 11 patients had both high Ca²⁺ and elevated [Ca]c (which remained normal in others). The risk factors of the disorder were burned surface (p = 0.017) and immobilisation (fluidised bed use: p < 0.05, duration: p = 0.02) followed by burned BSA. Acute renal failure tended to be more frequent in hypercalcaemic patients (five (23%) vs. three (6%): p = 0.11), while mortality was not increased. The disorder resolved with hydration and mobilisation in most cases: pamidronate was successful in three cases that were most severe.

Conclusion

Hypercalcaemia and associated acute renal failure occur more frequently and earlier than previously reported. Determining the ionised Ca rather than the total Ca with albumin correction enables earlier detection of hypercalcaemia. Bisphosphonates are an effective treatment option in controlling severe hypercalcaemia and preventing bone loss.     

Active surveillance for selected patients with renal masses: updated results with long-term follow-up

BACKGROUND: The objective of the current study was to evaluate the outcome of a surveillance strategy in patients with renal masses. METHODS: The medical records of patients with renal masses diagnosed between January 1992 and May 2006 were reviewed retrospectively. In all, 45 patients with renal masses under observation were identified. Of these, 35 patients with 44 renal masses measuring <4 cm in dimension at the time of diagnosis and who were followed for at least 6 months were included in the review. Patients elected observation because of age, comorbidity, solitary kidney, or bilateral renal masses. Medical records were reviewed to determine tumor size and volume changes as well as clinical progression requiring treatment, the development of metastatic disease, or death. RESULTS: A total of 35 patients (21 men and 14 women) with 44 renal masses were observed for a mean follow-up of 47.6 months. The mean age of these patients was 71.8 years. The majority of the patients (89%) were asymptomatic at the time of diagnosis. The mean and median initial tumor dimension was 2.2 cm and 2.2 cm, respectively (range, 0.5-4 cm). Of the 35 patients, 2 (5.7%) were lost to follow-up, 8 (22.9%) underwent surgical resection, and 9 (25.7%) died of other causes. The mean dimension growth rate was 0.21 cm/year (range, 0.03-1.9 cm/year). The mean and median volume growth rate was 2.7 cc/year and 1.4 cc/year, respectively. Progression to metastatic disease was identified in 2 patients (5.7%). CONCLUSIONS: The majority of renal masses will grow if observed and some may require treatment. Initial tumor size cannot predict the natural history of renal masses. A small but non-negligible risk of developing metastatic disease exists in this patient population. Further research should focus on the role of biopsy and on identification of prognostic parameters allowing more accurate prediction of tumor growth and metastasis.     

Magnetic resonance imaging assessment of a convective therapy delivery paradigm in a canine prostate model

PURPOSE: To quantitatively investigate the feasibility of MRI as a tool for assessing the spatial distribution of a convectively delivered agent using a canine prostate model. MATERIALS AND METHODS: Canine prostates (ex vivo, n = 3; in vivo, n = 12) were injected under several injection paradigms with a solution of gadolinium-DTPA for MR contrast and methylene blue as a grossly visible surrogate drug marker. Ex vivo and in vivo distributions were assessed at 1.5T and quantitatively compared. RESULTS: Measured distributions using MRI and methylene blue pathology photographs were analyzed using a Bland-Altman method. The fractional percentage volume covered (V frac) compared the measurements grossly: Pearson's correlation coefficients were R = 0.99 for ex vivo and R = 0.77 for in vivo (P < 0.05). The fractional percentage of area covered (A frac) demonstrated the high degree of spatial correlation between individual slices: R = 0.93 for ex vivo and R = 0.98 for in vivo (P < 0.05). There was no statistically observable bias in scale or offset between the measurements. CONCLUSION: Measured distributions using MRI and pathology were highly correlated and unbiased, indicating the potential of MRI as a tool for quantitative assessment of interstitial delivery of injected therapies in vivo.