Cutaneous angiosarcoma of the scalp: a multidisciplinary approach

BACKGROUND: Angiosarcoma is a malignant tumor of vascular endothelial cells that arises in the head and neck. It is a rare, difficult to treat, and lethal tumor. METHODS: Clinical data from patients who were diagnosed with angiosarcoma of the scalp between 1975 and 2002 at the University of Michigan were reviewed. Analysis was performed to assess for factors impacting time to recurrence and survival. RESULTS: The study was comprised of 29 patients with a median age of 71.0 years. Most patients presented after a delay in diagnosis with either a bruise-like macule (48.3%) or a nonbruise-like nodule (51.7%). Seventy-five percent of patients had pathologic Stage T2 disease, and 76% of patients had high-grade tumors. Virtually all patients underwent surgical excision (96.6%); however, negative surgical margins were achieved in only 21.4% of patients. Multiple lesions on presentation were associated with a shorter time to recurrence (P = 0.02). The median actuarial survival was 28.4 months. Younger patients and patients with Stage T1 disease had improved survival (P = 0.024 and P = 0.013, respectively). Radiation therapy was associated significantly with a decreased chance of death (hazard ratio, 0.16; P = 0.006). CONCLUSIONS: Although surgery remains the first option for the treatment of patients with angiosarcoma of the scalp, achieving negative margins often is impossible. Patients who are younger and who have less extensive disease fare better. Postoperative radiation therapy should be employed routinely, as it may lead to improved survival.     

Impaired gastric ulcer healing in diabetic rats: role of heat shock protein, growth factors, prostaglandins and proinflammatory cytokines

Gastric mucosa of diabetic rats is highly vulnerable to acute injury, but little is known about the influence of diabetic conditions on the healing of gastric ulcers. In this study, streptozotocin (70 mg/kg injected intraperitoneally) was used to induce diabetes mellitus in rats. Four weeks after streptozotocin injection, gastric ulcers were induced using the acetic acid method, and 10 days later, the healing rate and the gastric blood flow (GBF) were measured by planimetry and hydrogen (H(2))-gas clearance method, respectively. Six major groups of rats with gastric ulcers were used: (1) vehicle (saline); (2) streptozotocin alone; (3) insulin (4 IU/day intraperitoneally); (4) streptozotocin plus insulin; (5) pentoxifylline, an inhibitor of synthesis and release of tumor necrosis factor-alpha (TNF alpha); and (6) aspirin, a non-selective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2), and rofecoxib, the highly selective COX-2. In the diabetic rats, a significant delay in ulcer healing ( approximately by 300%), accompanied by a decrease in the gastric mucosal blood flow was observed. The prolongation of the healing in diabetic animals was associated with an increase in gastric mucosal expression and release of TNFalpha, interleukin-1 beta (IL-1 beta), suppression of the vascular endothelial growth factor (VEGF), platelet endothelial cell adhesion molecule-1 (PECAM-1) and the mucosal overexpression of heat shock protein 70 (HSP 70). Administration of insulin reversed the delay in ulcer healing and significantly decreased the expression of IL-1 beta and TNF-alpha, while producing the rise in the expression of VEGF and PECAM. Pentoxifylline, an inhibitor of TNF-alpha, which by itself accelerated ulcer healing in non-diabetic rats, counteracted the increase in the area of gastric ulcer induced by streptozotocin, raised significantly gastric blood flow and suppressed the plasma TNF-alpha levels. Aspirin and rofecoxib, that significantly suppressed the mucosal prostaglandin E(2) generation in ulcer area, delayed significantly the rate of ulcer healing and decreased the GBF at ulcer margin in non-diabetic rats, and these changes were significantly augmented in diabetic animals. We conclude that: (1) Experimental diabetes dramatically impairs ulcer healing, depending upon the increased release of proinflammatory cytokines and the attenuation of angiogenesis that can limit the ulcer healing effects of locally produced HSP 70 and TNF-alpha. (2) Insulin reversed this impairment of ulcer healing in diabetic rats, mainly due to the enhancement of angiogenesis and reduction in expression of cytokines in the ulcer area. (3) Classic non-steroidal anti-inflammatory drugs such as aspirin prolonged ulcer healing under diabetic conditions due to suppression of endogenous prostaglandins and the fall in the microcirculation at the ulcer margin and these effects were mimicked by selective, so called "safe" COX-2 inhibitor, rofecoxib, suggesting that both COX isoforms are important sources of prostaglandins that are essential in the ulcer healing in diabetes.     

Lack of effect of physical exercise on pharmacokinetics of acetaminophen tablets in healthy subjects

The study was designed to evaluate the effect of physical exercise on the pharmacokinetics of acetaminophen. Ten healthy volunteers were drawn to the investigation. Each person was subjected to the pharmacokinetic study twice, i.e. at rest and on an exercise day. On the exercise day the subjects were performing 3 hours long physical exercise which consisted of a walk on a treadmill at 3 mph for 20 minutes of each half an hour. Acetaminophen was given orally at a single dose of 1.0 g prior to the exercise. Blood for pharmacokinetic assay was sampled within 24 hours following the drug administration. Acetaminophen concentrations were determined by the FPIA method. The total concentrations versus time curve were described by the one-compartment open model for extravascular administration. It was revealed, that the standard submaximal physical exercise does not affect the pharmacokinetics of acetaminophen statistically significantly.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Detection of carbamyl phosphate synthetase 1 deficiency using duodenal biopsy samples

The activity of urea cycle enzymes was assayed in duodenal biopsy specimens obtained from a female infant who presented with neonatal hyperammonaemia. All enzyme levels were normal except N-acetyl glutamate-dependent carbamyl phosphate synthetase 1 (CPS1) which was half the mean activity in normal control specimens. A similar deficiency of CPS1 was also shown in duodenal specimens from the patient's mother who became slightly symptomatic after relatively high protein meals and during pregnancy, and had spontaneously modified her diet to one with protein restriction. The patient is growing normally on a dietary regimen similar to that spontaneously adopted by her mother. Urea cycle enzyme activity in the duodenal biopsy material from the controls was similar to that found in the normal human liver and appears to have distinct advantages as a means of assaying for urea cycle defects in patients with hyperammonaemia and their relatives.     

Rare detection of hepatitis B and hepatitis C virus genomes by polymerase chain reaction in seronegative donors with elevated alanine aminotransferase

BACKGROUND: Since screening for antibody to hepatitis C virus (HCV) was introduced in 1990, posttransfusion hepatitis has been reduced to nearly background levels. This has led to reconsideration of the value of testing donated blood for elevated alanine aminotransferase (ALT). The contribution of ALT testing in detecting seronegative infection was evaluated by the performance of polymerase chain reaction (PCR) for hepatitis B virus (HBV) or HCV in plasma from ALT-elevated blood units. STUDY DESIGN AND METHODS: Testing was performed on 375 units of plasma, derived from an equivalent of 47,500 blood donations, with a highly sensitive hemi-nested PCR procedure. Using a triplet of primers directed at the conserved regions of HBV DNA and 5'-noncoding regions of HCV RNA, the hemi-nested PCR assay can reliably amplify 10 viral molecules to levels detectable in ethidium bromide-stained agarose gels. Pools of plasma from groups of four donors were screened with hemi-nested PCR. For any reactive pools, the plasma from individual donors was retested twice on different aliquots. RESULTS: Two of 375 units, both with midrange ALT elevation, were repeatedly reactive in hemi-nested PCR (one each for HBV DNA and HCV RNA). However, samples from the two suspect donors tested 9 and 5 months later revealed no seroconversion, elevated ALT, or viral genomes in hemi-nested PCR. CONCLUSION: The lack of confirmed HBV or HCV infection in this study representing an estimated 47,500 voluntary blood donations suggests that routine ALT testing for further prevention of posttransfusion hepatitis after exclusion of HBV- and/or HCV-seropositive blood may be superfluous.     

Preoperative Estimated Risk of Microvascular Invasion is Associated with Prognostic Differences Following Liver Resection Versus Radiofrequency Ablation for Early Hepatitis B Virus-Related Hepatocellular Carcinoma

Annals of Surgical Oncology - The aim of this study was to examine prognostic differences between liver resection (LR) and percutaneous radiofrequency ablation (PRFA) for hepatocellular carcinoma...     

Liver-Directed Therapy in Metastatic Colorectal Cancer

Approximately 50–70 % of patients with colorectal cancer ultimately develop colorectal liver metastases. Determining which patients may benefit from aggressive treatment has historically been achieved through clinical predictive models. However, factors such as radiographic response to neoadjuvant therapy should also be taken into consideration. Recently, molecular markers have emerged as an adjunct to clinical-pathologic factors and provide a surrogate for tumor biology. With improved understanding of tumor biology, the likelihood of recurrence can be better predicted. However, when feasible, the best chance for cure entails surgical resection as a part of multimodal therapy, and select patients can achieve prolonged median survival. Alternatively, ablation techniques may be used in conjunction with surgery or as isolated therapy in patients who are not candidates for surgical resection. Transarterial therapy may also provide clinical benefit in certain patient subsets with unresectable disease. These strategies have allowed for a more tailored approach to patients with colorectal liver metastases.     

Association of pre-existing mental illness with all-cause and cancer-specific mortality among Medicare beneficiaries with pancreatic cancer

BackgroundAmong patients with pancreatic cancer, the association of pre-existing mental illness with long-term outcomes remains unknown.MethodsIndividuals diagnosed with pancreatic adenocarcinoma were identified in the SEER-Medicare database. Patients were classified as having mental illness if an ICD9/10CM code for anxiety, depression, bipolar disorder, schizophrenia or other psychotic disorder was recorded.ResultsAmong the 54,234 Medicare beneficiaries with pancreatic cancer, roughly 1 in 12 (n = 4793, 8.83%) individuals had a diagnosis of a mental illness. The majority (n = 4029, 84.1%) had anxiety or depression, while 16% (n = 764) had bipolar/schizophrenic disorders. On multivariable analysis, among patients with early stage cancer, individuals with pre-existing anxiety/depression and bipolar/schizophrenic disorders had 22% (OR 0.78, 95% CI 0.69–0.86) and 46% (OR 0.54, 95% CI 0.42–0.70) reduced odds, respectively, to undergo cancer-directed surgery. Furthermore, patients with a pre-existing history of bipolar/schizophrenic disorders had a 20% (HR 1.20, 95% CI 1.21–1.40) higher risk of all-cause mortality and 27% (HR 1.27, 95% CI 1.17–1.37) higher risk of pancreatic cancer-specific mortality compared to individuals without a history of mental illness.ConclusionOne in twelve patients with pancreatic cancer had a pre-existing mental illness. Individuals with mental illness were more likely to have worse overall and cancer-specific long-term outcomes.