Does induction chemotherapy have a role in the management of nasopharyngeal carcinoma? Results of treatment in the era of computerized tomography

To assess the outcomes of patients with nasopharyngeal carcinoma (NPC) whose treatment was determined by computerized tomography (CT) and/or magnetic resonance imaging staging and to analyze the impact of induction chemotherapy and accelerated fractionated radiotherapy.

The analysis is based on 122 of 143 previously untreated patients with NPC treated with radiation therapy at The University of Texas M. D. Anderson Cancer Center between 1983 and 1992. Excluded were 4 patients treated with palliative intent, 4 children, 12 patients not staged with CT, and 1 patients who died of a cerebrovascular accident prior to completion of treatment. The stage distribution was as follows: AJCC Stage I---2; Stage II---7, Stage III---12, Stage IV---101; T1---15; T2---33, T3---22; T4---52; N0---32; N1---10; N2---47, N3---32, Nx---1. Fifty-nine (48%) patients has sqamous cell carcinoma; 63 (52%) had lymphoepitheliomas, undifferentiated NPC or poorly differentiated carcinoma, NOS (UNPC). Sicty-seven patients (65 with Stage IV disease) received induction chemotherapy. Fifty-eight patients (24 of whom had induction chemotherapy) were treated with the concomitant boost fractionation schedule. The median follow-up for surviving patients was 57 months.

The overall actuarial 2- and 5-year survival rates were 78 and 68%, respectively. Forty-nine patients (40%) has disease recurrence. Thirty-three (27%) had local regional failures; 19 at the primary site only, 8 in the neck and 6 in both. Local failure occurred in 31% of patients staged T4 compared to 13% of T1–T3 (p = 0.007). Sixteen patients failed at distant sites alone. Among Stage IV patients the 5-year actuarial rates for patients who did and did not receive induction chemotherapy were as follows: overall survival: 68 vs. 56% p = 0.02), freedom from relapse; 64 vs. 37% (p = 0.01), and local control: 86 vs. 56% (p = 0.009). The actuarial 5-year distant failure rate in patients with UNPC who were treated with induction chemotherapy and controlled in the primary and neck was 13%. In patients who did not receive chemotherapy, the acturial 5-year local control rates for patients treated with concomitant boost or conventional fractionation were 66 and 67%, respectively.

While not providing conclusive evidence, this single institution experience suggests that neoadjuvant chemotherapy for Stage IV NPC patients improves both survival and disease control. Recurrence within the irradiated volume was the most prevalent mode of failure and future studies will evaluate regimens to enhance local regional control.     

Dietary beta-carotene stimulates cell-mediated and humoral immune response in dogs

The role of beta-carotene on immune response in domestic dogs is not known. Female Beagle dogs were fed 0, 2, 20 or 50 mg beta-carotene/d; blood was sampled at wk 0, 1, 2, 4 and 8 for analysis of the following: lymphoproliferation, leukocyte subpopulations and concentrations of interleukin-2 (IL-2), immunoglobulin (Ig)G and IgM. Delayed-type hypersensitivity (DTH) response was assessed at wk 0, 3 and 7. beta-Carotene supplementation increased plasma beta-carotene concentrations in a dose-dependent manner. Compared with unsupplemented dogs, those fed 20 or 50 mg of beta-carotene had higher CD4+ cell numbers and CD4:CD8 ratio. However, there was no treatment difference in CD8+, CD21+ and major histocompatability complex (MHC) class II+ cells. Plasma IgG, but not IgM concentration was higher in dogs fed beta-carotene throughout the study period. The DTH response to phytohemagglutinin (PHA) and vaccine was heightened in beta-carotene-supplemented dogs. beta-Carotene feeding did not influence mitogen-induced lymphocyte proliferation or IL-2 production. Immune response was impaired in dogs classified as low beta-carotene absorbers compared with similar dogs fed the same amount of beta-carotene. Therefore, dietary beta-carotene heightened cell-mediated and humoral immune responses in dogs.     

Anomalous portal venous connection to the suprahepatic vena cava: sonographic demonstration

The authors report a congenital portosystemic shunt which was detected with ultrasound in an infant with a fatal congenital hypertrophic cardiomyopathy. An aberration in primitive vitelline venous development may have contributed to the formation of this unusual vessel.     

Guanidinoacetate methyltransferase (GAMT) deficiency diagnosed by proton NMR spectroscopy of body fluids

In patients with guanidinoacetate methyltransferase (GAMT) deficiency several parameters may point towards the diagnosis of GAMT deficiency. These include the low levels of creatine and creatinine in urine, the high concentration of guanidinoacetic acid (GAA) in urine and the low levels of creatine and creatinine in the cerebrospinal fluid (CSF). In this study, body fluids from 10 GAMT deficient patients were analysed using ¹H NMR spectroscopy. The urine 1D ¹H NMR spectra of all the patients showed a doublet resonance at 3.98 ppm (pH 2.50) derived from GAA present in high concentration. For this compound, a good recovery and good correlation was found between an LC‐MS/MS method and ¹H NMR spectroscopy. In CSF NMR spectra of these patients, the singlet resonances of creatine and creatinine (3.05 and 3.13 ppm, respectively) were absent (normally always present in ¹H NMR spectra of CSF). Due to overlap by other resonances, the doublet of GAA could not be observed. Our data demonstrate that ¹H NMR spectroscopy of urine and CSF can be used to diagnose patients with GAMT deficiency. Copyright © 2009 John Wiley & Sons, Ltd.     

Brain tissue PO2, PCO2, and pH during cerebral vasospasm

BACKGROUND

The purpose of the present study was to assess brain tissue monitoring for detection of ischemia due to vasospasm in aneurysmal subarachnoid hemorrhage (SAH) patients.

METHODS

After obtaining informed consent, a burr hole was made in 10 patients and a Neurotrend 7 probe was inserted ipsilateral to the region of SAH. In eight patients the probe was inserted during surgery for clipping the aneurysm and in two patients the probe was inserted in the neurosurgery ICU. Brain tissue gases and pH were collected over 6-hour periods for 7 to 10 days until the termination of monitoring. The onset of vasospasm was confirmed by angiography and xenon computed tomography (Xe/CT) cerebral blood flow studies.

RESULTS

Seven patients did not develop vasospasm during monitoring and were considered as controls. In this group, brain tissue oxygen pressure (PO₂) remained above 20 mmHg, carbon dioxide pressure (PCO₂) stabilized at 40 mmHg and pH remained between 7.1 and 7.2. In three patients who developed vasospasm during monitoring, PO₂ was not different from the control group. However, PCO₂ increased to 60 mmHg and pH decreased to 6.7 (p < 0.001).

CONCLUSION

In this study, patients with SAH who developed vasospasm had significantly lower brain tissue pH and higher PCO₂ compared to controls. However, there was no significant change in PO₂ levels associated with vasospasm. Brain tissue monitoring can provide an indication of ischemia during vasospasm.     

Primary chronic sclerosing (Garré's) osteomyelitis in children.

Three children with unifocal nonpyogenic inflammatory bony lesions with a prolonged, fluctuating course are reported. The lesions were located at the metaphyseal region of long bones. Three was progressive sclerosis and hyperostosis in the tibia or femur, such as the changes described in Garré's osteomyelitis. No pus was released by exploration of the lesions. Tissue and blood cultures were negative. The histology was typical of chronic osteomyelitis: the symptoms returned intermittently over several years, together with the development of sclerosis but without disturbance of bone growth. It is not clear whether Garré's chronic sclerosing osteomyelitis is a different entity from chronic recurrent multifocal osteomyelitis.