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.     

Inhibition of fluorouracil-induced stomatitis by oral cryotherapy

Mucositis is a significant dose-limiting toxicity associated with fluorouracil (5FU), particularly when it is combined with leucovorin. We hypothesized that oral cryotherapy would cause local vasoconstriction and would temporarily decrease blood flow to the oral mucous membranes. If cryotherapy were used during the time of peak serum 5FU levels, then the oral mucous membranes would have less exposure to 5FU and thus develop less mucositis. To test this hypothesis, 95 patients scheduled to receive their first cycle of 5FU plus leucovorin were randomized to have oral cryotherapy at the time of chemotherapy administration or to serve as a control group. Subsequent mucositis was significantly reduced in the group assigned to receive cryotherapy as judged by the attending physicians (P = .0002) and by the patients themselves (P = .0001). We now routinely recommend this cryotherapy procedure for our patients receiving daily bolus 5FU plus leucovorin.     

Hilar masses: evaluation with CT-guided biopsy after negative bronchoscopic examination

Computed tomography (CT)-guided biopsies of 20 patients with hilar masses were performed after non-diagnostic bronchoscopic examination. Bronchoscopy included washings, brushings, routine biopsy, and, in many cases, transbronchial biopsy. In all but one case (95%), biopsy with a 22-gauge needle permitted a cytologic diagnosis of malignancy. In 14 of the 19 cases (74%), a diagnosis of primary lung carcinoma involving the hili was made, and in the remaining five of the 19 (26%), metastatic hilar adenopathy from an extrathoracic primary tumor was identified. A pneumothorax rate consistent with our average rate for CT-guided biopsies (25%) was obtained, and only one patient required chest tube placement. In this series, CT-guided biopsies of hilar masses were more consistently successful in obtaining tissue for diagnosis than were bronchoscopic biopsies. Transthoracic needle aspiration biopsy may be the preferred initial diagnostic procedure in many patients with hilar masses.     

IgM Monoclonal Gammopathy of Undetermined Significance and Smoldering Waldenström's Macroglobulinemia

Immunoglobulin M monoclonal gammopathy of undetermined significance (IgM-MUS) was diagnosed in 213 Mayo Clinic patients who were residents of 11 counties in southeastern Minnesota from 1960 to 1994. During long-term follow-up, 29 (14%) developed non-Hodgkin lymphoma (n = 17), Waldenström's macroglobulinemia (WM; n = 6), chronic lymphocytic leukemia (n = 3), and AL amyloidosis (n = 3) with relative risks of 15-, 262-, 6-, and 16-fold, respectively. The cumulative probability of progression to one of these disorders was 10% at 5 years, 18% at 10 years, and 24% at 15 years, approximately 1.5% per year. Smoldering WM was identified in 48 patients at Mayo Clinic from 1974 to 1995. During follow-up, 33 of the 48 patients progressed to symptomatic WM. The median time to progression was 4.6 years. The risk of progression to WM was 6% at 1 year, 39% at 3 years, and 55% at 5 years.     

Risk to Tourists Posed by Wild Mammals in South Africa

BACKGROUND: One of South Africa's principal tourist attractions is the opportunity to encounter Africa's large mammals in the wild. Attacks by these mammals can be exceptionally newsworthy with potentially deleterious effects on tourism. Little is known about the risk of injury and death caused by wild mammals to visitors to South Africa's nature reserves. The aim of this study was to determine the incidence of fatal and nonfatal attacks on tourists by wild mammals in South Africa and to ascertain avoidable factors, if any. METHODS: Commercial press records covering all South African Newspapers archived at the Independent Newspapers' central library were systematically reviewed for a 10-year period, January 1988 to December 1997 inclusive, to identify all deaths and injuries to domestic and international tourists resulting from encounters with wild mammals in South Africa. All of these incidents were analyzed to ascertain avoidable factors. RESULTS: During the review period seven tourists, including two students from Thailand and a German traveler, were killed by wild mammals in South Africa. Three of the four deaths ascribed to lions resulted from tourists carelessly approaching prides on foot in lion reserves. A judicial inquiry found that the management of a KwaZulu-Natal Reserve was culpable for the remaining death. Tourist ignorance of animal behavior and flagrant disregard of rules contributed to the two fatalities involving hippopotami. The unusual behavior manifested by the bull elephant responsible for the final death, resulted from discomfort caused by a dental problem to this pachyderm. During the same period there were 14 nonfatal attacks on tourists, including five by hippo, three by buffalo, two by rhino, and one each by a lion, leopard, zebra and musth elephant. Only the latter occurred while the visitor was in a motor vehicle. Tourist ethological naivete and failure to determine the experience of trail guides prior to travel, resulted in inadvertent agonistic behavior, unnecessary risk-taking and avoidable injury. CONCLUSIONS: This retrospective study has shown that attacks on tourists by wild mammals in South Africa are an uncommon cause of injury and death. Sensible precautions to minimize this risk include remaining in a secure motor vehicle or adequately fenced precincts while in the vicinity of large mammals, rigidly observing nature reserve instructions, never approaching animals that appear ill, malnourished, displaying aggressive behavior traits or female wild mammals with young, and demanding adequately trained and experienced game rangers when embarking on walking trails. Any behavior that might be construed as antagonistic and which could provoke an attack by large mammals should be avoided (e.g., driving directly at a lion). Visitors need to be informed of classic signs of aggression, in particular in elephants, which will allow timely avoidance measures to be taken. The risk-enhancing effect of excessive alcohol intake is undesirable in the game reserve setting, as is driving at high speed after dusk in areas where hippos graze. Local advice on personal safety in wildlife reserves and the credentials of trail guides should be obtained from lodge or reserve management, tourism authorities or the travel industry prior to travel to game reserves.     

Primary cutaneous carcinosarcoma: review and presentation of a case with emphasis on clinical characteristics and management

Carcinosarcomas are rare malignant biphasic tumours that contain intermingled carcinomatous and sarcomatous elements. Primary cutaneous carcinosarcomas (PCCS) are extremely rare. We present the 20th reported case and review the literature especially regarding histogenesis and clinical features such as diagnosis and management. PCCS resembles other non-melanocytic neoplasms of the skin. Diagnosis is obtained by primary excision with subsequent histologic and immunohistochemical examination. PCCS is a potentially lethal neoplasm, but radical surgery is successful in most cases.     

Disease-free survival after autologous bone marrow transplantation in patients with acute myelogenous leukemia

Autologous bone marrow transplantation (ABMT) makes it possible to escalate the dose of cytotoxic treatment to a lethal range. Disease- free survival (DFS) following myeloablative therapy and ABMT has been shown to be superior to conventional treatment in high risk patients with acute myelogenous leukemia (AML). It was the purpose of the present study to compare hematopoietic reconstitution, actuarial DFS, and relapse rate of patients transplanted in first complete remission (CR) of AML with those in second or subsequent CR, and to evaluate transplant related mortality. Fifty-two patients with AML, 22 in first CR (low risk) and 30 in second or subsequent CR (high risk), underwent total body irradiation (12.1 to 16.7 Gy) and cyclophosphamide (CY) treatment (200 mg/kg) followed by ABMT. The autograft was incubated with the active CY derivative Mafosfamide (ASTA Werke, Bielefeld, Federal Republic of Germany) to reduce the number of possibly contaminating clonogenic tumor cells. All patients showed three lineage engraftments with platelet recovery observed as being the slowest. The transplant related death rate was low at 5.8%. There was no significant difference in the kinetics of polymorphonuclear (PMN) cell or platelet reconstitution between the low and high risk patient subgroups. The estimated probability of DFS (relapse) after ABMT in first CR was 61% (36%) compared with 34% (65%) in second or subsequent CR, the longest follow-up being 55 months and 57 months, respectively (median follow-up 31 months and 19 months, respectively). ABMT offers a stable long-term DFS when performed in first CR with no relapses occurring in over a year after transplantation. Six later relapses, however, were seen after ABMT in second or subsequent CR, although DFS was not statistically different from that of first remission patients (P = .72).     

EMPHYSEMATOUS PYELONEPHRITIS RESPONDING TO MEDICAL THERAPY

We describe two type 2 diabetic patients with unilateral emphysematous pyelonephritis who responded to medical treatment alone. Escherichia coli was isolated in both patients. The presence of gas was confirmed early by ultrasound and CT scan of abdomen. Following treatment, good functional recovery was demonstrable in the affected kidneys by isotope renogram. We stress the need for early diagnosis of this condition and aggressive treatment with broad spectrum antibiotics.