Epidemiological aspects of Burkitt's lymphoma in children of Madagascar

RATIONALE: Burkitt lymphoma (LB), a frequent, very progressive cancer with multiple factors, can be cured. However, the mortality rate remains high in Madagascar. OBJECTIVE: To analyse the epidemiological aspects of LB as well as related socio-economical issues in order to improve successful treatment of the disease. METHODS: Retrospective study of files for children aged under 15 years, hospitalised for LB in the Antananarivo oncology unit from October 1985 to June 2000. The inclusion criteria were anatomo-pathological, clinical and/or X-ray results. Studied parameters included age, sex, ethnic group, medical history, and the distance covered by the child before his/her hospitalisation. FINDINGS: The 77 cases of LB represented 16% of all children aged under 15 years seen in the hospital. The characteristics of the cases corresponded to those of African endemic LB. Most of the children with LB came from areas with endemic malaria, the Eastern and the Centre of Madagascar. All of them belonged to underprivileged families. Early medical advice was sought but distance from services delayed treatment. Various units referred the children, but especially oral surgeons (stomatologists) and ORL physicians. CONCLUSION: A strategy to ensure rapid treatment for children suffering from LB should be developed, from their region of origin up until treatment. This should involve parents as well as all members of the medical staff in charge of these children.     

Successful low-dose concurrent chemotherapy and radiation for locally advanced or inoperable non-small cell lung carcinoma: a report of six cases

Many studies now demonstrate high overall response rates with concurrent chemotherapy and radiation (CCR) for locoregionally advanced or inoperable non-small cell lung carcinoma (NSCLC) but often with severe toxicity and only modest improvement in survival beyond 3 years. We report a simple CCR protocol for NSCLC that has resulted in long-term disease-free survival with low toxicity. In this retrospective review, 84 patients with NSCLC were seen between 1985 and 1991. Of these, 10 patients had stage IIIa or IIIb NSCLC without effusion or inoperable NSCLC, with no failed prior treatment at the time of referral for oncology evaluation. Six of these were treated with CCR consisting of three cycles of cisplatin and 5-fluorouracil administered concurrently with radiation treatment followed by maintenance chemotherapy for at least five additional cycles. All six patients treated with this protocol had complete response with minimal side effects. Survival times ranged from 4.5 to more than 10 years. Three patients survived in complete remission; three others were in complete remission at the time of death due to unrelated causes. Stage III NSCLC without effusion and inoperable NSCLC can be treated effectively with concurrent local and systemic treatment without significant toxicity. In patients with complete response, maintenance chemotherapy may overcome residual microscopic systemic disease, leading to long-term survival and possible cure. The CCR strategy that resulted in this favorable outcome is noteworthy and should be pursued in larger numbers of patients.     

IMRT with the use of simultaneous integrated boost in treatment of head and neck cancer: acute toxicity evaluation

Acute toxicity has been evaluated in head and neck cancer patients treated with intensity-modulated radiotherapy using simultaneous integrated boost (SIB-IMRT). The basis of the treatment protocol is an irradiation in 30 fractions with a total dose: 66 Gy to the region of macroscopic tumor, 60 Gy to the region of high-risk subclinical disease and 54 Gy to the region of low-risk subclinical disease. Between December 2003 and September 2005, 38 patients with carcinoma of different locations in the head and neck region were irradiated. Five patients underwent concurrent chemotherapy (weekly cisplatin). Acute toxicity was evaluated according to Radiation Therapy Oncology Group toxicity scale for skin, mucous membrane, salivary glands, pharynx and esophagus and larynx. All 38 patients completed the therapy without urgency of interruption due to acute toxicity of radiotherapy. No patient experienced grade 4 toxicity. More severe toxicity was observed in patients with concurrent chemotherapy. The results confirm that the irradiation according to our SIB-IMRT protocol is a therapy with acceptable toxicity and there is a space for radiobiological enhancement of this regimen by concurrent chemotherapy, e.g. weekly cisplatin.     

Patient understanding of genetic information influences reproductive decision making in retinoblastoma

Background: Retinoblastoma is the most common malignant tumour of the eye in childhood, with nearly all bilateral tumours and around 17% to 18% of unilateral tumours due to an oncogenic mutation in the RB1 gene in the germline. Genetic testing enables accurate risk assessment and optimal clinical management for the affected individual, siblings, and future offspring. Material and Methods: We carried out the first UK‐wide audit of understanding of genetic testing in individuals with retinoblastoma. A total of 292 individuals aged 16 to 45 years were included. Results: Patients with bilateral disease were significantly more likely to understand the implications of retinoblastoma for siblings and children. There was a significant association between not knowing the results of genetic testing or not understanding the implications and not having children, particularly in women. Surprisingly, this was also true for individuals treated for unilateral disease with a low risk of retinoblastoma for their offspring. Conclusion: We are concerned that individuals may be making life choices based on insufficient information regarding risks of retinoblastoma and reproductive options. We suggest that improvement in transition care is needed to enable individuals to make informed reproductive decisions and to ensure optimal care for children born at risk of retinoblastoma.     

Dental and maxillofacial abnormalities following treatment of malignant tumours in children

There is a wide range of malignant tumours with an embryonic origin that can affect children in their early childhood including Rhabdomyosarcoma, Osteosarcoma, Chloroma, Retinoblastoma and neuroblastoma. Different protocols have been developed over the past years to treat these tumours and different combinations of radiotherapy, surgery and chemotherapy were used. This improved the survival rate considerably. This treatment has a marked effect on growth of soft and hard tissues in the affected regions of the head and face, leading to facial and dental abnormalities that become evident with growth. The great effect of radiotherapy and chemotherapy on craniofacial skeletal growth should be considered in all cases undergoing treatment for tumours. The resulting dental and maxillofacial abnormalities should be expected in all cases and its management require involvement of different members of the medical team including maxillofacial surgeon, restorative dentist, orthodontist, psychologist, dietician, speech therapist, the patient and the parents in order to achieve maximum results. This paper presents four patients who underwent radiotherapy and chemotherapy for treatment of embryonic tumours and discusses the main side effects of the treatment.     

ES-IPO-97 treatment protocol for prognostically poor Ewing's sarcoma forms in children: results of implementation

The paper shows the high efficiency and moderate toxicity of inductive treatment in children with Young sarcoma and primitive neuroectodermal tumors by ES-Ipo-97 protocol that includes alternate chemotherapy by the scheme: vincristine, 1.5 mg/m2/day, on days 1, 8, 15; adriamycin, 37.5 mg/m2/day, on days 1 and 2 as 24-hour infusion; cyclophosphanum, 2.1 g/m2/day, on days 1 and 2 (Block A); iphosphamide, 2.4 g/m2/day on days 1 to 5, etoposide, 100 mg/m2/day, on days 1-5 (Block B). It provides evidence for that this therapy is promising and awaits further developments.     

Potential of interferon-alpha in solid tumours: part 2

The second part of this review examines the use of recombinant interferon-alpha (rIFNalpha) in the following solid tumours: superficial bladder cancer, Kaposi's sarcoma, head and neck cancer, gastrointestinal cancers, lung cancer, mesothelioma and ovarian, breast and cervical malignancies. In superficial bladder cancer, intravesical rIFNalpha has a promising role as second-line therapy in patients resistant or intolerant to intravesical bacille Calmette-Guérin (BCG). In HIV-associated Kaposi's sarcoma, rIFNalpha is active as monotherapy and in combination with antiretroviral agents, especially in patients with CD4 counts >200/mm(3), no prior opportunistic infections and nonvisceral disease. rIFNalpha has shown encouraging results when used in combination with retinoids in the chemoprevention of head and neck squamous cell cancers. It is effective in the chemoprevention of hepatocellular cancer in hepatitis C-seropositive patients. In neuroendocrine tumours, including carcinoid tumour, low-dosage (相似文献   

Flat in situ carcinoma of the bladder: cytological examination of urine in diagnosis, follow up, and assessment of response to chemotherapy.

Urine cytology was performed for the diagnosis and follow up of flat carcinoma in situ (CIS) of the bladder in a series of 35 patients without associated or previous bladder tumours. Ninety six per cent had positive or suspicious cytology at initial presentation. There were no false positive reports. Cytological diagnosis of malignancy was made before biopsy in 24 patients: CIS in voided urine presents as flat sheets of five to 15 cells with features of high grade malignancy. Development of tumour during follow up was suggested by the appearance of large thick sheets and clusters of 30 or more malignant cells which were large and pleomorphic in high grade tumours and relatively small and closely cohesive in low grade tumours. Eleven of 13 patients with these clusters had bladder or ureteric tumours and two had malignant disease in the prostate. Negative cytological results in the presence of degenerative changes caused by chemotherapy was an unreliable indicator of response to chemotherapy, and there were five patients with false negative reports during treatment, of whom three had developed tumour. Persistence of malignant cells with features similar to those seen in the urine before treatment reliably predicted failure to respond to chemotherapy.     

Effects of complete androgen blockade for 12 and 24 weeks on the pathological stage and resection margin status of prostate cancer

AIMS: To compare the pathological stage and surgical margin status in patients undergoing either immediate radical prostatectomy or 12 and 24 weeks of neoadjuvant hormonal treatment (NHT) in a prospective, randomised study. METHODS: Whole mount sections of 393 radical prostatectomy specimens were evaluated: 128 patients had immediate surgery, 143 were treated for 12 weeks and 122 for 24 weeks with complete androgen blockade. RESULTS: Histopathology revealed organ confined tumours in 40.4% of patients with clinical stage B disease in the immediate surgery group, whereas 12 and 24 weeks of NHT increased the number of organ confined tumours to 54.6% and 64.8%, respectively. Among patients with clinical stage C tumours, pathological staging found organ confined disease in 10.4%, 31.4%, and 61.2% in the immediate surgery, 12 weeks of NHT, and 24 weeks of NHT groups, respectively. Preoperative NHT caused a significant decrease in positive margins both in patients with clinical stage B and C disease. The extent of margin involvement was not influenced by preoperative treatment. CONCLUSIONS: Neoadjuvant androgenic suppression is effective in reducing both the pathological stage and the positive margin rate in patients with stage B and C prostatic cancer undergoing radical surgery. Some beneficial effects are evident in those patients treated for 24 weeks, and it is reasonable to assume that the optimal duration of NHT is longer than three months.     

Anal carcinoma—a histological review

Epidemiological evidence of an association between anal carcinoma and symptomatic HIV-related disease suggests that the number of cases of this disease may increase significantly over the next few years⁸. The role of oncogenic HPV types in the pathogenesis of anal carcinoma is substantiated by both epidemiological evidence that tumours are associated with a past history of anal warts and by experimental evidence showing that over 85% of tumours contain HPV 16/18 DNA on PCR. The physical state of the virus in the tumour cell genome is currently under investigation, and cellular interactions between HPV, HIV and other sexually transmitted viruses require further research. Clinical studies have shown that patients with anal warts and those who are HIV positive also show an increased tendency to develop dysplasia within the anal epithelium. However, the malignant potential of dysplasia remains unclear and, it presents problems in management, particularly when multifocal and high grade. Problems in classification of anal carcinomas involve both the site of the tumours and the histological appearance. Despite the difficulties which exist in estimating the origin of a tumour from canal or margin, this information does appear to have clinical significance and should therefore continue to be assessed. Recent morphological and keratin studies have emphasized the heterogeneity of these tumours and have revealed a similar heterogeneous profile of keratin expression in the normal anal epithelium. These results support the body of opinion which suggests that, with the exception of small cell carcinoma and adenocarcinoma, anal carcinomas should be considered as squamous cell tumours which are able to display a range of further morphological characteristics within which ductal differentiation and mucin production appear to carry the worst prognosis. Although there is no universally accepted staging system for anal carcinoma, depth of invasion and extent of spread at the time of diagnosis are the most important clinical factors determining survival and response to therapy. Randomized clinical trials are now under way to compare the outcome of various combinations of radiotherapy and chemotherapy, which have replaced radical surgery as a first line treatment and resulted in a significant decrease in patient morbidity from this disease.     

Comparative histopathologic analysis of osteogenic sarcomas before and after initial chemotherapy

We performed comparative histopathologic analysis of sections from diagnostic biopsy and surgical material obtained after antineoplastic chemotherapy. The sections were taken from 20 osteogenic sarcomas found in children and adolescents aged from 3 to 17. Chemotherapy used between samplings was based mainly on Adriamycin, and in four cases Methotrexate. Most frequent changes in histologic structure of the tumours after chemotherapy included further development of necrosis, a reduction of the structural homogeneity of the tumours and enhancement of cellular polymorphism. In many tumours we found enhancement or development of abilities to form cartilaginous foci. We did not observe maturation of the neoplasm induced by chemotherapy in the form of the development of highly differentiated bony tissue. The above-mentioned changes could be defected 3 to 4 weeks after chemotherapy initiation.     

Life-threatening asthma and anaphylaxis in schools: a treatment model for school-based programs.

BACKGROUND: Pediatric asthma is the No. 1 chronic disease in childhood and is responsible for significant morbidity and mortality. In Nebraska, the number of asthma-related deaths is greater than the national average, and in 1998, 2 students died of acute asthma attacks while attending school in the Omaha public schools (OPSs). In response, we designed and implemented a program to respond to this problem. OBJECTIVE: To implement and study a school-based program for the treatment of life-threatening asthma and anaphylaxis in the OPSs. METHODS: The Emergency Response to Life-Threatening Asthma or Systemic Allergic Reactions (Anaphylaxis) Protocol was designed and evaluated in 78 OPSs from 1998 to 2003. Nurses and school staff were trained in the protocol, which required the use of nebulized albuterol and/or intramuscular epinephrine in conjunction with an emergency response procedure. Outcomes were measured by improvement in acute care in schools and survival of students. Results: In the 5 years of evaluation, 98 students were treated successfully. One student died. Of those treated with the protocol, equal numbers had at school both asthma action plans (AAPs) and metered-dose inhalers (MDIs), MDIs only, or neither AAPs nor MDIs. As a result of the program, there has been an increased awareness from parents, teachers, and physicians about the necessity of an emergency response program. In 2002, an outcome of the OPS program resulted in the formation of Attack on Asthma Nebraska to ensure that Nebraska schools have the education, training, and medications to respond to anyone experiencing a life-threatening asthma or anaphylaxis attack at school. The following year, a revised protocol was approved by the Nebraska State Board of Education for use in all Nebraska schools. CONCLUSIONS: Emergency response protocols provide protection for children while in school. This program should serve as a national model for other school-based programs for children and adolescents with asthma and anaphylaxis.     

Adjuvant therapy with GnRH agonists/tamoxifen in breast cancer should be a good council for patients with hormone receptor-positive tumours and wish to preserve fertility

Infertility represents one of the main long-term consequences of the chemotherapy used for the adjuvant treatment of breast cancer. Approximately 60-65% of breast cancers express the nuclear hormone receptor in premenopausal women. Adjuvant endocrine therapy is an integral component of care for patients with hormone receptor-positive (HR+) tumours. The GnRH agonist (GnRHa) alone or in combination with tamoxifen produces results at least similar to those obtained with the different chemotherapy protocols in patients with HR+ breast cancer with respect to recurrence-free survival and overall survival. It is time to indicate adjuvant therapy with GnRHa associated with tamoxifen for patients with breast cancer (HR+ tumours) if they want to preserve their reproductive function. The evaluation of ovarian reserve tests: follicle stimulating hormone (FSH), anti-Mullerian hormone (AMH), inhibin B, antral follicle count (AFC) and ovarian volume 6 months, and 1 year after the end of therapy with GnRHa/tamoxifen must be realised. The recurrence-free survival and overall survival should be analysed. The major implication of this hypothesis will be to avoid adjuvant chemotherapy for patients with breast cancer (HR+ tumours) that request fertility preservation. It is expected that ovarian function should not be altered in almost all cases and subsequent pregnancy a real possibility.     

von Hippel-Lindau disease: Updated guideline for diagnosis and surveillance

von Hippel Lindau disease (vHL) is caused by a hereditary predisposition to multiple neoplasms, especially hemangioblastomas in the retina and CNS, renal cell carcinomas (RCC), pheochromocytomas, neuroendocrine pancreatic tumours (PNET) and endolymphatic sac tumours. Evidence based approaches are needed to ensure an optimal clinical care, while minimizing the burden for the patients and their families.This guideline is based on evidence from the international vHL literature and extensive research of geno- and phenotypic characteristics, disease progression and surveillance effect in the national Danish vHL cohort. We included the views and preferences of the Danish vHL patients, ensured consensus among Danish experts and compared with international recommendations.RecommendationsvHL can be diagnosed on clinical criteria, only; however, in most cases the diagnosis can be supported by identification of a pathogenic or likely pathogenic variant in VHL. Surveillance should be initiated in childhood in persons with, or at risk of, vHL, and include regular examination of the retina, CNS, inner ear, kidneys, neuroendocrine glands, and pancreas. Treatment of vHL manifestations should be planned to optimize the chance of cure, without unnecessary sequelae. Most manifestations are currently treated by surgery. However, belzutifan, that targets HIF-2α was recently approved by the U.S. Food and Drug Administration (FDA) for adult patients with vHL-associated RCC, CNS hemangioblastomas, or PNETs, not requiring immediate surgery. Diagnostics, surveillance, and treatment of vHL can be undertaken successfully by experts collaborating in multidisciplinary teams. Systematic registration, collaboration with patient organisations, and research are fundamental for the continuous improvement of clinical care and optimization of outcome with minimal patient inconvenience.     

Development of an experimental model for the study of the effects of cryotherapy on lung tumours

Adenocarcinomas are today the most frequent lung cancers. They are mainly treated by surgery or by chemotherapy, but for the most advanced stages a local cryotherapy can be proposed as a palliative option for bronchial desobstruction. AIM OF THE STUDY: The aim of this work was to establish an experimental model to study in vivo the biological effects of this technique to propose it as a neoadjuvant treatment. MATERIALS AND METHODS: A xenograft system was used: cells from the A549 cell line were injected subcutaneously into SCID mice. Tumour nodes could be treated after seven weeks. The histological study showed that these tumours faithfully reproduced the morphological features of adenocarcinoma, and developed an intratumoral neovascularization. Two protocols of cryotherapy (1 vs 3 cycles of freezing) were performed and the induction of apoptosis was analyzed by immunohistochemical staining of cleaved caspase-3. RESULTS: The basal expression of cleaved caspase-3 in untreated tumours (23%) increased after cryotherapy. The increase was maximal eight hours after treatment (up to 47% of positive cells) and was less important with the first protocol, suggesting a lesser efficiency in the induction of apoptosis. CONCLUSION: The establishment of this model, which is faithful to physiological features, allowed us to demonstrate in vivo time and dose-dependent effects of cryotherapy.     

Treatment of limb osteosarcoma at the turn of the century (half century of experience in research)]

The Russian Cancer Research Center has experience in diagnosing and treating more than 800 patients with osteosarcoma who have been treated at the Clinic of General Oncology since 1952. Survival rates were no more than 10% before the 1970s when the only treatment was surgical. The use of adjuvant chemotherapy after radical surgery has increased survival up to 45-60%. In 1982 to 1986, a protocol involving intraarterial chemotherapy with adriamycin, 90 mg/m2, radiation therapy in a dose of 40 Gy, preserving surgery, and adjuvant chemotherapy was used to improve local and regional guidance. Survival was 55-60%. The high incidence of purulent complications prompted us to do away with radiation therapy. A protocol of neoadjuvant therapy that implies preoperative intraarterial monotherapy with cisplatin, 120-150 mg/m2, adriamycin, 90 mg/m2 or large-dose methotrexate (8-10 g/m2) was implemented in 1986 to 1998. The best results were achieved only in patients with complete tumor necrosis, among whom survival being over 70%. Preserving surgery following ineffective chemotherapy caused a high incidence of local relapses (30%). The second line of chemotherapy did not greatly improve prognosis when a histological response was slight. Complete tumor necrosis was noted only 10% of more than 150 patients so survival in the whole group was 40%. In 1998, a new protocol was initiated to improve immediate and late outcomes. Preoperatively, 3-4 sessions with adriamycin, 90 mg/m2 and cisplatin, 120 mg/m2, are performed. Postoperatively, 3 or 4 sessions of chemotherapy with the same drugs are made if there is a marked therapeutical pathomorphism. If a response is weak, 6 sessions with ethoposide, 100 mg/m2 and iphosphamide, 1.8 g/m2 during 1-5 days are given. This study has covered just 30 patients. The rate of a full histological responses has increased by 4 times. In every second patient, an amputable tumor could be made a resectable one. The proportion of candidates for preserving surgery has increased up to 90%. Intensified chemotherapy increased the incidence of severe adverse effects, primarily degrees 3-4 hematological toxicity reaching 40%. At the turn of centuries, osteosarcoma is a highly promising curable disease. The survivals of 65-70% and satisfactory functional results can be achieved only at highly specialized centers.     

Immunohistochemical staining for ferritin in neuroblastomas

Immunohistochemical staining for ferritin was examined in 35 neuroblastomas from 27 children and compared with serum ferritin levels. All but two of the patients presented with advanced (stages III and IV) disease, and the adrenal was the most common primary site (20/27, 74%). Immunostaining was positive in only one of 14 tumour biopsies taken at the time of diagnosis (7%), but eight of 21 neuroblastomas (38%) marked for ferritin after chemotherapy. No consistent association was established between tumour- and serum-associated ferritins in the untreated or treated groups. Ferritin staining in treated neuroblastomas was usually more marked in partly differentiated tumour cells. The increased frequency of ferritin positive neuroblastomas after chemotherapy appeared to be associated with large local accumulations of ferritin and haemosiderin within the treated tumours, and (probably) with the blood transfusions which these children received.     

Motor and perceptual timing deficits among survivors of childhood leukemia

OBJECTIVE: There is growing evidence of cerebellar-frontal system change in children treated for leukemia with chemotherapy alone (Lesnik et al., 1998). METHODS: We compared 22 long-term survivors of acute lymphoblastic leukemia (ALL), aged 8-18, to 22 age- and gender-matched controls on tasks emphasizing cerebellar-frontal functioning including judgment of time duration and motor timing. Groups were also compared on a judgment of pitch task, used as a control measure. Children with ALL were at least 5 years from diagnosis, treated with intrathecal chemotherapy (methotrexate in all, hydrocortisone and cytarabine in 20/22), but not radiation therapy, and free from recurrence of disease. RESULTS: After controlling for IQ, the ALL group had poorer performance than controls on judgment of long duration and motor timing, but not judgment of pitch. CONCLUSIONS: Treatment with intrathecal and infusional chemotherapy for childhood ALL may be associated with skill deficits comparable to those seen in individuals with cerebellar-frontal abnormalities.     

Genetic diversity of Borrelia burgdorferi and detection of B. bissettii-like DNA in serum of north-coastal California residents

In North America, Lyme borreliosis (LB) is a tick-borne disease caused by infection with the spirochete Borrelia burgdorferi. We studied the genetic diversity of LB spirochetes in north-coastal California residents. Spirochete DNA was detected in 23.7% (27/114) of the study subjects using a PCR protocol optimized for increased sensitivity in human sera. Californians were most commonly infected with B. burgdorferi ospC genotype A, a globally widespread spirochete associated with high virulence in LB patients. Sequence analysis of rrf-rrl and p66 loci in 11% (3/27) of the PCR-positive study subjects revealed evidence of infection with an organism closely related to B. bissettii. This spirochete, heretofore associated with LB only in Europe, is widely distributed among ticks and wildlife in North America. Further molecular testing of sera from residents in areas where LB is endemic is warranted to enhance our understanding of the geographic distribution and frequency of occurrence of B. bissettii-like infections.     

Prehospital management of burns

The optimal assessment of the burn victim in the prehospital setting needs a clear understanding of the pathophysiological changes occurring locally and systemically after injury. For the mobile emergency unit it is essential to dispose of an appropriate protocol for the prevention of hypovolemia, hypothermia, hypoxemia. In the immediate survey, immediate life-threatening conditions should be clearly identified and treated as well as a through head-to-toe evaluation should be undertaken. Two phases of transport can be identified: the first from the scene of accident to the proximal emergency unit, specialized or not in burn care. The second is the transportation from the non-specialized proximal emergency unit to a burn intensive care unit according to the decision of the dispatching Centre 15.