Penicillin vs. erythromycin in the treatment of diphtheria

PURPOSE: To review the University of Florida experience in treating ependymomas, analyze prognostic factors, and provide treatment recommendations. METHODS AND MATERIALS: Forty-one patients with ependymoma and no metastases outside the central nervous system received postoperative radiotherapy with curative intent between 1966 and 1989. Ten patients had supratentorial lesions, 22 had infratentorial lesions, and 9 had spinal cord lesions. All patients had surgery (stereotactic biopsy, subtotal resection, or gross total resection). Most patients with high-grade lesions received radiotherapy to the craniospinal axis. Low-grade intracranial lesions received more limited treatment. Spinal cord lesions were treated using either partial spine or whole spine fields. RESULTS: Of 32 intracranial tumors, 21 recurred, all at the primary site; no spinal cord tumors recurred. Overall 10-year survival rates were 51% (absolute) and 46% (relapse-free); by tumor site: spinal cord, 100%; infratentorial, 45%; supratentorial, 20% (p = 0.002). On multivariate analysis, tumor site was the only factor that influenced absolute survival (p = 0.0004); other factors evaluated included grade, gender, age, duration of symptoms, resection extent, primary tumor dose, treatment field extent, surgery-to-radiotherapy interval, and days under radiotherapy treatment. CONCLUSIONS: Patients with supratentorial or infratentorial tumors receive irradiation, regardless of grade. Craniospinal-axis fields are used when spinal seeding is radiographically or pathologically evident. Spinal cord tumors are treated using localized fields to the primary site if not completely resected. Failure to control disease at the primary site remains the main impediment to cure.     

Treatment of intracranial ependymomas of children: review of a 15-year experience

PURPOSE: There are still major controversies in the optimal management of children with intracranial ependymomas. To assess the impact of tumor site, histology, and treatment, the outcome of children treated at the Institut Gustave Roussy was reviewed retrospectively. METHODS AND MATERIALS: Between 1975 and 1989, 80 children aged 4 months to 15.8 years were seen at the Institut Gustave Roussy for postoperative management of an intracranial ependymoma. Location of tumor was infratentorial in 63 cases and supratentorial in 17. Surgical treatment consisted of complete resection in 38, incomplete resection in 38 and biopsy only in 4. Postoperative irradiation was done in 65 patients and chemotherapy in 33. Surviving patients have been followed from 12-197 months with a median of 54 months. RESULTS: The 5-year actuarial survival and event-free survival are 56% and 38%, respectively. Thirty-four patients relapsed from 3-72 months after diagnosis (median 25 months). In 20 patients, the only site of failure was the original tumor site. Three patients failed locally and at distance, while 10 others failed only at distance. Survival at 5 years was significantly better for patients who had complete resection of the tumor (75% vs. 41%, p = 0.001) and for those who received radiation therapy (63% vs. 23%, p = 0.003). Event-free survival at 5 years was superior in patients with complete resection of the tumor (51% vs. 26%, p = 0.002) and in patients who received radiation therapy (45% vs. 0%, p < 0.001). Sex and tumor site had no impact on survival or event-free survival. There was no difference in survival, event-free survival, or pattern of failure between patients treated with local field, whole brain or craniospinal irradiation, while severe longterm sequelae were noted predominantly in the latter two groups. CONCLUSION: Considering that failures were predominantly local and that there was no apparent benefit from prophylactic irradiation, we recommend local field irradiation with doses above 50.0 Gy for all children with intracranial ependymomas, without meningeal dissemination at diagnosis. Special considerations are necessary for children < 3 years of age.     

Combined neck dissection and postoperative radiation therapy in the management of the high-risk neck: a matched-pair analysis

PURPOSE: Our purpose was to determine the sensitivity, specificity, and receiver operator characteristic (ROC) curve of a fast screening MR protocol in children and adolescents with suspected intracranial tumors. METHODS: One hundred forty-one patients (mean age, 9.7 years; range, 2 months to 23.5 years) with suspected brain tumor were entered in a case-control study. Eighty-seven patients had intracranial tumors (31 suprasellar/hypothalamic, 27 supratentorial, 26 infratentorial, and three pineal) and 54 patients in the control group had other disorders. Two neuroradiologists reviewed blindly a detailed three-sequence conventional protocol (acquisition time, 8 minutes 27 seconds) and a two-sequence fast screening MR protocol (acquisition time, 4 minutes 44 seconds). RESULTS: Sensitivity and specificity of the fast screening protocol for intracranial tumors was 100% and 92.6%, respectively. The areas under the ROC curves were 0.966 for the fast screening and 0.980 for the conventional MR protocol. No diagnostic performance difference was found between the ROC curves using the Az index. A kappa statistic of .93 for both examinations indicated excellent interobserver agreement. Additional MR sequences and other neuroimaging studies were not deemed necessary to exclude the presence of an intracranial tumor. CONCLUSION: A fast dual-plane brain MR protocol may be adequate to screen children and adolescents thought to have an intracranial tumor. The less than 5 minute acquisition time allows a complete examination (including preparation) to be performed in 10 to 15 minutes. Future studies are recommended before this time-efficient neuroimaging examination is incorporated into clinical practice.     

The potent antioxidant activity of the vitamin K cycle in microsomal lipid peroxidation

OBJECTIVE: To determine the outcomes of patients with neurotropic cutaneous tumors of the head and neck. DESIGN: A retrospective review was conducted of 7852 charts of patients who underwent micrographically controlled excisions of skin cancers of the head and neck between 1984 and 1995, identifying neurotropic tumors and the outcomes of their treatments. SETTING: Tertiary care center (university hospital). PATIENTS: Thirty-seven patients with neurotropic tumors were identified (and confirmed by secondary histological review), constituting 0.47% of all patients. The median age at presentation was 68 years and all except an albino were white. Nine patients had basal cell carcinomas and 28 had squamous cell carcinomas. Twenty-five patients (69%) were referred after at least 1 prior excision was performed a median of 16 months previously. INTERVENTION: All patients underwent micrographic mapping and excision of the cutaneous portion of the tumor. As necessitated by tumor spread, additional soft tissue, skull base, and/or intracranial surgery and postoperative irradiation were also conducted. MAIN OUTCOME MEASURES: Thirty-four patients (3 patients were unavailable for follow-up) were assessed by physician examination a minimum of 19 months after treatment (median, 33 months). RESULTS: Of 25 patients with extracranial disease only, 19 had no evidence of disease during follow-up and 1 died of intercurrent disease at 20 months without evidence of tumor persistence. Of the 9 patients with intracranial neurotropic tumors at the time of presentation, 1 remained with no evidence of disease, 1 died of intercurrent disease at 21 months without evidence of tumor persistence, and the other 7 either died of or are living with an intracranial tumor. CONCLUSIONS: Micrographic tissue mapping to detect and then encompass neurotropic cutaneous malignancies, along with conventional surgery for deeper tumor invasions and irradiation in selected cases, was successful in 19 patients (76%) with an extracranial tumor. For those with neurotropic tumors approaching or penetrating the skull base, the prognosis was poor regardless of therapy method.     

Infratentorial empyema: analysis of 22 cases

OBJECTIVE: Infratentorial empyema is an uncommon form of intracranial suppuration that is usually secondary to neglected otogenic infection. The diagnosis is frequently delayed and often confused with that of meningitis. The associated mortality is distressingly high, yet it has, as a clinical entity, received scant attention in the literature. We present a 13-year experience of this condition. PATIENTS AND METHODS: From a retrospective analysis of 3865 patients with intracranial suppuration during a 13-year period, 22 patients with infratentorial empyema were identified. The inpatient notes for these patients were analyzed with reference to clinical, radiological, bacteriological, operative, and outcome data. RESULTS: Twenty-two patients with infratentorial empyema accounted for 0.6% of admissions caused by intracranial suppuration during the study period. Of these 22 empyemas, 13 were subdural and 9 epidural. Hydrocephalus was present in 17 (77.3%). Except for two epidural empyemas that did not warrant neurosurgical intervention, all patients underwent standard surgical management (wide posterior fossa craniectomy). Nineteen underwent mastoidectomy because the source of infection was otogenic. Concomitant and persistent hydrocephalus was treated aggressively. Five patients died (mortality rate of 22.7%). All fatalities had subdural empyemas, and all three patients with cerebellopontine angle extension of subdural purulent collections died. CONCLUSION: Although rare, infratentorial empyema, especially when subdural, is a lethal disease. Cerebellopontine angle extension of pus was a particularly ominous sign in our experience. Early surgical drainage via wide posterior fossa craniectomy, aggressive treatment of associated hydrocephalus, eradication of the primary source of sepsis, and, finally, intravenous high dosage of appropriate antibiotics form the mainstay of treatment.     

Human basophil activation measured by CD63 expression and LTC4 release in IgE-mediated food allergy

BACKGROUNDS AND OBJECTIVES: We present the interim findings of our in-house protocol treating the tumor bed alone after lumpectomy with low-dose-rate (LDR) interstitial brachytherapy in selected patients with early-stage breast cancer treated with breast conserving therapy (BCT). METHODS: From 1 March 1993 through 1 January 1995, 50 women with early-stage breast cancer were entered into a protocol of tumor bed irradiation alone using an interstitial LDR implant. Patients were eligible if their tumor was an infiltrating ductal carcinoma < or =3 cm in diameter, surgical margins were clear by at least 2 mm, the tumor did not contain an extensive intraductal component, the axilla was surgically staged with < or =3 nodes involved with cancer, and a postoperative mammogram was performed. Implants were positioned using a template guide delivering 50 Gy over 96 hr to the lumpectomy bed plus a 1-2-cm margin. Local control, cosmetic outcome, and complications were assessed. RESULTS: Patients ranged in age from 40 to 84 years (median, 65). The median tumor size was 10 mm (range, 1-25). Seventeen of 50 patients (34%) had well-differentiated tumors, 22 (44%) had moderately differentiated tumors, and in 11 (22%) the tumor was poorly differentiated. Forty-five patients (90%) were node-negative while five (10%) had 1-3 positive nodes. A total of 23 (46%) patients were placed on tamoxifen and 3 (6%) received adjuvant systemic chemotherapy. No patient was lost to follow-up. The median follow-up for surviving patients is 47 months (range, 37-59). No patient has experienced a local, regional, or distant failure. Three patients have died at 19, 33, and 39 months after treatment. All were without clinical evidence of recurrent disease and all deaths were unrelated to treatment. Good-to-excellent cosmetic results have been observed in 49 of 50 patients (98%) (median cosmetic follow-up was 44 months with a range of 19-59). No patient has experienced significant sequelae related to their implant. CONCLUSIONS: Interim results with treatment of the tumor bed alone with an LDR interstitial implant appear promising. Long-term follow-up of these patients and additional studies will be necessary to establish the equivalence of this treatment approach compared to standard BCT.     

Cell kinetics of head and neck cancers

We measured the tumor cell proliferative rate in 26 patients with head and neck cancer, 22 of which were squamous cell carcinomas (SCCs). Patients received sequential infusions of iododeoxyuridine and bromodeoxyuridine, after which the tumor was biopsied and studied. The percentage of labeled cells [labeling index (LI)] in well-differentiated SCCs was 20.4 +/- 2.7% (mean +/- SE) and 23.8 +/- 2.1% in moderately differentiated SCCs (P = 0.135). The LIs of two poorly differentiated SCCs were 39.4 and 55.9%. The LI was 2.5% in a high-grade lymphoepithelioma and 24.8% in a malignant lymphoma. In one well-differentiated and one poorly differentiated mucoepidermoid tumor, the LIs were 3.0% and 29.1%, respectively. S-phase duration time measurements ranged from 5.1-21.5 h (12.8 +/- 1.5). The calculated potential doubling times ranged from 18.8-84.5 h (47.3 +/- 6.7). The duration of G2 was between 90 and 180 min. To track the fate of labeled cells, in four patients a repeat biopsy was obtained 7-14 days after the iododeoxyuridine/bromodeoxyuridine infusion. These patients did not receive treatment between the biopsies. Due to the dilution of the label, most labeled cells in the second biopsy demonstrated a "fragmented" pattern resulting from repeated cell divisions. In two patients, however, 25% of cells in the second biopsy had undiluted label, suggesting that these cells had not divided after incorporating iododeoxyuridine/bromodeoxyuridine. On Day 7 labeled cells migrated to keratinized parts of tumors and to necrotic foci. Thus, the arrest of cell cycle transition, tumor cell differentiation, and cell death may be major routes of tumor cell loss from the proliferative compartment. This may explain the difference between very short potential doubling times and the actual rate of tumor growth.     

Intermediate-risk endometrial cancer. A management approach

In the United States, endometrial cancer remains the most frequently diagnosed tumor of the female genital tract. The Gynecologic Oncology Group (GOG) has previously included patients with disease confined to the uterus and moderately or poorly differentiated tumors that invade at least half the myometrium in protocols designed for "intermediate levels of risk". Although such patients are ideally staged surgically, the role of adjuvant therapies such as postoperative pelvic irradiation remains unclear. This report offers a management approach for these women based on opportunities for enhanced local control with an acceptable level of morbidity according to supportive data from the available literature.     

Measurements of energy expenditure using isotope-labelled water (2H2(18)O) during an Arctic expedition

An abnormal DNA content has been associated with an unfavorable prognosis in a variety of cancers. In this study, tumor DNA content was measured in patients with gallbladder carcinoma in order to determine whether DNA ploidy pattern was a prognostic indicator. Thirty-six patients who had had a gallbladder carcinoma resected with curative intent were analyzed. Aneuploid tumor (20 cases, 56 per cent) was significantly associated with poorly differentiated adenocarcinoma (p < 0.05), invasion beyond the muscularis propria (p < 0.01), and a high mitotic index (p < 0.0001). A significant advantage in terms of five-year survival was demonstrated in patients with diploid tumors as compared with those with aneuploid tumors (80 per cent versus 24 per cent, respectively, p < 0.005). Aneuploid tumors invading the subserosal layer had a significantly poorer prognosis than diploid tumors with similar depth of invasion (p < 0.05). However, when tumor invasion had extended beyond the serosa, no significant advantage in survival was found between patients with aneuploid and those with diploid tumors. It is concluded that DNA ploidy pattern is a valuable addition to a staging protocol for gallbladder carcinoma.     

Brain tumors with symptomatic onset in the first two years of life

Eighty children who in the first 2 years of life had signs and symptoms relating to a cerebral neoplasm were studied over an 18-year period (1970-1987), the mean follow-up being 8.2 years. In each case age at onset, clinical presentation, tumor location and pathological diagnosis, extent of surgical resection, postoperative mortality, adjuvant therapy length of survival and quality of life were assessed. Supratentorial tumors (59%) were more common than infratentorial. The most frequent clinical presenting feature (70%) was increased intracranial pressure. Sixty-three patients (79%) were operated on and in all of these cases a histological diagnosis was obtained. Astrocytomas (41%) and medulloblastomas (20%) were the most common oncotypes. Surgical mortality was 17.4% and the 5-year survival rate was 54%. Quality of life was assessed for all long-term surviving patients using a specifically designed protocol. Normal physical and intellectual performances were found in 46% of cases, and all together 75% of the patients had sufficient autonomy in daily life. The prognosis is more closely related to tumor location and type of treatment than to histological diagnosis or age at onset.     

Aortopexy as a surgical treatment method in infantile congenital tracheo-chondrohypoplasia and tracheomalacia

In 1994 we reported on a small series of 3 children with malignant, marker-positive pineal nongerminomatous germ cell tumors treated with a 'sandwich' protocol. Here, we report on the long-term survival of these children. Preoperative chemotherapy consisted of two courses of bleomycin, etoposide, and cisplatin. En bloc resection of the tumors via the supracerebellar, infratentorial route was performed immediately after decline of tumor marker levels. Postoperatively, two courses of vinblastine, ifosfamide, and cisplatin were applied, followed by craniospinal irradiation. The patients showed no major neurological deficits and no evidence (neuroradiologically or with regard to tumor marker levels) of recurrence of disease after 66, 71, and 78 months, respectively. We propose this regimen for children with tumors of the pineal region in whom the tumor markers are positive. It should be started without histological classification of the tumor to avoid possible spillage of malignant tumor cells to the cerebrospinal fluid.     

Immature teratoma of the ovary with a neural component ("solid" teratoma). A clinicopathologic study of 20 cases

Twenty cases of immature teratoma of the ovary with a neural component are analyzed. A plea is made for use of the nomenclature adopted from the new World Health Organization classification of ovarian tumors, the past confusion over terminology and histogenesis of this rare tumor is discussed. All the primary tumors in the present series contained at least some immature tissues (predominantly of neural origin) and were thus graded from 1 to 3 according to the criteria of Thurlbeck and Scully. No grade 0 tumors ("benign solid teratomas") were identified. We believe that thorough sectioning almost always insures the identification of immature elements. The prognosis was closely related to the histologic grade, but correlated poorly withthe clinical stage, the latter being influenced by the common finding (25 per cent of the cases in this series) of peritoneal implants composed exclusively of mature glial tissue, which is associated with a benign clinical evolution. This phenomenon of maturation or differentiation appears to be the rule rather than the exception in this tumor, since implants are usually of better or equal differentiation when compared with their primary tumors and older patients tend to have lower grade tumors than younger patients. Since the majority of patients with this tumor are young, primary surgical therapy should be conservative, unilateral salpingooophorectomy often being sufficient. Spontaneous or operative rupture of the tumor capsule carries an increased risk of subsequent dissemination. We have noted impressive clinical responses in patients with disseminated tumors of a high histologic grade after treatment with triple chemotherapy (vincristine, actinomycin D, and cyclophosphamide) but do not recommend adjuvant therapy in patients with only grade 0 implants.     

Prognostic significance of ploidy level in human tumors. I. Carcinoma of the uterus

The 5-year survival rates of 540 patients with carcinoma of the cervix and 186 with carcinoma of the corpus uteri were assessed in relation to the modal DNA values of the tumors. Patients with squamous cell cervical carcinomas had more favorable prognoses if the modes were near-triploid or hypotetraploid; however, these high-ploidy tumors included more stage III cases than did the tumors with near-diploid modes. Patients with near-diploid endometrial carcinomas has considerably more favorable prognosis than did patients with the minority of tumors at this site, who had high modes; this prognostic difference was only partly related to a higher proportion of poorly differentiated tumors in the high-ploidy group since, among the poorly differentiated tumors, individuals with near-diploid modes again had significantly better prognoses than those with high modes.     

Cryptosporidium parvum--propagation of oocyst in neonatal calves

A retrospective analysis of treatment of 8 children aged 5 to 13 years with intracranial germ cell tumors (3 germinomas, 5 nongerminomatous cell tumors) is reported. All patients were initially operated. Five of them underwent total or incomplete removal of the tumor. After surgery 2 children received radiotherapy alone (1 germinome, 1 nongerminomatous germ cell tumors) and 5 (2 germinomas, 3 nongerminomatous germ cell tumors) combined radio- and chemotherapy. One patient (choriocarcinoma) didn't receive any adjuvant treatment after total tumor removal. All 3 children with germinomas show complete remission for 29, 40 and 93 months. Of 5 patients with nongerminomatous germ cell tumors in 2 the duration of remission was 22 and 53 months and 3 relapsed 4, 12 and 24 months after treatment. The data presented demonstrate that the treatment results of intracranial germ cell tumors in children depend on histologic type of the tumor. Thus, precise tumor type determination is most important for choosing optimally adequate treatment approach.     

Progression in and survival of patients with locally advanced prostate cancer (T3) treated with radical prostatectomy as monotherapy

PURPOSE: We determine the progression and survival rates in patients with locally advanced prostate cancer treated with radical prostatectomy without adjuvant treatment, and investigate subgroups of patients who may not benefit from this treatment. MATERIALS AND METHODS: Radical prostatectomy was performed in 83 patients with T3 prostate cancer. The patients were divided in subgroups with T3G1 to 2 and T3G3 tumors, which were evaluated for clinical progression, local recurrence, distant metastases, biochemical progression, and overall and cancer specific survival at 5 and 10 years by Kaplan-Meier curves. The results were compared to those of 190 patients with locally confined tumors. RESULTS: At 5 and 10 years overall survival was 75 and 60%, and cancer specific survival was 85 and 72%, respectively. At 5 and 10 years clinical progression was 41 and 69%, local recurrence 18 and 44%, and distant metastases 31 and 50%, respectively. Biochemical progression at 5 years was 71%. Patients with poorly differentiated tumors showed significantly lower survival and higher progression rates compared to those with well or moderately differentiated tumors. Progression and survival in patients with T3G1-2 tumor were not significantly different from those for patients with locally confined tumors. CONCLUSIONS: Radical prostatectomy as monotherapy in patients with locally advanced nonmetastatic prostate cancer (T3) produces acceptable results in those with well or moderately differentiated tumors. The results of progression and survival are not significantly different from those in patients with locally confined prostate cancer. However, patients with poorly differentiated tumors (T3G3) have early progression and need adjuvant treatment following surgery.     

Prognostic significance of Ki-67 and p53 antigen expression in carcinomas of bile duct and gallbladder

Ki-67 and p53 protein expression was evaluated immunohistochemically in 32 patients with intrahepatic, extrahepatic bile duct and gallbladder carcinomas, who underwent surgery at First Department of Surgery, The University of Tokushima School of Medicine. p53 expression was found more in the well differentiated group than poorly differentiated group (p = 0.007). MIB1 labelling index (MIB1 LI) was higher in EHC than in GBC (p = 0.0061). MIB1 LI (T), (MIB1 LI in tumor) was higher in cases with lymph node metastasis than in those without lymph node metastasis (p = 0.0189). Moreover, MIB1 LI (L) (MIB1 LI in metastasized lymph node) was higher in poorly differentiated than in well differentiated carcinoma (p = 0.0404). Prognostically, patients with high MIB1 LI (T) (> 56.93) had a worse prognosis after surgery than those with low MIB1 LI (T) (p < 0.05). There was no association between p53 positive tumors and MIB1 expression. These results suggest that cancer cell proliferative activity was markedly increased in cases with EHC compared to those with GBC and the poorly differentiated and lymph node metastasis group. MIB1 LI in tumor was found to be a good prognostic indicator whereas there was no association of p53 positive tumor with MIB1 expression and prognosis of the patients.     

Examinations of the motor conduction time between the motor cortex and the Erb point in patients suffering from tumors of the central nervous system

The cortical latency and the motor conduction time between the motor cortex and the Erb point were investigated in 85 patients with intracranial and in 9 patients with space-occupying spinal tumors. Electrophysiological examinations revealed pathological changes in 19% of intracranial events, and in 100% of cases of spinal tumors. In these latter cases close correlation was registered between the motor evoked potentials and the clinical symptoms of the patients.     

The "Nobel": Prize and swindle. The betrayed testament

Human glutathione S-transferase pi (GST-pi) may serve as a useful tumor marker because of the high frequency with which it is found in elevated levels in several tumor types. To determine whether GST-pi is useful as an indicator for cancers of the head and neck, expression of GST-pi mRNA was investigated by Northern analysis in this tumor type. Overexpression of GST-pi mRNA was detected in 9 of 36 (25%) primary head and neck squamous cell carcinomas (HNSCCs). When Southern blot analysis was used to examine the relationship between overexpression and amplification of the GST-pi gene, only 3 of 36 tumors (8%) showed GST-pi gene amplification. Thus, gene amplification is not critical to GST-pi mRNA overexpression in HNSCCs. Moderately and poorly differentiated HNSCCs tended to manifest elevated GST-pi mRNA compared with well differentiated tumors (30% for moderately and poorly differentiated tumors versus none of the well differentiated tumors examined). However, there was no significant correlation between GST-% mRNA overexpression and clinical stage, T stage (tumor size), N stage (neck nodal status), pathological nodes, or patient survival.     

Multiple schwannomas and meningiomas associated with irradiation in childhood

OBJECTIVE: To determine the pattern of neural tumors (schwannomas, vestibular schwannomas [acoustic neuromas], and meningiomas) that developed in 3013 people who received radiation treatment with x-ray beam therapy for benign conditions of the head and neck area before their 16th birthday. METHODS: The surgical and pathology reports and pathology slides were reviewed for all neural tumors in the cohort. Patients with more than 1 neural tumor were compared with those with 1 neural tumor and those with no neural tumors. RESULTS: There were 7 patients with multiple neural tumors and 63 with single neural tumors. The distribution of tumors in these 2 groups differed. The group with multiple tumors had more spinal nerve root schwannomas, while the group with single tumors had more cranial nerve schwannomas. Six of the 7 patients did not meet the diagnostic criteria for neurofibromatosis type 2. CONCLUSIONS: Our findings suggest that host factors that increase susceptibility to radiation may be involved in the development of the multiple neural tumors. Clinically, patients with multiple neural tumors who do not meet the diagnostic criteria for neurofibromatosis type 2 should be questioned about radiation exposure. If exposure is confirmed, then screening for other radiation-related tumors should be initiated.     

Nitric oxide-induced blood-brain barrier dysfunction is not mediated by inhibition of mitochondrial respiratory chain activity and/or energy depletion

The six reported cases were separated into 2 groups: 1) the tumors of sporadic type, carcinoids (n = 2) and neuro-endocrine carcinomas (n = 2); 2) the gastrin-promoted tumors (n = 2). The purpose of this retrospective study was to review for each group of tumors, the clinicopathologic characteristics, prognosis factors and optimal management. In the first group, patients with a small and well differentiated tumor revealed by digestive bleeding, were treated by wedge excision and are alive and well 24 and 22 years later; the patients with large, invasive and poorly differentiated tumors were treated by subtotal (n = 1) and total (n = 1) gastrectomy, and died 1 year and 3 years later with metastases. In the second group, one patient with a small asymptomatic carcinoid tumor revealing chronic atrophic gastritis, was treated by endoscopic resection, without recurrence 3 years later; another patient with asymptomatic multifocal carcinoid tumors (about 100) associated with Zollinger-Ellison syndrome and multiple endocrine neoplasia type 1, was treated by total gastrectomy and is alive and well 7 years later. No patient had carcinoid syndrome. Synaptophysin was the most sensitive marker and secretion of serotonine was detected in 2 tumors. Conclusion: Sporadic carcinoids serotonin and neuro-endocrine carcinomas are life-threatening tumors and need aggressive surgical therapy: their prognosis depends on tumors size, histological differentiation and mostly on tumor extension. In contrast, gastrin-promoted carcinoids do not result in disseminated disease and death, and a rather conservative approach seems appropriate.