Hearing preservation in acoustic tumor surgery: results and prognostic factors

A retrospective study was conducted to assess the hearing results in patients who underwent acoustic neuroma removal via the middle fossa approach. A statistical correlation of results with preoperative clinical and audiological data determined if any prognostic indicators could be associated with successful hearing preservation. Of 93 patients included in the study, useful hearing was preserved in 54 (58%), and hearing was preserved near preoperative levels in 42 (45%). The potential for hearing preservation appeared to be inversely related to the size of the acoustic tumor, with hearing preserved in 39 (60%) of 65 patients with tumors less than or equal to 0.5 cm extension into the cerebellopontine angle. Preoperative hearing levels and electronystagmography seemed to have no prognostic value. However, auditory brainstem response showed that a wave V latency of less than 6.8 msec was associated with an increased chance of hearing preservation, and the presence of vertigo as a preoperative complaint appeared to be a good prognostic indicator of successful hearing preservation.     

Survival and prognostic factors associated with metastatic nonseminomatous testicular and extragonadal germ cell tumors

To assess prognostic factors in patients with metastatic nonseminomatous germ cell tumors, 50 patients with testicular germ cell tumors (TGCT) and 10 patients with extragonadal germ cell tumors (EGGCT) were studied. The clinical staging system for testicular tumors proposed by The Japanese Urological Association and The Japanese Pathological Society was applied. All patients with EGGCT had primary sites in the retroperitoneum. The 3-year survival rates of TGCT and EGGCT were 71.9% and 60.0%, respectively, and there were no differences in patient characteristics. Patients had significantly worse survival rates if the following applied: choriocarcinoma in the primary tumors, serum lactate dehydrogenase level greater than twice the upper limit of normal, liver, brain, or mediastinal metastases, or retroperitoneal tumors greater than 10 cm. It was concluded that the poor-risk group could be defined as those patients having lymph nodal disease only (stage II or III A) with retroperitoneal tumors greater than 10 cm, having pulmonary disease (stage III B) with retroperitoneal tumors greater than 5 cm, or liver, bone or brain metastases (stage III C), and these criteria will predict the prognosis for patients with advanced disease because the good-risk patients (53% of all patients) and poor-risk patients (47%) in this study had 3-year survival rates of 88.7% and 49.7% (p < 0.0001), and complete response rates of 96.9% and 60.7% (p < 0.005), respectively.     

Epidermal growth factor receptor and labeling index are independent prognostic factors in glial tumor outcome

The aim of this study was to perform a multivariate analysis including clinical and biological prognostic factors on glial tumor outcome. Seventy-nine patients were analyzed (48 men and 31 women; mean age = 56 years, range = 16-77 years): 7 had a benign glial tumor (grades 1 and 2), 21 had an anaplastic glial tumor (grade 3), and 51 had a glioblastoma (grade 4). Median follow-up was 17.9 months for patients who survived (50 patients died). Biopsies were obtained at time of diagnosis (complete tumor resection in 62 patients and stereotaxic biopsies in 17 patients). Epidermal growth factor receptor (EGFR) was measured by a binding assay, and labeling index (LI) was measured by tritiated thymidine incorporation. EGFR varied from 4 to 73,110 fmol/mg protein (mean = 3912 fmol/mg protein; median = 374 fmol/mg protein; n = 79). LI varied between 0.1 and 16.5% (mean = 6.2%; median = 5.2%; n = 40). Log10 EGFR was significantly and positively correlated with patient age. LI was significantly different according to tumor histology. Univariate Cox analysis (end point was cancer death) showed that age (P = 0.027), log10 EGFR (P = 0.025), and LI (P = 0.0019) were significant continuous variables, the survival being shortened when the covariable increased; tumor resection (P = 0.015, relative risk = 0.45) and histology (P = 0.0009) were significant categorical factors. A multivariate Cox analysis (forward selection) including age, histology, tumor resection, log10 EGFR, and LI revealed that log10 EGFR, LI, and tumor resection were the only independent significant predictors of survival. This multivariate approach reveals that the clinical prognostic factors of glial tumors, namely age and tumor histology, disappear, to the benefit of intrinsic characteristics of the tumor, i.e., EGFR expression and LI, suggesting that coupled EGFR and LI determination could be a useful tool for better evaluation of glial tumor outcome.     

Giant cell tumor of bone: a clinicopathologic study of prognostic factors

Symptomatic autonomic neuropathy is a devastating occasional complication of diabetes mellitus, especially Type 1. Although the full-blown clinical syndrome is not common, dysfunction of the autonomic nerves is detectable in up to 40% of Type 1 diabetic patients but its aetiopathogenesis is poorly understood. There is evidence to suggest that the damage to the autonomic nerves may be immune-mediated. This evidence is reviewed in the following article.     

The value of prognostic factors in the management of stage I nonseminomatous germ cell testicular tumors (NSGCTT)

A patient with florid hypertrophic pulmonary osteoarthropathy (HPOA) associated with metastatic nasopharyngeal carcinoma is presented. Despite the presence of metastatic disease in the thorax and in bone, the patient's main symptom was severe pain from the HPOA, which was temporarily relieved by chemotherapy. Her disease subsequently progressed during chemotherapy and the pain became resistant to conventional treatment, including high dose morphine, non-steriodal anti-inflammatory agents and steriods. It was only with local radiation to the involved joints that the pain could be controlled. Our patient demonstrates that local radiotherapy is an option for the palliation of extreme HPOA.     

Radical prostatectomy and prognostic factors

We investigated ectopic bone formation by biphasic calcium phosphate (BCP) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2) in the rat dorsum. Under reduced pressure, rhBMP-2 was adsorbed onto BCP, which consisted of 80% beta-tricalcium phosphate and 20% hydroxyapatite uniformly distributed in granules. Twenty Wistar rats were separated into 4 groups consisting of 5 animals each dosed with 2, 10, and 50 micrograms/700 microliters of rhBMP-2 and a control group (BCP only). Pieces of the BCP-BMP complex or only BCP were implanted under the dorsal skin of the rats. Histological sections were examined three weeks later. New bone was formed in all rats given 50 micrograms doses, but not in the 2 micrograms and control groups. These results indicated that BCP combined with rhBMP-2 induced ectopic bone formation without additional carriers. Therefore, BCP granules alone can function as carriers for rhBMP-2 to induce bone formation.     

Laparoscopic resection of intra-abdominal testicular tumor

Synovitis, Acne, Pustulosis, Hyperostosis and Osteitis (SAPHO) syndrome is an osteoarticular-skin syndrome characterised by sterile inflammatory arthro-osteitis of the anterior chest wall. It is associated with various skin conditions including palmoplantar pustulosis, severe acnes and pustular psoriasis. A link between SAPHO syndrome and seronegative spondyloarthropathies has been suggested over the last 10 years. SAPHO syndrome mainly affects young and middle-aged adults. Treatment of SAPHO syndrome remains empirical as the underlying aetiopathogenesis is unclear.     

Molecular pathogenesis of bacterial infections

Somatosensory evoked potentials (SEPs) to median nerve stimulation were recorded in 3 patients with a brain-stem or medullary lesion documented by clinical and CT or MRI evidence. The positive P14 and negative N18 scalp far-fields were preserved. The results suggest that P14 reflects the spike volley in caudal medial lemniscus, and that the N18 neural generators are located in the medulla, probably in the dorsal column nuclei and/or the accessory inferior olives.     

Benign testicular tumor associated with Klinefelter's syndrome

Testicular tumors associated with Klinefelter's syndrome are rare. We report a benign testicular epidermal cyst that was diagnosed in a patient with Klinefelter's syndrome. The association between testicular tumors and Klinefelter's syndrome, and management of a testicular epidermal cyst are discussed.     

Role of androgens in testicular tumor development in inhibin-deficient mice

To understand gonadal tumor development, we have previously created a mouse model in which mice deficient in the inhibins develop gonadal sex cord-stromal tumors with essentially 100% penetrance. These tumors develop as early as 4 weeks of age and cause cancer cachexia-like symptoms and subsequent death in the inhibin-deficient mice. Gonadectomized inhibin-deficient mice eventually develop adrenal cortical tumors with nearly 100% penetrance. These studies have identified inhibin as a novel secreted tumor suppressor protein with specificity for the gonads and adrenal glands. Sex steroids have been implicated to influence gonadal tumor development in humans and mice. To determine the role of androgens in gonadal tumorigenesis in inhibin-deficient male mice, we have used a genetic intercross strategy, breeding inhibin alpha mutant mice with tfm (testicular feminization, a naturally occurring androgen receptor mutant) carrying females to eventually generate compound mutant male mice that lack inhibins and carry the tfm mutation. These compound mutant mice, like inhibin-deficient mice, continue to develop testicular tumors and the accompanying cancer cachexia-like wasting syndrome. Consistent with these findings, elevated levels of activins A and B secreted from the gonadal tumors are seen in the adult compound mutant mice as well as the secondary pathological consequences of these high activin levels in the livers and glandular stomachs. However, in contrast to male mice lacking only inhibin, in which essentially 100% of the testicular tumors are hemorrhagic, 65% of the tumors in these compound mutant male mice are less hemorrhagic, and approximately 50% of the compound mutants live longer than 17 weeks of age (95% of the male mice lacking only inhibin die by 12 weeks). These results suggest that androgens are not required for testicular tumor development in inhibin-deficient mice, but may play a regulatory role in testicular tumor progression.     

Thymoma: prognostic factors and treatment outcomes

BACKGROUND: The objective of this study was to establish prognostic factors for thymoma and determine the impact of surgery with or without postoperative radiotherapy. METHODS: Seventy patients treated at the University Hospital Düsseldorf during the period 1954-1991 were retrospectively studied. All thymoma patients underwent surgery, 22 received postoperative radiotherapy, and 3 also received chemotherapy. According to thymoma staging as described previously by Masaoka et al., 21% were Stage I, 26% Stage II, 43% Stage III, 7% Stage IVA, and 3% Stage IVB. Lymphocytic type disease was found in 36% of patients, lymphoepithelial type in 33%, epithelial type in 23%, and spindle cell type in 9%. The relevance of Karnofsky performance status (KPS), gender, age, myasthenia gravis, histology, tumor size, and stage to survival was determined by univariate analysis, and their independent significance was tested by multivariate analysis. Survival rates were calculated using the Kaplan-Meier method and the log rank test. RESULTS: In univariate analysis, KPS (P < 0.001), histologic type (P=0.0093), and stage (P=0.0001) proved to be significant predictors of overall survival. Spindle cell type was associated with the best and epithelial type the worst prognosis; patients with the latter type had a 5-year survival rate of 30%. Multivariate analysis revealed that stage, histology, and KPS were predictive of overall survival. In Stages III and IV, relapses were reduced by postoperative radiotherapy from 50% to 20%. The site of relapse was outside the irradiated area in 80% of patients. Disease free survival (P=0.36) and median survival (P=0.72) of patients with completely resected advanced thymomas did not differ from that for patients with incompletely resected tumors who received radiotherapy. CONCLUSIONS: Postoperative radiotherapy can improve local control in patients with advanced thymoma. Survival after incomplete resection is not compromised when postoperative radiotherapy is employed. KPS should be considered an important prognostic factor in future studies.     

Multiple myeloma--diagnosis, prognostic factors and treatment

The problem of diagnosis, prognostic factors and the efficacy of therapies were investigated in 330 patients with multiple myeloma (MM) and 51 patients with benign monoclonal gammopathy (BMG)/monoclonal gammopathy of undetermined significance (MGUS). Seven out of 51 patients with BMG/MGUS were transformed into MM. The mean time to the transformation was 61.6 months. M protein level in these patients had been gradually and constantly increasing until the transformation in contrast with stable level in non-transformed patients. In MM there was one year difference between median survival from the time of diagnosis and start of chemotherapies. It depended on the deferral of treatment in patients with stage I myeloma. No difference of survival time was found between initial and differed therapy for stage I myeloma. Earlier therapy is not advantageous in this stage. Stages and immunoglobulin classes of MM were prognostic factors. Stage I or IgG myeloma had the longest survival and stage III or BJP myeloma had the shortest one. The new protocol, DMVM plus natural interferon alpha therapy induced high complete remission rate of 37.1% in initial treatment patients. The survival rate at three years from the treatment was 70%.     

Clinical presentation and prognostic factors in sodium monofluoroacetate intoxication

From 1970 to 1992 a total of 63 patients underwent operation for ampullary tumor: 40 pancreatoduodenectomies (PDs), 3 total PDs, 8 ampullectomies, and 12 bypass or exploratory laparotomies. The resectability rate was 68%. There were 9 benign tumors, 1 anaplastic tumor, and 53 adenocarcinomas. According to Martin's classification, there were 7 stage I, 11 stage II, 14 stage III, and 21 stage IV tumors. All patients with stage I, II, and III tumors underwent resection. Patients with stage IV tumors had either resection (n = 11) or bypass (n = 10). The mean duration of hospital stay was 20.6 days. Operative mortality was 12.7% for the whole series and 7.5% after PD (2.5% for the last 10 years). Overall survival was 40% at 5 years (85% for stage I, 65% for stage II, 44% for stage III, and 8% for stage IV). Survival was better for stages I, II, and III after PD than after ampullectomy. For stage IV patients survival was 70% after PD versus 20% after bypass at 1 year and 25% versus 0% after 2 years. In our opinion, PD should be proposed even for benign lesions because two of our patients had to undergo repeat operation (PD) 4 and 22 years later, respectively, for stage IV disease. PD is our choice for all tumors of the ampulla.     

Control of testicular vasomotion by testosterone and tubular factors in rats

We have compared the pharmacological and molecular characteristics of 2 cell lines derived from the C6 rat glioblastoma, and selected for resistance either to doxorubicin (C6 0.5 line) or to vincristine (C6 IV line). Each line displays a preferential 400-fold resistance towards the drug used for selection, the C6 IV line being especially weakly resistant to doxorubicin (13-fold). Verapamil completely restored doxorubicin sensitivity in the C6 IV line as well as vincristine resistance in the C6 0.5 line, but could not completely reverse doxorubicin resistance in the C6 0.5 line or vincristine resistance in the C6 IV line. This suggests that specific mechanisms of resistance against each drug were added to a common P-glycoprotein-mediated multidrug-resistance mechanism. Doxorubicin efflux was total within 2 hr in the C6 IV line, whereas it remained 8 to 10% of drug in the C6 0.5 line 4 hr after drug removal, despite a more rapid efflux of the drug in the first 30 min. This 2-compartment behavior could be related to a special sub-cellular distribution of doxorubicin in C6 0.5 cells. Northern and Western blot analysis of the mdrI gene and of the P-glycoprotein expressed by the 2 resistant cell lines made it possible to quantify their degree of over-expression; when compared with the C6 wild strain, the C6 0.5 line over-expressed both the mdrI gene and the P-glycoprotein to a slightly higher level than the C6 IV line. Northern and Western blot analysis also suggested that C6 0.5 cell preferentially over-expressed the mdrIa gene, whereas the C6 IV cells preferentially over-expressed the mdrIb gene. This differential over-expression was confirmed after polymerase-chain-reaction amplification of the cDNA sequences transcribed from total RNA extracted from the 2 lines. It can be concluded therefore that the mdrIa gene product is more efficient than the mdrIb gene product in extruding anti-cancer drugs from the cells; and that the mdrIb gene product might preferentially extrude vincristine rather than doxorubicin.     

Bcl-2 expression in testicular cancer in relation to tumor progression

Bcl-2 expression has been studied extensively in a variety of human tumors. However, there are lack of clinical data in regard to its expression in germ cell testicular tumors (GCTTs). In this study we screened bcl-2 expression in 70 patient with GCTTs using the immunohistochemistry (IHC) and streptavidin biotin alkaline phosphatase method. Furthermore, we correlated this expression with metastatic behaviour and clinical stage. Overall, 41 (58%) carcinomas stained with anti-bcl-2 (DAKO-124) monoclonal antibody, By histologic type, these lesions included 11 (42.3%) of 26 seminomas (S) and 30 (68.18%) of 44 non seminomatous germ cell testicular tumors (NSGCT). The incidence of bcl-2 immunostaining was higher (P = 0.05, two-tailed, Fisher's test) in NSGCT than in seminomas. Bcl-2 expression was higher in tumors from metastatic patients than in tumors from metastatic-free patient (p = 0). There was a significant difference between the three stages of disease as to the expression of bcl-2 (chi 2 = 0). High level of bcl-2 was clearly dominant in tumors of advanced stages. The present finding revealed that bcl-2 expression occurs in GCTTs. Further, they suggested that bcl-2 is associated with a more progressed malignant phenotype in these tumors.     

Molecular basis for evasion of host immunity and pathogenesis in malaria

The article relates the ability of the malaria parasite Plasmodium falciparum to avoid a protective immune response, and to induce pathological changes, to the properties of specific parasite molecules. Cytoadherence and rosetting are important features of cerebral malaria and involve proteins located on the surface of the infected red blood cell. Proinflammatory cytokines, particularly tumour necrosis factor (TNF), play a role in protective immunity and in inducing pathology. Glycophosphatidyl inositol membrane anchors of parasite proteins possess insulin like activity and induce TNF synthesis. People subject to repeated infections in malaria endemic areas rarely develop complete or sterile immunity to malaria. They frequently carry small numbers of parasites in the blood, with little symptoms of the disease, illustrating a phenomenon termed semi-immunity. The basis for semi-immunity is incompletely understood. Malaria parasites are susceptible to several immunological effector mechanisms. The presence of extensive repetitive regions is a feature of many P. falciparum proteins. Available evidence suggests that the structural characteristics of the repeats and their location on the surface of parasite proteins promote immunogenicity. The repeats may help the parasite evade host immunity by (i) exhibiting sequence polymorphism, (ii) preventing the normal affinity and isotype maturation of an immune response, (iii) functioning possibly as B cell superantigens, (iv) generating predominantly thymus independent antibody responses, and (v) acting as a sink for binding protective antibodies. Sequence diversity in non-repetitive regions and antigenic variation in parasite molecules located on the surface of infected red blood cells also play a role in immune evasion. Some sequence homologies between parasite and human proteins may be due to molecular mimicry. Homologies in other instances can cause autoimmune responses. The immune evasion mechanisms of the parasite need to be considered in developing vaccines. Protective immunity and pathology may be delicately balanced in malaria.