Low Histopathological Grade Research Articles

Aberrant Regulation of the BST2 (Tetherin) Promoter Enhances Cell Proliferation and Apoptosis Evasion in High Grade Breast Cancer Cells

Normal cellular phenotypes that serve an oncogenic function during tumorigenesis are potential candidates for cancer targeting drugs. Within a subset of invasive primary breast carcinoma, we observed relatively abundant expression of Tetherin, a cell surface protein encoded by the Bone Marrow Stromal Cell Antigen (BST2) known to play an inhibitory role in viral release from infected immune cells of the host. Using breast cancer cell lines derived from low and intermediate histopathologic grade invasive primary tumors that maintain growth-suppressive TGFβ signaling, we demonstrate that BST2 is negatively regulated by the TGFβ axis in epithelial cells. Binding of the transcription factor AP2 to the BST2 promoter was attenuated by inhibition of the TGFβ pathway thereby increasing BST2 expression in tumor cells. In contrast, inherent TGFβ resistance characteristic of high grade breast tumors is a key factor underlying compromised BST2 regulation, and consequently its constitutive overexpression relative to non-malignant breast epithelium, and to most low and intermediate grade cancer cells. In both 2-dimensional and 3-dimensional growth conditions, BST2-silenced tumor cells displayed an enhancement in tamoxifen or staurosporine-induced apoptotic cell death together with a reduction in the S-phase fraction compared to BST2 overexpressing counterparts. In a subset of breast cancer patients treated with pro apoptotic hormonal therapy, BST2 expression correlated with a trend for poor clinical outcome, further supporting its role in conferring an anti apoptotic phenotype. Similar to the effects of gene manipulation, declining levels of endogenous BST2 induced by the phytoalexin – resveratrol, restored apoptotic function, and curbed cell proliferation. We provide evidence for a direct approach that diminishes aberrant BST2 expression in cancer cells as an early targeting strategy to assist in surmounting resistance to pro apoptotic therapies.

Subcutaneous tumor seeding after biopsy in gliomatosis cerebri

We observed a patient with subcutaneous seeding from gliomatosis cerebri with a low-grade histopathology. A 33-year-old woman with neurofibromatosis type 1 presented with progressive headache, diplopia, dysphagia, and a rightward instability. On neurological examination dysarthria, gait ataxia, and left-sided central facial and hypoglossal palsies were determined. MRI of the brain demonstrated diffuse, infiltrative non-enhancing lesions in the pons, both cerebellar hemispheres, the parahippocampal gyrus, and the thalamus. A stereotactic biopsy demonstrated an astrocytoma WHO grade 2. These characteristics confirmed gliomatosis cerebri. Three months later, the patient presented with hydrocephalus and a subcutaneous swelling directly underneath the surgical scar. The subcutaneous swelling was removed and the hydrocephalus was treated by ventriculoperitoneal shunting. Histopathological examination confirmed a subcutaneous manifestation of low-grade oligoastrocytoma. Gliomatosis cerebri with low-grade histology can seed subcutaneously.

Practical value of MIB-1 index in predicting behavior of astrocytomas

The MIB-1 labeling index (LI) has proved to be useful in assigning grading and prognosis to astrocytomas. The purpose of our study was to analyze the utility of MIB-1 LI in differentiating astrocytomas of varying grades and the possible relationships of MIB-1 LI with clinical parameters like age and sex. We also wanted to study the prognostic role of MIB-1 index in predicting behavior of astrocytomas. Our study included 145 patients with astrocytic tumors of varying grades. Immunolabeling for all patients was done using MIB-1 antibody. Survival data could be obtained for 64 patients. A Mann-Whitney U test was used to test the difference in MIB-1 LI between different histological grades. The univariate analysis was done by the Kaplan-Meier method, and the multivariate analysis for survival was performed using the Cox proportional hazard model. Significant differences were noted in mean MIB-1 LI of high-grade and low-grade diffuse astrocytomas. MIB-1 LI did not vary significantly with age and sex. Univariate analysis showed favorable prognostic factors for low histopathological grade, young patient age and low MIB-1 LI; however, multivariate analysis showed that only histopathological grade had independent prognostic significance. Our study proves that MIB-1 LI is not dependent on factors like age and sex and is solely dependent on histological grade. Though the average level of MIB-1 LI varies considerably in the different grades of astrocytomas, considerable overlap can be observed between them. MIB-1 LI is a very useful adjunct to the histopathological diagnosis and can be of great help in situations where the clinical and radiological findings do not correlate with histological diagnosis.

Clinicopathological characteristics and surgical treatment of tumors associated with medically intractable epilepsy

Objective To analyze the spectrum of neoplasms associated with refractory epilepsy and to evaluate the optimum surgical treatment of these patients. Method The clinical, electrophysiological, operative,and histopathological data of 45 patients who underwent surgery for medically intractable epilepsy were retrospectively evaluated. Results The majority of tumors were located in the temporal lobe(n = 34) and frontal lobe (n = 8). The most frequent tumors were neuronal and mixed neuronal-glial tumors (76%), including gangliocytoma or ganglioglioma(n = 15), dysembryoplastic neuroepithelial tumour(n = 7). All the tumors were low histopathological grade (WHO Ⅰ or Ⅱ). In all patients, complete resection of tumor and epileptogenic area was intended. Complications were encountered in 5 patients. Of the 45 patients who had postoperative follow-up more than one year, 78% were seizure-free and no patient died. Conclusions The neoplasms associated with medically intractable epilepsy constitute a distinct clinicopathological group of tumors. Complete surgical removal of the tumors and the epileptogenic area can achieve excellent seizure control Key words: Epilepsy; Brain neoplasms; Surgical procedures,operative

Defining Surgical Indications for Type I Gastric Carcinoid Tumor

Most gastric carcinoid tumors (GC) (type I) occur in association with achlorhydria, hypergastrinemia, atrophic gastritis and exhibit low-grade histopathology. The management of this indolent disease is controversial. The aim of this study was to evaluate endoscopic surveillance (ES) compare with surgical resection (SR) for type I GC. Between 1985 and 2007, 65 patients with type IGC were identified. Data analysis included: demographics, biochemical and endoscopic assessment, type of operation performed, and pathologic evaluation. The primary endpoints were disease-specific survival (DSS) in both groups and recurrence-free survival (RFS) in SR patients. Median follow-up was 30 months (range 1-176 months); most patients were female (83%) with median age of 58 years (range 29-91 years). Type I GC was diagnosed by evidence of hypergastrinemia and/or positive autoimmune antibodies with histopathologic confirmation. Patients underwent ES with polypectomy (n=46) or gastric resection (n=19). SR was performed with larger tumor size, increased depth of invasion, and solitary tumors. Although the 5-year RFS in SR patients was 75%, the DSS in both groups was 100%. However, concomitant adenocarcinoma was identified in 4/19 resected cases; 2/4 were detected on preoperative biopsies. All cases with coexisting gastric adenocarcinoma had larger carcinoid tumors and more advanced carcinoid disease. The DSS is excellent for type I GC patients treated with either ES or SR. SR should be considered with more advanced carcinoid disease given its association with an increased risk of adenocarcinoma. ES is appropriate to assess both the status of carcinoid disease and dysplasia or adenocarcinoma that can develop in association with type I GC.

Chondrosarcoma of the Arytenoid Cartilage: A Case Report and Review of the Literature

We report the case of a 56-year-old black woman with a locally aggressive chondrosarcoma at an unusual tumor site: the right arytenoid cartilage. The tumor extended from the superior pole of the right arytenoid cartilage to the soft-tissue areas of the right aryepiglottic fold, piriform sinus, and interarytenoid area. We undertook a conservative surgical approach by performing an endoscopic transoral CO2 laser resection, a right arytenoidectomy with wide soft-tissue margins, and a tracheotomy in anticipation of postoperative edema. Surgical exploration revealed that the tumor extended into the cricoid cartilage. Histopathology demonstrated a low-grade chondrosarcoma of the conventional variant. Clear margins were obtained by staged procedures. Chondrosarcomas of the larynx typically exhibit low-grade histopathology, and affected patients have a low incidence of metastasis and a good prognosis. Even so, these tumors can present diagnostic and therapeutic challenges. Surgical resection provides adequate airway protection and sound oncologic safety while preserving speech and swallowing, and these should be the surgeon's goals in this setting. Options include open laryngofissure, thyrotomy, organ preservation with partial laryngectomy, and endoscopic laser resection.

A Modular Analysis of Breast Cancer Reveals a Novel Low-Grade Molecular Signature in Estrogen Receptor–Positive Tumors

Previous reports using genome-wide gene expression data to classify breast tumors have typically used standard unsupervised or supervised techniques, both of which have known limitations. We hypothesized that novel clinically relevant information could be revealed in these data sets by an alternative analytic approach. Using a recently described algorithm, signature analysis (SA), we identified "modules," comprising groups of tightly coexpressed genes that are conditionally linked to particular tumors, in a series of breast tumor gene expression profiles. The SA successfully identified multiple breast cancer modules specifically linked to distinct biological functions. We identified a novel module, TuM1, whose presence was not readily discernible by conventional clustering techniques. The TuM1 module is expressed in a subset of estrogen receptor (ER)-positive tumors and is significantly enriched with genes involved in apoptosis and cell death. Clinically, TuM1-expressing tumors are associated with low histopathologic grade, and this association is independent of the inherent ER status of a tumor. We confirmed the robustness and general applicability of TuM1 module by demonstrating its association with low tumor grade in multiple independent breast cancer data sets generated using different array technologies. In vitro, the TuM1 module is down-regulated in ER+ MCF7 cells upon treatment with tamoxifen, suggesting that TuM1 expression may be dependent on active signaling by ER. Initial data is also suggestive that TuM1 expression may be clinically associated with a patient's response to antihormonal therapy. Our results suggest that modular-based approaches toward gene expression data can prove useful in identifying novel, robust, and biologically relevant signatures even from data sets that have been the subject of substantial prior analysis.

Tubular carcinoma of the breast and associated intra-epithelial lesions: a comparative study with invasive low-grade ductal carcinomas

Ductal intra-epithelial lesions of the breast are associated with invasive neoplasms and comprise a large spectrum of histological patterns. We have examined 23 cases of pure tubular carcinomas (TCs) of the breast and 53 cases of invasive ductal low-grade carcinomas to determine the relationship and distribution of intra-epithelial lesions, mainly of ductal in situ carcinoma type, but including also lobular intra-epithelial neoplasia (LIN) in both entities. Eleven cases of TC showed flat epithelial atypia (FEA) (47.8%), and, in 14 and 6 cases, micropapillary and cribriform low-grade ductal carcinoma in situ (DCIS) were present (60.7 and 26.1%, respectively). On the opposite, in ductal grade I invasive carcinomas, the most frequent architectural pattern was low-grade DCIS growing in arcades in 26 cases (49%). While absent in TCs, low-grade DCIS of solid type was found in five (9.4%) cases of ductal invasive carcinomas, where FEA were present in seven (13.2%) cases. LIN lesions were present in four (17.4%) cases of TC, whereas they represented 7.5%, as reported by Carstens et al. (Am J Clin Pathol 58:231-238, 1972), of cases of low-grade carcinomas. These results suggest that invasive pure TC and low-grade ductal carcinomas of the breast are different lesions, and support the fact that TC, of low histopathological grade, is a particular distinct tumoural entity.

What do breast cancer patients benefit from staging bone scintigraphy?

A review and analysis of breast cancer treatment records were conducted to establish criteria for performing disease staging by bone scintigraphy in Japanese breast cancer patients. Records from 5538 consecutive Japanese breast cancer patients from January 1988 to December 1998 were reviewed and analyzed to determine bone metastasis status at the time of initial treatment. Correlation between metastasis to bone and factors known before and after surgery was analyzed using logistic regression. The overall incidence of metastasis to bone was 2.13% [95% confidence interval (CI): 1.77-2.55%, 118/5538]. Multivariate logistic analysis revealed that tumor size, nodal involvement and histopathology correlated with metastasis to bone. Patients with tumors larger than 30 mm had a significantly higher probability of metastasis to bone, as did patients with lymph node evaluation results N > or = 1. The incidence of metastasis to bone was 0% in patients with stage 0 disease, 0.08% in stage I patients, 1.09% in stage II patients, 9.96% in stage III patients and 34.04% in stage IV patients. Stage II patients were sub-classified by tumor size T (small, 21-30 mm; and large, 31-50 mm), nodal involvement N and histopathology. The incidence of metastasis to bone in stage II patients was higher in patients with large tumors, scirrhous carcinoma or invasive lobular carcinoma or both. Bone metastasis correlated with tumor size (T), lymph node involvement (N) and histopathology. Using the criteria that bone scintigraphy is not necessary in populations with a < 1% incidence of bone metastasis, but is recommended at incidence > 3%, the following conclusions were drawn. Staging by bone scintigraphy provided no benefit to patients whose disease was stage I or less, stage II with small tumors or stage II with large tumors marked by low-grade histopathology (papillotubular cancer). Bone scintigraphy is recommended in patients whose disease is stage II with large tumors marked by high-grade histopathology (scirrhous or invasive lobular cancer), stage III or stage IV. Consequently, staging by bone scintigraphy could be avoided in 71% (3943/5538) of Japanese breast cancer patients.

Prognostic factors for the outcome of chemotherapy in advanced soft tissue sarcoma: an analysis of 2,185 patients treated with anthracycline-containing first-line regimens--a European Organization for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group Study.

A total of 2,185 patients with advanced soft tissue sarcomas who had been treated in seven clinical trials investigating the use of doxorubicin- or epirubicin-containing regimens as first-line chemotherapy were studied in this prognostic-factor analysis. Overall survival time (median, 51 weeks) and response to chemotherapy (26% complete response or partial response) were the two end points. The cofactors were sex; age; performance status; prior therapies; the presence of locoregional or recurrent disease; lung, liver, and bone metastases at the time of entry onto the trial; long time period between the initial diagnosis of sarcoma and entry onto the study; and histologic type and grade. Univariate analyses showed (a) a significant, favorable influence of good performance status, young age, and absence of liver metastases on both survival time and response rate, (b) a significant, favorable influence of low histopathologic disease grade on survival time, despite a significantly lower response rate, (c) increased survival time for patients with a long time period between the initial diagnosis of sarcoma and entry onto the study, despite equivalent response rates, and (d) increased survival time with liposarcoma or synovial sarcoma, a decreased survival time with malignant fibrous histiocytoma, a lower response rate with leiomyosarcoma, and a higher response rate with liposarcoma (P < .05 for all log-rank and chi2 tests). The Cox model selected good performance status (P < .0001), absence of liver metastases (P = .0001), low histopathologic grade (P = .0002), long time lapse since initial diagnosis (P = .0004), and young age (P = .0045) as favorable prognostic factors of survival time. The logistic model selected absence of liver metastases (P < .0001), young age (P = .0024), high histopathologic grade (P = .0051), and liposarcoma (P = .0065) as favorable prognostic factors of response rate. This analysis demonstrates that for advanced soft tissue sarcoma, response to chemotherapy is not predicted by the same factors as is overall survival time. This needs to be taken into account in the interpretation of trials assessing the value of new agents for this disease on the basis of response to treatment.

Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines

Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.

Gastrin inhibits motility, decreases cell death levels and increases proliferation in human glioblastoma cell lines.

Whether they are of low or high histopathological grade, human astrocytic tumors are characterized by a marked propensity to diffuse into large areas of normal brain parenchyma. This invasion relates mainly to cell motility, which enables individual cell migration to take place. The present study characterizes in vitro the gastrin-mediated effects on both the growth (cell proliferation vs. cell death) and motility dynamics of the human U87 and U373 glioblastoma cell lines. A computer-assisted phase-contrast microscope was used to track the number of mitoses versus cell deaths every 4 min over a 72-h period and so to quantitatively describe the trajectories of living U373 and U87 cells growing on plastic supports in culture media both with and without the addition of 0.1, 5, or 100 nM gastrin. While 5 or 100 nM gastrin only weakly (p < .05 to p < .01) increased cell proliferation in the U87 cell line and not in U373 one, it very significantly (p < .001) inhibited the amount of cell death at 5 and 100 nM in both the U87 and U373 lines. In addition, 5 nM gastrin markedly inhibited cell mobility in U87 (p < .00001) and U373 (p < .0001) glioblastoma models. All these data strongly suggest that gastrin plays a major role in the biological behavior of the in vitro U87 and U373 human glioblastoma cell lines in matters concerning their levels of cell motility and growth dynamics.

Prognostic significance of methyl-p-hydroxy-phenyllactate-esterase activity in laryngeal squamous cell carcinoma

We assayed methyl-p-hydroxyphenyllactate esterase (MeHPLAase) activity in 63 cases of primary laryngeal squamous cell carcinoma. MeHPLAase activity did not show any correlation with oestrogen, progesterone and epidermal growth factor (EGF) receptor levels. No significant relationship was found between MeHPLAase activity and age, sex, tumour site, T classification, stage of disease and EGFR status, whereas a significant inverse relationship was found between enzymatic activity and neck lymph node positivity at presentation. The median value of MeHPLAase activity tended to be higher in tumours with low histopathological grade than in those with high histopathological grade. During the follow-up period (median 50 months, range 2-90 months) locoregional recurrences were observed in 31 out of 63 (49%) cases. At the end of the study, 27 out of 63 (43%) patients had died of cancer. Cox univariate analysis using MeHPLAase activity as a continuous covariate showed that the levels of enzymatic activity were inversely associated with the risk of death and relapse. Assuming the mean value of enzymatic activity as the cut-off value, we found a statistically significant relationship between high MeHPLAase activity and longer relapse-free and overall survival. MeHPLAase activity status retained its prognostic significance also in the lymph node-negative subgroup of patients. On multivariate analysis, both EGFR and MeHPLAase activity proved to be independent factors for predicting a short relapse and the overall survival.

The role of radical gastrectomy with systematic lymphadenectomy for the diagnosis and treatment of primary gastric lymphoma.

We evaluated the therapeutic efficacy of radical gastrectomy for primary B-cell lymphoma of the stomach and attempted to identify patients who could be adequately treated with surgery alone. Several recent gastric lymphoma reports have discussed the therapeutic benefits of various treatment strategies for stage IE and IIE lymphoma. However, few studies have been based on patients accurately staged by systematic lymphadenectomy with subsequent pathologic examination. A retrospective study was performed to evaluate the survival and biologic behavior of lesions in 60 patients with gastric lymphoma who were treated by radical gastrectomy alone. Tumors were classified according to the histopathologic concept of mucosa-associated lymphoid tissue (MALT)-derived lymphoma. A low histopathologic grade was associated with a significantly lower incidence of nodal metastasis (p = 0.07) and less extensive infiltration of the gastric wall (p < 0.005) despite larger tumor size. A 5-year survival rate of >95% was attained with surgery alone for MALT lymphoma and for true stage IE lymphoma diagnosed by pathologic examination of up to N2 lymph nodes routinely performed after radical gastrectomy. Surgery alone is adequate treatment for stage IE or pure MALT lymphoma, provided that the staging is performed after radical gastrectomy.

Endometrial carcinoma stage I

Standard staging and therapeutic approach to endometrial cancer involves lymph node sampling (LNS) at the time of total abdominal hysterectomy (TAH) and bilateral salpingo-oophorectomy (BSO). Lymphadenectomy prolongs time of surgery and increases the risk of morbidity; where other predictors are available, it may not contribute important supplementary information. 185/247 women with stage I endometrial carcinoma underwent the standard surgery while 62 underwent TAH+BSO. Recurrence and survival were monitored for a mean of 6.5 years and retrospectively reviewed: the rates for groups with and without known lymph node status were alike [13.5% (25/185) recurrence for the former and 12.9% (8/62) for the latter, and 5-year survival rates of 75.7% (140/185) for the former and 74.2 (46/62) for the latter]. Myometrial invasion and histological grade appeared to have been highly accurate predictors without lymph node information. Because information on histological grade is available early and is highly predictive, its use could be incorporated into a revised management algorithm for stage I endometrial cancer which would depend upon ensuring lymphadenectomy for women with low grade histopathology and omitting it for those with high grades on the grounds that no further information is necessary to act appropriately.

Surgical Pathology of Chronic Epileptic Seizure Disorders

The surgical treatment of chronic epilepsies is increasing rapidly and involves neuropathologists in the care of patients with chronic and medically intractable seizure disorders. Herein we review the histopathologic findings in 279 consecutive surgical specimens of patients with chronic pharmacoresistant epileptic disorders. Aspects that are relevant to the diagnostic surgical pathologist such as the terminology of developmental lesions and Ammon's horn sclerosis are discussed. In 87 cases (31.2%), there were tumors in which all but two were of low histopathological grade (WHO grade I or grade II). The most common tumors were gangliogliomas, pilocytic astrocytomas, oligodendrogliomas, fibrillary astrocytomas and dysembryoplastic neuroepithelial tumors. Among the most frequent non-neoplastic focal lesions, microscopic glioneuronal hamartias, circumscribed vascular malformations, glioneuronal hamartomas and porencephalic defects were most frequent. The hippocampal formation was structurally well preserved in 71 specimens of patients with temporal lobe epilepsy. In 51 of these (71.8%) cases, Ammon's horn sclerosis was present. The findings suggest that the structural lesions observed in the great majority of the specimens are closely related to the pathogenesis of intractable seizures.

Surgical Pathology of Temporal Lobe Epilepsy. Experience with 216 Cases

The surgical treatment of chronic epilepsies is increasing rapidly. Here we report the histopathologic findings in 216 consecutive surgical specimens of patients with chronic pharmacoresistant temporal lobe epilepsy. In 75 cases (34.7%) there were tumors, all but two of which were of low histopathological grade (WHO grade I or II). The most common tumors were gangliogliomas (34 cases), pilocytic astrocytomas (17 cases), oligodendrogliomas (9 cases), fibrillary astrocytomas (6 cases), and dysembryoplastic neuroepithelial tumors (6 cases). There were 51 cases with non-neoplastic focal lesions and an additional 13 cases with tumors and non-neoplastic focal lesions within the same specimen. The most frequent non-neoplastic focal lesions were microscopic glioneuronal hamartias (32 cases), glioneuronal hamartomas (7 cases), and vascular malformations (13 cases). The hippocampal formation was structurally well preserved in 71 specimens. In 51 of these (71.8%) there was Ammon's horn sclerosis. Presurgical placement of depth electrodes was invariably associated with circumscribed defects of the brain parenchyma. The implantation of subdural electrodes was sometimes followed by chronic inflammatory changes of the leptomeninges. Our findings indicate that in the majority of patients with medically intractable temporal lobe epilepsy there are significant histopathologic findings, many of which are only rarely encountered otherwise.

Complex cytogenetic aberrations in a well-differentiated chondrosarcoma

The cytogenetic analysis of a well-differentiated (grade I) chondrosarcoma is presented. Despite a low-grade histopathology, metaphase preparations of tumor cells were characterized by numerous structural chromosome aberrations and a striking degree of genetic instability; the t(9;22)(q31;q12) that has been described recently in extraskeletal myxoid chondrosarcoma was not observed. This report suggests that chondrosarcomas may be heterogeneous cytogenetically. In chondrosarcoma, it appears that “high-grade” cytogenetic abnormalities do not necessarily engender a high-grade histology. These findings offer a possible explanation for the clinical aggressiveness of certain low-grade chondrosarcomas.

Intrinsic brainstem tumors in childhood: surgical indications.

Sixty-six children with intrinsic brainstem gliomas diagnosed between 1980 and 1986 underwent radical surgical resection. Retrospective analysis permitted classification of tumors into four categories: diffuse, focal, cystic and cervicomedullary. All 27 patients with diffuse tumors had malignant neoplasms, were not benefitted by surgery and died within 12-18 months. Five of nine cystic tumors, three of five focal tumors and twenty of twenty-four cervicomedullary tumors had low grade histopathology and are alive one to six years postoperatively. The authors propose a clinical-neuroradiological criteria that accurately predict which patients with brainstem tumors are likely to benefit from radical surgical intervention.

Ampullary cancer in chemical workers.

Although a relatively uncommon neoplasm, cancer of the ampulla of Vater does account for over 300 deaths a year in the United States.1 Among biliary tract tumours, ampullary cancer is regarded as having a favourable prognosis because the early onset of symp toms, low grade histopathology, and late and infre quent m?tastases allow the possibility of surgical cure; nevertheless, high operative mortality and overall five year survival figures of between 4% and 40%, depending on type of tumour and disease spread at diagnosis, show that these cancers cannot be consid ered as having a good prognosis.J These figures also serve to underline the importance of the identification of underlying aetiological factors for these tumours. In previous research we had identified the possible importance of chemical exposures in the development of these tumours; however, statistical significance was limited by the small numbers involved.1 2 Expansion of these studies has now confirmed our previous pre dictions.