Non-tumoral Causes Research Articles

Incidental presentation of appendix neuroendocrine tumor: Long-term results from a single institution.

Appendix neuroendocrine tumors (NETs) are the most common tumors of the appendix and are most often diagnosed incidentally. The aim of this study was to retrospectively evaluate appendix NETs diagnosed incidentally in our clinic. Of 8304 patients who underwent appendectomy with the diagnosis of acute appendicitis in Ankara Training and Re-search Hospital, General Surgery Clinic between January 2009 and January 2022, 33 had histopathology results evaluated as appendix NET, and a retrospective analysis was made of these cases. The patients were evaluated in terms of age, gender, tumor infiltration, tumor location, tumor size, surgical margin, tumor World Health Organization grade, surgery performed, lymph node metastasis, Ki67 index, number of mitosis, follow-up time, and survival. The rate of appendix NET was found to be 0.4%. The 33 cases comprised 15 (45.5%) males and 18 (54.5%) females with a mean age of 35.48 years (range: 16-84 years). Positive surgical margin was determined in 1 (3.03%) case, in which right hemicolectomy was performed. All other cases were followed up after appendectomy. The median follow-up was 89 (7-145) months. No recurrence was observed in any case. Mortality developed during follow-up in one case due to non-tumoral causes. Appendix NETs are generally asymptomatic and appear incidentally after appendectomy due to acute appendicitis. Appendix NETs diagnosed incidentally are generally below 2 cm and have a good prognosis.

Abstract #1322277: A Young Female With Secondary Amenorrhea and Hirsutism-Steroid Cell Tumor of Ovary – A Rare Case Report

Polycystic ovary syndrome is the most prevalent cause of hyperandrogenism in young females. Other causes of hirsutism are congenital adrenal hyperplasia (CAH), androgen-producing tumors and drugs. The severity and tempo of virilization help in differentiating the tumoral from nontumoral causes. Here, we report a case of young female with secondary amenorrhea and hirsutism for 5 years diagnosed as steroid cell tumor of ovary.

Mild hyperprolactinemia in a couple: What impact on fertility?

Mild-to-moderate hyperprolactinemia is a frequent finding in young women presenting with infertility. Prolactin (PRL) concentration should be determined accurately, whether or not the patient has other symptoms suggestive of excess PRL such as galactorrhea or menstrual cycle disorder. After confirmation of persistent hyperprolactinemia on a second blood sample (avoiding conditions known to raise prolactin) and exclusion of macroprolactinemia, prolactinoma and other identifiable non-tumoral causes of hyperprolactinemia must be ruled out. Mildly elevated PRL levels may cause luteal insufficiency in cycling women and are associated with recurrent miscarriage. Any confirmed hyperprolactinemia should be treated in a woman who wishes or fails to become pregnant. Preference is given to cabergoline at the lowest possible dose that normalizes PRL, restoring fertility in the vast majority of cases.Evidence is much less robust in men, in whom PRL concentrations are less prone to increase and the reproductive system is less sensitive to the negative effects of hyperprolactinemia. Nevertheless, chronic and significant hyperprolactinemia in men may impair fertility or cause infertility (with or without hypogonadism) and must be treated, as in women. However, more clinical studies are clearly needed concerning male reproductive function.The significance of mild but persistent hyperprolactinemia in either member of a couple incidentally discovered during assisted reproductive technology (ART) procedures is unclear, and future evidence-based studies are needed to determine whether normalizing prolactin can improve ART outcome.

Identification of immunosuppressive factors in retinoblastoma cell secretomes and aqueous humor from patients.

The microenvironment of retinoblastoma, the solid malignancy of the developing retina, is immunosuppressive. To study the interactions between tumor-associated microglia/macrophages (TAMs) and tumor cells in retinoblastomas, we analyzed immunohistochemistry markers in 23 patient samples and characterized 105 secreted cytokines of 11 retinoblastoma cell models in culture. We detected profuse infiltration of CD163+ protumoral M2-like polarized TAMs in eyes enucleated due to cancer progression. Previous treatment of patients increased the number of TAMs but did not affect M2-like polarization. M2-like microglia/macrophages were almost absent in five eyes obtained from children enucleated due to nontumoral causes. CD8+ tumor-infiltrating lymphocytes (TILs) were moderately abundant in tumor eyes and very scarce in nontumoral ones. The expression of the immune checkpoint molecule PD-L1 was absent in 95% of the tumor samples, which is concordant with the finding of FOXP3+ Tregs infiltrating tumors. We confirmed the pathology results using single-cell transcriptome analysis of one tumor. We identified the cytokines extracellular matrix metalloproteinase inducer (EMMPRIN) and macrophage migration inhibitory factor (MIF), both with reported immunosuppressive activity, secreted at high levels in retinoblastoma primary cell cultures. Gene expression analysis of a large retinoblastoma cohort and single-cell transcriptome analysis confirmed that MIF and EMMPRIN were significantly upregulated in retinoblastomas, which led us to quantify both proteins by immunoassays in liquid biopsies (aqueous humor obtained from more than 20 retinoblastoma patients). We found a significant increase in the concentration of MIF and EMMPRIN in cancer patients, compared to 12 noncancer ones. Finally, we showed that macrophages derived from peripheral blood mononuclear cells increased the expression of markers of M2-like polarization upon exposure to retinoblastoma-conditioned medium or recombinant MIF. Overall, our findings suggest that retinoblastoma cell secretions induce the protumoral phenotype of this tumor. Our results might have clinical impact in the fields of biomarkers and treatment. © 2022 The Pathological Society of Great Britain and Ireland.

Distribution and evaluation of bone and soft tissue tumors operated in a tertiary care center

ObjectiveThe aim of this study was to retrospectively evaluate the patients who were operated in our orthopedics and traumatology clinic with the suspection of bone and soft tissue tumors. MethodsA total of 3133 patients (1146 (46.5%) female and 1318 (53.5%) male) who presented to our tertiary clinic from different regions of Turkey between January 2002 and July 2013 with the presumed diagnosis of bone and soft tissue tumors were analyzed according to age, gender, bone/soft tissue localization, tumoral localization, histopathological diagnosis, tumor size and incidence. ResultsOf all operated patients, 2464 (78%) were diagnosed with tumor, while non-tumoral causes were found in 669 (22%) patients. Of the cases diagnosed with tumor, 1139 were bone localized, 1004 soft tissue localized, and 321 metastasis. The most common benign bone tumors were osteochondroma (130, 20%), enchondroma (96, 15%), and simple bone cysts (90, 14%), while the most common malignant bone tumors were osteosarcoma (241, 44%), ewing's sarcoma (89, 16%), and chondrosarcoma (77, 14%); respectively. The most common benign soft tissue tumors were lipoma (141, 22%), giant cell tumors (108, 16%) and ganglion (107, 16%), while the most common malignant soft tissue tumors were liposarcoma (55, 16%), synovial sarcoma (53, 16%) and malignant mesenchymal tumors (45, 13%); respectively. ConclusionMusculoskeletal tumors are rare, but descriptive data in any region are important in order to reduce mortality and improve treatment. No significant difference was found between the data of our hospital regarding epidemiology of the musculoskeletal system tumors and those from the other regions around the world. Level of evidenceLevel IV, Therapeutic study.

Etiology of hypopituitarism in tertiary care institutions in Turkish population: analysis of 773 patients from pituitary study group database

Hypopituitarism in adult life is commonly acquired and the main causes are known as pituitary tumors and/or their treatments. Since there are new insights into the etiology of hypopituitarism and presence of differences in various populations, more studies regarding causes of hypopituitarism are needed to be done in different ethnic groups with sufficient number of patients. Therefore, we performed a multi-center database study in Turkish population investigating the etiology of hypopituitarism in 773 patients in tertiary care institutions. The study was designed and coordinated by the Pituitary Study Group of SEMT (The Society of Endocrinology and Metabolism of Turkey). Nineteen tertiary reference centers (14 university hospitals and 5 training hospitals) from the different regions of Turkey participated in the study. It is a cross-sectional database study, and the data were recorded for 18 months. We mainly classified the causes of hypopituitarism as pituitary tumors (due to direct effects of the pituitary tumors and/or their treatments), extra-pituitary tumors and non-tumoral causes. Mean age of 773 patients (49.8 % male, 50.2 % female) was 43.9 ± 16.1 years (range 16-84 years). The most common etiology of pituitary dysfunction was due to non-tumoral causes (49.2 %) among all patients. However, when we analyze the causes according to gender, the most common etiology in males was pituitary tumors, but the most common etiology in females was non-tumoral causes. According to the subgroup analysis of the causes of hypopituitarism in all patients, the most common four causes of hypopituitarism which have frequencies over 10 % were as follows: non-secretory pituitary adenomas, Sheehan's syndrome, lactotroph adenomas and idiopathic. With regard to the type of hormonal deficiencies; FSH/LH deficiency was the most common hormonal deficit (84.9 % of the patients). In 33.8 % of the patients, 4 anterior pituitary hormone deficiencies (FSH/LH, ACTH, TSH, and GH) were present. Among all patients, the most frequent cause of hypopituitarism was non-secretory pituitary adenomas. However, in female patients, present study clearly demonstrates that Sheehan's syndrome is still one of the most important causes of hypopituitarism in Turkish population. Further, population-based prospective studies need to be done to understand the prevalence and incidence of the causes of hypopituitarism in different countries.

Impact of Clinical, Hormonal, Radiological, and Immunohistochemical Studies on the Diagnosis of Postmenopausal Hyperandrogenism

Postmenopausal biochemical hyperandrogenism occurs rarely. The presence of an underlying tumor in women with this condition may be missed without careful evaluation. Androgen excess in these women is the result of either tumoral or nontumoral causes. Factors that distinguish between tumoral and nontumoral etiology have not been identified. The primary goal of this retrospective study was to identify specific characteristics that could help differentiate between tumoral or nontumoral etiology among postmenopausal women suspected of having an androgen-secreting tumor. Participants were 22 postmenopausal women with biochemical hyperandrogenism referred to a medical center between 1995 and 2009. Clinical, biological, and morphological evaluations were performed in all women. Surgical resection of both ovaries was most often proposed for women without adrenal tumors, and immunocytochemical studies of the ovaries were performed. Among the 22 participants, 8 cases of ovarian tumors were identified based on ultrasound and/or magnetic resonance imaging. Two additional cases had an adrenal tumor diagnosed by computed tomography. The remaining 12 women had various nontumoral conditions. The clinical presentation in women with and without tumors was very similar. Some differences between the 2 groups, however, were found in the biological phenotype. Compared with women without tumors, women with tumors had significantly higher levels of testosterone [2.6 (2.7) vs 0.9 (0.9) ng/mL, P < 0.05] and lower levels of basal follicle-stimulating hormone [FSH; 26.5 (22.9) vs 66.5 (26.0) IU/L, P < 0.01] and luteinizing hormone [12.0 (8.6) vs 24.1 (8.9) IU/L, P < 0.05]. Based on the likelihood ratio, the risk of having a testosterone level of 1.4 ng/mL or greater or an FSH level of 35 IU/L or less in postmenopausal women with a tumor was 8.4 and 10.8 times higher, respectively. Immunochemistry using P450c17α antibody allowed identification of an elevated number of ovarian androgen-producing cells in 5 patients with tumors undetectable by conventional histology. These findings show no differences in clinical phenotype that can be used to discriminate between androgen-secreting tumors and other nontumoral causes of postmenopausal hyperandrogenism. The data suggest that 2 hormonal phenotypes, testosterone and basal FSH levels, may be discriminating markers.

Impact of clinical, hormonal, radiological, and immunohistochemical studies on the diagnosis of postmenopausal hyperandrogenism

Evaluation of postmenopausal women with suspicion of androgen-secreting tumor. We retrospectively studied 22 postmenopausal women referred to our center for suspicion of androgen-secreting tumor. All patients had clinical, biological, and morphological evaluation. In absence of adrenal tumors, ovarian surgery was most often proposed and immunohistochemistry (IHC) studies were performed. Ovarian tumors were detected by ultrasound and/or magnetic resonance imaging in eight patients. Two adrenal androgen-secreting tumors were diagnosed by an adrenal computed tomography (CT) scan. The clinical presentation of the women with or without tumors was similar. Nevertheless, women with tumor exhibited significantly higher testosterone levels and lower basal FSH and LH levels than the other women (2.6±2.7 vs 0.9±0.9 ng/ml, P<0.05; 26.5±22.9 vs 66.5±26.0 IU/l, P<0.01; and 12.0±8.6 vs 24.1±8.9 IU/l, P<0.05 respectively). Based on a likelihood ratio test, patients with a tumor had 8.4 and 10.8 times higher risk of having a testosterone level ≥1.4 ng/ml or an FSH level ≤35 IU/l. Finally, IHC analysis with an anti-P450c17α antibody allowed the identification of an elevated number of ovarian androgen-producing cells in five patients in whom no tumor was found. Androgen-secreting tumors are clinically difficult to discriminate from other causes of postmenopausal hyperandrogenism. Testosterone and FSH were the two discriminative markers in a multivariate analysis. Ovarian and adrenal tumors were detected by imaging studies. However, ovarian non-tumoral causes of hyperandrogenism may be difficult to detect with conventional histology.

Glomérulonéphrite extramembraneuse paranéoplasique au cours d’un mélanome

Membranous glomerulonephritis (MG) is generally idiopathic. Causes of secondary MG (15% of cases), namely solid or haematological cancers, are common, with parallel development between the two diseases suggesting paraneoplastic syndrome. However, paraneoplastic syndrome is rare in melanoma. We report a case of a patient with stage III melanoma presenting MG developing in parallel to the melanoma. A 61-year-old man was referred for melanoma on the right side with a Breslow index of 3mm, and without ulceration. While the patient had no adenopathy, he was presenting severe hypertension diagnosed two months earlier as well as diffuse pitting oedema, with weight gain of 15kg in one month. Additional treatment of the patient's melanoma included extended excision, examination of the two right axillary sentinel nodes (positive), and axillary lymph node dissection revealing four more metastatic nodes. A thoracic-abdominal-pelvic CAT scan showed no further metastasis. Investigation of the oedema revealed nephrotic syndrome with hypoalbuminaemia of 14g/L and proteinuria of 5g/24h. Renal biopsy resulted in the diagnosis of MG. Histological and immunohistochemical examination (HMB-45, Melan A, S100 protein) showed no tumour cells in the kidney, and urinary cytology was negative. Non-tumoral causes of MG were thus ruled out. The oedema regressed rapidly following surgical treatment of the melanoma, with no specific renal or oncological treatment being given. Two years after axillary lymph node dissection, the patient was in complete remission of his melanoma and renal tests showed spontaneous regression of nephrotic syndrome, with disappearance of the oedema, normalisation of blood pressure and gradual correction of serum albumin (40g/L) and proteinuria (1g/24h). Paraneoplastic MG has been described particularly in patients with gastrointestinal and pulmonary cancer. To our knowledge, this is only the second case associated with melanoma. Our report suggests the need for routine cutaneous examination as part of the initial investigations for MG.

Congenital Hypopituitarism: Clinico-Radiological Correlation

Non-tumoral causes constitute a major group of childhood hypopituitarism. The structural abnormalities of the stalk and the pituitary gland correlate with number and severity of concurrent hormone deficiencies. We describe clinico-radiological correlates in patients with non-tumoral hypopituitarism. Thirty-one children (23 boys) with congenital hypopituitarism, aged 1-17 years, with a peak GH levels of < 7 ng/ml after two pharmacological stimuli (insulin induced hypoglycemia [IIH] and clonidine) were included in the study. MRI tetrad of absent or hypoplastic pituitary, empty sella, redundant or absent stalk and absent/ectopic posterior pituitary bright spot (EPPBS) was considered as a radiological diagnostic criterion and these abnormalities were correlated with number of hormone deficiencies, severity of GH deficiency and mode of presentation at the time of delivery. Twenty (66%) children had vertex presentation, nine breech, and two children were delivered by lower segment Cesarean section (LSCS). Seven (78%) out of nine in the breech delivery group, 14 (70%) out of 20 in the vertex group and one out of two (50%) in the LSCS group had multiple pituitary hormone deficiencies (MPHD) (p = 0.665). Hypoplastic pituitary gland and posterior pituitary abnormalities were more frequent in patients with isolated growth hormone deficiency (IGHD) as opposed to MPHD (87.5% vs 65.2%, p = 0.08, 63% vs 47%, p = 0.64), whereas empty sella and stalk abnormalities were found more frequently in MPHD than in the IGHD group (76% vs 50%, p = 0.45 and 82.6% vs 37.5%, p = 0.01). Higher frequency of MR abnormalities was found in those with a peak GH response of < 3 ng/ml irrespective of the number of other pituitary hormone deficiencies (82.6% vs 37.5%, p = 0.02). Sixteen patients had MRI tetrad and it was more prevalent in the IGHD than in the MPHD group (75% and 44%, p = 0.01) and correlated with the severity of GH deficiency (r = 0.57, p = 0.01). The imaging abnormalities were also more prevalent in children with breech as compared to vertex presentation and correlated with severity of GH deficiency (100% vs 60%, p = 0.03, r = 0.52). Imaging abnormalities are frequent in patients with non-tumoral hypopituitarism and correlate best with severity of GH deficiency rather than number of hormone deficiencies and breech presentation.

Down‐staging of hepatocellular carcinoma prior to liver transplantation

We enjoyed the article by Yao et al. in the recent issue of HEPATOLOGY1 in which they report an excellent outcome of liver transplantation (LT) following preoperative down-staging of hepatocellular carcinoma (HCC). Yao et al. selected HCCs without vascular invasion by imaging studies and out of the Milan criteria2 but meeting the following criteria: single nodule measuring 5-8 cm, 2-3 nodules measuring 3-5 cm (total ≤8 cm), 4-5 nodules measuring ≤3 cm (total ≤8 cm). They needed to meet the Milan criteria after chemoembolization (TACE), percutaneous ablation techniques, or liver resections. Thirty-five patients received LT without tumor recurrence after a median follow-up of 25 months. Two cases died due to nontumoral causes. The efficacy of patient selection based on clinical response to preoperative treatments is confirmed by our recent down-staging study, which is similar in terms of inclusion criteria and follow-up.3 In an intention-to-treat analysis, our recurrence rate and patient survival were not as excellent as those reported by Yao et al., but they were comparable to our control group meeting the Milan criteria. We think it remarkable that LT can achieve good results even in a population with many multinodular (>3) HCCs (58.3%), in contrast with the 5 out of 61 cases (8.2%) of the University of California, San Francisco (UCSF) series. Furthermore, many of our cases showed microvascular invasion and poorly differentiated tumor, whereas none of the UCSF cases revealed these unfavorable features, providing a fairly surprising picture in contrast with several previous series.4-8 As discussed by the authors, these results may have been generated by the selection of tumors with more favorable biology during the down-staging process. Nonetheless, we had quite different results following a very similar selection process. We wonder if they applied other specific selection criteria that we failed to understand. As described by the authors, most patients received a biopsy before LT, and in the same period two different studies were performed: the present one, where patients must meet the Milan criteria after down-staging procedure, and another in which patients were listed with slightly extended Milan criteria (UCSF criteria) without any restrictions concerning treatments during the waiting time.4 We would like to know how the authors decided whether to include a case in one study or the other, if the pre-liver biopsy played any role, if all cases were first HCC diagnosis, and if patients progressed during follow-up could be still eligible for down-staging procedures. Finally, because the authors showed the efficacy of the UCSF criteria, it would be interesting to know how many patients met these criteria in the down-staging group before any treatments. In conclusion, both the UCSF and Bologna studies confirm the power of selection to improve LT results for HCC and suggest how it should be properly applied. We have learned how to minimize the graft/patient loss for tumor recurrence; now we are learning how to offer to patients with HCC—even those outside the Milan criteria—the same chance of survival of those listed for LT with other indications. Matteo Ravaioli M.D.*, Gian Luca Grazi M.D.*, Matteo Cescon M.D.*, Franco Trevisani M.D. , Fabio Piscaglia M.D. , Giorgio Ercolani M.D.*, Antonio Daniele Pinna M.D.*, * Department of Liver and Multi-organ Transplantation, Sant 'Orsola-Malpighi Hospital, University of Bologna, Italy, Department of Gastroenterology and Internal Medicine, Sant 'Orsola-Malpighi Hospital, University of Bologna, Italy.

Sex steroids in androgen-secreting adrenocortical tumors: clinical and hormonal features in comparison with non-tumoral causes of androgen excess

Adrenocortical tumors (ACT) account for no more than 0.2% of the causes of androgen excess (AE). Conversely, these rare tumors have a very poor prognosis. It is difficult and important to exclude this diagnosis whenever there is AE. Retrospective investigation of androgen profiles in a large consecutive series of androgen-secreting (AS) ACT to assess their relative diagnostic value. A total of 44 consecutive female patients with ACT-AS and a comparison group of 102 women with non-tumor causes of AE (NTAE). Patients with ACT-AS were older than the ones with NTAE (37.7 vs 24.8 years; P<0.001) and the prevalence of hirsutism, acne, and oligo/amenorrhea were not different. Free testosterone was the most commonly elevated androgen in ACT-AS (94%), followed by androstenedione (90%), DHEAS (82%), and total testosterone (76%), and all three androgens were simultaneously elevated in 56% of the cases. Androgen serum levels became subnormal in all ACT-AS patients after complete tumor removal. In NTAE, the most commonly elevated androgen was androstenedione (93%), while all three androgens were elevated in only 22% of the cases. Free testosterone values above 6.85 pg/ml (23.6 pmol/l) had the best diagnostic value for ACT-AS (sensitivity 82%, confidence interval (CI): 57-96%; specificity 97%, CI: 91-100%). Basal LH and FSH levels were significantly lower in the ACT-AS group. Free testosterone was the most reliable marker of ACT-AS. However, the large overlap of androgen levels between ACT-AS and NTAE groups suggests that additional hormonal and/or imaging investigations are required to rule out ACT-AS in case of increased androgens.

Etiological diagnosis of hyperprolactinemia

There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic–pituitary MRI is the reference morphological examination. In clinical practice, it is usually performed very early, following the discovery of increased plasma concentrations of PRL. This approach is warranted for marked increase in PRL in the absence of drugs with hyperprolactinemic effects (> 10 × upper limit of normal) since a diagnosis of PRL adenoma is extremely likely under such circumstances. When hyperprolactinemia is moderate, which is the most common finding in practice, all etiologies are possible in theory and it is important to follow a rational diagnostic plan (history-taking to identify use of any drugs with hyperprolactinemic effects paying attention to renal and hepatic history, investigation for endocrine diseases occasionally associated with hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS), confirmation of hyperprolactinemia by a second assay when the initial level is less than five times the upper normal limit, pregnancy testing for women of childbearing age) in order to rule out all non-tumoral causes of hyperprolactinemia before proceeding with imaging. Absence of any consequences of hyperprolactinemia on gonadic function or the existence of a concomitant disease that could account for the clinical signs, demonstration of wide variations in PRL from one assay to another in a single patient could prompt screening for macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in the case of normal or doubtful MRI or discrepancy in response to medical or surgical treatment. T1- and T2-weighted coronal sections (with or without T1 after gadolinium injection) are generally sufficient for diagnosis of microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear. Gadolinium injection with sagittal and axial sections is essential for examination of large lesions. In this case, when the increase of PRL is moderate (< 150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a hook effect. Careful analysis of the images allows differentiation between tumoral lesions and pituitary hyperplasia.

Diagnostic étiologique d'une hyperprolactinémie

There are numerous etiologies of hyperprolactinemia, a common reason for consultation. Diagnostic measures must be capable of identifying the tumors, the most frequent of which are prolactin adenomas. Hypothalamic-pituitary MRI is the reference morphological examination. In clinical practice, it is usually performed very early, following the discovery of increased plasma concentrations of PRL. This approach is warranted for marked increase in PRL in the absence of drugs with hyperprolactinemic effects (> 10 x upper limit of normal) since a diagnosis of PRL adenoma is extremely likely under such circumstances. When hyperprolactinemia is moderate, which is the most common finding in practice, all etiologies are possible in theory and it is important to follow a rational diagnostic plan (history-taking to identify use of any drugs with hyperprolactinemic effects paying attention to renal and hepatic history, investigation for endocrine diseases occasionally associated with hyperprolactinemia such as hypothyroidism or polycystic ovary syndrome (PCOS), confirmation of hyperprolactinemia by a second assay when the initial level is less than 5 times the upper normal limit, pregnancy testing for women of childbearing age) in order to rule out all non-tumoral causes of hyperprolactinemia before proceeding with imaging. Absence of any consequences of hyperprolactinemia on gonadic function or the existence of a concomitant disease that could account for the clinical signs, demonstration of wide variations in PRL from one assay to another in a single patient could prompt screening for macroprolactinemia before MRI is ordered. Macroprolactinoma could also occur in the case of normal or doubtful MRI or discrepancy in response to medical or surgical treatment. T1- and T2-weighted coronal sections (with or without T1 after gadolinium injection) are generally sufficient for diagnosis of microprolactinoma. Dynamic tests may be useful if MRI is normal or unclear. Gadolinium injection with sagittal and axial sections is essential for examination of large lesions. In this case, when the increase of PRL is moderate (< 150 mg/ml), a non-lactotropic lesion may be suspected without misdiagnosing a hook effect. Careful analysis of the images allows differentiation between tumoral lesions and pituitary hyperplasia.

Fractionated irradiation of cerebellopontine angle neurinoma: 12 years' experience of the Bordeaux University Hospital Center

To evaluate retrospectively the long-term results of fractionated radiation therapy (RT) in cerebello-pontine angle neurinomas (CPA). From January 1986 to October 1995, 29 patients with stage III and IV neurinomas were treated with external fractionated RT. One patient was irradiated on both sides and indications for RT were as follows: (1) general contraindications for surgery (16 patients); (2) hearing preservation in bilateral neurinomas after controlateral tumor exeresis (six patients); (3) partial tumor removal (five patients); and, (4) non-surgical recurrence (three patients). A three to four fields technique with coplanar static beams and conformal cerobend blocks was used; doses were calculated on a 95 to 98% isodoses and were given five days a week for a median total dose of 51 Gy (1.8 Gy/fraction). Most patients were irradiated with 6 to 10 MV photons). Median follow-up was 66 months (seven to 120 months). Seven patients died, two with progressive disease, five from non-tumoral causes. Tumor shrinkage was observed in 13 patients (43.3%), stable disease in 14 (46.6%), and tumor progression in three. Two patients underwent total tumor removal after RT (one stable and one growing tumor). Hearing was preserved in four out of six patients. No patient experienced facial or trigeminal neuropathy. Fractionated RT is a well tolerated and efficacious treatment of large non-surgical CPA neurinomas.

Fractionated Radiation Therapy in the Treatment of Cerebello-Pontine Angle Neurinomas: 12 Years of Experience in 29 Cases

The purpose of this research was to reevaluate long-term results of frationated radiation therapy (RT) in two previously published series of cerebello-pontine angle (CPA) neurinomas. From January 1986 to October 1995, 29 patients with stage III and IV CPA neurinomas were treated with external fractionated RT. One patient was irradiated on both sides and indications for radiotherapy were as follows: (a) poor general condition or old age contraindicating surgery, 16 cases; (b) hearing preservation in bilateral neurinomas after contro-lateral tumor removal, 6 cases; (c) partial resection or high risk of recurrence after subsequent surgery for relapse, 5 cases; (d) nonsurgical relapse, 3 cases. Most patients were irradiated with 6 to 10 MV photons. A three- to four-field technique with coplanar static beams and conformal blocks was used. Doses were calculated on a 95% isodose and were given 5 days a week for a mean total dose of 51 Gy (1.80 Gy/fraction). Median follow-up from RT was 66 months (7 to 120); 7 patients died, 2 with progressive disease, 5 from nontumoral causes. Two patients underwent total tumor removal after RT (1 stable and 1 growing tumor). On the whole, tumor shrinkage was observed in 13 patients (43.3%), stable disease in 14 (46.6%), and tumor progression in 3. Hearing was maintained in 4 out of 6 hearing patients. No patient experienced facial or trigeminal neuropathy. Long-term efficacy of fractionated RT is well documented in this series. Acute and delayed tolerance was excellent. Hearing can be preserved for a long time.

Five-year results of 1000 patients operated on for cancer of the larynx.

The five-year results of 1000 consecutive cases of cancer of the larynx operated on at the Clinic of Otolaryngology of the University of Florence are presented. The treatment was cordectomy for T1a glottic cancers and total laryngectomy for the other cases. The five year cure rate is 66.5% of the 606 supraglottic cancers, 76.9% of the 294 glottic cancers and 54% of the 100 subglottic cancers. These crude survival rates consider the 7.6% of patients who died from non-tumoral causes and the 1.1% of untraced patients.

Ventriculocisternostomia de Torkildsen no tratamento do hidrocefalo não comunicante: resultados em 67 casos

Sixty-seven cases of non-communicating hydrocephalus treated according to the Torkildsen's procedure are reported. The spinal fluid blockage was caused in 55 cases by supratentorial and in 10 cases by infratentorial tumors; in the remaining cases the spinal fluid interruption was due to non-tumoral causes. Ventriculography was the most important examination performed as far as the local diagnosis was concerned. 15 patients in this series disclosed lethal complications with signs of brain stem lesions. Patient survival was 3.9 years with variation ranging from 1 to 9 years. The following conclusions were drawn: 1) Ventriculocisternostomy is a valious method for the treatment of non-communicating hidrocephalus for it allows a more physiological drainage of the spinal fluid besides favouring the exploration of the posterior fossa in cases of doudtful pre-operative diagnosis. This procedure is of low cost and involves a relatively simple tecnique as compared with other procedures which demand the use of special valves. 2) According to the review of the pertinent literature the best results have been accomplished in cases where there is a non-tumoral aqueduct stenosis as well as in inoperable tumors of the third ventricle. 3) Bilateral drainage is mandatory in cases of bilateral obstruction of Monro's foramina. It has also been indicated in all cases as a precaution due to the possibility of occlusion of one catheter. 4) Ventriculocisternostomy should also be indicated as a prophylactic treatment of non-communicating hydrocephalus in cases of inoperable tumors of the sela or the basal ganglia with compression of the third ventricle but without completly blockage of the ventricle system. 5) Ventriculocisternostomy should be indicated with some reserve in cases of infratentorial tumors as well as in great supratentorial space-occupying lesions. It is however contra-indicated in cases of large tumors and in the inflammatory process involving the posterior fossa. 6) In the present series the obstruction of the draining-system was very uncommon being observed in only three patients. 7) No cases of spinal fluid fistula or meningitis were observed in the present study.