Adjuvant chemotherapy in adult medulloblastoma: is it an option for average-risk patients?

The standard treatment in children with average-risk medulloblastoma (MB) is reduced-dose radiotherapy (RT) followed by chemotherapy. However, in adults, there is no agreement on the use of adjuvant chemotherapy. We performed a retrospective analysis of adult MB patients with average-risk disease, defined as no postsurgical residual (or ≤1.5 cm(2)) and no metastatic disease (M0). Main inclusion criteria were: age >16 years, post-surgical treatment with craniospinal irradiation with or without adjuvant chemotherapy (cisplatin and etoposide ± cyclophosphamide). From 1988 to 2012 were accrued 43 average-risk MB patients treated with surgery and adjuvant RT. Fifteen (34.9 %) patients received also chemotherapy: 7 before RT, 5 after RT, and 3 before and after RT. Reasons to administer chemotherapy were presence of residual disease (even if ≤1.5 cm) and delay in RT. After a median follow up time of 10 years (range: 8-13), median survival was 18 years (95 % CI 9-28) in patients who receive RT alone, and was not reached in patients treated with RT plus chemotherapy. The survival rates at 5, 10 and 15 years were 100 %, 78.6 % (95 % CI 60.0-97.2 %) and 60.2 % (95 % CI 36.9-83.5 %), in patients treated with RT alone, and 100, 100 and 100 %, in patients treated with RT plus chemotherapy (p = 0.079). Our findings suggest a role for adjuvant chemotherapy in the treatment of average-risk MB adult patients. Further improvements might drive to add chemotherapy in average-risk setting with less favourable biological signatures (i.e., non-WNT group).

The Brazilian Family Health Program and secondary stroke and myocardial infarction prevention: a 6-year cohort study.

OBJECTIVES: We compared the incidence of recurrent or fatal cardiovascular disease in patients using Brazil's government-run Family Health Program (FHP) with those using non-FHP models of care. METHODS: From 2005 to 2010, we followed outpatients discharged from city public hospitals after a first ever stroke for stroke recurrence and myocardial infarction, using data from all city hospitals, death certificates, and outpatient monitoring in state-run and private units. RESULTS: In the follow-up period, 103 patients in the FHP units and 138 in the non-FHP units had exclusively state-run care. Stroke or myocardial infarction occurred in 30.1% of patients in the FHP group and 36.2% of patients in non-FHP care (rate ratio [RR] = 0.85; 95% confidence interval [CI] = 0.61, 1.18; P = .39); 37.9% of patients in FHP care and 54.3% in non-FHP care (RR = 0.68; 95% CI = 0.50, 0.92; P = .01) died. FHP use was associated with lower hazard of death from all causes (hazard ratio [HR] = 0.58; P = .005) after adjusting for age and stroke severity. The absolute risk reduction for death by all causes was 16.4%. CONCLUSIONS: FHP care is more effective than is non-FHP care at preventing death from secondary stroke and myocardial infarction.

Melanotic neuroectodermal tumor of the epididymis in infancy: case report and review of the literature.

Melanotic neuroectodermal tumor of infancy (MNTI) is a rare, benign tumor that usually involves the upper or lower jaw, but it may also arise in other sites. We describe a case of MNTI located in the left epididymis of a 6-month-old boy. Left orchiectomy was performed. Immunohistochemical and ultrastructural studies revealed two types of cells: small, poorly differentiated cells that were positive for neuron-specific enolase protein and vimentin, and larger epithelial cells that were positive for melanoma antigen (HMB45) and frequently contained large and elongated melanosomes, similar to those described in retinal pigmented epithelium. At 12 months of follow-up, no recurrences or metastases were seen. Primary involvement of the epididymis has been previously reported in only 16 cases. Immunohistochemical and ultrastructural studies suggest that the neoplasm is of neural crest origin.

Panencephalopathic type of Creutzfeldt-Jakob disease with neuropathologic features similar to Pick's disease.

The panencephalopathic type of Creutzfeldt-Jakob disease is characterized by a serious degeneration of the white matter in addition to the other pathological features of the classic Creutzfeldt-Jakob disease. The clinical and neuropathological findings of a new case are described in a woman aged 62, who died after a year of illness. The brain appeared seriously affected by atrophy and white matter degeneration. Microscopically, it showed a marked cortical spongiosis, with gemistocytic astrogliosis and degeneration of the white matter of both hemispheres. Although a serious loss of nerve cells was evident, some residual neurons with a ballooned aspect were found in the fronto-temporal cortex. Other neurons presented argyrophilic inclusions similar to Pick bodies. By means of immunohistochemical techniques and monoclonal antineurofilaments antibodies some neurons with swollen cytoplasm and enlargement of the first tract of the neurites were detected in the basal layers of the frontal and temporal cortex. These abnormal features were due to the accumulation of phosphorylated 200 Kd neurofilaments. The relations between Creutzfeldt-Jakob and Pick's diseases are analyzed on the basis of the neuropathological findings. There is evidence from the immunohistochemical data of an interference in the axonal transport of neurofilaments.

Carotid stenting with filter protection. Correlation of ACT values with angiographic and histopathologic findings.

BACKGROUND AND PURPOSE: Filter cerebral protection during carotid stenting has been proposed as a new tool to reduce brain embolism. Angiographic findings (filter patency), pathological analysis of the collected materials inside the filters and coagulation parameters were analyzed to identify potential down sides in the use of these protection devices. METHODS: 29 consecutive endovascular treatments with filter cerebral protection in 27 patients affected by symptomatic internal carotid stenosis>70% were considered. Angiographic findings, activated clotting times and histopathologic specimens were recorded and correlated. RESULTS: Satisfactory dilatation of the stenosis was always achieved with a complication rate of 3% (1 transient neurological deficit). During the procedure, 9 filters (31%) appeared occluded, with temporary flow impairment. Histopathologic examination demonstrated material inside the filters in 86% of cases but this material was fibrin alone in 38% and plaque debris in 48%. Significant statistical correlation (p=0.009) was found between low activated clotting time and occlusion of the filter. CONCLUSION: Distal protection filters can collect plaque fragments occurring during carotid stenting. Significant proportion of the debris found in the filters consisted of thrombotic material. Precise monitoring of heparin anticoagulation is recommended to prevent filter occlusion.

[Primary malignant neoplasia of the exocrine pancreas: epidemiological findings, risk factors, early diagnosis. Personal case reports, 1970-1981]. / Neoplasie primitive maligne del pancreas esocrino: rilievi epidemiologici, fattori di rischio, diagnostica precoce. Casistica personale 1970-1981.

The Authors report their own casuistry of malignant tumours of exocrine pancreas, collected in the period from 1970 up to 1981. The question was of 214 cases, namely 136 of head and 78 of body-tail or diffused. The male/female ratio was 2.3:1, the most affected decades were 6th and 7th, with a range of 27-86 years. The resecability was 27% for tumours of head and 24% for those of tail; the operative mortality was 10.8% and 17.6% respectively; the survival after 3 years was 6.8% (head) and 5.8% (body-tail), after 5 years 6% (head) and zero (body-tail). In analysing the etiopathogenetic rôle of some factors and some pathological associations, the Authors particularly point out the predisposing rôle of both tobacco smoke and diabetes, remarked in 50% and 33% of the cases observed, respectively. From a symptomatologic standpoint, the symptoms are subdivided into initial symptoms (retrospectively interpreted as first manifestation of the disease), symptoms of alarma (leading to the attending physician's), symptoms at the entrance (hospitalization), and importance is given to the exploitation of the initial symptoms for the purpose to reach a diagnosis as precocious as possible, since 40% of the tumours of head are hospitalized only after 8-16 weeks and 33% of the tumours of body-tail after 16-32 weeks from the arising of the first symptom.

[Cystic neoformations of the retroperitoneal space (4 case reports)]. / Neoformazioni cistiche dello spazio retroperitoneale (contributo di 4 casi).

Based on the study of four cases of retroperitoneal cysts, the complex histopathogenesis of these neoplasms - the clinical diagnosis of which has recorded substantial progress thanks to the use of the computed tomography - has been analyzed. The practice of exeresis, though comparatively simple and radical in most cases (as recorded in 3 out of the 4 cases reported) owing to the little adhesions of these neoplasms to the contiguous anatomical formations and also to their histological benignity, may, in some instances, present such unexpected difficulties due to the expansion in volume and the complex and delicate anatomical connections, that palliative operations have to be opted for.

[Bilemia. Considerations apropos of a case]. / Bilemia. Considerazioni a proposito di un caso.

The Authors report a case of bilemia, a complication of hepatic biopsy. They analyse the physiopathogenetic problems and those of surgical tactics, and emphasize the importance of retrograde and/or interoperative cholangiography ii the diagnostics of such disease.

[Benign epithelial neoplasms of Vater's ampulla. Usefulness of the "epithelial dysplasia" concept in prognosis and surgical strategy]. / Neoplasie epiteliali benigne della papilla di Vater. Utilità del concetto di "displasia epiteliale" nella prognosi e nella tattica chirurgica.

The surgical behaviour in front of the benign epithelial tumors (adenomas) of Vater's ampulla is object of discrepancies due to the possible malignant evolution of such neoplasms. The authors stress the basic importance of a careful examination of histological bioptic material before and/or during operation, which, through the identification of the degree of epithelial dysplasia, may lead to the choice of the tecnique to be adopted. In 2 of the 3 cases reported by the authors, showing a low degree dysplasia of the papillary tumor, a submucous papillectomy was performed; in the third case, where histology showed severe dysplasia and some other elements of risk were present (patient's age and macroscopic features of the tumors), the surgeons performed a duodenopancreatectomy. Semiseriated histological sections of the surgical specimen revealed the presence of carcinomatous areas. The authors think simple papillectomy to be the surgical procedure to follow when low grade dysplasia of ampulla is documented, and duodenopancreatectomy to be performed in high risk conditions as high grade dysplasia and macroscopic features suggestive of malignancy. In addition, the authors deal with epidemiology, clinics and instrumental diagnostics of such benign neoplasms of ampulla, on the basis of their own experience and the review of the few cases reported in literature.

[Vascular problems in pancreatic demolitory surgery]. / Problemi vascolari nella chirurgia demolitiva pancreatica.

Obstacles of vascular type may hinder or prevent pancreatic destruction for tumours of the pancreas or periampullary tumours. Out of 72 major pancreatic demolitions (cephalic duodenopancreatectomy or subtotal pancreatectomy from rt to lt) there were vascular difficulties on 26 occasions (36%), of which 15 were in existence prior to development of the neoplasia (anomalies of rise and course of peripancreatic vessels, stenosis/obliteration of the common hepatic artery in pancreatic head or periampullary tumours) and 11 due to tumoral growth (direct involvement of the mesenteric-portal tract, the hepatic artery and the superior mesenteric artery). The technical solutions used are discussed individually in the light of the physiopathological repercussions consequent on any temporary or permanent interruption of important hepatic and splanchnic vascularisation vessels (hepatic artery and various mesenteric a.), in relation to operating mortality and the prospects of long-term survival. In the most complex cases of direct vascular involvement by the neoplasia, the Author's trend was orientated to a position which, while accepting demolition decisions useful for the widening of the surgical radicality margins, nevertheless avoids extensive demolition solutions imposed by conditions of necessity or considerations of principle that probably do not bring significant advantages as regards long-term prognosis for these tumours.

[Vascular problems in destructive pancreatic surgery]. / Problemi vascolari nella chirurgia demolitiva pancreatica.

Obstacles of vascular type may hinder or prevent pancreatic destruction for tumours of the pancreas or periampullary tumours. Out of 72 major pancreatic demolitions (cephalic duodenopancreatectomy or subtotal pancreatectomy from rt to lt) there were vascular difficulties on 26 occasions (36%), of which 15 were in existence prior to development of the neoplasia (anomalies of rise and course of peripancreatic vessels, stenosis/obliteration of the common hepatic artery in pancreatic head or periampullary tumours) and 11 due to tumoral growth (direct involvement of the mesenteric-portal tract, the hepatic artery and the superior mesenteric artery). The technical solutions used are discussed individually in the light of the physiopathological repercussions consequent on any temporary or permanent interruption of important hepatic and splanchnic vascularisation vessels (hepatic artery and various mesenteric a.), in relation to operating mortality and the prospects of long-term survival. In the most complex cases of direct vascular involvement by the neoplasia, the Author's trend was orientated to a position which, while accepting demolition decisions useful for the widening of the surgical radicality margins, nevertheless avoids extensive demolition solutions imposed by conditions of necessity or considerations of principle that probably do not bring significant advantages as regards long-term prognosis for these tumours.

[Cavitary lesions and carcinoma of the pancreas. Diagnostic difficulties and errors]. / Lesioni cavitarie e carcinoma del pancreas. Difficoltà ed errori diagnostici.

Among 197 pancreatic and periampullar tumours operated between 1970 and 1979, an associated cystic of pseudocystic lesion was found on 15 occasions (a rate of 16%). In 10 cases it was a question of pseudocysts located at the bodytail, while the tumour occupied a distinct site (periampullar tumour or carcinoma of the head); in 5 cases the cavitary lesion coincided with the tumour (2 endocrine tumours of the head, 2 cystoadenocarcinomas and one adenocarcinoma of the body-tail). In 6 cases (of which 5 operated) the error in diagnosis led to misappreciation of the tumour: only 3 of these cases could be treated with radical surgery. In the other 9, correct diagnosis was possible from the start and in 6 radical surgery was performed. Stress is placed on the need for prompt and early diagnosis, in order to allow adequate treatment of the tumour in line with the canons of radical action.

[Exocrine pancreas cancers: our experience (author's transl)]. / Le neoplasie del pancreas esocrino: la nostra esperienza.

The AA. report 136 cases of exocrine pancreas carcinomata that they have observed in 8 years in Surgical Hospital in Verona and they tackle diagnostic problems and surgical therapy. They confirmed the utility for the diagnosis of echotomography (ECO), computerizing axial tomography (T.A.C.), retrograde-endoscopic-cholangio-pancreatography (PTC). Considering the survival, at a distance of the cases that had an operation and life quality, the AA. incline, if possible, for a destroying surgical operation.

[Pseudocystic pleural fistula documented by retrograde cholangiopancreatography]. / Fistola pseudocisto-pleurica documentata mediante colangiopancreatografia retrograda.

The use of recently introduced methods such as computerised axial tomography (CAT), in addition to endoscopic retrograde cholangiopancreatography (ERCP), has in recent years led to attainment of new targets in the diagnosis of pancreatic diseases. The Authors present a clinical case of massive and recurring left pleural effusion in a patient with a pseudocyst at the level of the cauda pancreatis. They report the clinico-diagnostico-instrumental factors leading to pre-operative diagnosis of pseudocystic-pleural fistula.

[Cystadenocarcinoma of the pancreas. Considerations on a clinical case]. / Cistoadenocarcinoma del pancreas. Considerazioni su un caso clinico.

A case of pancreatic cystoadenocarcinoma treated surgically four years earlier as a pancreatic pseudocyst is reported. The problems of differential diagnosis between cystic tumours (cystoadenoma and cystoadenocarcinoma) and the more common pseudocystic lesions are analysed. Stress is laid on the importance of correct intra-operative diagnosis, mainly based on multiple biopsy of the cyst wall, and the need for radical exeresis.

[Insular tumours of the pancreas (author's transl)]. / Tumori insulari del pancreas.

The use of immunohistochemistry and radioimmunological assay of the pancreatic polypeptides in the plasma has contributed substantial advances to the histophysiopathology and preoperative diagnosis of tumours of the endocrine pancreas and the related functional syndromes. Consequently, in addition to furthering knowledge on clinical pictures already known for some time, it has been possible to define new categories of the disease which were previously misunderstood or confused with others. The physiopathology and diagnostic methodology (clinical, biohumoral and instrumental) of each main known syndrome (insulinoma, Zollinger-Ellison Syndrome, Verner-Morrison disease and glucagonoma) are described in detail; there are notes on hormonal syndromes that are not fully known and which constitute a field of research in evolution (pluriendocrine and carcinoid syndromes, polypeptidoma, somatostatinoma, nesidioblastosis). The problems of preoperative preparation, intraoperative diagnostic tactics and surgical technique are illustrated. Lastly the possibilities of alternative therapeutic treatment are outlined.

[The biological results of duodenocephalopancreatectomy. Clinical evaluations based on a long-term follow-up]. / Le conseguenze biologiche della duodenocefalopancreatectomia. Valutazioni cliniche sulla base di un follow-up a distanza.

The authors discuss the main features of the complex pathophysiology of patients subjected to duodenocephalopancreatectomy, and particularly the difficulties inherent in clinical assessment of the digestive and metabolic impairment consequent upon the duodeno-gastro-pancreatic mutilation. Out of a total of 57 cases of this description, they singled out for recheck 23 patients who had undergone duodenocephalopancreatectomy not less than six months and not more than seven years before (chronic pancreatitis, 11 cases; various malignancies of the periampullar area, 10 cases; Zollinger-Ellison syndrome, 1 case; retroperitoneal lymphoma, 1 case). Seventy-six per cent of patients who had been gainfully employed were able to resume their jobs after surgery. Steatorrhea, assessed in terms of fecal fats, was present in all cases; notwithstanding, 70% of the patients gained weight (average increase 7 kg). All patients were on enzyme replacement therapy. Only 4% developed diabetes, and none developed postoperative peptic ulcers. Conversely there was a high incidence (65%) of bone structure reshuffling, signally osteoporosis, probably imputable to steatorrhea and vitamin D malabsorption, plus the often associated increase of serum alkaline phosphatase activity.

[Alteratiions of calcium and phosphorus metabolism in patients treated with duodenoencephalopancreatectomy]. / Alterazioni del metabolismo del calcio-fosforo negli operati di duodenocefalopancreatectomia.

In a followup study of 14 patients treated by duodeno-cephalo-pancreatectomy at least one year before, the authors detected radiological evidence of bone tissue reshuffling in 64 per cent of the cases. Of these, 70 per cent showed high serum alkaline phosphatase content not attributable to cholestasis, liver metastasis, or specific bone disease. The authors call attention to the significance of this biochemical parameter for diagnostic purposes and therapeutic guidance.

[Retroperitoneal tumors. Tactics, technics and surgical results]. / I tumori retroperitoneali. Tattica, tecniche e risultati chirurgici.

Out of 33 cases of retroperitoneal tumours (TRP), collected throughout 11 years (1970-1981), 8 (24%) resulted benign, 25 (76%) malignant. Liposarcoma resulted the most frequent tumour. In 11 of the 25 cases of malignant TRP (44%), a radical removal of the tumour was performed; in 8 (32%), a palliative demolition, and in the remaining 6 (24%) a simple diagnostic laparotomy. In 10 of the 19 demolitive operations (53%) the removal was extended to contiguous organs: kidney, adrenal glands, colon, pancreas, spleen, bladder, stomach. The postoperative mortality was 6%. The cases of recurrence after operations considered radical were 5 (45%). Out of the 8 patients suffering from benign neoformations, 7 underwent simple removal, and result recovered. The global survival for malignant TRP was 20% after 5 years and 8% after 10 years; as related to the cases subjected to radical removal, it results 45% and 18% respectively. The Authors maintain the essential function of computerized axial tomography (TAC) in the preoperative anatomo-topographic outlining of the retroperitoneal mass and in the early recognition of the remote recurrences. An aggressive surgical behaviour seems to be presently the primary therapeutical solution; nevertheless, the encouraging results obtained through the complementary treatment (radiotherapy and chemotherapy) command the necessity of a pluridisciplinary management of the treatment of TRP as an essential condition for the improvement of the remote results.