The genome of chemorefractory chronic lymphocytic leukemia reveals frequent mutations of NOTCH1 and SF3B1.

Next-generation whole-exome sequencing has revealed two novel genes, namely NOTCH1 and SF3B1, whose mutations predict poor outcome and preferentially associate with chemorefractory chronic lymphocytic leukemia (CLL). Analysis of 539 CLL cases documents that NOTCH1 mutations i) represent one of the most frequent cancer gene mutations involved at presentation; ii) cluster with cases harboring trisomy 12 and tend to be mutually exclusive with TP53 disruption among genetic subgroups; iii) identify high-risk patients showing poor survival similar to that associated with TP53 abnormalities; and iv) exert a prognostic role independent of widely accepted clinical and genetic risk factors. Mutations of SF3B1, a splicing factor that is a critical component of the spliceosome, recurrently associate with fludarabine-refractory CLL, occur at a low rate at CLL presentation and have a minor role in Richter transformation, corroborating the notion that CLL histological shift is molecularly distinct from chemorefractory progression without the Richter transformation.

[Gastrointestinal stromal tumors]. / I tumori stromali gastrointestinali.

Gastrointestinal stromal tumors (GIST) are generally found in the stomach or small intestine and less commonly in the colon or rectum. Complete surgical removal remains the best current therapy for GISTs. The treatment of advanced GIST patients is with imatinib, a selective tyrosine kinase inhibitor. In our series, 23 patients observed between 1994 and 2004 and affected by GIST were treated with complete negative margin resections (three cases by laparoscopy).

[Retroperitoneal liposarcoma]. / I liposarcomi retroperitoneali.

Liposarcoma is the most frequent histotype of the rare and malignant retroperitoneal tumours. This neoplasm has a remarkable tendency to recurrence after surgical excision, rarely to metastasize. Recurrence usually shows a more aggressive behaviour than primitive disease with a higher tendency to penetrate into adjacent organs. The symptomatology often appears late and the first sign is frequently a palpable abdominal mass. Preoperative study involves using CT and MRI. The surgical resection is the only tool able to modify natural history with regard to survival and local recurrence. Prognosis is severe, with a survival of 5 years, variable from 12 to 50% in the different series. A very important prognostic factor is the degree of tumour and radical surgical treatment. From 1990 to 2001, 32 operations for malignant retroperitoneal tumors were performed by our surgical unit in 19 patients; in 7 of them the tumor was a liposarcoma (4 male and 3 female). Total operations for retroperitoneal liposarcoma were 15, in 4 patients a second operation was performed for recurrence, in 3 a third operation and in 1 a fourth. Eleven cases out of 15 have undergone exeresis of sarcoma. Average survival consisted in 4 years and 2 months. Intraoperative radiotherapy, performed in 3 patients, perhaps is able to offer some advantages in relation to local control of the disease and of the survival. A possible resection of eventual recurrence justifies a early follow up with CT and MRI.

Motor sequencing deficits in schizophrenia: a comparison with Parkinson's disease.

Motor abnormalities occur in schizophrenia (SZ) and may arise from striatal dysfunction. This study examined whether the pattern of performance on simple and complex motor abilities in SZ was similar to that of patients with Parkinson's disease (PD). Quantitative tests of speeded movement and motor and cognitive sequencing were used to assess 25 SZ, 16 PD, and 84 normal controls (NCs). Sequencing performance was also examined with motor rigidity taken into account. Compared with the NC group, the SZ and PD groups were impaired on measures of motor rigidity and motor sequencing. With rigidity accounted for, the SZ group was significantly more impaired than the PD group on motor sequencing; cognitive and motor processes contributed to the motor deficit. Cognitive sequencing performance predicted motor sequencing performance in PD but not SZ. Although both SZ and PD resulted in significant motor and cognitive sequencing deficits, the pattern and correlates of these deficits differ, suggesting that the affected neural systems underlying motor deficits in SZ are different from those involved in PD.

Remote memory for public figures in Alzheimer's disease: relationships to regional cortical and limbic brain volumes.

This study examined the relationships between regional cortical and hippocampal brain volumes and components of remote memory (recall, recognition, sequencing, and photo naming of presidential candidates) in 13 individuals with Alzheimer's disease (AD). Recognition and sequencing of remote memory for public figures were associated with regional cortical volumes. Specifically, lower recognition and sequencing scores were associated with smaller parietal-occipital cortical volumes; poorer sequencing was also associated with smaller prefrontal cortical volumes. By contrast, poorer anterograde but not remote memory scores were correlated with smaller hippocampal volumes. Within the constraints of the brain regions measured, these findings highlight the importance of the posterior cortical areas for selective remote memory processes and provide support for the dissociation between cortically mediated remote memory and hippocampally mediated anterograde memory.

Extent, pattern, and correlates of remote memory impairment in Alzheimer's disease and Parkinson's disease.

Content and contextual memory for remote public figures and events was assessed with a modified version of the Presidents Test in patients with Alzheimer's disease (AD) or Parkinson's disease (PD). Contributions of executive functioning, semantic memory, and explicit anterograde memory to remote memory abilities were also examined. The AD group had temporally extensive deficits in content and contextual remote memory not accountable for by dementia severity. The PD group did not differ from the control group in remote memory, despite anterograde memory impairment. These results support the position that different component processes characterize remote memory, various mnemonic and nonmnemonic cognitive processes contribute to remote memory performance, and anterograde and remote memory processes are dissociable and differentially disrupted by neurodegenerative disease.

Structural brain correlates of verbal and nonverbal fluency measures in Alzheimer's disease.

This study examined the relationships between regional brain volumes and semantic, phonological, and nonverbal fluency in 32 participants with Alzheimer's disease (AD). Object but not animal semantic fluency correlated with frontal and temporal gray matter volumes. Phonological fluency was not significantly associated with any brain volume examined. Nonverbal fluency was selectively associated with bilateral frontal gray matter volumes. Hippocampal volumes, although markedly reduced in these patients, were not related to any of the fluency measures. Results lend evidence to the importance of the frontal lobes in the directed generation of nonverbal and verbal exemplars by AD patients. Furthermore, both left- and right-hemisphere regions contribute to the generation of verbal and nonverbal exemplars.

Brain structural and cognitive correlates of clock drawing performance in Alzheimer's disease.

The Clock Drawing Test (CDT) is widely used in the assessment of dementia and is known to be sensitive to the detection of deficits in neurodegenerative disorders such as Alzheimer's disease (AD). CDT performance is dependent not only on visuospatial and constructional abilities, but also on conceptual and executive functioning; therefore, it is likely to be mediated by multiple brain regions. The purpose of the present study was to identify component cognitive processes and regional cortical volumes that contribute to CDT performance in AD. In 29 patients with probable AD, CDT performance was significantly related to right-, but not left-hemisphere, regional gray matter volume. Specifically, CDT score correlated significantly with the right anterior and posterior superior temporal lobe volumes. CDT scores showed significant relationships with tests of semantic knowledge, executive function, and visuoconstruction, and receptive language. These results suggest that in AD patients, CDT performance is attributable to impairment in multiple cognitive domains but is related specifically to regional volume loss of right temporal cortex.

Structural MRI correlates of recognition memory in Alzheimer's disease.

Neuroimaging and lesion studies have demonstrated that hippocampal volume correlates with memory performance, but material-specific lateralization of this structure-function relationship has been inconsistent. This MRI study examined the relative contributions of left and right temporal lobe volumes to verbal and nonverbal recognition memory in a group of 20 Alzheimer's disease (AD) patients. There was a significant relationship between extent of right hippocampal and right temporal gray matter tissue volume deficit and performance on the face recognition subtest of the Warrington Recognition Memory Test. The face recognition test correlated with right hemisphere volume but not to left, indicating a material-specific relationship between brain structure and function in this patient group. Right temporal horn volume did not account for a significant proportion of variance in face recognition memory. Although word recognition was not significantly correlated with either left or right hippocampal volume in the total group, there was a strong correlation between left hippocampal volume and word recognition memory in the female AD patients. Thus, face recognition shows a material specific relationship with select lateralized hippocampal and temporal cortical volumes in AD patients, regardless of gender, whereas the verbal recognition-left-hippocampal volume relationship may be mediated by gender.

Selective cortical and hippocampal volume correlates of Mattis Dementia Rating Scale in Alzheimer disease.

OBJECTIVE: To examine whether each of the 5 Mattis Dementia Rating Scale (DRS) scores related to magnetic resonance imaging-derived volumes of specific cortical or limbic brain regions in patients with Alzheimer disease (AD). DESIGN: Relations between DRS measures and regional brain volume measures were tested with bivariate and multivariate regression analyses. SETTING: The Aging Clinical Research Center of the Stanford (Calif) University Department of Psychiatry and Behavioral Science and the Geriatric Psychiatry Rehabilitation Unit of the Veterans Affairs Palo Alto Health Care System, Palo Alto, Calif. PATIENTS AND OTHER PARTICIPANTS: Fifty patients with possible or probable AD. Magnetic resonance imaging data from 136 healthy control participants, age 20 to 84 years, were used to correct brain volumes for normal variation arising from intracranial volume and age. MAIN OUTCOME MEASURES: The DRS scores and volumes of regional cortical gray matter and of the hippocampus. RESULTS: Memory scores of the patients with AD were selectively related to hippocampal volumes. Attention and construction scores were related to several anterior brain volume measures, with attention showing a significantly greater association to right than left hemisphere measures. Initiation/perseveration scores were not significantly correlated with any measure of regional gray matter volume, but performance was related to prefrontal sulcal widening, with a greater association with the left than right sulcal volume. CONCLUSIONS: Certain DRS subtests are predictably correlated with selective regional brain volumes in AD. The specific relation between memory and hippocampal volumes and the nonsignificant relations between memory and regional cortical volumes suggest a dissociation between cortical and hippocampal contributions to explicit memory performance.

[Rupture of the duodenum caused by closed abdominal trauma]. / Rottura di duodeno da trauma addominale chiuso.

A duodenal lesion due to blunt abdominal trauma is an infrequent eventi which makes important diagnostic and therapeutic problems. The preoperative diagnosis is not always easy, especially with retroperitoneal lesion or in injured patients. A plain abdominal radiography or a duodenal radiography with soluble contrast medium helps to achieve a proper diagnosis. Prognosis strictly depends on time between injury and surgical procedures. We report two successfully treated lesions of fourth duodenal due to a blunt abdominal trauma.

[Intestinal obstruction due to endometriosis of the ileocecal valve]. / Occlusione intestinale da endometriosi della valvola ileo-cecale.

Intestinal endometriosis can rarely show itself bowel obstruction. An accurate anamnesis, radiological tests and endoscopy are of some use for correct diagnosis. Frequently however, differential diagnosis with others of pathology is not possible either in preoperative or in postoperative management, but by means of histological finding. We present here a case of acute bowel obstruction secondary to ileo-cecal endometriosis.

Bleeding peptic ulcer occurring in hospitalized patients: analysis of predictive and risk factors and comparison with out-of-hospital onset of hemorrhage.

We reviewed 84 consecutive cases of peptic ulcer hemorrhage, which occurred, in an area of 270,000 people, from 1986 to 1988, in patients already hospitalized for other diseases (in-bleeders). These subjects were compared with a prospective series of 386 patients who initially bled as out-patients and were then admitted (out-bleeders). Of 84 hemorrhages in hospitalized patients, 41 followed major surgery, while 43 were associated with other severe conditions. Bleeding site was duodenal in two thirds. Mean age was 67 +/- 15 years versus 59 +/- 15 among out-bleeders. Fifty percent of in-bleeders had recently received nonsteroidal antiinflammatory drugs (NSAIDs), and one third were on anticoagulants and 10% on corticosteroids; in 39 (46%) bleeding was shown to be persistent or recurrent, 5 (5.9%) underwent endoscopic and 18 (21%) surgical therapy; 29 died (34%). The corresponding figures among out-bleeders were: further bleeding 80 (20.7%), endoscopic therapy 12 (3.1%), surgery 25 (6.5%), deaths 17 (4.4%). As regards in-bleeders, only active bleeding and endoscopic stigmata emerged as statistically significant risk factors for further bleeding. The latter was shown to be significantly related to mortality. The most relevant finding was, however, that NSAIDs and anticoagulants, in association with stress and aging, are very frequently involved in peptic ulcer bleeding of hospitalized patients. The fatal outcome of one third, despite all available treatments, highlights the importance of prevention against drug- and stress-related mucosal damage in in-patients suffering from severe diseases.

[Perforation of the colon by a foreign body]. / Perforazione del colon da corpo estraneo.

Perforation of the colon carries a high mortality and morbidity. Perforations caused by foreign bodies are relatively rare and appear to be less often associated with postoperative complications than perforations due to organ disease. Depending upon the extent of the perforation and its anatomical site, as well as on the basis of the presence of diffuse or circumscribed peritonitis, the treatment of foreign-body perforation will vary from simple suturing, with or without a protective colostomy, to exteriorization in the form of a colostomy, and the Hartmann operation.

Drug and alcohol use and neuropsychological performance in asymptomatic HIV infection.

The effect of drug and alcohol abuse on neuropsychological performance was examined in 132 human immunodeficiency virus-seropositive gay or bisexual men. Syndromal (diagnostic) criteria of alcohol/drug abuse based on DSM-III-R were used, and quantitative estimates of alcohol consumption were obtained. Very few differences appeared between substance abuse subgroups formed on the basis of recency or severity of drug use. There were some correlations with the quantitative estimate of alcohol use, but not on the measures previously found to differentiate seronegative and asymptomatic seropositive gay men. These data indicate that alcohol use does affect neuropsychological performance but does not account for the differences observed in studies of seronegative and seropositive subjects.

[Gastrointestinal hemorrhage from a duodenal diverticulum]. / Emorragia gastrointestinale da diverticolo duodenale.

Duodenal diverticuli are often asymptomatic and are occasionally found during the course of X-ray tests or autopsy. They are sometimes manifested in the form of symptoms related to a complication (hemorrhage, perforation, occlusion). The paper reports a case of gastrointestinal hemorrhage caused by a duodenal diverticulum which was then successfully operated. The Authors affirm that in these cases the resection of the portion of the duodenum with the diverticulum (provided the papilla is not affected) is preferable to direct hemostasis or duodenocephalopancreatectomy.

Splenic torsion: a rare cause of splenomegaly.

The authors report a rare case of splenomegaly, caused by recurring splenic torsion in a 31-year-old patient. On the basis of this experience and literature data, pathogenetic, symptomatological, diagnostic and therapeutic aspects are discussed. Analysis of the clinical history and diagnostic procedures confirm the difficulty in ascertaining this condition preoperatively. In any case, splenic torsion should be considered in the differential diagnosis of painful splenomegalies.

[Rupture of the cervical esophagus. Apropos of a case of perforation by a foreign body]. / Rottura dell'esofago cervicale. A proposito di un caso di perforazione da corpo estraneo.

The Authors describe a case of perforation of the cervical oesophagus by a foreign body (dental prosthesis). After outlining the clinical and instrumental elements which may be useful in the diagnosis, the Authors go on to tackle the topic of the most appropriate choice of therapy in the course of foreign-body perforation and in perforation of the oesophagus in general.

[Hemorrhages of the lower digestive tract: the diagnostic and therapeutic approach]. / Emorragie del tratto digestivo inferiore: approccio diagnostico e terapeutico.

The authors describe their experience with colo-rectal haemorrhage. They stress the tendency towards spontaneous arrest of such haemorrhages (92.6% of cases) as the usefulness of emergency colonoscopy in diagnosing the cause and/or site of the haemorrhagic lesion (85.7% of positive results in the present series). Therapy may be conservative (endoscopic or in the course of angiography) or surgical. Surgery is indicated in cases failing to respond to conservative therapy and in cases of unarrestable haemorrhage and usually consists in segmental resection of the portion of the intestinal tract involved.