Clinical, genetic and quality-of-life study of a cohort of adult patients with tuberous sclerosis.

BACKGROUND AND OBJECTIVE: Tuberous sclerosis (TS) is a condition whose manifestations in childhood have been extensively described, but whose presentation in adults is less well known. This study describes the clinical and genetic characteristics, therapeutic management and quality of life of a cohort of adult patients with TS. A comparative study of the characteristics of patients diagnosed in childhood and adulthood is also carried out. MATERIAL AND METHODS: This observational, retrospective, cross-sectional study included a large cohort of adult patients (≥ 16 years old) followed for 5 years in a specific rare diseases unit. RESULTS: Fifty-seven patients with a diagnosis of tuberous sclerosis were included, more than 50% of whom were diagnosed as adults. The mean age of the patients was 42 years (20-86). The central nervous system was the main area affected (97%), followed by the skin (80.7%) and kidneys (73%). The most frequent genetic alteration was a mutation in the TSC2 gene (47.7%). Among patients diagnosed in adulthood, there was less neurological involvement, with less frequency of epileptic seizures (30.8% vs 60.79% of patients diagnosed in childhood) and astrocytomas (3.8% vs 53.6%), less intellectual disability (11.5% vs 71.4%) and less expressiveness of the condition. 42% of patients were treated with mTOR pathway inhibitors, and presence of an angiomyolipoma was the main indication. In a quality-of-life analysis, the means of the summary indices were below the scores of the average Spanish population: (47.42 (SD ± 9.82) on the physical health scale, 45.61 (SD ± 7.99) on the mental health scale) versus 50 (SD ± 10) for the general population. CONCLUSIONS: Up to 50% of adult patients with TS were diagnosed in adulthood, and the condition is less severe with less frequent epileptic seizures and intellectual disability. 42% require treatment with mTOR inhibitors, in most cases due to the presence of AMLs. The quality of life of adult patients with TS is diminished compared to the general population.

Prognostic factors in cancer of unknown primary site.

AIMS AND BACKGROUND: Patients with cancer of an unknown primary site (CUP) usually have a poor outcome. The identification of prognostic factors that affect survival can help clinicians find a better approach to such cases in terms of diagnostic and therapeutic management. METHODS: We conducted a retrospective study including the cases of CUP recorded at the University Hospital 12 de Octubre Tumor Registry between 1999 and 2003. RESULTS: CUP was diagnosed in 265 patients during the analyzed period. One hundred and seventy-one were men (64.5%) and the mean age of the patients was 66.9 years (range 32-98 years). The median survival was 2.5 months, and the survival rate was 35.1% 6 months from diagnosis (95% CI: 28.9-41.3) and 24.5% 1 year from diagnosis (95% CI: 18.7-30.3). Univariate analysis revealed as significant predictive variables of a better outcome age under 70 years; involvement of a single organ; normal serum levels of alkaline phosphatase and albumin; normal erythrocyte sedimentation rate; normal levels of the serum tumor markers CEA, CA 19.9 and CA 15.3; squamous carcinoma histology; clinical presentation as lymph node enlargement; and the administration of treatment. Multivariate analysis showed that albumin and alkaline phosphatase levels, squamous carcinoma histology, age and treatment were the most important prognostic factors. Other variables analyzed (liver, bone or lung involvement, lactate dehydrogenase levels, gender) did not affect survival. CONCLUSIONS: CUP has a poor prognosis. Some prognostic factors that affect survival in these patients, however, may be identified.

Primary retroperitoneal liposarcoma: clinical and histological analysis of ten cases.

Retroperitoneal liposarcoma constitutes an uncommon and locally aggressive malignancy. We performed a retrospective analysis of 10 patients (6 males; mean age: 63.2+/-11 years) with histologically proven retroperitoneal liposarcoma seen at our institution between 1999 and 2007. Presence of a palpable abdominal mass was the main symptom at diagnosis. All patients underwent complete surgical resection. Negative microscopic margin was achieved in four cases. Histological analysis revealed the following subtypes: well-differentiated (6 cases), dedifferentiated (two cases), pleomorphic, and myxoid/round cell (one case each). Concomitant resection of adjacent organs was needed in five cases. Half of the patients developed tumor recurrence, mainly limited to the retroperitoneum or abdominal cavity. The mean recurrence-free survival was 43.3 months (95%CI: 25.7-60.8), with 3- and 5-year overall survival rates of 79% and 61%, respectively. Patients undergoing complete resection with clear margins showed a near-significant trend toward increased recurrence-free survival (62.9 vs. 29.3 months; P=0.06).

Multiple primary malignancies in Spanish patients with hepatocellular carcinoma: analysis of a hospital-based tumor registry.

BACKGROUND AND AIM: Little is known about the etiological associations and clinical features of extrahepatic primary malignant (EHPM) neoplasms in subjects with hepatocellular carcinoma (HCC). The aim of this study was to characterize this phenomenon in a consecutive series of Spanish patients in order to define its natural history and influence on survival. METHODS: A retrospective analysis of 245 patients with HCC during the period 1999-2003 was performed. Subjects identified with a second primary malignancy elsewhere constituted the EHPM group and were compared to patients with HCC alone. RESULTS: Eighteen patients (7.3%) had one or two associated extrahepatic malignancies (mean age 67.7 +/- 9.7 years); of these, 17 had double cancer and one patient, triple. Nine of the 19 EHPM occurred before HCC diagnosis. The associated cancers included five cases of colorectal carcinoma, four cases of head and neck carcinoma, three cases of genitourinary cancer, two cases of lymphoproliferative disorder, one lung carcinoma, one skin melanoma, one breast carcinoma, and two cancers of unknown origin. Age and sex distribution, etiology of underlying hepatopathy, and liver function tests did not differ significantly between both groups. There was no difference between the overall survival rates. CONCLUSIONS: EHPM is not rare among Spanish patients with HCC, although no specific clinicopathological features were detected in this population. Our results suggest that the association of another primary tumor with HCC does not imply a worse prognosis. The possibility of development of EHPM should be kept in mind when deciding on therapy and follow-up of HCC.

[Prognostic prediction in patients with hepatocellular carcinoma not amenable to locoregional treatment]. / Predicción pronóstica en pacientes con carcinoma hepatocelular no subsidiario de tratamiento locorregional.

BACKGROUND AND OBJECTIVE: Patients with hepatocellular carcinoma (HCC) not amenable to locoregional therapy have some specific clinical characteristics (advanced cirrhosis or extrahepatic spread) that lead us to ascertain the prognostic efficacy of the different staging systems proposed for this entity. PATIENTS AND METHOD: We analyze 100 patients (69 males) with a mean age of 70.2 (10.7) years. Tumor staging was performed at baseline according to the following systems: Okuda, Cancer of the Liver Italian Program (CLIP), Barcelona Clinic Liver Cancer (BCLC), and Japan Integrated Staging (JIS) score. We determine the area under the receiver operating characteristic curve (AUC) using the 6 and 12-month mortality as endpoint. RESULTS: The BCLC system had the best predictive power for mortality both at 6 (AUC, 0.871) and 12 months (AUC, 0.924) from diagnosis. In the Cox multivariate analysis, this model showed an independent prognostic effect [hazard ratio: 9.14 for BCLC stage C versus A (p<0.001), and 9.53 for stage D versus A (p=0.004)]. CONCLUSIONS: The BCLC system provided the best prognostic stratification for patients with HCC not amenable to locoregional therapy.

Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of literature on skull sarcoidosis.

Bone sarcoidosis of the skull is an infrequent presentation of sarcoidosis. We describe a 51-year-old man who consulted due to inflammatory-appearing nodulation in the right supraorbital region. Images showed a solitary osteolytic lesion extending to soft tissues with increased scintigraphic uptake. The anatomopathological study revealed the presence of non-caseating epithelioid granulomas, compatible with sarcoidosis. Steroid treatment led to a marked remission of the lesion, without evidence of relapse during a follow-up period of 1 year. The literature dealing with skull sarcoidosis is reviewed.

Delayed Leukoencephalopathy: Three Case Reports and a Literature Review.

BACKGROUND: Delayed leukoencephalopathy (DL) is a rare entity associated with cerebral hypoxia and heroin consumption. We describe the clinical course of three cases of DL due to non-heroin drug use. MATERIAL AND METHODS: We describe the cases of three DL patients admitted to our hospital in 2012. DISCUSSION: These cases contribute to the aetiological spectrum of DL since multifactorial causes could account for the clinical symptoms. LEARNING POINTS: Substances toxic to the CNS can damage the CNS directly (direct toxicity) or by depressing the respiratory centre (cerebral hypoxia).As clinical manifestations can appear after a time lag, we recommend a period of initial monitoring.Histological and radiological findings can contribute to better understanding of the pathophysiological mechanisms and causes involved.

Acute Small Bowel Obstruction and Small Bowel Perforation as a Clinical Debut of Intestinal Endometriosis: A Report of Four Cases and Review of the Literature.

Endometriosis is a quite common pathology, however, intestinal endometriosis is a rare condition, which typically occurs with chronic symptoms. Its acute presentation is very infrequent. We herein report four cases of intestinal endometriosis, in which the clinical debut occurred acutely: two as an acute small bowel obstruction and two as a small bowel perforation. None of the cases had a preoperative diagnosis of endometriosis. The interest of these cases lies in this exceptional form of presentation, such as a surgical acute abdomen. Therefore, intestinal endometriosis should be taken into account in the differential diagnosis of an acute obstructive or perforative process of the small or large bowel.

Hip fracture in three elderly populations of central Spain: data from the NEDICES study.

There is a paucity of data concerning the specific associations between hip fracture in the elderly and other age-related conditions, as well as its impact on long-term survival. This study was aimed to estimate the prevalence, risk factors, and outcome of self-reported hip fracture (srHF) in a cohort of Spanish elderly individuals. Neurological Disorders in Central Spain (NEDICES) is a census population-based survey of the prevalence and incidence of major age-associated conditions in three areas of central Spain. Data on health status and several chronic conditions were evaluated in the baseline questionnaire (1994-1995). Odds ratios for the association between srHF and other comorbidities and health-related variables were assessed by logistic regression. A Cox model estimated the impact of srHF on 13-year all-cause mortality. The final cohort comprised 5,278 community-living elderly subjects. A total of 166 participants (3.1%) had srHF. Prevalence was associated with higher age, female gender, degree of urbanisation of residence place, lower body mass index (BMI), higher number of chronic medications, higher Pfeffer FAQ score, being unmarried (P < 0.001 for all), and infantile living conditions (P = 0.007). Participants with srHF had a higher number of associated chronic conditions (P < 0.001). In the multivariate analysis, self-reported osteoporosis, lower BMI category, rural environment during childhood, and higher age were identified as independent risk factors for srHF. Adjusted hazard ratio for mortality in the srHF group was 1.40 (95% confidence interval 1.15-1.71; P = 0.001). srHF is a common condition among community-living elderly population in Spain, and has a significant impact upon long-term all-cause mortality.

Prevalencia de los factores de riesgo para el desarrollo de necrosis avascular de cadera en un hospital de tercer nivel / Prevalence of risk factors for the development of avascular hip necrosis in a third-level hospital

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Streptococcus bovis bacteraemia revisited: clinical and microbiological correlates in a contemporary series of 59 patients.

OBJECTIVE: To characterise the clinical features, associations and outcome in a contemporary series of patients with Streptococcus bovis bacteraemia (SBB). METHODS: Retrospective analysis of all episodes of SBB at the University Hospital 12 de Octubre (Madrid, Spain) between January 1997 and November 2008 was performed. Patient data were reviewed, focusing on clinical and microbiological associations with the different biotypes of S. bovis. RESULTS: Fifty-nine episodes of SBB were documented in 59 adult patients (30 males; mean age: 70.9 ± 15.0 years). Chronic liver disease was identified in 20 patients (33.9%). Sixteen patients (27.1%) presented infective endocarditis (IE) and 14 (23.7%) had a biliary source of bacteraemia. Thirty-three patients (55.9%) underwent colonic evaluation, adenomatous polyps being the most common finding (21 patients). Malignancy was diagnosed following SBB in 9 cases, including 6 patients with colorectal carcinoma (18.2% of those who underwent colonic evaluation). Of 22 isolates biotyped, 12 were S. bovis biotype I and 10 were S. bovis biotype II. IE was more frequent among patients with S. bovis biotype I (P =0.010), whereas bacteraemia due to biotype II species was more likely to be of biliary origin (P=0.078). CONCLUSIONS: S. bovis biotyping identifies some clinically relevant associations.

Comorbidity negatively influences prognosis in patients with extrahepatic cholangiocarcinoma.

AIM: To study the outcome and prognostic factors in a series of patients with extrahepatic cholangiocarcinoma and determine the impact of comorbidity on survival. METHODS: A retrospective analysis of 68 patients with extrahepatic cholangiocarcinoma (perihilar, n=37; distal, n=31) seen at a single tertiary-care institution during the period 1999-2003 was performed. Data on presentation, management, and outcome were assessed by chart review. Pathologic confirmation was obtained in 37 cases (54.4%). Comorbidity was evaluated by using the Charlson comorbidity index (CCI). RESULTS: Mean age at diagnosis was 73.4+/-11.5 years. Jaundice was the most common symptom presented (86.8%). Median CCI score was 1 (range, 0 to 4). Nineteen patients (27.9%) underwent tumor resection. Palliative biliary drainage was performed in 39 patients (57.4%), and 6 patients (8.8%) received only best supportive care. Tumor-free margin status (R0) was achieved in 15 cases (78.9% of resection group). Baseline serum carbohydrate antigen 19-9 (CA 19-9) level was revealed to be an independent predictor of surgical treatment (P=0.026). Overall median survival was 3.1+/-0.9 mo, with 1- and 2-year survival rates of 21% and 7%, respectively. In the univariate analysis, tumor resection, CCI score, and serum CA 19-9 levels correlated significantly with outcome. In the multivariate analysis, only resection (HR 0.10; 95% CI, 0.02-0.51, P=0.005) and a CCI score>or=2 (HR 3.36; 95% CI, 1.0-10.9, P=0.045) were found to independently predict survival. CONCLUSION: Tumor resection and comorbidity emerged as significant prognostic variables in extrahepatic cholangiocarcinoma. Comorbidity evaluation instruments should be applied in the clinical management of such patients.

Evolution of the incidence and aetiology of fever of unknown origin (FUO), and survival in HIV-infected patients after HAART (Highly Active Antiretroviral Therapy).

BACKGROUND: Fever of unknown origin (FUO) is common among HIV-infected patients with a CD4+ T-lymphocyte cell count below 200 cells/ml. The use of HAART has transformed the evolution of AIDS and related diseases. DESIGN AND METHOD: Case-control study, nested on a historical cohort of 3777 HIV-infected patients who were attended at "12 de Octubre" University Hospital in Madrid, Spain, between 1994 and 2000. RESULTS: 276 FUO episodes were recorded, 58 of which occurred in patients receiving HAART. The significant decrease on the accumulated FUO incidence along the study period of 7.3 episodes per 100 HIV-infected patients after 1997 corresponded with the introduction of HAART. FUO was more frequent in patients who did not receive HAART. The aetiological spectrum of FUO was transformed by the introduction of HAART: the incidence of tuberculosis decreased while that of leishmaniasis increased. The four year survival in the non-FUO group increased when compared to that of patients who had had FUO. Similarly, this four year survival increased in patients who received HAART at the time of FUO versus those not receiving it. CONCLUSIONS: Our results confirm that the incidence of FUO has significantly decreased with the introduction of HAART. HAART has also transformed the aetiological spectrum related to FUO considerably. The most frequent cause of FUO in non-HAART patients on this study was the disseminated infection by Mycobacterium avium intracellulare (MAI), followed by tuberculosis, while leishmaniasis was its most common cause in patients receiving HAART. Survival decreased in patients who developed FUO; however, patients who received HAART at the time of FUO had longer survival than patients who did not.

Splenic abscess: a review of 22 cases in a single institution.

PURPOSE: To describe the demographics, clinical features, etiology, imaging findings, bacteriologic profile, treatment and outcome in patients presenting splenic abscess in a European tertiary hospital. METHODS: Review of the medical charts of patients in whom splenic abscess was diagnosed at a tertiary hospital in Madrid (Spain) within a nine-year period. RESULTS: Twenty-two cases (13 males, 9 females) were found. Mycobacterium tuberculosis was the most frequent causative microorganism, accounting for 8 cases, and immunosuppression the main predisposing factor (in 63.6% of the patients). Symptoms were quite unspecific, leading to a long, median time until diagnosis (17 days). The overall mortality rate was 18.2% and it was 25% in patients with tuberculosis and 14.28% in patients with other causes of splenic abscesses (p=0.6). CONCLUSIONS: Immunosuppressed states are the predisposing condition for splenic abscess in almost two thirds of the patients. We found a higher percentage of M. tuberculosis than that previously reported in the English literature.

Cerebral neuroschistosomiasis: a rare clinical presentation and review of the literature.

The symptomatic presentation of cerebral schistosomiasis is uncommon. The case of a 25-year-old woman from Equatorial Guinea with headache and seizures secondary to cerebral neuroschistosomiasis, as confirmed by histopathological examination and microbiological study, is presented. A review of the literature on this subject is also provided.

Fever of unknown origin in a patient with common variable immunodeficiency associated with multisystemic granulomatous disease.

Non-caseating epithelioid granulomas have been described in a small number of patients with common variable immunodeficiency (CVID). We report a 26-year-old woman diagnosed with CVID nine years earlier, who developed non-caseating granulomas in the liver, bone marrow and skin. She was referred to our department for a fever of more than one year duration without apparent focus. Extensive search for underlying malignancy or occult infection was unremarkable. Empirical treatment with prednisone was begun and the patient showed a marked improvement. The literature on the association between CVID and non-caseating granulomatous disease, and the differential diagnosis of hepatic granulomas as a cause of fever of unknown origin, is also reviewed.