[Primary Sjögren syndrome in a child]. / Syndrome de Goujerot-Sjögren primitif de l'enfant : à propos d'un cas.

Sjögren syndrome is uncommon in children and occurs most often in association with autoimmune diseases (secondary Sjögren syndrome). We describe the clinical and biological features of a 7-year-old girl with primary Sjögren syndrome revealed by recurrent parotiditis. CASE REPORT: A 7-year-old girl was referred for investigation of multiple episodes of parotid swelling since age 4 years, without systemic symptoms. The examination was unremarkable except for enlarged and painless parotid glands. Laboratory investigations and labial salivary gland biopsy revealed Sjögren syndrome without associated disease. Hydroxychloroquine was prescribed with clinical improvement. CONCLUSION: Recurrent parotiditis in children is an uncommon condition. The onset of parotid swelling at 5 years or over deserves screening for disimmune disorders, sarcoidosis, or Sjögren syndrome. Diagnosis of Sjögren syndrome is based on diagnostic criteria.

Lung cancer risk test trial: study design, participant baseline characteristics, bronchoscopy safety, and establishment of a biospecimen repository.

BACKGROUND: The Lung Cancer Risk Test (LCRT) trial is a prospective cohort study comparing lung cancer incidence among persons with a positive or negative value for the LCRT, a 15 gene test measured in normal bronchial epithelial cells (NBEC). The purpose of this article is to describe the study design, primary endpoint, and safety; baseline characteristics of enrolled individuals; and establishment of a bio-specimen repository. METHODS/DESIGN: Eligible participants were aged 50-90 years, current or former smokers with 20 pack-years or more cigarette smoking history, free of lung cancer, and willing to undergo bronchoscopic brush biopsy for NBEC sample collection. NBEC, peripheral blood samples, baseline CT, and medical and demographic data were collected from each subject. DISCUSSION: Over a two-year span (2010-2012), 403 subjects were enrolled at 12 sites. At baseline 384 subjects remained in study and mean age and smoking history were 62.9 years and 50.4 pack-years respectively, with 34% current smokers. Obstructive lung disease (FEV1/FVC <0.7) was present in 157 (54%). No severe adverse events were associated with bronchoscopic brushing. An NBEC and matched peripheral blood bio-specimen repository was established. The demographic composition of the enrolled group is representative of the population for which the LCRT is intended. Specifically, based on baseline population characteristics we expect lung cancer incidence in this cohort to be representative of the population eligible for low-dose Computed Tomography (LDCT) lung cancer screening. Collection of NBEC by bronchial brush biopsy/bronchoscopy was safe and well-tolerated in this population. These findings support the feasibility of testing LCRT clinical utility in this prospective study. If validated, the LCRT has the potential to significantly narrow the population of individuals requiring annual low-dose helical CT screening for early detection of lung cancer and delay the onset of screening for individuals with results indicating low lung cancer risk. For these individuals, the small risk incurred by undergoing once in a lifetime bronchoscopic sample collection for LCRT may be offset by a reduction in their CT-related risks. The LCRT biospecimen repository will enable additional studies of genetic basis for COPD and/or lung cancer risk. TRIAL REGISTRATION: The LCRT Study, NCT 01130285, was registered with Clinicaltrials.gov on May 24, 2010.

Ecthyma gangrenosum: A manifestation of community-acquired Pseudomonas aeruginosa septicemia in three infants.

OBJECTIVES: Pseudomonas aeruginosa sepsis usually carries a high mortality rate in immunocompromised children. Ecthyma gangrenosum is a known cutaneous manifestation due mainly to Pseudomonas infection with or without septicemia. We describe clinical, biological, and therapeutic data. PATIENTS AND METHODS: Of those children admitted to the pediatric intensive care unit, three pediatric cases of community-acquired P. aeruginosa septicemia associated with ecthyma gangrenosum were retrospectively reviewed. RESULTS: The three patients were aged 5 months, 9 months, and 1 year. Underlying hypogammaglobulinemia was detected in the oldest patient. Pseudomonas aeruginosa was isolated in all patients in blood and once in cultures of skin lesions and endotracheal aspirate. Two deaths occurred due to septic shock and multisystem organ failure despite numerous aggressive resuscitation attempts. CONCLUSIONS: P. aeruginosa sepsis should be treated as early as possible. Recognition of ecthyma gangrenosum allows early diagnosis and prescription of adequate antibiotic therapy without awaiting blood culture reports.

[Auto-immune hepatitis in chronic granulomatous disease in a 2-year-old girl]. / Hépatite auto-immune associée à une granulomatose septique chronique chez une fille de 2 ans.

BACKGROUND: Chronic granulomatous disease is a rare inherited primary immune deficiency disease characterized by recurrent infection and an increased susceptibility to autoimmunity disorders. We report on the case of a girl with autoimmune hepatitis in chronic granulomatous disease to describe the clinical and biological features and treatment implications for patients with chronic granulomatous disease associated with autoimmune disorders. CASE REPORT: An 18-month-old girl was referred to our department for investigation of hepatomegaly. She was the third child of non-consanguineous parents. Her two elder sisters had died from infectious diseases at an early age. She had elevated liver transaminase levels with a normal gamma globulin concentration. Negative results were found for all autoimmune markers (antinuclear antibody, anti-smooth muscle, anti-liver-kidney microsomal, anti-liver cytosol and anti-soluble liver antigen). Her liver biopsy showed features of interface hepatitis with portal fibrosis. The diagnosis of seronegative autoimmune hepatitis was established. Treatment with corticosteroids and azathioprine led to clinical improvement with normalization of transaminases. Six months after initial presentation, at the age of 2 years, she was readmitted for fever. Staphylococcus aureus bacteremia was identified with multiple foci of infection (skin infection, arthritis of the right elbow, pneumonia, buttock abscess). The immunological workup revealed chronic granulomatous disease. The course was marked by a fatal outcome despite appropriate antibiotics and intensive care. CONCLUSION: Early diagnosis of the association between chronic granulomatous disease and autoimmune disorders allows for appropriate treatments, improves the quality of life for affected patients, and reduces the risk of mortality.

[Crohn's disease or intestinal tuberculosis: a diagnostic challenge]. / Tuberculose intestinale ou maladie de Crohn : un défi diagnostique.

Distinguishing intestinal tuberculosis from Crohn disease is difficult and can result in misdiagnosis, especially when active pulmonary infection is absent. A 13-year-old girl was admitted to our hospital with a 2-month history of watery diarrhea, abdominal pain, and 12-kg weight loss. Based on clinical, radiological, endoscopic, and histological findings, she was initially misdiagnosed as having Crohn disease and treated with glucocorticosteroids, with a poor response after 4 weeks. Intestinal tuberculosis was then suspected. Improvement was observed during the 1st week of antituberculous treatment. The differentiation of intestinal tuberculosis from Crohn disease may be very difficult in some patients. A positive response to antituberculous treatment associated with clinical, endoscopic, and histological features argue in favor of the diagnosis of intestinal tuberculosis.

Early-onset of multiple sclerosis in a 5-year-old girl.

Childhood multiple sclerosis is a rare demyelinating autoimmune disease with particular features. Onset of multiple sclerosis is extremely uncommon in early childhood, particularly before 6 years of age. We report the case of a 5-year-old girl admitted to the hospital for altered consciousness and rapid onset of right hemiparaplegia. Magnetic resonance imaging (MRI) of the brain showed multifocal white matter disease with T2 hyperintense oval lesions in subcortical, periventricular, and cerebellar hemispheres. Treatment with high dose intravenous methylprednisolone (30 mg/kg/day for 3 days) improved symptoms. Intravenous corticosteroid therapy was followed by 1mg/kg/day of oral prednisone. A second MRI, 40 days later, revealed new disseminated T2 hyperintense lesions in the frontal periventricular white matter, corpus callosum, left middle cerebellar peduncle, and dorsal spinal cord, leading to the diagnosis of multiple sclerosis. Azathioprine (2.5 mg/kg/day) was started and the steroid dose was tapered before being stopped after 3 months. After 2 years of follow-up, the patient has remained asymptomatic with a normal neurological exam and with no relapse or side effects of azathioprine. This work shows the particularities in clinical and radiological features of multiple sclerosis in a child aged less than 6 years.

Type 2 autoimmune hepatitis overlapping with primary sclerosing cholangitis in a 10-year-old boy.

BACKGROUND: Overlap syndrome of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is considered when the patient presents with the diagnostic criteria of both diseases at some stage of the medical history, either simultaneously or consecutively. AIM: To report on a new case of overlap syndrome and describe the clinical presentation, progression, radiological studies, histological characteristics, and therapeutic options of this rare association. CASE REPORT: A 10-year-old boy presented with jaundice and hepatosplenomegaly. Levels of plasma aminotransferases, gamma-glutamyl transferase, serum alkaline phosphatase and gammaglobulins were elevated. Anti-liver cytosol and perinuclear antineutrophilic cytoplasmic antibodies were positive. Liver biopsy showed features of interface hepatitis with ductopenia. Magnetic resonance cholangiography revealed bile duct stenosis and dilations. Serological findings associated with radiological and histological features confirmed the diagnosis of overlap syndrome of AIH with PSC. Treatment with prednisone, azathioprine, and ursodeoxycholic acid led to a good response. CONCLUSION: The possibility of AIH-PSC overlap syndrome should be considered in all children with AIH and, with clinical, biochemical, or histological signs of PSC, complementary investigations should be done to confirm the diagnosis so as to urgently initiate appropriate treatment with immunosuppressive medication and ursodeoxycholic acid.

Endoftalmitis endógena por Serratia marcescens en el curso de una sepsis neonatal temprana / Endogenous endophthalmitis due to Serratia marcescens in the course of early neonatal sepsis

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Downstaging by regional chemotherapy of non-resectable isolated colorectal liver metastases.

AIMS: To improve the course of isolated non-resectable colorectal liver metastases (CRLM) by hepatic arterial infusion treatment. Patients with CRLM have a worse prognosis than those whose liver metastases are resectable. Systemic (i.v.) chemotherapy for CRLM/colorectal metastases with 5-fluorouracil+folinic acid (5-FU+FA) i.v. may result in median survival times of 6.4-14.3 months. Hepatic artery infusion (HAI) with 5-fluorodeoxyuridine (5-FUDR) has been demonstrated in a meta-analysis of randomized trials to be superior to i.v. treatment/palliative care (median survival 15 vs. 10 months). The benefit of HAI with 5-FUDR, although recommended as treatment for CRLM, is severely compromised by the 5-FUDR induced hepatotoxicity, leading eventually to sclerosing cholangitis (SC)/liver cirrhosis. We have developed a stepwise protocol for HAI in CRLM, which is superior to HAI with 5-FUDR and to systemic chemotherapy. METHODS: Between 1982 and 1997, 168 CRLM patients were treated within the following protocols. In protocol A, 48 CRLM patients received HAI with 5-FUDR. In protocol B, 46 patients received 5-FUDR i.a. (HAI)+i.v. In protocol C 5-FU+FA were delivered via HAI in 24 patients with CRLM. In protocol D, based on in vitro phase II studies and the results of protocol C, mitoxantrone and mitomycin C were added to 5-FU+FA (MFFM). Fifty (50) CRLM patients received HAI with HFFM. RESULTS: The response rates, median survival time, systemic toxicity and SC rate were: 42%, 20.8 months, 0-19% and 38% for protocol A; 46%, 20.8 months, 0-20% and 41% for protocol B; 45%, 19.8 months, 4-25% and 0% for protocol C; and 66%, 27.4 months, 2-26% and 0% for protocol D. The surgically placed ports for HAI in protocols C and D functioned in 90%, 82% and 76% of patients, 6, 9, and 11 months after beginning HAI. Quality of life in protocol D was high. Nine patients from protocols C and D with either partial (PR, seven patients) or complete (CR, two patients) remissions received a secondary liver resection without hospital mortality, and seven of nine patients are alive 2-58 months after liver resection. The other two died 11 and 22 months after resection. CONCLUSIONS: Optimal treatment of CRLM was found to be protocol D: HAI with MFFM. The results of this protocol, including high remission rate, long median survival time, good port function, good quality of life and, interestingly, the possibility of downstaging and resecting primarily non-resectable metastases, seem to be superior to HAI with 5-FUDR or 5-FU+FA and to systemic chemotherapy with 5-FU+FA. This hypothesis is currently being examined in a phase III study (HAI with MFFM vs. 5-FU+FA i.v.).

[Surgical management of liver rupture]. / Chirurgische Versorgung von Leberrupturen.

The management of 178 patients with liver trauma (132 male, 46 female; mean age 34 years (range 3-88) presenting from January 1979 to August 1996 is reviewed. There were 165 cases of blunt trauma and 13 cases of penetrating injury. 110 cases were classified as simple injuries (grade I or II) and 68 cases as complex injuries (grade III to V). The overall mortality was 32% (57 patients). The mortality for true hepatic injury was 15.7%. None of the patients with penetrating injuries died. Mortality was influenced by the type of liver injury and the number of associated injuries. The postoperative complication rate was 55%. The most-frequent postoperative complications related to the hepatic injury were intrahepatic or subcapsular hematoma (12.9%) and postoperative bleeding (9.6%). Intraabdominal abscess formation was seen in 2.8%. Operative therapy for liver injuries depends on the grade of the injury. The majority of liver injuries can be managed by simple techniques, including electrocautery and application of hemostatic agents. In complex injuries hepatotomy, direct vessel ligation, and debridement of necrotic tissue is the method of choice (Pachter's procedure). In non-controlled bleeding, perihepatic picking is a standard method.

p53 genetic alterations, protein expression and autoantibodies in human colorectal carcinoma: A comparative study.

This study investigated a total number of 120 colorectal malignant tumor tissues by applying a new quantitative luminometric assay (LIA)-mat, immunohistochemistry (IHC) (n=100), PCR/SSCP (n=42), and sequencing (n=7). Sera were collected from 235 patients suffering from colorectal carcinoma in addition to 195 healthy individuals as a control group. Manual ELISA kit was developed to detect p53 autoantibodies in the sera of those patients. Our data demonstrated that the LIA-mat yields reliable estimates of p53 expression in soluble cell extracts as compared with results obtained by immunohistochemistry which showed positive immunostaining in 63% of the studied cases. Using a cut-off value of 1.8 ng/mg protein, 65 tumors out of 120 (54%) were classified to be positive by LIA-mat, manifesting protein overexpression, while 22 out of 42 (52%) tumor samples showed p53 gene alteration when applying single strand conformation polymorphism (SSCP) analysis on polymerase chain reaction products. In tumor samples without a p53 gene alteration, the median soluble p53 protein level was 4.3 ng/mg protein, whereas the median p53 protein level for tumor samples with p53 gene alteration was 7.5 times higher. Despite a significant correlation between the outcome of LIA and SSCP, a disagreement was found in 30% of cases. We found no significant correlation between p53 protein overexpression and clinicopathological findings except for distant metastasis (p=0.33), indicating p53 immunoreactivity to be an independent prognostic factor. Our data showed that 18% of patients suffering from colorectal cancer developed autoantibodies against p53 in their sera which might be an early indicator for tumor development and distant metastasis.

Prognostic value of CA 19-9 serum course in pancreatic cancer.

BACKGROUND/AIMS: The aim of this study was to determine the sensibility and specificity of a new assay in the diagnosis of pancreatic cancer and predictability of resection rates. In addition, the serum CA19-9 levels was utilised as a prognostic indicator. METHODOLOGY: Serum expression of the tumor marker CA 19-9 was studied in 2119 patients. RESULTS: The discriminating capacity of CA 19-9 between benign and malignant disease was high, especially in patients with pancreatic cancer (n = 347). The sensitivity of CA 19-9 was 85%. In patients who were Lewis blood type positive, the sensitivity increased to 92%. The CA 19-9 levels were significantly lower in patients with resectable tumors (n = 126) than in those with unresectable tumors (n = 221, p < 0.0001) (sensitivity 74% versus 90%). The CA 19-9 levels dropped sharply after resection but normalized only in 29%, 13%, and 10% of patients with stage I, II, and III, respectively. In unresectable tumors, no significant decrease in CA 19-9 levels after laparotomy or bypass was found. Among patients with the same tumor stage, the median survival time of those whose CA 19-9 levels returned to normal after resection was significantly longer than those with postoperative CA 19-9 levels that decreased but did not return to normal (stage I: 33 versus 11.3 months; stage II: 41 versus 8.6 months; stage III: 28 versus 10.8 months). In patients with recurrent disease, 88% had an obvious rise in CA 19-9 levels. CONCLUSION: CA 19-9 measurement is a simple test which can be used for diagnostic purposes, as well as the prediction of resectability, survival rate after surgery, and the potential for recurrence.

[Duodenum-preserving pancreatic head resection--a standard method in chronic pancreatitis]. / Die duodenumerhaltende Pankreaskopfresektion--Ein Standardverfahren bei chronischer Pankreatitis.

In patients with chronic pancreatitis the inflammatory process in the pancreatic head is frequently the pacemaker of the disease. In these cases an inflammatory tumor develops which leads to local complications in half of the patients. Duodenum-preserving pancreatic head resection, contrary to procedures used in the past, offers the possibility to preserve stomach, duodenum, biliary tree, and the insulin secretory capacity. Duodenum-preserving pancreatic head resection is a subtotal resection of the pancreatic head. In a series of 380 patients the hospital mortality rate was 0.8%, the frequency of reoperation 5.3%, and the median hospitalisation time 13.9 days. The early postoperative glucose metabolism was deteriorated in 2% and improved in 9% of cases. After a median follow-up time of 6 years, 88% of the patients were completely painfree or suffered pain rarely. Sixty-three percent were gainfully employed; the late mortality was 8.9%. Only 10% of the patients had further bouts of pancreatitis. The decisive advantage of duodenum-preserving pancreatic head resection over Kausch-Whipple resection is preservation of the endocrine pancreatic function and of neighbouring organs.

Thymidylate synthase is a predictor for response and resistance in hepatic artery infusion chemotherapy.

The value of intratumoral thymidylate synthase (TS) quantitation as a predictive parameter for hepatic artery infusion (HAI) chemotherapy in patients with colorectal liver metastases was investigated. Relative TS mRNA levels were determined in 29 tumor samples using a quantitative RT-PCR amplification method. The median level of expression was 3.0 x 10(-3) (no units) and varied considerably among the tumors over a range of 135-fold. Patients with low TS levels were 4.1-fold more likely to respond (P < 0.03) compared to patients with high TS levels. Our results indicate that TS quantitation is a valuable predictive marker for tumor response to HAI therapy.

[Clinical value of the CA 19-9 tumor marker with special reference to the Lewis phenotype]. / Klinische Aussagekraft des Tumormarkers CA 19-9 unter besonderer Berücksichtigung des Lewis-Phänotyps.

BACKGROUND: Because of structure and biosynthesis of CA 19-9, it was postulated that patients with the Lewis phenotype Le(a-b-) are not able to synthesize CA 19-9. But some patients with Le(a-b-) on red blood cells showed elevated levels of this tumor marker. PATIENTS AND METHOD: In 164 patients suffering from benign or malignant diseases both CA 19-9 and the Lewis phenotype were determined in sera. In addition in 51 patients red blood cells were tested for Lewis substances. RESULTS: The frequencies of the different Lewis phenotypes on red blood cells were compared with the results found in sera. The prevalence of the phenotype Le(a-b-) on erythrocytes was significantly higher than in sera. In 51 patients both determinations were performed. These results were compared additionally. The phenotype Le(a-b-) found on red blood cells agreed with the results found in sera only in 30% of the cases. A loss of Lewis substances on erythrocytes could be seen both in malignant and benign diseases. Only in patients with Lewis substances found in sera elevated levels of CA 19-9 could be seen. CONCLUSION: Considering only the Lewis phenotype in sera, it could be confirmed that patients with the genotype Le(a-b-)are not able to express elevated concentrations of CA 19-9.