Is intra-arterial hepatic chemotherapy painful?

BACKGROUND: Liver metastases are mainly supplied by the hepatic artery, allowing the administration of intra-arterial hepatic chemotherapy (IAHC) while preserving normal parenchyma. The progression-free survival and response rate are prolonged by IAHC which can improve the rate of secondary resectability. Severe abdominal pain requiring high-dose opioids can appear during HIAC administration. This pain is related to extrahepatic infusion and gastroduodenal ulceration. However, intense abdominal pain was observed under oxaliplatin IAHC specifically without any extrahepatic infusion. METHOD: We retrospectively reviewed the charts of 68 patients who received IAHC in our center between 2011 and 2015. Patient's demographics and disease characteristics were collected. Other variables such as the type, duration, and dosage of the chemotherapy administered, as well as the usage of painkillers before, during, or after intra-arterial administration, were also registered. RESULTS: The mean age of the patients was 59 years. 61.7% were male (n = 42). The mean dose of oxaliplatin administered was 162 mg per cure over 6.7-h course. Fifty percent were diagnosed with a left colon cancer, and 85.2% had synchronous liver metastasis. While 47% of patients received IAHC as a third-line therapy, the main chemotherapeutic drug was oxaliplatin (85.2% of cases; n = 58), then OPTILIV protocol (5FU, irinotecan, oxaliplatin) (13.3%; n = 9), and mitomycin C (1.5%; n = 1). A dose reduction of 23.6% had been noted in 58.8% (n = 40) cases due to adverse effects. Among patients who received opioids during IAHC (n = 40), 20% required opioids in intercure. Before, during, and after IAHC administration, patients complained of abdominal pain in 8.8%, 58.8%, and 19.1%, and opioids were used in 10.2%, 57.3%, and 19.1%, respectively. The main onset of pain occurs during the third cycle of chemotherapy. Among our patients, 11.7% and 22% had ulcer and extrahepatic perfusion, respectively, while 7.3% of them were asymptomatic. The mean occurrence of these signs was during the fourth cycle of IAHC. 33.8% and 52.9% of patients had abdominal pain while an extended and short infusion time, respectively. CONCLUSION: Lengthening of the infusion time did not prevent the occurrence of abdominal pain significantly but was nonetheless decreased compared with patients undergoing short infusion durations. Pain was more common in patients who did not have a dose reduction and who presented with ulcer and extrahepatic perfusion. Abdominal pain occurred on average one cycle before ulcer or extrahepatic perfusion diagnosis. In current practice, pain should be an alarming indicator in patients receiving IAHC, as it may be associated with ulcer or extrahepatic perfusion and thus requiring opioids.

Post-first-line FOLFOX chemotherapy for grade 3 neuroendocrine carcinoma.

There is no standard for second-line chemotherapy in poorly differentiated grade 3 neuroendocrine carcinoma (G3-NEC) patients. We analyzed the antitumor efficacy of 5-fluorouracil and oxaliplatin (FOLFOX) chemotherapy in this population. A single-center retrospective analysis of consecutive G3-NEC patients treated with FOLFOX chemotherapy after failure of a cisplatinum-based regimen between December 2003 and June 2012 was performed. Progression-free survival (PFS), overall survival (OS), response rate, and safety were assessed according to RECIST 1.1 and NCI.CTC v4 criteria. Twenty consecutive patients were included (seven males and 13 females; median age 55; range 23-87 years) with a performance status of 0-1 in 75% of them. Primary location was gastroenteropancreatic in 12, thoracic in four, other in two, and unknown in two patients. There were 12 (65%) large-cell and 7 (30%) small-cell G3-NEC tumors, and 1 (5%) unknown. All patients had distant metastases. Twelve (60%) patients received FOLFOX as second-line treatment and 8 (40%) as third-line treatment or later and the median number of administered cycles was 6 (range 3-14). The median follow-up was 19 months. Median PFS was 4.5 months. Among the 17 evaluable patients, five partial responses (29%), six stable diseases (35%), and six progressive diseases (35%) were observed. Median OS was 9.9 months. Main Grade 3-4 toxicities were neutropenia (35%), thrombopenia (20%), nausea/vomiting (10%), anemia (10%), and elevated liver transaminases (10%). Our results indicate that the FOLFOX regimen could be considered as a second-line option in poorly differentiated G3-NEC patients after cisplatinum-based first-line treatment but warrant further confirmation in future larger prospective studies.

Peritoneal carcinomatosis from solid pseudopapillary neoplasm (Frantz's tumour) of the pancreas treated with HIPEC.

Solid pseudopapillary neoplasm (SPN) is a rare malignant tumour accounting for 0.1% to 2.7% of all pancreatic neoplasms and affecting young women. Peritoneal carcinomatosis (PC) is even rarer, with only 11 reported cases. We describe a twelfth case occurring 13 years after the resection of an SPN which ruptured peroperatively. This 35-year-old woman had first undergone complete cytoreductive surgery (CCRS) alone and disease had relapsed within 8 months. Ultimately, further CCRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC) with oxaliplatin and irinotecan. The patient is now alive and disease free 31 months after her last operation. In the literature, the surgical treatment of PC from an SPN has yielded disappointing results, with a 58% recurrence rate at intervals ranging from 1 to 19 years. As none of these patients developed distant metastases, indicating a strictly peritoneal disease, HIPEC might be a solution for preventing such recurrences.

Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis.

PURPOSE: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). PATIENTS AND METHODS: From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). RESULTS: PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). CONCLUSION: Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

Toxicity and antioxidant activity in vitro and in vivo of two Fucus vesiculosus extracts.

The consumption of seaweeds has increased in recent years. However, their adverse and beneficial effects have scarcely been studied. Two extracts from the brown seaweed Fucus vesiculosus containing 28.8% polyphenols or 18% polyphenols plus 0.0012% fucoxanthin have been obtained and studied to determine their toxicity in mice and rats and also their antioxidant activity. Both extracts were shown to lack any relevant toxic effects in an acute toxicity test following a 4 week daily treatment in rats. The extracts exhibited antioxidant activity in noncellular systems and in activated RAW 264.7 macrophages, as well as in ex vivo assays in plasma and erythrocytes, after the 4 week treatment in rats. Our ex vivo results indicated that compounds from extract 2 may be more easily absorbed and that the antioxidants in their parent or metabolized form are more active. These findings support the view that the daily consumption of F. vesiculosus extract 2 (Healsea) would have potential benefits to humans.

Endoscopic ultrasonography is an independent predictive factor of prognosis in locally advanced esophageal cancer. Results from the randomized FFCD 9102 study from the Fédération Francophone de Cancérologie Digestive.

BACKGROUND: No multivariate study has assessed the independent prognostic role of endoscopic ultrasonography (EUS) in esophageal cancer, even when considering computed tomography (CT). OBJECTIVE: To evaluate the prognostic value of EUS in esophageal cancer before exclusive or preoperative radiochemotherapy. METHODS: From 1993 to 1999, the FFCD 9102 study enrolled 444 patients who had cancer of the thoracic esophagus, stages T3-4, N0-1 and M0 on CT. The patients received two sessions of chemotherapy in addition to radiotherapy. The 259 patients with objective response and no contraindications for further treatment were randomized to undergo surgery or to continue with radiochemotherapy. EUS was performed in 174 patients enrolled in the trial (mean age: 59 years). Tumor characteristics and lymph node status were prospectively recorded. A Cox statistical model was used to identify any predictive prognostic factors among the clinical, EUS and CT data. RESULTS: In the multivariate analysis, three factors were associated with a poor prognosis: inability to ingest solid food (OR: 1.98; P=0.0008); more than three neoplastic subdiaphragmatic lymph nodes (LN) on EUS (OR: 2.41; P<0.0045) and age>65 (OR: 1.53; P<0.056). Their prognostic value persisted after adjustment for type of treatment given. Two- and five- year survival rates were 21.5 and 10.5%, respectively, in the presence of three neoplastic subdiaphragmatic LN, and 43 and 30%, respectively, in all other cases. CONCLUSION: Degree of dysphagia, age and presence of neoplastic subdiaphragmatic LN on EUS were independently predictive of the prognosis for locally advanced esophageal cancer. EUS results should be taken into account in future trials.

The safety of endoscopic sphincterotomy in patients receiving antiplatelet agents: a case-control study.

OBJECTIVE: To determine whether antiplatelet agents are associated with endoscopic sphincterotomy-related haemorrhage as few well-controlled data exist on this controversial issue. METHODS: A case-control study in a tertiary care setting included cases with bleeding following endoscopic sphincterotomy, matched with 2-3 controls selected according to age +/- 15 years, sex, and procedural date+/- 2 years. Cases and controls were compared for possible risk factors of postendoscopic sphincterotomy bleeding (presence of a coagulopathy and cholangitis). The main outcome measurement was the association between the use of antiplatelet medications and postendoscopic sphincterotomy bleeding after adjustment for possible confounding. RESULTS: The 40 cases [mean age 68 +/- 17 (s.d.) years, 50% female] and 86 controls [68 +/- 16 years, 50% female] were comparable except for differences noted in International Normalized Ratio (INR) (>2 in four cases vs. two controls), and pre-endoscopic sphincterotomy cholangitis (45% vs. 20%). Amongst cases, 13% were on aspirin and 3% on clopidogrel; 17% of controls took aspirin, and 4% a non-steroidal anti-inflammatory drug. 53% of cases bled immediately; the remainder haemorrhaged at 2 +/- 3 days. After adjustment for an elevated INR and cholangitis, exposure to antiplatelet agents was not significantly associated with procedure-related bleeding (odds ratio = 0.41, 95% CI [ 0.13; 1.31]). CONCLUSION: This case-control study provides controlled data suggesting that antiplatelet agents do not significantly increase the risk of clinically-important bleeding related to endoscopic sphincterotomy. The low prevalences of non-steroidal anti-inflammatory drugs and clopidogrel use limit any definite conclusion on their elective use before endoscopic sphincterotomy.

[MR-endoscopic US correlation for loco-regional staging of rectal carcinoma]. / Corrélation IRM-échoendoscopie dans le bilan d'extension locorégional initial du cancer du rectum.

INTRODUCTION: To correlate findings at high-resolution MR and endoscopic US (EUS) for preoperative loco-regional staging of rectal carcinoma. PATIENTS AND METHODS: Fifty-two patients with rectal carcinoma underwent high-resolution MR imaging. Only 43 of these patients underwent EUS due to technical limitations and stenosing carcinomas. Morphological imaging features and TNM staging were evaluated for both imaging modalities. The degree of correlation and accuracy were calculated for both. RESULTS: The correlation between MR and EUS was good for tumor length and thickness (r=0.7 and 0.61) for for nodal (N) staging (k=0.53). Correlation was good for T1 and T2 stages (k=0.51) and T3 stage (k=0.43) and very poor for stage 4 (k= -0.09), because no T4 lesion was detected at EUS. 81.8% of patients where T stage was over-estimated on MRI and 100% of patients where T stage was over-estimated on EUS had received preoperative radiation therapy. Therefore, results should be interpreted with caution. The predictive evaluation of tumor resectability (absence of perirectal fascia invasion) with a circumferential margin on MR> or =5 mm was 93%. CONCLUSION: Correlation between MR and EUS was moderate for T staging, because of limitations of EUS for large tumors. Results confirm that high-resolution MRI is useful for loco-regional staging of rectal carcinoma, especially for large tumors. EUS should be limited to the valuation of superficial tumors of the rectum.

Video capsule endoscopy for investigation of obscure gastrointestinal bleeding: feasibility, results, and interobserver agreement.

BACKGROUND AND STUDY AIMS: The aim of the study was to assess the feasibility, diagnostic yield, and interobserver agreement of capsule endoscopy in the investigation of patients with obscure or occult gastrointestinal bleeding. PATIENTS AND METHODS: A total of 64 consecutive patients with occult bleeding (31 %) or overt bleeding (69 %) were assessed using capsule endoscopy after negative upper and lower endoscopy and small-bowel radiology. The quality of visualization of the small-bowel mucosa was scored from 1 (poor) to 4 (excellent). Thirty video capsule recordings with normal or abnormal findings were blindly assessed by four independent endoscopists. Interobserver agreement was evaluated using the kappa index. RESULTS: The small bowel was completely visualized in 57/64 patients (89 %). Incomplete small-bowel transit was most commonly due to prolonged gastric retention (five patients). The mucosa visualization scores (means) for the proximal, middle, and distal thirds of the small bowel were 3.7, 3.3, and 2.2 respectively. Visualization of the distal ileum was good (> or = 3) in 38 % and a bleeding site was found in 45 % of patients. Push-enteroscopy was also performed in 56 patients. The results of the two techniques were similar in 37 patients, capsule endoscopy was superior in 12 patients, and push-enteroscopy was superior in seven patients. Interobserver agreement was good for bleeding and for angiodysplasia, but poor for ulcers and tumors. Mean interobserver agreement was better among experienced endoscopists than among junior endoscopists. CONCLUSIONS: Capsule endoscopy allowed the whole small intestine to be explored in 89 % of patients, with good visualization of the mucosa, except distally. Interobserver agreement was better among the experienced endoscopists and was better for red-colored abnormalities (bleeding and angiodysplasia) than for ulcers and tumors.

Adjuvant chemotherapy with 5-fluorouracil and cisplatin compared with surgery alone for gastric cancer: 7-year results of the FFCD randomized phase III trial (8801).

BACKGROUND: The aim of this study was to evaluate the efficacy of adjuvant chemotherapy after resection for gastric cancer in a randomized controlled trial. PATIENTS AND METHODS: After curative resection, stage II-III-IVM0 gastric cancer patients were randomly assigned to postoperative chemotherapy or surgery alone. 5-Fluorouracil (5-FU) 800 mg/m(2) daily (5-day continuous infusion) was initiated before day 14 after resection. One month later, four 5-day cycles of 5-FU (1 g/m(2) per day) plus cisplatin (100 mg/m(2) on day 2) were administered every 4 weeks. RESULTS: The study was closed prematurely after enrollment of 260 patients (79.7% N+), owing to poor accrual. At 97.8 months median follow-up, 5- and 7-year overall survival were 41.9% and 34.9% in the control group versus 46.6% and 44.6% in the chemotherapy group (P=0.22). Cox model hazard ratios were 0.74 [95% confidence interval (CI) 0.54-1.02; P=0.063] for death and 0.70 (95% CI 0.51-0.97; P=0.032) for recurrence. An invaded/removed lymph nodes ratio >0.3 was the main independent poor prognostic factor identified by multivariate analysis (P=0.0001). Because of toxicity, only 48.8% of patients received more than 80% of the planned dose. CONCLUSION: There was no statistically significant survival benefit with this toxic cisplatin-based adjuvant chemotherapy, but a risk reduction in recurrence was observed.

Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients.

AIMS: To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks. METHODS: Three open label, non-controlled, multiple topical dose studies were conducted in children aged 8-14 years (study A, ten patients), and in infants aged 8-30 months (study B, eight patients) and 4-11 months (study C, eight patients). Pimecrolimus blood concentrations were determined on days 4 and 22 of treatment, and at end of study. Efficacy was assessed using the Eczema Area and Severity Index (EASI). RESULTS: Pimecrolimus blood concentrations were consistently low, typically (81%) below 1 ng/ml, with more than half of the measurements below the assay limit of quantitation (0.5 ng/ml) in studies A and B. The highest blood concentration measured throughout the three studies was 2.6 ng/ml. The cream was well tolerated, locally and systemically. The most common adverse event suspected to be related to study medication was a transient mild to moderate stinging sensation at the application site in 5/26 patients. There was no indication of any systemic adverse effect. The patients responded well to therapy with a rapid onset of action, usually within four days. Median reductions of EASI from baseline at day 22 were 55% (study A), 63% (study B), and 83% (study C). CONCLUSION: Three weeks treatment of children and infants with extensive atopic dermatitis, using pimecrolimus cream 1% twice daily, is well tolerated and results in minimal systemic exposure, at which no systemic effect is expected.

Evaluation of the permeability of pancreaticogastric anastomoses (PGA) with dynamic magnetic resonance pancreatography after secretin stimulation (secretin MRCP).

BACKGROUND: Because some investigators have reported the systematic occurrence of exocrine pancreatic insufficiency after pancreaticoduodenectomy with pancreaticogastric anastomosis (PGA), we assessed PGA patency after pancreaticoduodenectomy. METHODS: Nineteen patients underwent pancreaticoduodenectomy, and their PGAs were studied prospectively with secretin magnetic resonance cholangiopancreatography (MRCP). After administration of negative bowel contrast agent, single-shot fast spin-echo T2-weighted dynamic MR pancreatograms were obtained before and every minute for 12 min after secretin injection. Morphologic features of the pancreatic parenchymal and pancreatic duct were monitored (diameter and winding aspect of the pancreatic duct, pancreatic thickness, direct visualization of the anastomotic site). PGA permeability was classified into four grades, from 0 (obstruction) to 3 (good permeability). Pancreatic function was assessed by fecal-1 elastase concentration, fasting blood glucose, and fasting serum insulin level. RESULTS: MRCP grades were 0 in two patients, 1 in four, 2 in five, and 3 in eight. The anastomotic site was visualized in 10 patients. Pancreatic parenchymal atrophy was discovered in four patients. There were statistically significant relations between secretin MRCP permeability grade and fecal-1 elastase concentration (p < 0.03) and between secretin MRCP permeability grade and pancreatic atrophy (p < 0.005). In contrast, fecal-1 elastase concentration was lower than the normal value in all but one case. There was no statistically significant relation between fecal-1 elastase concentration and other morphologic data. CONCLUSION: Secretin MRCP may indicate PGA stenosis or dysfunction, but it is not the only factor suggesting exocrine pancreatic insufficiency. Thus the major role of PGA may be the preservation of long-term endocrine function.

[Value of tissue harmonic imaging in biliary lithiasis]. / Apport de l'imagerie harmonique dans la pathologie lithiasique du système biliaire.

AIM OF THE STUDY: To define the role of harmonic imaging in the study of biliary lithiasis. SUBJECTS AND METHODS: We included 50 consecutive patients with suspected biliary lithiasis. Three independent observers compared results of harmonic imaging and conventional ultrasonography. RESULTS: This study showed a better interobserver agreement with harmonic imaging for acoustic shadow (kappa=0.87 vs 0.68) and intra-hepatic biliary stones (kappa=0.79 vs 0.49). More stones and more lithiasic gallbladders were seen with harmonic imaging (27 vs 24) and visualization of gallbladder sludge and the acoustic shadow from stones (P=0.01) was better. Ultrasound examination appears to be easier and faster and the diagnosis is more certain with harmonic imaging than with conventional ultrasonography (P=0.005). CONCLUSION: Harmonic imaging provides more information on biliary lithiasis and a more certain diagnosis.

[Abdominoperineal resection for locally recurrent rectal cancers following anterior resection]. / Amputation abdominopérinéale pour récidives locales des cancers du rectum après résection antérieure.

STUDY AIM: The aim of this retrospective study was to evaluate the short and long term results of abdominoperineal resection for local recurrence following low anterior resection of a rectal adenocarcinoma and to determine the prognostic factors. PATIENTS AND METHODS: From January 1978 to December 1996, 35 patients (17 women, 18 men) with a mean age of 59.4 years, underwent an abdominoperineal resection for local recurrence after low anterior resection of a rectal adenocarcinoma. The primary tumor was below the peritoneum in 29 cases, and the mean security margin was 3 cm under the tumor. Tumor staging at the time of primary surgery included 23 Dukes B, 11 Dukes C, and 1 Dukes D. The mean time elapsed between low anterior resection and local recurrence was 16.4 months. The histological diagnosis of recurrence was obtained preoperatively in 29 cases (82.8%). RESULTS: Resection was curative in 12 patients and palliative only in 23 patients. The recurrence was intramural in 3 cases, extramural in 10 cases, and mixed in 22 cases. Ten patients had an extended "en bloc" resection including one or several adjacent organs, and a synchronous metastasis was resected in 2 cases. The mortality rate was 2.8% (n = 1) and the morbidity rate was 23% (n = 8). The 1-year and 5-year survival rates were respectively 77 and 30.2% with the univariate analysis of prognosis factors of survival, there were four pretherapeutic factors (age, staging of the primary tumor, delay of the recurrence, CEA rate) and four therapeutic factors (curative resection, extramural recurrence, staging of the recurrence, postoperative radiotherapy). The curative or not curative type of resection was the only independent predictor of survival with multivariate analysis. CONCLUSION: The results of this study seem to justify an abdominoperineal resection for local recurrence after low anterior resection whenever possible. Long-term results may possibly be improved by using adjuvant treatment.

Anal carcinoma: prognostic value of endorectal ultrasound (ERUS). Results of a prospective multicenter study.

BACKGROUND AND STUDY AIMS: The classification of anal carcinoma is based on the clinical examination and the estimation of the tumor height (Union Internationale Contre le Cancer (UICC) 1987 Classification). This classification has a direct therapeutic application since tumors which are designated T1 and T2 are generally treated by radiotherapy whereas T3, T4 or N+ lesions are treated by concomitant radiation and chemotherapy. The aim of this prospective multicenter study was to evaluate endorectal ultrasound (ERUS) and to define an ERUS-based classification. PATIENTS AND METHODS: Between January 1994 and May 1997, 146 patients (42 men and 104 women; mean age, 63) from eight different centers were studied prospectively. The ERUS classification incorporates disease of the anal canal and the perirectal lymph nodes, thus: usT1 describes involvement of the mucosa and submucosa with sparing of the internal sphincter; usT2, involvement of the internal sphincter with sparing of the external sphincter; usT3, involvement of the external sphincter; usT4, involvement of a pelvic organ; N0 describes no suspicious perirectal lymph nodes, and N+, perirectal lymph nodes fulfilling endosonographic criteria for malignancy (e.g. round, hypoechoic). Tumors classified as UICC T1-T2 (<4cm) N0 were treated by radiotherapy alone, whereas lesions with a UICC classification of T2 (> 4 cm), T3-T4, N0-N1-2-3 received combined radiochemotherapy. RESULTS: Data concerning the treatment and follow-up were available for 115/146 patients (78.7%). We compared the prognostic importance of the two classification schemes for treatment response and the rate of local relapse (chi-squared test). A significantly greater proportion of T1-T2N0 lesions classified by ERUS had a complete response to treatment than those classified by conventional UICC staging (94.5% vs. 80%, respectively; P = 0.008). The ERUS T and N stage were significant predictors of relapse (P=0.001 and P=0.03, respectively) whereas the corresponding clinical (UICC) stages were not (P = 0.4 and P = 0.5, respectively). Using a Cox model, usT stage was the only significant predictive factor for patient survival. CONCLUSION: This muticenter prospective study demonstrated the superiority of ERUS-based staging over traditional clinical staging in the prediction of important outcomes such as local tumor recurrence and patient survival.

First experience of topical SDZ ASM 981 in children with atopic dermatitis.

BACKGROUND: SDZ ASM 981 is a selective inhibitor of inflammatory cytokine release under development for the topical treatment of atopic dermatitis. OBJECTIVES: This first paediatric study was designed to measure the systemic exposure to SDZ ASM 981 in young children with atopic dermatitis treated on extensive skin areas. METHODS: Children 1-4 years of age referred to a tertiary care centre for their atopic dermatitis were treated twice daily for 3 weeks with 1% SDZ ASM 981 cream. SDZ ASM 981 blood concentrations were measured on day 4 and 22 (last day) of treatment, and 1 week after the last application, using a radioimmunoassay with a limit of quantification of 0.5 ng mL(-1). Efficacy was assessed by the Eczema Area Severity Index (EASI). RESULTS: The 10 patients included had 23-69% of their body surface area (BSA) affected at baseline. Of the 63 SDZ ASM 981 blood concentrations measured, 63% were < 0.5 ng mL(-1); the maximum value observed was 1.8 ng mL-1. No accumulation was evidenced between days 4 and 22. The first two patients experienced a flare of atopic dermatitis that was not controlled by the study medication. In the other patients, the EASI improved by 8-89% at 3 weeks of treatment. CONCLUSIONS: In these children 1-4 years of age, blood concentrations of SDZ ASM 981 during topical treatment with the 1% cream were consistently low even in the children with the most extensive areas treated (up to 69% of their BSA).

[Staging for locoregional extension of rectal adenocarcinoma]. / Recherche de l'extension locorégionale dans l'adénocarcinome rectal.

The treatment of rectal carcinoma is mainly determined by its local extension. Preoperative staging of rectal carcinoma was assessed by different methods: digital rectal examination, transrectal ultrasound, computed tomography, and magnetic resonance imaging. Digital rectal examination had a diagnostic accuracy between 68 and 83 per cent. The accuracy of transrectal ultrasound was between 67 and 93 per cent for tumor staging and between 62 and 88 per cent for lymph node staging. The accuracy of computed tomography was between 33 and 77 per cent for tumor staging and between 22 and 73 per cent for lymph node staging. The overall accuracy of magnetic resonance imaging with body coil was between 59 and 95 per cent, and between 39 and 95 per cent for lymph node staging. Use of an endorectal coil allows a slightly more consistent degree of accuracy, with tumor staging accuracy between 66 and 91 per cent, and lymph node staging accuracy between 72 and 79 percent. Preoperative radiation therapy makes transrectal ultrasound and computed tomography less effective as staging techniques.

Use of half-dose gadolinium-enhanced MRI and magnetization transfer saturation in brain tumors.

The aim of this study was to search if half-dose gadolinium (Gd)-enhanced MR imaging with magnetization transfer saturation (MT) can replace standard-dose T1-weighted spin echo (SE) without MT saturation in brain tumors. Thirty patients with a total of 33 brain tumors (14 gliomas, 13 meningiomas, 6 metastases) were prospectively studied using T1-weighted SE half-dose of Gd with MT, and T1-weighted SE standard-dose Gd without MT. The contrast-to-noise ratio (CNR) of the two sequences was calculated and four radiologists reviewed qualitatively the images of the two sequences. There was no significant difference between both techniques for quantitative analysis (Wilcoxon test). However, there was a good agreement between sequences to evidence an intraclass correlation coefficient (r = 0.70) of all lesions. In cases of meningioma, the agreement was better (r = 0.84). The results show a difference in the qualitative data between the two sequences, suggesting the use of the T1-weighted MR images with MT and half-dose of Gd with good results in the whole tested parameters except the lesional edema and the presence of artifacts. Half-dose T1-weighted SE with MT can replace standard-dose T1-weighted SE without MT with no loss of contrast enhancement in investigation of meningiomas and saving 50% of the contrast material.