Capi-score: a quantitative algorithm for identifying disease patterns in nailfold videocapillaroscopy.

OBJECTIVES: The European Alliance of Associations for Rheumatology (EULAR) supports the use of nailfold videocapillaroscopy (NVC) to identify disease patterns (DPs) associated with systemic sclerosis (SSc) and Raynaud's phenomenon (RP). Recently, EULAR proposed an easy-to-manage procedure, a so-called Fast Track algorithm, to differentiate SSc from non-SSc patterns in NVC specimens. However, subjectivity among capillaroscopists remains a limitation. Our aim was to perform a software-based analysis of NVC peculiarities in a cohort of samples from SSc and RP patients and, subsequently, build a Fast Track-inspired algorithm to identify DPs without the constraint of interobserver variability. METHODS: NVCs were examined by 9 capillaroscopists. Those NVCs whose DPs were consensually agreed (≥2 out of 3 interobservers) were subsequently analysed with an in-house developed software. Each variable's results were grouped according to the consensually agreed DPs in order to identify useful hallmarks to categorise them. RESULTS: Eight-hundred and fifty-one NVCs (21 957 images) whose DPs had been consensually agreed were software-analysed. Appropriate cut-offs set in capillary density and percentage of abnormal and giant capillaries, tortuosities and hemorrhages allowed DP categorization and the development of the CAPI-Score algorithm. This consisted of 4 rules: Rule 1, SSc vs non-SSc, accuracy 0.88; Rules 2 and 3, SSc-early vs SSc-active vs SSc-late, accuracy 0.82; Rule 4, non-SSc normal vs non-SSc non-specific, accuracy 0.73. Accuracy improved when the analysis was limited to NVCs whose DPs had achieved full consensus among interobservers. CONCLUSIONS: The CAPI-Score algorithm may become a useful tool to assign DPs by overcoming the limitations of subjectivity.

Usefulness of high-frequency ultrasonography in the evaluation and monitoring of sclerosing dermatoses: a cohort study.

BACKGROUND: Monitoring of disease activity in sclerosing dermatoses (SD) can be challenging and tools to support clinical decision-making are lacking. AIM: To analyse the impact of high-frequency ultrasonography (HFUS) on the clinical management of SD and to describe the US characteristics of disease activity. METHODS: This was a cohort study of patients with various SD [morphoea, systemic sclerosis (SS) and chronic graft-versus-host disease (cGvHD)] who underwent HFUS between January 2017 and August 2019. HFUS criteria for diagnosing active SD were increased Doppler vascularity and/or meeting all B-mode greyscale US signs of activity. Discordance in SD activity between HFUS and clinical examination was evaluated at the time of the first US assessment. Changes in patient management were instituted after HFUS were recorded. RESULTS: In total, 72 patients (31 with morphoea, 19 with SS and 22 with cGvHD), who underwent 163 HFUS sessions in total, were included. All HFUS-active morphoea lesions exhibited increased vascularity, and all HFUS-active SS exhibited dermal thickening and dermal hypoechogenicity. HFUS-active cGvHD displayed increased dermal thickness and loss of definition of the dermal-hypodermal junction, and there were signs of panniculitis in 80% of cases and of increased vascularity in 70%. Discordance in disease activity between clinical and HFUS evaluation was found in 17 (23.6%) patients. Changes in clinical management after HFUS were made for 14 (19.4%) patients: treatment discontinuation for 6 patients (42.9%), treatment initiation for 5 (35.7%), medication change for 2 (14.3%) and skin biopsy taken for 1 (7.1%). CONCLUSION: HFUS seems an efficacious support tool in the monitoring of SD activity with a notable impact on clinical management. Further studies are warranted to evaluate the impact of HFUS-supported management changes on SD outcomes.

Late toxicities and clinical outcome at 5 years of the ACCORD 12/0405-PRODIGE 02 trial comparing two neoadjuvant chemoradiotherapy regimens for intermediate-risk rectal cancer.

BACKGROUND: Outcome of intermediate risk rectal cancer may be improved by the addition of oxaliplatin during 5-fluoruracil concomitant neoadjuvant chemoradiotherapy. The purpose of this study is to analyze the main clinical results of the ACCORD12 trial (NCT00227747) in rectal cancer after 5 years of follow-up. PATIENTS AND METHODS: Inclusion criteria were as follows: rectal adenocarcinoma accessible to digital examination staged T3-T4 Nx M0 (or T2 Nx distal anterior rectum). Two neoadjuvant chemoradiotherapy regimens were randomized: CAP45 (RT 45 Gy + capecitabine) and CAPOX50 (RT 50 Gy + capecitabine and oxaliplatin). Main end point was sterilization of the operative specimen. Acute and late toxicities were prospectively analyzed with dedicated questionnaires. RESULTS: Between November 2005 and July 2008, 598 patients were included in the trial. After a median follow-up of 60.2 months, there was no difference between treatment arms in multivariate analysis either for disease-free survival or overall survival (OS) [P = 0.9, hazard ratio (HR)=1.02; 95% confidence interval (CI), 0.76-1.36 and P = 0.3, HR = 0.87; 95% CI, 0.66-1.15, respectively]. There was also no difference of local control in univariate analysis (P = 0.7, HR = 0.92; 95% CI, 0.51-1.66). Late toxicities were acceptable with 1.6% G3 anal incontinence, and <1% G3 diarrhea, G3 rectal bleeding, G3 stenosis, G3-4 pain, G3 urinary incontinence, G3 urinary retention and G3 skeletal toxicity. There was a slight increase of erectile dysfunction over time with a 63% rate of erectile dysfunction at 5 years. There was no significant statistical difference for these toxicities between treatment arms. CONCLUSIONS: The CAPOX50 regimen did not improve local control, disease-free survival and overall survival in the ACCORD12 trial. Late toxicities did not differ between treatment arms.

Quality-of-life findings from a randomised phase-III study of XELOX vs FOLFOX-6 in metastatic colorectal cancer.

BACKGROUND: A phase-III trial showed the non-inferiority of oral capecitabine plus oxaliplatin (XELOX) vs 5-fluorouracil/leucovorin plus oxaliplatin (FOLFOX-6) in terms of efficacy in first-line treatment of metastatic colorectal cancer. A secondary objective was to compare the quality of life (QoL) and health-care satisfaction of patients. METHODS: Patients were randomised to receive XELOX (n=156) or FOLFOX-6 (n=150) for 6 months. Quality of life and satisfaction were assessed by the Quality of Life Questionnaire-C30 (QLQ-C30) and Functional Assessment of Chronic Illness Therapy Chemotherapy Convenience and Satisfaction Questionnaire (FACIT-CCSQ), respectively. Patients completed questionnaires at baseline, at Cycle3 (C3) and Cycle (C6) (XELOX) or at C4 and C8 visits (FOLFOX-6) and at their final visit. RESULTS: A total of 245 and 225 patients were assessed using QLQ-C30 and FACIT-CCSQ, respectively. The completion rates were >80%. Global QoL scores did not differ significantly between groups during the study. According to FACIT-CCSQ, XELOX seemed more convenient (C3/C4, P<0.001; C6/C8, P=0.009) and satisfactory to patients (C6/C8, P=0.003) than FOLFOX-6. At the final visit, XELOX patients spent fewer days on hospital visits (3.3 vs 5.3 days, P=0.045) and lost fewer hours of work/daily activities (10.2 vs 37.1 h lost, P=0.007). CONCLUSION: XELOX has a similar QoL profile, but seemed to be more convenient in terms of administration at certain time points and reduced time lost for work or other activities compared with FOLFOX-6.

Cost-minimisation analysis in first-line treatment of metastatic colorectal cancer in France: XELOX versus FOLFOX-6.

OBJECTIVE: In a recent randomized study, we demonstrated that XELOX (oxaliplatin + oral capecitabine) was well tolerated and not inferior in terms of efficacy to the infusional FOLFOX-6 regimen in first-line treatment of metastatic colorectal cancer (mCRC). The objective of this additional analysis was to compare the cost of XELOX and FOLFOX-6. METHODS: This cost-minimisation study took into account costs related to drug acquisition, hospital care for chemotherapy administration and for serious adverse event management. Hospital care costs were based on French 'diagnosis-related group' tariffs. Drug acquisition costs were drawn from French official sources. Analysis was performed from the French health insurance perspective. RESULTS: Baseline characteristics of the 282 patients included (143 XELOX, 139 FOLFOX-6) were well balanced. Patients reported less and shorter hospitalisations (day and overnight hospital care) with XELOX: 6.4 ± 2.2 hospitalisations versus 9.7 ± 3.1 (p < 0.001); 11.4 ± 10.6 days versus 17.7 ± 11.8 (p < 0.001). Mean disease management cost per patient was significantly lower with XELOX (EUR 12,918 ± 5,075 vs. EUR 17,229 ± 8,665, p < 0.001). CONCLUSION: In the perspective of our analysis, taking into account hospitalisation and drug acquisition costs, the treatment of mCRC patients with XELOX in comparison to FOLFOX-6 significantly decreased the costs, as well as the mean overall hospitalisation length of stay.

Efficacy of FOLFIRI-3 (irinotecan D1,D3 combined with LV5-FU) or other irinotecan-based regimens in oxaliplatin-pretreated metastatic colorectal cancer in the GERCOR OPTIMOX1 study.

BACKGROUND: Second-line irinotecan-based chemotherapy is commonly used in metastatic colorectal cancers after first-line oxaliplatin-based chemotherapy. No standard schedule of irinotecan has been established in this situation. PATIENTS AND METHODS: Metastatic colorectal cancer patients included in the OPTIMOX1 phase III study received first-line oxaliplatin-based chemotherapy (FOLFOX). No second line was defined in the protocol, but data concerning second line were prospectively registered. Inclusion criterion was patients receiving an irinotecan-based second-line chemotherapy. Second-line progression-free survival (PFS) and tumor response were evaluated according to type of irinotecan-based regimen administered. RESULTS: A total of 342 patients received irinotecan-based chemotherapy as second-line chemotherapy: FOLFIRI-3 [n = 109, irinotecan 100 mg/m(2) days 1 and 3 combined with leucovorin (LV) 400 mg/m(2) day 1 and 46-h continuous 5-fluorouracil (5-FU) 2000 mg/m(2)], FOLFIRI-1 (n = 112, irinotecan 180 mg/m(2) day 1 combined with LV 400 mg/m(2) day 1, 5-FU bolus 400 mg/m(2) and 46-h continuous 5-FU 2400 mg/m(2)) and other various irinotecan-based regimens (n = 121). Median second-line PFS was 3.0 months (FOLFIRI-3: 3.7 months; FOLFIRI-1: 3.0 months; other regimens: 2.3 months). In multivariate analysis, FOLFIRI-3 regimen (relative risk 0.43, 95% confidence interval 0.28-0.68, P = 0.0003) and lactate deshydrogenase level at inclusion (P = 0.0006) in OPTIMOX1 were associated with a longer second-line PFS. CONCLUSION: In unselected patients pretreated with oxaliplatin, PFS in second line appeared to be improved by FOLFIRI-3 regimen.

FOLFOX in patients with metastatic colorectal cancer and high alkaline phosphatase level: an exploratory cohort of the GERCOR OPTIMOX1 study.

BACKGROUND: Alkaline phosphatase (ALP) is a strong prognostic factor in patients with metastatic colorectal cancer (MCRC). Patients with ALP more than three times the upper limit of normal (ULN) were excluded from our previous studies evaluating chemotherapy. An exploratory cohort of patients with ALP >3 ULN was included in the OPTIMOX1 study. PATIENTS AND METHODS: Previously untreated patients with MCRC were randomized to FOLFOX4 until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles and reintroduction of FOLFOX7 (arm B). Patients were stratified according to ALP level

Cetuximab efficacy and safety in a retrospective cohort of elderly patients with heavily pretreated metastatic colorectal cancer.

BACKGROUND: Few data are available from clinical trials for elderly patients receiving cetuximab. PATIENTS AND METHODS: The clinical data of consecutive patients aged > or =70 years given cetuximab for metastatic CRC were retrospectively captured from hospital pharmacy registries in seven centers. RESULTS: Fifty-six patients received cetuximab+/-with irinotecan. Median age was 76 years (70-84), 86% of patients were pretreated with fluoropyrimidines, irinotecan and oxaliplatin and 69.6% had documented resistance to irinotecan. Objective response rate was 21% (95% CI: 11-32%). The median progression-free survival was 4.4 months (95% CI: 3.0-5.7 months) and the median overall survival was 16.0 months (95% CI: 13.5-18.5 months). Skin rash occurred in 75% of the patients (11% grade 3) and diarrhea in 80% (20% grades 3-4). CONCLUSION: Tolerability of cetuximab was acceptable in elderly patients with pretreated metastatic CRC. Efficacy appeared similar to that observed in younger patients.

Gemcitabine in combination with oxaliplatin compared with gemcitabine alone in locally advanced or metastatic pancreatic cancer: results of a GERCOR and GISCAD phase III trial.

PURPOSE: Gemcitabine (Gem) is the standard treatment for advanced pancreatic cancer. Given the promising phase II results obtained with the Gem-oxaliplatin (GemOx) combination, we conducted a phase III study comparing GemOx with Gem alone in advanced pancreatic cancer. PATIENTS AND METHODS: Patients with advanced pancreatic cancer were stratified according to center, performance status, and type of disease (locally advanced v metastatic) and randomly assigned to either GemOx (gemcitabine 1 g/m2 as a 100-minute infusion on day 1 and oxaliplatin 100 mg/m2 as a 2-hour infusion on day 2 every 2 weeks) or Gem (gemcitabine 1 g/m2 as a weekly 30-minute infusion). RESULTS: Three hundred twenty-six patients were enrolled; 313 were eligible, and 157 and 156 were allocated to the GemOx and Gem arms, respectively. GemOx was superior to Gem in terms of response rate (26.8% v 17.3%, respectively; P = .04), progression-free survival (5.8 v 3.7 months, respectively; P = .04), and clinical benefit (38.2% v 26.9%, respectively; P = .03). Median overall survival (OS) for GemOx and Gem was 9.0 and 7.1 months, respectively (P = .13). GemOx was well tolerated overall, although a higher incidence of National Cancer Institute Common Toxicity Criteria grade 3 and 4 toxicity per patient was observed for platelets (14.0% for GemOx v 3.2% for Gem), vomiting (8.9% for GemOx v 3.2% for Gem), and neurosensory symptoms (19.1% for GemOx v 0% for Gem). CONCLUSION: These results confirm the efficacy and safety of GemOx, but this study failed to demonstrate a statistically significant advantage in terms of OS compared with Gem. Because GemOx is the first combined treatment to be superior to Gem alone in terms of clinical benefit, this promising regimen deserves further development.

Gemcitabine combined with oxaliplatin in advanced pancreatic adenocarcinoma: final results of a GERCOR multicenter phase II study.

PURPOSE: Based on preclinical in vitro synergy data, this study evaluated the activity and toxicity of a gemcitabine/oxaliplatin combination in patients with metastatic and locally advanced pancreatic adenocarcinoma. PATIENTS AND METHODS: Previously untreated metastatic and locally advanced unresectable pancreatic adenocarcinoma patients were enrolled onto this multicenter phase II study. Patients received gemcitabine 1,000 mg/m(2) as a 10-mg/m(2)/min infusion on day 1 and oxaliplatin 100 mg/m(2) as a 2-hour infusion on day 2 every 2 weeks. Patients with metastatic disease were treated until evidence of progressive disease, whereas patients with locally advanced disease received six cycles in the absence of progression, followed when appropriate by concomitant radiochemotherapy. RESULTS: Among 64 eligible patients included in eight centers, 30 had locally advanced and 34 had metastatic disease. Response rate for the 62 patients with measurable disease was 30.6% (95% confidence interval, 19.7% to 42.3%), 31.0% for locally advanced and 30.3% for metastatic patients. Among 58 assessable patients, 40% had clinical benefit. Median progression-free survival and median overall survival (OS) were 5.3 and 9.2 months, respectively, with 36% of patients alive at 1 year. Median OS for patients with metastatic disease and locally advanced disease were 8.7 and 11.5 months, respectively. With 574 treatment cycles (median per patient, nine; range, zero to 27), grade 3/4 toxicity per patient was 11% for neutropenia and thrombocytopenia, 14% for nausea or vomiting, 6.2% for diarrhea, and 11% for peripheral neuropathy, with no toxic deaths. CONCLUSION: Palliative effects, response rate, and survival observed with this well-tolerated gemcitabine/oxaliplatin combination deserve additional evaluation. A comparative study of combination therapy versus gemcitabine alone is ongoing.

Lack of preferential transmission of diabetic HLA alleles by healthy parents to offspring in Spanish diabetic families.

HLA-DR3 or -DR4 segregation distortion to normal or insulin-dependent (ID) diabetic offspring of 108 Spanish families whose parents were healthy was not observed; however, DR3 or DR4 ID offspring is significantly increased in the present study, since parents were chosen after tracing ID children. These results are discrepant with those found by others in families with diabetic parents in other ethnic groups. These conflicting data could be due to sampling errors or segregation distortion. Thus, ethnic group differences in a genetic (T/t-like) or metabolic mechanism might confer advantages to DR3- or DR4-bearing gametes from ID diabetic parents, but segregation distortion might only affect certain HLA DR3 or DR4 extended haplotypes which are frequent and characteristic for certain ethnic groups (i.e. B8-DR3-BfS-C4AQOB1 and Bw62-DR3-BfS-C4A383 in most caucasians) but not for other haplotypes in other ethnic groups (Spaniards; B18-DR3-BfF1-C4A3BQO and BwX-DR4-BfX-C4AXBX).

Exclusive HLA-DQ factors do not explain susceptibility to insulin-dependent diabetes.

DQA1, DQA2, DQB1, and DRB1 alleles have been determined and the DQA1 and DQB1 DNA gene sequences assigned by using restriction fragment length polymorphisms in 67 diabetic individuals and 72 controls. It has been found that: 1) DQA2 (U allele) is not a susceptibility factor, 2) non-aspartic acid homozygosity in residue 57 (Asp 57 negative) of the DQ beta chains is positively correlated with insulin-dependent diabetes mellitus (IDDM), and 3) DQ beta Asp-57-negative and DQ alpha arginine-52-positive (Arg-52-positive) individuals are increased among diabetic patients; this latter analysis shows a higher etiologic fraction (delta) value than the one obtained when considering only homozygous DQ beta Asp-57-negative individuals. However, if only non-DR3 or DR4 individuals were considered (both in DQ beta Asp-57-negative homozygous and in DQ beta Asp-57-negative/DQ alpha Arg-52-positive individuals) the correlation with disease disappears. In addition, the postulated risk DQ beta Asp 57-negative and DQ alpha Arg 52 positive is absent in six patients. These data do not discard the possibility that DR3/DR4 may contain the primary susceptibility factors. It is concluded that it is not possible to assign the susceptibility to IDDM to a specific HLA locus and that several loci within the same or the trans haplotype may be involved.

Study of bone loss in diabetes mellitus type 1.

While people with type 1 diabetes mellitus (DM) often have bone deficiency, the relation between this deficiency and the duration or control of diabetes remains controversial. To assess the possibility of such an interrelationship, we studied parameters relating to mineral metabolism (Ca, P, alkaline phosphatase, Mg, PTH, and hydroxyproline (OHP)); bone remodeling (osteocalcin); diabetic control (HbA1c); and radiological study of the second metacarpal of the left hand and of bone age in 87 children with type 1 DM. The mineral parameters were not abnormal among the diabetics. Diabetic children had similar levels of fasting osteocalcin as normals (10.05 +/- 4.9 vs. 9.79 +/- 3.34 ng/ml, mean +/- SD); this did not differ by sex. The bone age fell within two standard deviations of the mean, and 9.5% of the diabetics had a bone mass deficit (less than the mean cortical thickness) greater than 2 SD. There was no correlation between osteocalcin and Ca, P, glycemia, HbA1c, PTH, Mg, or OHP. Our results do not support any association between bone mass loss and the severity or duration of type 1 diabetes. Bone turnover, measured by serum osteocalcin, was normal. Therefore the pathogenesis of osteopenia in type 1 DM remains unclear, and requires further investigation.

Coeliac- and enteropathy-associated autoantibodies in Spanish insulin-dependent diabetes mellitus patients and their relation to HLA antigens.

The frequency of reticulin (ARA), endomysium (EmA), and gut epithelial cell (GECA) autoantibodies, and gliadin antibodies (AGA), was investigated in 86 Spanish diabetic patients by indirect immunofluorescence (IFI) and ELISA, along with their HLA phenotype. Four patients (5%) showed ARA-IgG (R1 pattern), eight (9%) showed AGA-IgG, and eight (9%) showed AGA-IgA. No EmA or GECA-positive patients were found. In diabetic patients, HLA-DR7 is increased in ARA-IgG+ vs. ARA-IgG- (though not significantly), and HLA-DR6 and HLA-DQ1 are significantly increased in the AGA-IgG+ group vs. the AGA-IgG- group. Comparison with a non-diabetic coeliac group showed that HLA-DR4 and HLA-DQ3 are significantly increased in the AGA-IgA+ group, whereas HLA-DQ2 shows a significant decrease in the AGA-IgG+ and AGA-IgA+ patients. Finally, when compared to the healthy group, HLA-DR7 frequency is decreased in the ARA-IgG- group, while HLA-DQ3 is significantly increased and HLA-DR6 and HLA-DQ1 significantly decreased in the AGA-IgG- group.Altogether, these data suggest that the genetic background leading to the appearance of coeliac-specific autoantibodies in Spanish diabetic patients differ depending on the autoantibody produced and is also different to the genetic background leading to diabetes in Spain.

Assessment of tumour response to chemotherapy for metastatic colorectal cancer: accuracy of the RECIST criteria.

Evaluation of tumour size modifications in response to treatment is a critical issue in the management of advanced malignancies. In 1981, the World Health Organization (WHO) established guidelines for tumour response assessment. These WHO1981 criteria were recently simplified in a revised version, named RECIST (Response Evaluation Criteria in Solid Tumours), which uses unidimensional instead of bidimensional measurements, a reduced number of measured lesions, withdrawal of the progression criteria based on isolated increase of a single lesion, and different shrinkage threshold for definitions of tumour response and progression. In order to validate these new guidelines, we have compared results obtained with both classifications in a prospective series of 91 patients receiving chemotherapy for metastatic colorectal cancer. Data from iterative tomographic measurements were fully recorded and reviewed by an expert panel. The overall response and progression rates according to the WHO1981 criteria were 19% and 58%, respectively. Using RECIST criteria, 16 patients were reclassified in a more favourable subgroup, the overall response rate being 28% and the progression rate 45% (non-weighted kappa concordance test 0.72). When isolated increase of a single measurable lesion is not taken into account for progression with the WHO1981 criteria, only 7 patients were reclassified and the kappa test was satisfying, i.e. > or =0.75, for the whole population as well as for each of the responding and progressive subgroups. Since it provides concordant results with a simplified method, the use of RECIST criteria is recommended for evaluation of treatment efficacy in clinical trials and routine practice.

Any clinical benefit from the use of oncofoetal markers in the management of chemotherapy for patients with metastatic colorectal carcinomas?

AIMS: Computed tomography (CT) is the reference technique for evaluating response to chemotherapy. The potential helpfulness of tumour markers is debated. MATERIALS AND METHODS: From March 1997 to January 1999, 91 consecutive patients receiving chemotherapy for metastatic colorectal carcinoma underwent whole-body spiral CT, estimates of anti-carcinoembryonic antigen (CEA) and CA19-9 every 8 weeks. RESULTS: CEA and CA19-9 levels were above normal in 78 (85.7%) and 61 (67.5%) patients, respectively. Tumour response evaluation according to the RECIST criteria was obtained at 8-week evaluation in 83 (91%) patients. The positive predictive values (PPV) for response of a decrease of the marker levels were 53.8 for CEA and 41.7 for CA19-9 using a 30% decrease threshold, and 60/52.2, respectively, using a 50% decrease threshold. Meaningful PPV values (> 90%) for progression of an increase of the marker levels were only obtained using the 200% increase threshold for CEA alone or a combination of CEA and CA 19-9. A 100% CEA increase between baseline and the 8-week evaluation was correlated to overall survival (P = 0.0023). The need for a radiological confirmation of tumour progression could be avoided by the systematic dosage of tumour markers at baseline and after 8 weeks of treatment only in a sub-population of 13% of the patients with a 200% increase of CEA or CA 19-9 at 8 weeks. CONCLUSIONS: CEA, CA 19-9, or both should be used with caution for tumour response evaluation to chemotherapy in addition to CT in metastatic colorectal carcinoma.

[Hyponatremia in the postoperative period after a neurosurgical tumor condition]. / Hiponatremia en el postoperatorio de la patología tumoral neuroquirúrgica.

A four-year-old girl suffered difficult-to-diagnose hyponatremia resistant to treatment following surgery for a suprasellar tumor. The final diagnosis was diabetes insipidus evolving in three stages. Hyponatremia is a common problem following surgery to remove brain tumors. Early diagnosis and treatment of this electrolytic imbalance are essential for preventing serious neurological symptoms or death. The conditions most closely related to hyponatremia are inappropriate antidiuretic hormone secretion syndrome (IADHSS) and cerebral salt wasting syndrome (CSWS). The latter has become more common in recent years among patients undergoing brain surgery. Whereas IADHSS is treated by restricting fluids, CSWS requires administration of salt and volume fluid volume. We believe that for differential diagnosis of postoperative hyponatremia, a fluid restriction test takes priority over of fluid loading following neurosurgery. The course of hyponatremia must be carefully monitored and a complete endocrinological workup must be performed to detect the possible presence of hypophyseal deficiencies, particularly hypothyroidism and suprarenal insufficiency.

Novel (60%) and recurrent (40%) androgen receptor gene mutations in a series of 59 patients with a 46,XY disorder of sex development.

BACKGROUND: Androgen receptor (AR) gene mutations are the most frequent cause of 46,XY disorders of sex development (DSD) and are associated with a variety of phenotypes, ranging from phenotypic women [complete androgen insensitivity syndrome (CAIS)] to milder degrees of undervirilization (partial form or PAIS) or men with only infertility (mild form or MAIS). OBJECTIVE: The aim of the study was to characterize the contribution of the AR gene to the molecular cause of 46,XY DSD in a series of Spanish patients. SETTING: We studied a series of 133 index patients with 46,XY DSD in whom gonads were differentiated as testes, with phenotypes including varying degrees of undervirilization, and in whom the AR gene was the first candidate for a molecular analysis. METHODS: The AR gene was sequenced (exons 1 to 8 with intronic flanking regions) in all patients and in family members of 61% of AR-mutated gene patients. RESULTS: AR gene mutations were found in 59 individuals (44.4% of index patients), of whom 46 (78%) were CAIS and 13 (22%) PAIS. Fifty-seven different mutations were found: 21.0% located in exon 1, 15.8% in exons 2 and 3, 57.9% in exons 4-8, and 5.3% intronic. Twenty-three mutations (40.4%) had been previously described and 34 (59.6%) were novel. CONCLUSIONS: AR gene mutation is the most frequent cause of 46,XY DSD, with a clearly higher frequency in the complete phenotype. Mutations spread along the whole coding sequence, including exon 1. This series shows that 60% of mutations detected during the period 2002-2009 were novel.

[Definitive treatment of anal canal carcinoma with radiotherapy: adverse impact of a pre-radiation resection. A retrospective study of 57 patients treated with curative intent]. / Radiothérapie à visée curative du carcinome du canal anal : impact défavorable d'une résection préalable. Etude rétrospective de 57 patients traités en intention curative.

PURPOSE: To describe retrospectively the overall survival, the cancer specific survival and the tumor control in an homogeneous series of patients with epidermoid carcinoma of the anal canal treated with definitive radiotherapy; to assess the impact of brachytherapy, chemotherapy and pre-radiotherapy resection on the risk of recurrence. PATIENTS AND METHODS: From 1997 to 2007, 57 patients (pts) presenting with an epidermoid carcinoma of the anal canal (T1: 14, T2: 33, T3-4: 10, N0: 31, N1: 19, N2: 3, N3: 4, M0: 57) were treated with definitive radiotherapy by the same radiation oncologist. The treatment included an external beam irradiation (EBRT) given to the posterior pelvis (45Gy/25 fractions) and, six weeks later, a boost delivered with interstitial brachytherapy (37/57) or external beam irradiation (20/57). Twelve pts had undergone a surgical resection of the tumour before radiotherapy. A belly board was used for EBRT in 13 pts. A concurrent platinum based chemotherapy was done in 42 pts. The mean follow-up was 57 months. RESULTS: The overall survival rate at 5 years was 89% with a cause specific survival of 96%. Five patients recurred (5-year rate: 12%: four had local relapse (5-year rate: 8%), four had groin recurrence, and distant metastases were seen in two. In univariate analysis, the risk of relapse was higher in patients who had undergone a pre-radiation excision (p=0.018), in those who did not receive chemotherapy (p=0.076) and in those who were irradiated on a belly board (p=0.049). In multivariate analysis, a pre-radiotherapy resection (p=0.084) had an inverse impact on the tumour control reaching the level of statistical significance and the use of a belly board was of marginal influence (p=0.13). CONCLUSION: Radiotherapy and chemoradiation with cisplatine-based chemotherapy cure a vast majority of patients with epidermoid carcinoma of the anal canal. Therapeutic factors that may interfere with the definition of the target volume and the patients' repositioning may decrease the efficacy of radiotherapy. Pre-radiotherapy surgical resection should be avoided.

First-line simplified GEMOX (S-GemOx) versus classical GEMOX in metastatic pancreatic cancer (MPA): results of a GERCOR randomized phase II study.

PURPOSE: GemOx was defined as a D1-D2 schedule, based on preclinical data. In order to improve convenience for patients, we evaluated a simplified D1-D1 GemOx regimen (S-GemOx) in MPA. PATIENTS AND METHODS: Patients (pts) with MPA were 2:1 randomly assigned for first-line treatment to S-GemOx (gemcitabine 1,000 mg/m(2), 100-minute infusion D1 immediately followed by oxaliplatin 100 mg/m(2), 120-minute infusion) or to GemOx (Gem D1 and ox D2). Treatment was repeated in each arm every 2 weeks until disease progression. Stratification was performed on center and PS. RESULTS: Fifty-seven pts were enrolled, S-GemOx = 37 (PS 2: 22%), GemOx = 20 (PS 2: 20%). Populations were well balanced for age (64.9 vs 66.6 years); gender (57 vs 65% male), location of primary tumor (pancreas head: 49 vs 50%), and metastatic sites (liver 76 vs 85%; peritoneum 24 vs 20%; lung 16 vs 10%; lymph nodes 14 vs 15%; other 5 vs 5%). Tumor differentiation significantly differed between the 2 groups (S-GemOx: 8% poorly differentiated vs GemOx: 36%). Response rate was 27% (95% CI: 12-42) in arm S-GemOx and 10% (95% CI: 0-23) in GemOx. Median PFS was 4.0 and 2.5 months in S-GemOx and GemOx, respectively. Median OS was 7.6 and 3.2 months in S-GemOx and GemOx, respectively. Since more cycles were administered in S-GemOx (8.5 [1-29] vs 5.8 [2-12]), grade 3 oxaliplatin-induced neuropathy was higher in S-GemOx [21.6 vs 0%]). CONCLUSIONS: Activity and tolerance of S-GemOx are in the same range as compared to our previous experiences of classical GemOx in metastatic pancreatic cancer. The very bad outcome of patients randomized in GemOx arm could at least be in part explained by the high-rate of poorly differentiated tumors.