Performances of preoperative CT scan to predict the pTN stage for MSI/dMMR localized colon cancers.

BACKGROUND: Neoadjuvant immunotherapy emerges as a promising strategy for patients with localized colon cancer (CC) harboring microsatellite instability/mismatch repair deficiency (MSI/dMMR). The aim of this study is to evaluate the concordance between clinical cTN stage assessed by preoperative computed tomography (CT) scan and pTN stage of MSI/dMMR CC. PATIENTS AND METHODS: Consecutive patients diagnosed for localized MSI/dMMR CC and treated with upfront surgery between 2013 and 2022 in two French centers were eligible. Two independent radiologists, blinded to pathological findings, reviewed all preoperative CT scans and assessed cTN stage, with a third radiologist reviewing discordant cases. Radiological predictive diagnostic accuracy for pT4 and pN+ (N+ = N1 or N2) were calculated. RESULTS: One hundred and thirteen patients were included (right CCs = 79%). CT scan diagnostic performances for pT4 were sensitivity (Se) = 33.3%; specificity (Sp) = 94.0%; positive predictive value (PPV) = 66.7%; and negative predictive value (NPV) = 79.6% and for pN+ were Se = 70.3%; Sp = 59.2%; PPV = 45.6%; and NPV = 80.4%. When pT-pN were combined, 37.5% of tumors identified as cT4 and/or cN+ were actually pT1-3 and pN0, and 23.1% of the pT4 and pN+ population was not identified as such radiologically. CONCLUSION: The ability of preoperative CT scan to predict pT and pN stages is limited for localized MSI/dMMR CCs. Reassessing neoadjuvant strategies' benefit-risk balance in this population is needed.

Vaccination of teenagers in France over a 10-year period (2012-2021).

OBJECTIVES: The objectives were to assess trends over the past 10 years in vaccination coverage rates (VCR) among adolescents in France aged 14-15 years, factors influencing decisions to vaccinate, and mothers' opinions on adolescent vaccination. PATIENTS AND METHODS: The 'Vaccinoscopie' internet survey is completed each year by mothers of adolescents, with questions about vaccinations received by their children, and their attitudes and barriers to vaccination. The 2012 to 2021 surveys were analyzed in this study, including data from 1500 adolescents in 2012 and 1000 adolescents each year from 2013 to 2021. RESULTS: None of the adolescent VCR targets were met, despite significant increases since 2012 for vaccines with the lowest coverage rates and vaccines with high but insufficient coverage i.e., meningococcal C (28.7% to 60.8%), HPV in girls (14.2% to 40.8%), hepatitis B (31.6% to 47.3%) and pertussis (76.3% to 91.0%). Physicians remained the primary source of vaccination information for 90.4% of mothers, and their advice had a real impact on improving VCRs. Adolescents were increasingly involved (40.1%) in decisions about vaccination. Depending on the vaccine, over 80% of mothers currently consider adolescent vaccination as useful or essential. Since 2017, they also feel better informed. CONCLUSIONS: Low and under-target VCRs put adolescents at risk of severe disease, and do not enable herd immunity or reduced transmission to other vulnerable age groups to be accomplished. Healthcare professionals must take every opportunity to check adolescents' vaccination status and recommend catch-up vaccines where applicable. Vaccination in schools should be considered.

Immune checkpoint inhibitors for POLE or POLD1 proofreading-deficient metastatic colorectal cancer.

BACKGROUND: POLE and POLD1 proofreading deficiency (POLE/D1pd) define a rare subtype of ultramutated metastatic colorectal cancer (mCRC; over 100 mut/Mb). Disease-specific data about the activity and efficacy of immune checkpoint inhibitors (ICIs) in POLE/D1pd mCRC are lacking and it is unknown whether outcomes may be different from mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) mCRCs treated with ICIs. PATIENTS AND METHODS: In this global study, we collected 27 patients with mCRC harboring POLE/D1 mutations leading to proofreading deficiency and treated with anti-programmed cell death-ligand 1 alone +/- anti-cytotoxic T-lymphocyte antigen-4 agents. We collected clinicopathological and genomic characteristics, response, and survival outcomes after ICIs of POLE/D1pd mCRC and compared them with a cohort of 610 dMMR/MSI-H mCRC patients treated with ICIs. Further genomic analyses were carried out in an independent cohort of 7241 CRCs to define POLE and POLD1pd molecular profiles and mutational signatures. RESULTS: POLE/D1pd was associated with younger age, male sex, fewer RAS/BRAF driver mutations, and predominance of right-sided colon cancers. Patients with POLE/D1pd mCRC showed a significantly higher overall response rate (ORR) compared to dMMR/MSI-H mCRC (89% versus 54%; P = 0.01). After a median follow-up of 24.9 months (interquartile range: 11.3-43.0 months), patients with POLE/D1pd showed a significantly superior progression-free survival (PFS) compared to dMMR/MSI-H mCRC [hazard ratio (HR) = 0.24, 95% confidence interval (CI) 0.08-0.74, P = 0.01] and superior overall survival (OS) (HR = 0.38, 95% CI 0.12-1.18, P = 0.09). In multivariable analyses including the type of DNA repair defect, POLE/D1pd was associated with significantly improved PFS (HR = 0.17, 95% CI 0.04-0.69, P = 0.013) and OS (HR = 0.24, 95% CI 0.06-0.98, P = 0.047). Molecular profiling showed that POLE/D1pd tumors have higher tumor mutational burden (TMB). Responses were observed in both subtypes and were associated with the intensity of POLE/D1pd signature. CONCLUSIONS: Patients with POLE/D1pd mCRC showed more favorable outcomes compared to dMMR/MSI-H mCRC to treatment with ICIs in terms of tumor response and survival.

Prediction of response to immune checkpoint blockade in patients with metastatic colorectal cancer with microsatellite instability.

BACKGROUND: Mismatch repair-deficient (dMMR) tumors displaying microsatellite instability (MSI) represent a paradigm for the success of immune checkpoint inhibitor (ICI)-based immunotherapy, particularly in patients with metastatic colorectal cancer (mCRC). However, a proportion of patients with dMMR/MSI mCRC exhibit resistance to ICI. Identification of tools predicting MSI mCRC patient response to ICI is required for the design of future strategies further improving this therapy. PATIENTS AND METHODS: We combined high-throughput DNA and RNA sequencing of tumors from 116 patients with MSI mCRC treated with anti-programmed cell death protein 1 ± anti-cytotoxic T-lymphocyte-associated protein 4 of the NIPICOL phase II trial (C1, NCT03350126, discovery set) and the ImmunoMSI prospective cohort (C2, validation set). The DNA/RNA predictors whose status was significantly associated with ICI status of response in C1 were subsequently validated in C2. Primary endpoint was progression-free survival by immune RECIST (iRECIST) (iPFS). RESULTS: Analyses showed no impact of previously suggested DNA/RNA indicators of resistance to ICI, e.g. MSIsensor score, tumor mutational burden, or specific cellular and molecular tumoral contingents. By contrast, iPFS under ICI was shown in C1 and C2 to depend both on a multiplex MSI signature involving the mutations of 19 microsatellites hazard ratio cohort C2 (HRC2) = 3.63; 95% confidence interval (CI) 1.65-7.99; P = 1.4 × 10-3] and the expression of a set of 182 RNA markers with a non-epithelial transforming growth factor beta (TGFB)-related desmoplastic orientation (HRC2 = 1.75; 95% CI 1.03-2.98; P = 0.035). Both DNA and RNA signatures were independently predictive of iPFS. CONCLUSIONS: iPFS in patients with MSI mCRC can be predicted by simply analyzing the mutational status of DNA microsatellite-containing genes in epithelial tumor cells together with non-epithelial TGFB-related desmoplastic RNA markers.

Efficacy of immunotherapy in mismatch repair-deficient advanced colorectal cancer in routine clinical practice. An AGEO study.

BACKGROUND: Immunotherapy demonstrated remarkable efficacy in metastatic colorectal cancers (mCRCs) with mismatch repair deficiency (MMRd)/microsatellite instability (MSI). However, data regarding efficacy and safety of immunotherapy in the routine clinical practice are scarce. PATIENTS AND METHODS: This is a retrospective, multicenter study aiming to evaluate efficacy and safety of immunotherapy in routine clinical practice and to identify predictive markers for long-term benefit. Long-term benefit was defined as progression-free survival (PFS) exceeding 24 months. All patients who received immunotherapy for an MMRd/MSI mCRC were included. Patients who received immunotherapy in combination with another known effective therapeutic class agent (chemotherapy or tailored therapy) were excluded. RESULTS: Overall, 284 patients across 19 tertiary cancer centers were included. After a median follow-up of 26.8 months, the median overall survival (mOS) was 65.4 months [95% confidence interval (CI) 53.8 months-not reached (NR)] and the median PFS (mPFS) was 37.9 months (95% CI 30.9 months-NR). There was no difference in terms of efficacy or toxicity between patients treated in the real-world or as part of a clinical trial. Overall, 46.6% of patients had long-term benefit. Independent markers associated with long-term benefit were Eastern Cooperative Oncology Group-performance status (ECOG-PS) 0 (P = 0.025) and absence of peritoneal metastases (P = 0.009). CONCLUSIONS: Our study confirms the efficacy and safety of immunotherapy in patients with advanced MMRd/MSI CRC in the routine clinical practice. ECOG-PS score and absence of peritoneal metastases provide simple markers that could help identify patients who benefit the most from this treatment.

BRCA carriers after risk-reducing bilateral salpingo-oophorectomy: menopausal hormone therapy knowledge gaps, and the impact of physicians' recommendations.

OBJECTIVE: Female carriers of BRCA1/2 gene mutations are at an increased lifetime risk for breast and ovarian cancers. They are recommended to undergo risk-reducing surgery, including bilateral salpingo-oophorectomy (RR-BSO), upon completion of childbearing. RR-BSO surgery decreases morbidity and mortality but results in early menopause. Menopausal hormone therapy (MHT) is under-utilized despite being shown as safe for carriers. We aim to evaluate the factors associated with decision-making regarding MHT use following RR-BSO in healthy BRCA mutation carriers. METHODS: Female carriers aged <50 years who underwent RR-BSO and were followed in a multidisciplinary clinic completed online multiple-choice and free-text questionnaires. RESULTS: A total of 142 women met the inclusion criteria and filled the questionnaire: 83 were MHT users and 59 were non-users. MHT users underwent RR-BSO earlier than non-users (40.82 ± 3.91 vs. 42.88 ± 4.34; p < 0.0001). MHT usage was positively associated with MHT explanation (odds ratio 4.318, 95% confidence interval [CI] [1.341-13.902], p = 0.014), and knowledge regarding the safety of MHT and its effects on general health (odds ratio 2.001, 95% CI [1.443-2.774], p < 0.0001). MHT users and non-users retrospectively evaluated their comprehension of RR-BSO consequences as significantly lower than before surgery (p < 0.001). CONCLUSION: Post-RR-BSO outcomes, including the effects on women's quality of life and its possible mitigation through MHT use, need to be addressed pre surgery by healthcare providers.

Measuring the melting curve of iron at super-Earth core conditions.

The discovery of more than 4500 extrasolar planets has created a need for modeling their interior structure and dynamics. Given the prominence of iron in planetary interiors, we require accurate and precise physical properties at extreme pressure and temperature. A first-order property of iron is its melting point, which is still debated for the conditions of Earth's interior. We used high-energy lasers at the National Ignition Facility and in situ x-ray diffraction to determine the melting point of iron up to 1000 gigapascals, three times the pressure of Earth's inner core. We used this melting curve to determine the length of dynamo action during core solidification to the hexagonal close-packed (hcp) structure. We find that terrestrial exoplanets with four to six times Earth's mass have the longest dynamos, which provide important shielding against cosmic radiation.

Long-term endoscopic follow-up after sleeve gastrectomy.

BACKGROUND: Endoscopic follow-up after sleeve gastrectomy (SG) sometime reveals worrisome findings as the presence of major digestive lesions such as esophagitis, Barrett's esophagus (BE), and also esophageal cancer. OBJECTIVES: The aim of this study was to investigate the frequency and severity of esophageal and gastric lesions after SG. METHODS: Our team collected the results of esogastric endoscopies performed on patients who underwent SG up to five years before in our hospital, from April 2010 to August 2014. Summons were sent by mail to all patients operated on between those dates. The results were collected from January 2018 to June 2019. RESULTS: Of the 765 patients who underwent SG up to five years before, only 78 (10.2%) agreed to undergo an upper digestive endoscopy. The average age before surgery was 51 years (range: 25-70 years). The mean preoperative body mass index (BMI) was 44.2±4.6kg/m2. For 12 out of these 78 patients (15.4%) it was revisional surgery: 9 SG after gastric banding, and 3 revisional SG (Re-SG). With an average follow-up of 6.3±0.8 years, the endoscopic results of the 78 patients were found to be normal in 31 cases (39.7%): gastritis was found in 28 patients (35.9%), severe grade C or D esophagitis was found in 15 cases (19.2%), hiatal hernia in 18 cases (23.1%), a benign gastric polyp in 2 cases (2.6%). Of the 28 patients with gastritis, HelicobacterPylori was detected in 8 cases (28.6%). No cancer was diagnosed, and BE after SG was found in only one case (1.3%) (normal before surgery). Six of 15 patients with esophagitis (40%) had reflux symptoms. Fourteen of these patients (93.3%) developed de novo esophagitis. CONCLUSION: Only 10.2% of operated patients agreed to a long-term esogastric endoscopy. The frequency and severity of endoscopic anomalies observed with an average follow-up of more than 6 years pleads for a policy of systematic upper endoscopies of long-term control after SG.

Combining tumor deposits with the number of lymph node metastases to improve the prognostic accuracy in stage III colon cancer: a post hoc analysis of the CALGB/SWOG 80702 phase III study (Alliance)☆.

BACKGROUND: In colon cancer, tumor deposits (TD) are considered in assigning prognosis and staging only in the absence of lymph node metastasis (i.e. stage III pN1c tumors). We aimed to evaluate the prognostic value of the presence and the number of TD in patients with stage III, node-positive colon cancer. PATIENTS AND METHODS: All participants from the CALGB/SWOG 80702 phase III trial were included in this post hoc analysis. Pathology reports were reviewed for the presence and the number of TD, lymphovascular and perineural invasion. Associations with disease-free survival (DFS) and overall survival (OS) were evaluated by multivariable Cox models adjusting for sex, treatment arm, T-stage, N-stage, lymphovascular invasion, perineural invasion and lymph node ratio. RESULTS: Overall, 2028 patients were included with 524 (26%) TD-positive and 1504 (74%) TD-negative tumors. Of the TD-positive patients, 80 (15.4%) were node negative (i.e. pN1c), 239 (46.1%) were pN1a/b (<4 positive lymph nodes) and 200 (38.5%) were pN2 (≥4 positive lymph nodes). The presence of TD was associated with poorer DFS [adjusted hazard ratio (aHR) = 1.63, 95% CI 1.33-1.98] and OS (aHR = 1.59, 95% CI 1.24-2.04). The negative effect of TD was observed for both pN1a/b and pN2 groups. Among TD-positive patients, the number of TD had a linear negative effect on DFS and OS. Combining TD and the number of lymph node metastases, 104 of 1470 (7.1%) pN1 patients were re-staged as pN2, with worse outcomes than patients confirmed as pN1 (3-year DFS rate: 65.4% versus 80.5%, P = 0.0003; 5-year OS rate: 87.9% versus 69.1%, P = <0.0001). DFS was not different between patients re-staged as pN2 and those initially staged as pN2 (3-year DFS rate: 65.4% versus 62.3%, P = 0.4895). CONCLUSION: Combining the number of TD and the number of lymph node metastases improved the prognostication accuracy of tumor-node-metastasis (TNM) staging.

Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer.

BACKGROUND: DNA mismatch repair system deficiency (dMMR) is found in 15% of colorectal cancers (CRCs). Two methods are used to determine dMMR, immunohistochemistry (IHC) of MMR proteins and molecular testing of microsatellite instability (MSI). Only studies with a low number of patients have reported rates of discordance between these two methods, ranging from 1% to 10%. MATERIALS AND METHODS: Overall, 3228 consecutive patients with CRCs from two centers were included. Molecular testing was carried out using the Pentaplex panel and IHC evaluated four (MLH1, MSH2, MSH6, and PMS2; cohort 1; n = 1085) or two MMR proteins (MLH1 and MSH2; cohort 2; n = 2143). The primary endpoint was the rate of discordance between MSI and MMR IHC tests. RESULTS: Fifty-one discordant cases (1.6%) were initially observed. Twenty-nine out of 51 discordant cases were related to IHC misclassifications. In cohort 1, after re-reading IHC and/or carrying out new IHC, 16 discordant cases were reclassified as nondiscordant. In cohort 2, after the addition of MSH6/PMS2 IHC and re-examination, 13 were reclassified as nondiscordant. In addition, 10 misclassifications of molecular tests were identified. Finally, only 12 discordant cases (0.4%) remained: 5 were proficient MMR/MSI and 7 were dMMR/microsatellite stable. CONCLUSIONS: Our study confirmed the high degree of concordance between MSI and MMR IHC tests. Discordant cases must be reviewed, and if needed, tests must be repeated and analyzed by an expert team.

Reconciliation of Experiments and Theory on Transport Properties of Iron and the Geodynamo.

We measure the electrical resistivity of hcp iron up to ∼170 GPa and ∼3000 K using a four-probe van der Pauw method coupled with homogeneous flattop laser heating in a DAC, and compute its electrical and thermal conductivity by first-principles molecular dynamics including electron-phonon and electron-electron scattering. We find that the measured resistivity of hcp iron increases almost linearly with temperature, and is consistent with our computations. The results constrain the resistivity and thermal conductivity of hcp iron to ∼80±5 µΩ cm and ∼100±10 W m^{-1} K^{-1}, respectively, at conditions near the core-mantle boundary. Our results indicate an adiabatic heat flow of ∼10±1 TW out of the core, supporting a present-day geodynamo driven by thermal and compositional convection.

Molecular characterisation of methicillin-resistant Staphylococcus aureus from chronically colonised cystic fibrosis paediatric patients in Brazil.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) infection in cystic fibrosis (CF) patients has been associated with a more rapid decline in lung function, increased hospitalisation and mortality. The aim of this study was to evaluate the clonal relationships among 116 MRSA isolates from 12 chronically colonised CF pediatric patients over a 6-year period in a Rio de Janeiro CF specialist centre. Isolates were characterised by antimicrobial resistance, SCCmec type, presence of Panton-Valentine Leukocidin (PVL) genes and grouped according to DNA macrorestriction profile by pulsed-field gel electrophoresis (PFGE) and spa gene type. High resistance rates were detected for erythromycin (78%) and ciprofloxacin (50%) and SCCmec IV was the most common type (72.4%). Only 8.6% of isolates were PVL positive. High genetic diversity was evident by PFGE (39 pulsotypes) and of nine that were identified spa types, t002 (53.1%) and t539 (14.8%) were the most prevalent. We conclude that the observed homogeneity of spa types within patients over the study period demonstrates the persistence of such strain lineages throughout the course of chronic lung infection.

Guidelines of the French Society of Otorhinolaryngology (SFORL): Nonsteroidal anti-inflammatory drugs (NSAIDs) and pediatric ENT infections. Short version.

OBJECTIVES: To present the guidelines of the French Society of Otolaryngology-Head and Neck Surgery concerning the use of non-steroidal anti-inflammatory drugs (NSAIDs) in pediatric ENT infections. METHODS: Based on a critical analysis of the medical literature up to November 2016, a multidisciplinary workgroup of 11 practitioners wrote clinical practice guidelines. Levels of evidence were classified according to the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) system: GRADE A, B, C or "expert opinion". The first version of the text was reworked by the workgroup following comments by the 22 members of the reading group. RESULTS: The main recommendations are: NSAIDs are indicated at analgesic doses (e.g. 20-30 mg/kg/day for ibuprofen) in combination with paracetamol (acetaminophen) in uncomplicated pediatric ENT infections (acute otitis media, tonsillitis, upper respiratory infections, and maxillary sinusitis) if: o pain is of medium intensity (visual analogue scale (VAS) score 3-5 or "Evaluation Enfant Douleur" (EVENDOL) child pain score 4-7) and insufficiently relieved by first-line paracetamol (residual VAS≥3 or EVENDOL≥4); o pain is moderate to intense (VAS 5-7 or EVENDOL 7-10). When combined, paracetamol and ibuprofen are ideally taken simultaneously every 6h. It is recommended: (1) o not to prescribe NSAIDs in severe or complicated pediatric ENT infections; (2) o to suspend NSAIDs treatment in case of unusual clinical presentation of the infection (duration or symptoms); (3) o not to prescribe NSAIDs for more than 72h.

Prospective, multicentric, comparative study between sleeve gastrectomy and Roux-en-Y gastric bypass, 277 patients, 3 years follow-up.

BACKGROUND: Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en Y gastric bypass (LRYGB) are commonly performed, but few studies have shown superiority of one strategy over the other. OBJECTIVE: Simultaneously compare LSG and LRYGB in terms of weight loss and morbimortality over a 36-month follow-up period. SETTING: University hospital and bariatric surgery centers, France. METHODS: Prospective, comparative study between LSG and RYGBP. The primary endpoint of this study was a joint hypothesis during the 36-month follow-up: the first primary outcome pertained to the frequency of patients with an excess weight loss (EWL) greater than 50% (% EWL>50%) after LSG or RYGB; the second primary outcome was defined as a composite endpoint of at least one major complication. Secondary objectives were regression of comorbidities and improvement in quality of life. RESULTS: Two hundred and seventy-seven patients were included (91 RYGBP, 186 LSG). The mean age was 41.1±11.1 years, and average preoperative body mass index of 45.3±5.5kg/m2. After 36months, the %EWL>50% was not inferior in the case of LSG (82.2%) relative to LRYGB (82.1%); while major complications rates were significantly higher in LRYGB (15.4%) vs. LSG (5.4%, P=0.005). After 36months, all secondary objectives were comparable between groups while only gastroesophageal reflux disease (GERD) increased in LSG group and decreased in LRYGB group. CONCLUSIONS: LSG was found non-inferior to LRYGB with respect to weight loss and was associated with lower risk of major complications during a 3-year follow-up. But GERD increased in LSG group and decreased in LRYGB group.

Novel WWOX deleterious variants cause early infantile epileptic encephalopathy, severe developmental delay and dysmorphism among Yemenite Jews.

The human WW Domain Containing Oxidoreductase (WWOX) gene was originally described as a tumor suppressor gene. However, recent reports have demonstrated its cardinal role in the pathogenesis of central nervous systems disorders such as epileptic encephalopathy, intellectual disability, and spinocerebellar ataxia. We report on six patients from three unrelated families of full or partial Yemenite Jewish ancestry exhibiting early infantile epileptic encephalopathy and profound developmental delay. Importantly, four patients demonstrated facial dysmorphism. Exome sequencing revealed that four of the patients were homozygous for a novel WWOX c.517-2A > G splice-site variant and two were compound heterozygous for this variant and a novel c.689A > C, p.Gln230Pro missense variant. Complementary DNA sequencing demonstrated that the WWOX c.517-2A > G splice-site variant causes skipping of exon six. A carrier rate of 1:177 was found among Yemenite Jews. We provide the first detailed description of patients harboring a splice-site variant in the WWOX gene and propose that the clinical synopsis of WWOX related epileptic encephalopathy should be broadened to include facial dysmorphism. The increased frequency of the c.517-2A > G splice-site variant among Yemenite Jews coupled with the severity of the phenotype makes it a candidate for inclusion in expanded preconception screening programs.

Determinants of the interindividual variability in serum cytidine deaminase activity of patients with solid tumours.

AIMS: Cytidine deaminase (CDA) activity in cancer patients' serum has been proposed as a predictive biomarker for efficacy and toxicity of nucleoside analogues. However, discrepant results about its predictive value have been reported due to the high interindividual variability in CDA activity. This study aimed at identifying determinants of this interindividual variability. METHODS: From December 2014 to November 2015, 183 patients were prospectively included. Serum CDA activity, biological and clinical characteristics as well as five common single nucleotide polymorphisms (SNPs) in the CDA gene (c.-451C > T, c.-92A > G, c.-33_-31delC, c.79A > C, c.435 T > C) were analysed. Associations between clinical characteristics, pharmacogenetic variants and CDA activity were univariately tested. P < 0.1-candidate variables were analysed through a multivariate analysis. The association between CDA activity and toxicity was assessed for the 56 gemcitabine-treated patients. Intraindividual variability in CDA activity was explored in six pancreatic cancer patients treated with gemcitabine. RESULTS: Median CDA activity was 3.97 U mg-1 (range 1.53-15.49 U mg-1 ). A univariate analysis showed that CDA activity was statistically associated with Eastern Cooperative Oncology Group performance status, mild or severe malnutrition, inflammatory syndrome, leucocyte count, neutrophil count, albumin, C-reactive protein and -c.-33_-31delC single nucleotide polymorphism. A multivariate analysis identified that only neutrophil count (P < 0.0001) and severe malnutrition (P = 0.0278) were independently associated with CDA activity. Low CDA activity (<2 U mg-1 ) was not statistically associated with severe gemcitabine-related toxicities (P = 0.16). A decrease in CDA activity was observed during the longitudinal follow-up of six pancreatic cancer patients treated with gemcitabine (P = 0.03). CONCLUSIONS: These results suggest that neutrophil count and malnutrition should be considered for the interpretation of pretherapeutic CDA activity.