Hereditary hypotransferrinemia can lead to elevated transferrin saturation and, when associated to HFE or HAMP mutations, to iron overload.

As our understanding of iron metabolism improves through the more accurate description of iron metabolism actors, new causes of iron overload are identified. We, here, report 16 cases of hereditary hypotransferrinemia related to 4 previously undescribed TF (transferrin) mutations (p.Val221Gly, p.Arg609Trp, p.Glu370Lys, p.Tyr533X and p.Cys421Arg). We show that, besides increasing serum transferrin saturation without iron overload, hypotransferrinemia, when associated to mutations in HFE or HAMP or to acquired factors, can lead to clinically relevant iron burden. These cases emphasize the usefulness of serum transferrin determination in the diagnostic evaluation of iron overload and the importance for clinicians to be aware of this syndrome.

Nomograms to predict late urinary toxicity after prostate cancer radiotherapy.

OBJECTIVE: To analyze late urinary toxicity after prostate cancer radiotherapy (RT): symptom description and identification of patient characteristics or treatment parameters allowing for the generation of nomograms. METHODS: Nine hundred and sixty-five patients underwent RT in seventeen French centers for localized prostate cancer. Median total dose was 70 Gy (range, 65-80 Gy), using different fractionations (2 or 2.5 Gy/day) and techniques. Late urinary toxicity and the corresponding symptoms (urinary frequency, incontinence, dysuria/decreased stream, and hematuria) were prospectively assessed in half of the patients using the LENT-SOMA classification. Univariate and multivariate Cox regression models addressed patient or treatment-related predictors of late urinary toxicity (≥grade 2). Nomograms were built up, and their performance was assessed. RESULTS: The median follow-up was 61 months. The 5-year (≥grade 2) global urinary toxicity, urinary frequency, hematuria, dysuria, and urinary incontinence rates were 15, 10, 5, 3 and 1 %, respectively. The 5-year (≥grade 3) urinary toxicity rate was 3 %. The following parameters significantly increased the 5-year risk of global urinary toxicity (≥grade 2): anticoagulant treatment (RR = 2.35), total dose (RR = 1.09), and age (RR = 1.06). Urinary frequency was increased by the total dose (RR = 1.07) and diabetes (RR = 4). Hematuria was increased by anticoagulant treatment (RR = 2.9). Dysuria was increased by the total dose (RR = 1.1). Corresponding nomograms and their calibration plots were generated. Nomogram performance should be validated with external data. CONCLUSIONS: The first nomograms to predict late urinary toxicity but also specific urinary symptoms after prostate RT were generated, contributing to prostate cancer treatment decision.

Interference With VIP to Distinguish Between Real and False VIPoma: National Study From the French Endocrine Tumors Group.

Background: Vasoactive intestinal peptide (VIP)-secreting tumors (VIPomas) are digestive neuroendocrine tumors in which the hormonal secretion is life-threatening. Biological confirmation is obtained by demonstrating an elevation in plasma VIP, usually using radioimmunoassay (RIA). In some cases, analytical interference is suspected. We developed 3 different techniques to detect interference in VIP RIA. Methods: Three techniques were used: RIA after Sephadex column chromatography separation, RIA after polyethylene glycol precipitation, and 125I-labeled VIP binding test. We included patients with suspicion of false positive VIP (FPV) elevation. We then compared results with those of a group of "real," proven VIPoma (RV). Results: A total of 15 patients with FPV elevation and 9 RV patients were included. Interference was detected in all FPV patients vs none in RV. Clinical and biochemical parameters did not differ between FPV and RV patients, but VIP concentration in RIA was significantly higher in FPV patients than in RV patients (228 pmol/L vs 66 pmol/L, P = .038). Using a 125I-labeled VIP binding test, median proportion of radioactivity in the pellet was significantly higher in FPV than in RV patients (53% vs 13%, P < .0001). A 20.5% threshold presented excellent performances (sensitivity 100% [79.6-100], specificity 100% [70.1-100]). Conclusion: We developed 3 different laboratory techniques to reveal interference in RIA VIP assays. The diagnostic performance of all 3 was excellent. These techniques must be employed in cases of discordance between VIP elevation and clinical presentation.

Nomogram to predict rectal toxicity following prostate cancer radiotherapy.

BACKGROUND: To identify predictors of acute and late rectal toxicity following prostate cancer radiotherapy (RT), while integrating the potential impact of RT technique, dose escalation, and moderate hypofractionation, thus enabling us to generate a nomogram for individual prediction. METHODS: In total, 972 patients underwent RT for localized prostate cancer, to a total dose of 70 Gy or 80 Gy, using two different fractionations (2 Gy or 2.5 Gy/day), by means of several RT techniques (3D conformal RT [3DCRT], intensity-modulated RT [IMRT], or image-guided RT [IGRT]). Multivariate analyses were performed to identify predictors of acute and late rectal toxicity. A nomogram was generated based on the logistic regression model used to predict the 3-year rectal toxicity risk, with its accuracy assessed by dividing the cohort into training and validation subgroups. RESULTS: Mean follow-up for the entire cohort was 62 months, ranging from 6 to 235. The rate of acute Grade ≥2 rectal toxicity was 22.2%, decreasing when combining IMRT and IGRT, compared to 3DCRT (RR = 0.4, 95%CI: 0.3-0.6, p<0.01). The 5-year Grade ≥2 risks for rectal bleeding, urgency/tenesmus, diarrhea, and fecal incontinence were 9.9%, 4.5%, 2.8%, and 0.4%, respectively. The 3-year Grade ≥2 risk for overall rectal toxicity increased with total dose (p<0.01, RR = 1.1, 95%CI: 1.0-1.1) and dose per fraction (2Gy vs. 2.5Gy) (p = 0.03, RR = 3.3, 95%CI: 1.1-10.0), and decreased when combining IMRT and IGRT (RR = 0.50, 95% CI: 0.3-0.8, p<0.01). Based on these three parameters, a nomogram was generated. CONCLUSIONS: Dose escalation and moderate hypofractionation increase late rectal toxicity. IMRT combined with IGRT markedly decreases acute and late rectal toxicity. Performing combined IMRT and IGRT can thus be envisaged for dose escalation and moderate hypofractionation. Our nomogram predicts the 3-year rectal toxicity risk by integrating total dose, fraction dose, and RT technique.

Azathioprine for refractory ulcerative proctitis: A retrospective multicenter study.

BACKGROUND: Efficacy of azathioprine (AZA) in refractory ulcerative proctitis (UP) is unknown. METHODS: All patients treated with AZA for refractory UP in three referral centers between 2002 and 2012 were included. "Treatment success" in the long-term was defined as the absence of colectomy during follow-up, no need for anti-TNF during follow-up, no ongoing systemic steroids use, no adverse event leading to AZA withdrawal, and clinically quiescent disease at last follow-up. RESULTS: Of the 1279 adult patients with ulcerative colitis, 25 patients were treated with AZA for refractory UP (median disease duration 4.9 years). Of these, 4 had no short-term clinical assessment. Of the remaining 21, 4 were primary non responders to AZA, 7 discontinued AZA for adverse events and 10 showed clinical improvement. At the long-term assessment at last follow up after a median of 46 months, 5 patients had treatment success and were still on AZA treatment, the remaining 20 were treatment failures. Of these, 5 discontinued AZA for adverse events and 15 were treated with infliximab (clinical response in 11 patients, primary non-response in one patient, and 3 underwent colectomy). CONCLUSION: AZA may be efficacious in maintaining clinical response in one-fifth of patients with refractory UP in a real-life setting.

On feature extraction and classification in prostate cancer radiotherapy using tensor decompositions.

External beam radiotherapy is commonly prescribed for prostate cancer. Although new radiation techniques allow high doses to be delivered to the target, the surrounding healthy organs (rectum and bladder) may suffer from irradiation, which might produce undesirable side-effects. Hence, the understanding of the complex toxicity dose-volume effect relationships is crucial to adapt the treatment, thereby decreasing the risk of toxicity. In this paper, we introduce a novel method to classify patients at risk of presenting rectal bleeding based on a Deterministic Multi-way Analysis (DMA) of three-dimensional planned dose distributions across a population. After a non-rigid spatial alignment of the anatomies applied to the dose distributions, the proposed method seeks for two bases of vectors representing bleeding and non bleeding patients by using the Canonical Polyadic (CP) decomposition of two fourth order arrays of the planned doses. A patient is then classified according to its distance to the subspaces spanned by both bases. A total of 99 patients treated for prostate cancer were used to analyze and test the performance of the proposed approach, named CP-DMA, in a leave-one-out cross validation scheme. Results were compared with supervised (linear discriminant analysis, support vector machine, K-means, K-nearest neighbor) and unsupervised (recent principal component analysis-based algorithm, and multidimensional classification method) approaches based on the registered dose distribution. Moreover, CP-DMA was also compared with the Normal Tissue Complication Probability (NTCP) model. The CP-DMA method allowed rectal bleeding patients to be classified with good specificity and sensitivity values, outperforming the classical approaches.