A new mobile self-dispensing and administering system for 18F-FDG: evaluation of operator dose reduction.

PURPOSE: Recently new mobile systems for dispensing positron emitters have been produced, designed to guarantee dispensing cycles in an aseptic environment. The aim of the present work was to assess the advantage of one of these systems in radiation protection of operators in clinical settings. METHODS: Recently, in our centre the new self-dispensing system named KARL100 by Tema Sinergie was adopted for 18F-FDG radiopharmaceuticals. The system is associated with an automatic Rad-inject infuser. The system that was previously used was a fixed isolator NMC DSI (Tema Sinergie), equipped with a µDDS-An activity fractioning system, together with a pneumatic post for the syringe delivery. The dosimetric evaluations on both systems were carried out through environmental measurements with an ionisation chamber and with the use of personal dosimeters. RESULTS: The operations of preparation and administration of 18F-FDG dose to the patient, with the use of Karl100 + RadInject, involve exposures much lower than those obtained by the fixed isolator. The average body exposure of the technician was reduced by 31%, and for the physician by 77%. On the extremities, the equivalent dose to the hands of the technician was reduced by 78%, and for the physician by 96%. Also the additional dosimeters worn by the technician confirmed the estimated environmental assessments. CONCLUSIONS: The exposures of the working personnel were significantly reduced with the introduction of the new KARL100 system.

Fifteen different 18F-FDG PET/CT qualitative and quantitative parameters investigated as pathological response predictors of locally advanced rectal cancer treated by neoadjuvant chemoradiation therapy.

PURPOSE: The aim of this study was to correlate qualitative visual response and various PET quantification factors with the tumour regression grade (TRG) classification of pathological response to neoadjuvant chemoradiotherapy (CRT) proposed by Mandard. METHODS: Included in this retrospective study were 69 consecutive patients with locally advanced rectal cancer (LARC). FDG PET/CT scans were performed at staging and after CRT (mean 6.7 weeks). Tumour SUVmax and its related arithmetic and percentage decrease (response index, RI) were calculated. Qualitative analysis was performed by visual response assessment (VRA), PERCIST 1.0 and response cut-off classification based on a new definition of residual disease. Metabolic tumour volume (MTV) was calculated using a 40 % SUVmax threshold, and the total lesion glycolysis (TLG) both before and after CRT and their arithmetic and percentage change were also calculated. We split the patients into responders (TRG 1 or 2) and nonresponders (TRG 3-5). RESULTS: SUVmax MTV and TLG after CRT, RI, ΔMTV% and ΔTLG% parameters were significantly correlated with pathological treatment response (p < 0.01) with a ROC curve cut-off values of 5.1, 2.1 cm(3), 23.4 cm(3), 61.8 %, 81.4 % and 94.2 %, respectively. SUVmax after CRT had the highest ROC AUC (0.846), with a sensitivity of 86 % and a specificity of 80 %. VRA and response cut-off classification were also significantly predictive of TRG response (VRA with the best accuracy: sensitivity 86 % and specificity 55 %). In contrast, assessment using PERCIST was not significantly correlated with TRG. CONCLUSION: FDG PET/CT can accurately stratify patients with LARC preoperatively, independently of the method chosen to interpret the images. Among many PET parameters, some of which are not immediately obtainable, the most commonly used in clinical practice (SUVmax after CRT and VRA) showed the best accuracy in predicting TRG.

Post-Vasectomy Semen Analysis: Optimizing Laboratory Procedures and Test Interpretation through a Clinical Audit and Global Survey of Practices.

PURPOSE: The success of vasectomy is determined by the outcome of a post-vasectomy semen analysis (PVSA). This article describes a step-by-step procedure to perform PVSA accurately, report data from patients who underwent post vasectomy semen analysis between 2015 and 2021 experience, along with results from an international online survey on clinical practice. MATERIALS AND METHODS: We present a detailed step-by-step protocol for performing and interpretating PVSA testing, along with recommendations for proficiency testing, competency assessment for performing PVSA, and clinical and laboratory scenarios. Moreover, we conducted an analysis of 1,114 PVSA performed at the Cleveland Clinic's Andrology Laboratory and an online survey to understand clinician responses to the PVSA results in various countries. RESULTS: Results from our clinical experience showed that 92.1% of patients passed PVSA, with 7.9% being further tested. A total of 78 experts from 19 countries participated in the survey, and the majority reported to use time from vasectomy rather than the number of ejaculations as criterion to request PVSA. A high percentage of responders reported permitting unprotected intercourse only if PVSA samples show azoospermia while, in the presence of few non-motile sperm, the majority of responders suggested using alternative contraception, followed by another PVSA. In the presence of motile sperm, the majority of participants asked for further PVSA testing. Repeat vasectomy was mainly recommended if motile sperm were observed after multiple PVSA's. A large percentage reported to recommend a second PVSA due to the possibility of legal actions. CONCLUSIONS: Our results highlighted varying clinical practices around the globe, with controversy over the significance of non-motile sperm in the PVSA sample. Our data suggest that less stringent AUA guidelines would help improve test compliance. A large longitudinal multi-center study would clarify various doubts related to timing and interpretation of PVSA and would also help us to understand, and perhaps predict, recanalization and the potential for future failure of a vasectomy.

Polymorphisms of estrogen receptors alpha and beta in idiopathic, infertile Brazilian men: a case-control study.

Estrogen plays an important role in the human reproductive system and its action is mediated mainly by two specific receptors: α (ERα) and ß (ERß). There are polymorphic variants in both ER genes, and studies showed their association with reproductive outcomes. We aimed to determine the distribution of ERα and ERß gene polymorphisms in idiopathic, infertile Brazilian patients in a case-control study comprising 187 idiopathic, infertile Brazilian men with nonobstructive azoospermia (NOA, n = 78) or severe oligozoospermia (SO, n = 109) and 216 fertile men. Detection of ERα (PvuII and XbaI) and ERß (AluI and RsaI) gene polymorphisms were performed using TaqMan PCR. The results were analyzed statically, and a P-value < 0.05 was considered significant. Single-marker analysis revealed that neither PvuII nor XbaI polymorphisms of the ERα gene were associated either with NOA group (P = 0.662 and P = 0.527, respectively) or SO group (P = 0.777 and P = 1.0, respectively). Regarding ERß polymorphisms, no statistical difference was observed between the AluI polymorphism and NOA group compared to controls (P = 1.0) or between SO group and controls (P = 0.423). We found similar results with the RsaI polymorphism. Statistical analysis did not reveal a difference between NOA (P = 0.740) and SO (P = 0.920) groups compared to controls. Combined genotypes of ERα and ERß polymorphisms did not identify a haplotype associated with idiopathic infertility. Thus, in the Brazilian population, genetic variations in both estrogen receptors alpha (PvuII and XbaI) and beta (AluI and RsaI) were not relevant to idiopathic infertility.

Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service.

PURPOSE: To determine the frequency of genetic alterations in a population of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia. MATERIALS AND METHODS: Retrospective study of a group of 143 infertile men with severe oligozoospermia or non-obstructive azoospermia from the Andrology Outpatient Clinic of the Human Reproduction Service at the ABC School of Medicine. Of these patients, 100 had severe oligozoospermia, and 43 non-obstructive azoospermia. All patients underwent a genetic study which included karyotype analysis and Y-microdeletion investigation. RESULTS: Genetic abnormalities were found in 18.8% of the studied patients. Chromosomal abnormalities were found in 6.2% of the patients, being more prevalent in the azoospermia group (11.6%) than in the oligozoospermia group (4%). Chromosomal variants were found in 8.3%, and Y-chromosome microdeletions in 4.2% of patients. CONCLUSION: The high frequency of genetic alterations (18.8%) in our series justified performing a genetic investigation in a population with idiopathic infertility, as results may help determine the prognosis, as well as the choice of an assisted reproduction technique. Moreover, a genetic investigation could minimize the risk of transmitting genetic abnormalities to future generations such as genetic male infertility, mental retardation, genital ambiguity and/or birth defects.

Tissue and sperm handling before assisted reproductive technology (ART): A systematic review.

OBJECTIVE: : To explore the medical literature on techniques of tissue and sperm handling after surgical retrieval for intracytoplasmic sperm injection (ICSI). METHODS: : A search was performed in PubMed and Google Scholar databases, according to a modified Preferred Reporting Items for Systemic Reviews and Meta-Analyses (PRISMA) guideline, considering the studies investigating tissue handling and sperm selection techniques for ICSI. RESULTS: : Overall, 42 articles were included in this study, investigating sample handling, methods for sperm selection, and the use of chemical compounds to improve sperm motility and fertilisation rates. CONCLUSION: : The ideal sperm handling method should provide a high sperm count, high vitality and appropriate sperm function, without side-effects. In this review the most common and useful techniques are described and the best combination strategies discussed in clinical scenarios.

Dramatic Impact of Centralization and a Multidisciplinary Bladder Cancer Program in Reducing Mortality: The CABEM Project.

PURPOSE: Muscle-invasive bladder cancer (MIBC) is an aggressive disease with a complex treatment. In Brazil, as in most developing countries, data are scarce, but mortality seems exceedingly high. We have created a centralization program involving a multidisciplinary clinic in a region comprising seven municipalities. The aim of this study is to evaluate the impact of a multidisciplinary clinic and a centralization-of-care program (CABEM program) on MIBC treatment in Brazil. PATIENTS AND METHODS: A total of 116 consecutive patients were evaluated. In group 1, 58 patients treated for MIBC before establishing a bladder cancer program from 2011 to 2017 were retrospectively evaluated. Group 2 represented 58 patients treated for MIBC after the implementation of the CABEM centralization program. Age, sex, staging, comorbidity indexes, mortality rates, type of treatment, and perioperative outcomes were compared. RESULTS: Patients from group 2 versus 1 were older (68 v 64.2 years, P = .02) with a higher body mass index (25.5 v 22.6 kg/m2, P = .017) and had more comorbidities according to both age-adjusted Charlson Comorbidity Index (4.2 v 2.8, P = .0007) and Isbarn index (60.6 v 43.9, P = .0027). Radical cystectomy (RC) was the only treatment modality for patients in group 1, whereas in group 2, there were 31 (53%) RC; three (5%) partial cystectomies; seven (12%) trimodal therapies; 13 (22%) palliative chemotherapies; and three (5%) exclusive transurethral resections of the bladder tumor. No patient in group 1 received neoadjuvant chemotherapy, whereas it was offered to 69% of patients treated with RC. Ninety-day mortality rates were 34.5% versus 5% for groups 1 versus 2 (P < .002). One-year mortality was also lower in group 2. CONCLUSION: Our data support that a centralization program, a structured bladder clinic associated with protocols, a multidisciplinary team, and inclusion of chemotherapy and radiotherapy treatments can pleasingly improve outcomes for patients with MIBC.

A Global Survey of Reproductive Specialists to Determine the Clinical Utility of Oxidative Stress Testing and Antioxidant Use in Male Infertility.

PURPOSE: The use of antioxidants is common practice in the management of infertile patients. However, there are no established guidelines by professional societies on antioxidant use for male infertility. MATERIALS AND METHODS: Using an online survey, this study aimed to evaluate the practice pattern of reproductive specialists to determine the clinical utility of oxidative stress (OS) testing and antioxidant prescriptions to treat male infertility. RESULTS: Responses from 1,327 participants representing 6 continents, showed the largest participant representation being from Asia (46.8%). The majority of participants were attending physicians (59.6%), with 61.3% having more than 10 years of experience in the field of male infertility. Approximately two-thirds of clinicians (65.7%) participated in this survey did not order any diagnostic tests for OS. Sperm DNA fragmentation was the most common infertility test beyond a semen analysis that was prescribed to study oxidative stress-related dysfunctions (53.4%). OS was mainly tested in the presence of lifestyle risk factors (24.6%) or sperm abnormalities (16.3%). Interestingly, antioxidants were prescribed by 85.6% of clinicians, for a duration of 3 (43.7%) or 3-6 months (38.6%). A large variety of antioxidants and dietary supplements were prescribed, and scientific evidence were mostly considered to be modest to support their clinical use. Results were not influenced by the physician's age, geographic origin, experience or training in male infertility. CONCLUSIONS: This study is the largest online survey performed to date on this topic and demonstrates 1) a worldwide understanding of the importance of this therapeutic option, and 2) a widely prevalent use of antioxidants to treat male infertility. Finally, the necessity of evidence-based clinical practice guidelines from professional societies is highlighted.

How to harmonize SUVs obtained by hybrid PET/CT scanners with and without point spread function correction.

State of the art point-spread function (PSF) corrections implemented in positron emission tomography/computed tomography (PET/CT) reconstruction improved image quality and diagnostic performance but caused an increase in the standardized uptake value (SUV) compared to a conventional OSEM reconstruction system. The EANM suggested one produce two reconstructions, one optimised for maximum lesion detection and one for semi-quantitative analysis. In this work we investigated an alternative methodology, using a single reconstruction data set together with a post-reconstruction algorithm for SUV harmonization. Data acquisition was performed on a Siemens Biograph mCT system equipped with lutetium oxyorthosilicat crystals, PSF and time-of-flight algorithms and on a General Electric Discovery STE system equipped with BGO crystals. Both a EANM double reconstruction method and a dedicated post-reconstruction algorithm (marketed as EQ-filter) were tested to harmonize the quantitative values of the two PET/CT scanners. For phantom measurements we used a NEMA IQ phantom and a Jaszczak cylindrical phantom equipped with small spheres (lesion to background ratios of 8:1 and 4:1). Several different reconstruction settings were tested in order to provide a general methodology. Data obtained by phantom measurements were validated on seven oncologic patients who performed a one-bed extra acquisition on a different scanner. The evaluation regarded 39 small lesions (diameters: 0.3-2.6 cm) and was performed by two experienced nuclear medicine physicians. The SUV recoveries measured with the PSF reconstruction exceeded those obtained by the OSEM reconstruction with deviations ranging from 16% to 150%. These discrepancies resulted below 7% applying the optimized value of the EQ.filter or the double-reconstruction methods. For each reconstruction setting the optimal value of the EQ.filter was identified in order to minimize these discrepancies. Patient data, analyzed by Wilcoxon statistical test, confirmed and validated phantom measurements. EQ.filter can harmonize SUV values between different PET/CT scanners using a single reconstruction optimized to maximum lesion detectability. In this way, the second reconstruction proposed by EANM/EARL is avoided.

Concurrent boost radiotherapy as preoperative treatment for locally advanced rectal carcinoma: a new beam arrangement.

PURPOSE: To describe a new beam arrangement for preoperative concurrent boost radiotherapy in locally advanced rectal carcinoma. MATERIAL AND METHODS: Three different volumes, ie posterior pelvis, total mesorectal space, and gross tumor volume plus 2 cm, are selected to receive radiation doses of 47 Gy, 51 Gy, and 54 Gy, respectively, in 24 fractions. There are two prerequisites for the use of such a radiotherapy schedule: complete displacement of the small bowel outside the boost volume, and horizontal positioning of the rectal long axis. Both conditions can be attained by patient positioning on a new device, the "Up-Down Table" (UDT). The dose gradient between the three volumes is realized with two daily arc rotation fields with an isocenter that is different from the three additional multileaf collimator pelvic fields (postero-anterior + 2 laterolateral). RESULTS: The treatment data are reported according to the ICRU 62 criteria. A comparison was made between concurrent arc rotation and concomitant static boost techniques. CONCLUSION: The new beam arrangement, with the use of the UDT, allows to administer different radiation doses to three volumes with different tumor cell density in order to obtain the same probability of local response in all target volumes without increasing the toxicity.

Variants in endothelial nitric oxide synthase (eNOS) gene in idiopathic infertile Brazilian men.

PURPOSE: In recent years, considerable concern has been expressed about the deleterious effects of reactive oxygen species (ROS) on sperm function, because ROS at high levels is potentially detrimental to sperm function and quality. Nitric oxide (NO) is a powerful anti-oxidant present in seminal plasma. The aim of the study was to analyze the distribution of the of endothelial nitric oxide synthase (eNOS) gene (T-786C, G894T, e 4a/b) polymorphisms in idiopathic infertile Brazilian men and evaluate the possible role of these polymorphisms in sperm count. METHODS: A case-control study was performed comprising 208 infertile men [n=74 with non-obstructive azoospermia and n=134 with severe oligozoospermia] and 201 fertile men as controls. Genotyping of eNOS polymorphisms was performed by real time (T-786C and G894T) and conventional PCR (4a/b). The results were analyzed statistically and a p-value<0.05 was considered significant. RESULTS: According to the sperm count, relatively similar eNOS polymorphism genotypes and allele frequencies were found among the groups. Combined genotypes of the eNOS polymorphisms did not identify a haplotype associated with idiopathic infertility, even when the patients were separated in non-obstructive azoospermia or severe oligozoospermia. CONCLUSION: In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, T-786C, G894T, and e 4a/b, of the eNOS gene are not associated with male infertility.

Phantom study of the impact of reconstruction parameters on the detection of mini- and micro-volume lesions with a low-dose PET/CT acquisition protocol.

PURPOSE: Every PET scanner suffers of the partial volume effect (PVE), that is a loss of contrast in small lesions causing a worsening in standardized uptake value (SUV) accuracy, that is critical if quantitative PET/CT imaging is used for diagnosis and therapy. METHODS: In order to quantify PVE and optimize our clinical protocols to minimize this effect in a last generation PET/CT scanner, we utilized a cylindrical phantom equipped with ten mini- and micro-volume hollow spheres. The lesion detectability and the SUV accuracy were evaluated at a fixed spheres to background intrinsic contrast (activity concentration ratio 8:1) but in different scan conditions: (a) acquisition modality (3D vs. 2D), (b) number of subset per iteration, (c) type of post-reconstruction filter and (d) activity concentration (i.e. total counts). Also the effect of different absorber thickness was evaluated. RESULTS: Small lesion detectability resulted better in images acquired in 3D mode rather than 2D, mainly because of the lower noise produced by the fully-3D algorithm. The number of reconstruction iterations and the post-processing filter used affected both the contrast underestimation and the spatial resolution. Decreasing the (18)F activity injected according to the low-dose protocol, the small lesions could be distinguished from the background down to a diameter of 6.2mm and the SUV accuracy did not deteriorate. Adding absorber thickness around the phantom, the image noise slightly increased while SUV accuracy did not change. CONCLUSIONS: The hybrid PET/CT scanner we evaluated showed good performances, mainly in 3D acquisition modality. The phantom measurements showed that the most appropriate reconstruction protocol derived from a compromise between the contrast accuracy and the noise variance in PET images. The low-dose protocol clinically used demonstrated no loss in SUV accuracy and an adequate lesion detectability for lesions down to 6.2mm in diameter.

Variants in follicle-stimulating hormone receptor gene in infertile Brazilian men and the correlation to FSH serum levels and sperm count.

The aim of the study was to analyze the distribution of the follicle-stimulating hormone (FSH) receptor (FSHR) Ala307Thr and Asn680Ser polymorphisms in infertile Brazilian men and evaluate the possible role of these polymorphisms on the serum levels of FSH and in sperm count. A case-control study was performed comprising138 infertile men with nonobstructive azoospermia (n = 53) or severe oligozoospermia (n = 85), and 217 fertile men as controls. Genotyping of FSHR polymorphisms was performed by real-time polymerase chain reaction (PCR). The results were analyzed statistically and a P value <.05 was considered significant. According to the sperm count, relatively similar FSHR polymorphisms genotype and allele frequencies were found among the groups, and combined genotypes of 2 polymorphisms did not identify a haplotype associated with sperm count. Considering FSH serum level according to genotypes of the Ala307Thr and Asn680Ser polymorphisms individually, statistical analysis showed no difference among the groups. When the combined genotypes of the FSHR polymorphisms were compared to FSH serum levels, no difference was also found among the groups. In conclusion, the findings demonstrate that, in Brazilian population studied, genetic variations, Asn680Ser and Thr307Ala, of the FSHR gene are not correlated with serum FSH levels or sperm count in male infertility.

A new methodological approach for PET implementation in radiotherapy treatment planning.

In this paper, a new methodological approach to using PET information in radiotherapy treatment planning has been discussed. Computed tomography (CT) represents the primary modality to plan personalized radiation treatment, because it provides the basic electron density map for correct dose calculation. If PET scanning is also performed it is typically coregistered with the CT study. This operation can be executed automatically by a hybrid PET/CT scanner or, if the PET and CT imaging sets have been acquired through different equipment, by a dedicated module of the radiotherapy treatment planning system. Both approaches have some disadvantages: in the first case, the bore of a PET/CT system generally used in clinical practice often does not allow the use of certain bulky devices for patient immobilization in radiotherapy, whereas in the second case the result could be affected by limitations in window/level visualization of two different image modalities, and the displayed PET volumes can appear not to be related to the actual uptake into the patient. To overcome these problems, at our centre a specific procedure has been studied and tested in 30 patients, allowing good results of precision in the target contouring to be obtained. The process consists of segmentation of the biological target volume by a dedicated PET/CT console and its export to a dedicated radiotherapy system, where an image registration between the CT images acquired by the PET/CT scanner and a large-bore CT is performed. The planning target volume is contoured only on the large-bore CT and is used for virtual simulation, to individuate permanent skin markers on the patient.

XX testicular disorder of sex differentiation: case report.

The 46 XX, testicular sex differentiation disorder, or XX male syndrome, is a rare condition detected by cytogenetics, in which testicular development occurs in the absence of the Y chromosome. It occurs in 1:20,000 to 25,000 male newborns and represents 2% of cases of male infertility. About 90% of individuals present with normal phenotype at birth and are generally diagnosed after puberty for hypoganadism, gynecomastia, and/or infertility. The authors present the report of an XX male with complete masculinization and infertility.

Methylenetetrahydrofolate reductase polymorphisms are related to male infertility in Brazilian men.

OBJECTIVE: The objective of this study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C polymorphisms in idiopathic infertile Brazilian patients with nonobstructive azoospermia (NOA) or severe oligozoospermia and fertile Brazilian men as controls to explore the possible association of these polymorphisms and male infertility. METHODS: A case-control study was carried out, including 156 idiopathic infertile Brazilian patients with NOA (n=49) or severe oligozoospermia (n=107) and 233 fertile men as controls. Polymorphisms C677T and A1298C were studied by quantitative polymerase chain reaction and the results were statistically analyzed. RESULTS: The frequency of genotypes MTHFR 677CC, 677CT, and 677TT in idiopathic infertile men with NOA were 55.1%, 30.6%, and 14.3% (p=0.0305); 50.6%, 42.0%, and 7.5% (p=0.0006) regarding the severe oligozoospermic men; and 71.7%, 53.0%, and 5.6% in the control group. As for polymorphism A1298C, regarding the NOA group, the frequencies of the 1298AA, 1298AC, and 1298CC genotypes were 53.0%, 28.6%, and 18.4% (p=0.0132); 42.0%, 44.9%, and 13.1% (p=0.0188) among the severe oligozoospermic group; and 55.8%, 38.2%, and 6.0% (14/233) in the control group. CONCLUSION: The data suggest that MTHFR C677T and A1298C could be important genetic factors predisposing to infertility in Brazilian infertile men.

Polymorphisms in folate-related enzyme genes in idiopathic infertile Brazilian men.

The aim of the study was to analyze the distribution of the methylenetetrahydrofolate reductase (MTHFR), methionine synthase reductase (MTRR), and methionine synthase (MTR) polymorphisms in idiopathic infertile Brazilian men and fertile men. Case-control study comprising 133 idiopathic infertile Brazilian men with nonobstructive azoospermia ([NOA] n = 55) or severe oligozoospermia ([SO] n = 78) and 173 fertile men as controls. MTHFR C677T, A1298C, and G1793A; MTRR A66G; and MTR A2756G polymorphisms were studied by quantitative polymerase chain reaction (qPCR). The results were analyzed statistically and a P value <.05 was considered significant. Single-marker analysis revealed a significant association among MTHFR C677T polymorphism and both NOA group (P = .018) and SO group (P < .001). Considering the MTHFR A1298C, MTHFR G1793A, and MTRR A66G polymorphisms, no difference was found between NOA group and SO group. Regarding the MTR A2756G polymorphism, a significant difference was found between NOA and controls, P = .017. However, statistical analysis revealed no association between SO group and controls. Combined genotypes of 3 MTHFR polymorphisms did not identify a haplotype associated with idiopathic infertility. The combinatory analysis of the 3 polymorphisms MTHFR, MTRR, and MTR did not show difference between cases and controls. The findings suggest the MTHFR C677T and MTR A2756G polymorphisms could be an important genetic factor predisposing to idiopathic infertility in Brazilian men.

Development and external validation of a predictive model for pathological complete response of rectal cancer patients including sequential PET-CT imaging.

PURPOSE: To develop and validate an accurate predictive model and a nomogram for pathologic complete response (pCR) after chemoradiotherapy (CRT) for rectal cancer based on clinical and sequential PET-CT data. Accurate prediction could enable more individualised surgical approaches, including less extensive resection or even a wait-and-see policy. METHODS AND MATERIALS: Population based databases from 953 patients were collected from four different institutes and divided into three groups: clinical factors (training: 677 patients, validation: 85 patients), pre-CRT PET-CT (training: 114 patients, validation: 37 patients) and post-CRT PET-CT (training: 107 patients, validation: 55 patients). A pCR was defined as ypT0N0 reported by pathology after surgery. The data were analysed using a linear multivariate classification model (support vector machine), and the model's performance was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS: The occurrence rate of pCR in the datasets was between 15% and 31%. The model based on clinical variables (AUC(train)=0.61±0.03, AUC(validation)=0.69±0.08) resulted in the following predictors: cT- and cN-stage and tumour length. Addition of pre-CRT PET data did not result in a significantly higher performance (AUC(train)=0.68±0.08, AUC(validation)=0.68±0.10) and revealed maximal radioactive isotope uptake (SUV(max)) and tumour location as extra predictors. The best model achieved was based on the addition of post-CRT PET-data (AUC(train)=0.83±0.05, AUC(validation)=0.86±0.05) and included the following predictors: tumour length, post-CRT SUV(max) and relative change of SUV(max). This model performed significantly better than the clinical model (p(train)<0.001, p(validation)=0.056). CONCLUSIONS: The model and the nomogram developed based on clinical and sequential PET-CT data can accurately predict pCR, and can be used as a decision support tool for surgery after prospective validation.

Male infertility related to an aberrant karyotype, 46,XY,9ph,9qh+.

OBJECTIVE: To report a man with primary infertility and variant karyotype. DESIGN: Case report. SETTING: Private practice. PATIENT(S): A 37-year-old man with 4 years of primary infertility due to oligoasthenozoospermia. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): G- and C-banding. Polymerase chain reaction for SRY, DBY, RBMY, DAZ, AMELX, and AMELY. RESULT(S): G-band analysis of the proband revealed a 46,XY,9ph,9qh+ karyotype. C-banding confirmed increase in the heterochromatin in one chromosome 9 and inversion in the other. CONCLUSION(S): The morphologic difference between the homologous chromosomes 9 may have been responsible for an error in crossing-over, leading to aberrant spermatozoa and consequently to infertility.

The role of dual-time combined 18-fluorodeoxyglucose positron emission tomography and computed tomography in the staging and restaging workup of locally advanced rectal cancer, treated with preoperative chemoradiation therapy and radical surgery.

PURPOSE: In patients with locally advanced rectal cancer (LARC) staging and, after preoperative chemo-radiation therapy (CRT), restaging workup could be useful to tailor therapeutic approaches. Fluorine-18-fluorodeoxyglucose positron emission tomography ([(18)F]FDG-PET) is a promising tool for monitoring the effect of antitumor therapy. This study was aimed to evaluate the possible role of dual time sequential FDG-PET scans in the staging and restaging workup of LARC. METHODS AND MATERIALS: Eighty-seven consecutive patients with LARC were enrolled. CRT consisted of external-beam intensified radiotherapy (concurrent boost), with concomitant chemotherapy PVI 5-FU (300 mg/m(2)/day) followed 8-10 weeks later by surgery. All patients underwent [(18)F]FDG-PET/CT before and 5-6 weeks later after the completion of CRT. Measurements of FDG uptake (SUV(max)), and percentage of SUV(max) difference (Response Index = RI) between pre- and post-CRT [(18)F]FDG-PET scans were evaluated. RESULTS: Six of 87 patients were excluded due to protocol deviation. Following CRT, 40/81 patients (49%) were classified as responders according to Mandard's criteria (TRG1-2). The mean pre-CRT SUV(max) was significantly higher than post-CRT (15.8, vs 5.9; p < 0.001). The mean RI was significantly higher in responders than in nonresponder patients (71.3% vs 38%; p = 0.0038). Using a RI cut-off of 65% for defining response to therapy, the following parameters have been obtained: 84.5% sensitivity, 80% specificity, 81.4% positive predictive value, 84.2% negative predictive value, and 81% overall accuracy. CONCLUSION: These results suggest the potential role of [(18)F]FDG-PET in the restaging workup after preoperative CRT in LARC. RI seems the best predictor to identify CRT response.