Technical considerations for isolated limb perfusion: A consensus paper.

BACKGROUND: Isolated limb perfusion (ILP) is a well-established surgical procedure for the administration of high dose chemotherapy to a limb for the treatment of advanced extremity malignancy. Although the technique of ILP was first described over 60 years ago, ILP is utilised in relatively few specialist centres, co-located with tertiary or quaternary cancer centres. The combination of high dose cytotoxic chemotherapy and the cytokine tumour necrosis factor alpha (TNFα), mandates leakage monitoring to prevent potentially serious systemic toxicity. Since the procedure is performed at relatively few specialist centres, an ILP working group was formed with the aim of producing technical consensus guidelines for the procedure to streamline practice and to provide guidance for new centres commencing the technique. METHODS: Between October 2021 and October 2023 a series of face to face online and hybrid meetings were held in which a modified Delphi process was used to develop a unified consensus document. After each meeting the document was modified and recirculated and then rediscussed at subsequent meeting until a greater than 90% consensus was achieved in all recommendations. RESULTS: The completed consensus document comprised 23 topics in which greater than 90% consensus was achieved, with 83% of recommendations having 100% consensus across all members of the working group. The consensus recommendations covered all areas of the surgical procedure including pre-operative assessment, drug dosing and administration, perfusion parameters, hyperthermia, leakage monitoring and theatre logistics, practical surgical strategies and also post-operative care, response evaluation and staff training. CONCLUSION: We present the first joint expert-based consensus statement with respect to the technical aspects of ILP that can serve as a reference point for both existing and new centres in providing ILP.

Comparison of hydraulic, pneumatic and electric linear actuation systems.

Different applications or industries use different systems for linear actuation, such as hydraulic, pneumatic or electric. Electric systems are becoming increasingly popular and are already replacing hydraulic systems in various applications. These are known to be potentially harmful to the environment, as large amounts of fluid can be released into the environment in the event of a pipe burst or other accident. This paper presents the results of a comparison between hydraulic, pneumatic and electric systems under variable conditions but with similar loads in all three systems. The common feature of all three systems is the input power, which was limited to 1.1 kW. There was no hydraulic accumulator in the hydraulic system and no pressure vessel in the pneumatic system, so no stored energy could influence the system behaviour or results. The main difference between the systems studied was the profile of displacement and power consumption. The most consistent response and lowest power consumption were obtained with the electric system, although both hydraulic and pneumatic systems can achieve consistent response with some modifications.

Vascular and Urinary Tract Anatomic Variants Relevant to Para-Aortic Lymphadenectomy in Women with Gynecological Cancers.

BACKGROUND: Para-aortic lymphadenectomy is an essential part of gynecologic oncologic surgical treatment. The surgeon should be aware of the complex usual anatomy and its common variants. METHODS: Between January 2021 and May 2023, 58 women underwent para-aortic lymphadenectomy for gynecologic malignancies. RESULTS: Vascular and urinary tract anatomic variants were retrospectively reviewed from the prospective institutional database and results were compared with preoperative contrast-enhanced abdominal CT. Of these 58 women, 47 women had no vascular or urinary tract variants. One woman had a double inferior vena cava, two patients were found to have a retro-aortic left renal vein, four had accessory renal arteries, two had a double left ureter, one had a ptotic kidney in the iliac fossa, and one patient had bilateral kidney malrotation. Anatomic variants in the preoperative CT were described by a radiologist in only two patients, and additional vascular and urinary tract variants were found incidentally at the time of surgery. CONCLUSIONS: Acknowledgment of vascular and urinary tract variants is helpful for the surgeon to establish an appropriate surgical plan and to avoid iatrogenic surgical trauma.

The use of hydrodynamic cavitation for waste-to-energy approach to enhance methane production from waste activated sludge.

Anaerobic digestion in wastewater treatment plants converts its unwanted end product - waste activated sludge into biogas. Even if the process is well established, pre-treatment of the sludge can further improve its efficiency. In this study, four treatment regimes for increasing methane production through prior sludge disintegration were investigated using lab-scale cavitation generator and real sludge samples. Three different cavitating (attached cavitation regime, developed cloud shedding cavitation regime and cavitation in a wake regime) and one non-cavitating regime at elevated static pressure were studied in detail for their effectiveness on physical and chemical properties of sludge samples. Volume-weighted mean diameter D[4,3] of sludge's particles decreased by up to 92%, specific surface area increased by up to 611%, while viscosity (at a shear rate of 3.0 s-1) increased by up to 39% in the non-cavitating and decreased by up to 24% in all three cavitating regimes. Chemical changes were more pronounced in cavitating regimes, where released soluble chemical oxygen demand (sCOD) and increase of dissolved organic matter (DOM) compounds by up to 175% and 122% were achieved, respectively. Methane production increased in all four cases, with the highest increase of 70% corresponding to 312 mL CH4 g-1 COD. However, this treatment was not particularly efficient in terms of energy consumption. The best energy balance was found for the regime with a biochemical methane potencial increase of 43%.

A Review on Methods for Measurement of Free Water Surface.

Turbulent free-surface flows are encountered in several engineering applications and are typically characterized by the entrainment of air bubbles due to intense mixing and surface deformation. The resulting complex multiphase structure of the air-water interface presents a challenge in precise and reliable measurements of the free-water-surface topography. Conventional methods by manometers, wave probes, point gauges or electromagnetic/ultrasonic devices are proven and reliable, but also time-consuming, with limited accuracy and are mostly intrusive. Accurate spatial and temporal measurements of complex three-dimensional free-surface flows in natural and man-made hydraulic structures are only viable by high-resolution non-contact methods, namely, LIDAR-based laser scanning, photogrammetric reconstruction from cameras with overlapping field of view, or laser triangulation that combines laser ranging with high-speed imaging data. In the absence of seeding particles and optical calibration targets, sufficient flow aeration is essential for the operation of both laser- and photogrammetry-based methods, with local aeration properties significantly affecting the measurement uncertainty of laser-based methods.

Detection and localization of hyperfunctioning parathyroid glands on [18F]fluorocholine PET/ CT using deep learning - model performance and comparison to human experts.

BACKGROUND: In the setting of primary hyperparathyroidism (PHPT), [18F]fluorocholine PET/CT (FCH-PET) has excellent diagnostic performance, with experienced practitioners achieving 97.7% accuracy in localising hyperfunctioning parathyroid tissue (HPTT). Due to the relative triviality of the task for human readers, we explored the performance of deep learning (DL) methods for HPTT detection and localisation on FCH-PET images in the setting of PHPT. PATIENTS AND METHODS: We used a dataset of 93 subjects with PHPT imaged using FCH-PET, of which 74 subjects had visible HPTT while 19 controls had no visible HPTT on FCH-PET. A conventional Resnet10 as well as a novel mPETResnet10 DL model were trained and tested to detect (present, not present) and localise (upper left, lower left, upper right or lower right) HPTT. Our mPETResnet10 architecture also contained a region-of-interest masking algorithm that we evaluated qualitatively in order to try to explain the model's decision process. RESULTS: The models detected the presence of HPTT with an accuracy of 83% and determined the quadrant of HPTT with an accuracy of 74%. The DL methods performed statistically worse (p < 0.001) in both tasks compared to human readers, who localise HPTT with the accuracy of 97.7%. The produced region-of-interest mask, while not showing a consistent added value in the qualitative evaluation of model's decision process, had correctly identified the foreground PET signal. CONCLUSIONS: Our experiment is the first reported use of DL analysis of FCH-PET in PHPT. We have shown that it is possible to utilize DL methods with FCH-PET to detect and localize HPTT. Given our small dataset of 93 subjects, results are nevertheless promising for further research.

Characterization of cavitation under ultrasonic horn tip - Proposition of an acoustic cavitation parameter.

Acoustic cavitation, generated by a piezo-driven transducer, is a commonly used technique in a variety of processes, from homogenization, emulsification, and intensification of chemical reactions to surface cleaning and wastewater treatment. An ultrasonic horn, the most commonly used acoustic cavitation device, creates unique cavitation conditions under the horn tip that depend on various parameters such as the tip diameter, the driving frequency of the horn, its amplitude, and fluid properties. Unlike for hydrodynamic cavitation, the scaling laws for acoustic cavitation are poorly understood. Empirical relationships between cavitation dynamics, ultrasonic horn operating conditions, and fluid properties were found through systematic characterization of cavitation under the tip. Experiments were conducted in distilled water with various sodium chloride salt concentrations under different horn amplitudes, tip geometries, and ambient pressures. Cavitation characteristics were monitored by high-speed (200,000 fps) imaging, and numerous relations were found between operating conditions and cavitation dynamics. The compared results are discussed along with a proposal of a novel acoustic cavitation parameter and its relationship to the size of the cavitation cloud under the horn tip. Similar to the classical hydrodynamic cavitation number, the authors propose for the first time an acoustic cavitation parameter based on experimental results.

Computational analysis of flow conditions in hydrodynamic cavitation generator for water treatment processes.

The research on the potential of cavitation exploitation is currently an extremely interesting topic. To reduce the costs and time of the cavitation reactor optimization, nowadays, experimental optimization is supplemented and even replaced using computational fluid dynamics (CFD). One of the approaches towards sustainable water treatment is the use of the cavitation reactor with bluff elements mounted on its stator and rotor. The experimental results show that, besides the rotational speed, the spacing of the rotor pins has the most significant effect on the cavitation intensity and effectiveness, while the pin diameter and the surface roughness are less significant design parameters. The present paper uses a simplified CFD approach to investigate the conditions in the reactor and to select the optimal among a number of geometry variations.

Intraoperative parathormone increase after focused parathyroidectomy in a patient with sarcoidosis - Case report.

INTRODUCTION: Hypercalcaemia is most commonly a sign of primary hyperparathyroidism but can also be a sign of an active granulomatous disease. Standard treatment for primary hyperparathyroidism caused by a solitary parathyroid gland adenoma identified by localisation studies is minimally invasive focused parathyroidectomy. If unsuccessful, bilateral neck exploration is recommended. CASE PRESENTATION: We report the case of hypercalcaemia and ostheoporosis in a 63-year -old woman with a history of sarcoidosis and suspected primary hyperparathyroidism. Localisation studies for parathyroid adenoma were inconclusive due to active cervical and mediastinal granulomatous lymph nodes. Sarcoidosis was treated with corticosteroids but hypercalcaemia persisted. Focused parathyroidectomy was attempted with intraoperative parathyroid hormone measurement but an increase in parathyroid hormone levels was observed. However, with high clinical probability of a successfully removed adenoma and frozen section evaluation, we decided not to proceed with bilateral neck exploration. Serum parathyroid hormone and calcium levels dropped accordingly the following day. CLINICAL DISCUSSION: We explored all possible underlying mechanisms for persistent elevated parathyroid hormone level described in literature. CONCLUSION: We conclude that Wisconsin Criteria with intraoperative parathyroid hormone measured 20 minutes after adenoma removal should be applied in such cases.

Challenges of numerical simulations of cavitation reactors for water treatment - An example of flow simulation inside a cavitating microchannel.

The research on the potential of cavitation exploitation is currently an extremely interesting topic. To reduce the costs and time of the cavitation reactor optimization, nowadays, experimental optimization is supplemented and even replaced using computational fluid dynamics (CFD). This is a very inviting opportunity for many developers, yet we find that all too often researchers with non-engineering background treat this "new" tool too simplistic, what leads to many misinterpretations and consequent poor engineering. The present paper serves as an example of how complex the flow features, even in the very simplest geometry, can be, and how much effort needs to be put into details of numerical simulation to set a good starting point for further optimization of cavitation reactors. Finally, it provides guidelines for the researchers, who are not experts in computational fluid dynamics, to obtain reliable and repeatable results of cavitation simulations.

Reduction of overtreatment without reduction of overdiagnosis in patients with differentiated thyroid cancer: mission impossible.

PURPOSE: Lateral neck nodal metastases are common in patients with differentiated thyroid cancer (DTC) and usually have an indolent nature. They may be detected via neck palpation or preoperative ultrasound (US) of the neck. We hypothesized that preoperative neck metastases detected with US did not affect regional recurrence or long-term survival. METHODS: A retrospective analysis of patients' records treated for DTC at our institution between January 2006 and December 2016 was performed. Information about preoperative US of the neck, treatment, demographics, staging, and histopathology was obtained. The endpoints for the study were nodal recurrence and survival. Differences in survival were analyzed between three groups of patients divided by presence or lack of preoperative US and/or palpable cervical lymph nodes (PLN). Furthermore, the prognostic value of multiple variables was tested by univariate and multivariate analysis. RESULTS: There were 1108 patients with DTC, 221 males and 887 females. The median age was 48.3 years (range 3 to 86), the median time of observation was 68 months (range 0 to 142). Eight hundred sixty-two patients without PLN or preoperative US represented group 1, 112 patients with PLN were in group 2, and 134 patients without PLN and with preoperative US were in group 3. Only five patients had a regional recurrence, one died due to distant metastases. There was no statistically significant difference in survival between the groups (p = 0.841) and neck US was not significantly associated with overall survival neither in univariate nor in multivariate analysis. CONCLUSION: In patients with DTC, the benefits of preoperative US of cervical lymph nodes are probably limited and "less is more" approach is advised.

Birth cohort-specific trends of sun-related behaviors among individuals from an international consortium of melanoma-prone families.

BACKGROUND: Individuals from melanoma-prone families have similar or reduced sun-protective behaviors compared to the general population. Studies on trends in sun-related behaviors have been temporally and geographically limited. METHODS: Individuals from an international consortium of melanoma-prone families (GenoMEL) were retrospectively asked about sunscreen use, sun exposure (time spent outside), sunburns, and sunbed use at several timepoints over their lifetime. Generalized linear mixed models were used to examine the association between these outcomes and birth cohort defined by decade spans, after adjusting for covariates. RESULTS: A total of 2407 participants from 547 families across 17 centers were analyzed. Sunscreen use increased across subsequent birth cohorts, and although the likelihood of sunburns increased until the 1950s birth cohort, it decreased thereafter. Average sun exposure did not change across the birth cohorts, and the likelihood of sunbed use increased in more recent birth cohorts. We generally did not find any differences in sun-related behavior when comparing melanoma cases to non-cases. Melanoma cases had increased sunscreen use, decreased sun exposure, and decreased odds of sunburn and sunbed use after melanoma diagnosis compared to before diagnosis. CONCLUSIONS: Although sunscreen use has increased and the likelihood of sunburns has decreased in more recent birth cohorts, individuals in melanoma-prone families have not reduced their overall sun exposure and had an increased likelihood of sunbed use in more recent birth cohorts. These observations demonstrate partial improvements in melanoma prevention and suggest that additional intervention strategies may be needed to achieve optimal sun-protective behavior in melanoma-prone families.

Diagnostic value of [18F]Fluorocholine PET/CT in detection of primary medullary thyroid cancer.

OBJECTIVE: Medullary thyroid cancer (MTC) is a challenging neuroendocrine malignancy where the role of nuclear medicine imaging is currently limited. This paper investigates the potential diagnostic value of [18F]Fluorocholine PET/CT in primary MTC. METHODS: We prospectively enrolled 25 patients (10 male, 15 female) with suspicion for primary MTC based on fine-needle aspiration biopsy (FNAB). All patients had a baseline three phase [18F]Fluorocholine PET/CT (2.5 MBq/kg): two regional head and neck and upper mediastinum studies at 5 min (first phase) and 120 min (third phase) and a whole-body PET/CT (from the skull vertex to mid-thighs) at 60 min (second phase). Any non-physiological radiotracer uptake was regarded as MTC positive. All patients referred to surgery had a preoperative neck-US. True lesion status was assessed using either histopathology, FNAB results or follow-up imaging and laboratory (calcitonin, CEA) results. Results with p < 0.05 were considered statistically significant. RESULTS: Nineteen of 25 patients (76%) were surgically treated and histopathology reports were obtained. Patient-based sensitivity and positive predictive value for detection of any MTC lesion using [18F]Fluorocholine PET/CT were both 100%. Neck-US was more specific (100% vs 70%; p = 0.002) and had a higher positive predictive value than [18F]Fluorocholine PET/CT (100% vs 55%; p = 0.018) for N1a and N1b staging. [18F]Fluorocholine PET/CT had a higher sensitivity (100% vs 50%; p = 0.025) and higher negative predictive value (100% vs 81%; p = 0.026) than neck-US for N1b staging. The optimal SUVmax cut-off to differentiate malignant from benign neck lesions at 60 and 120 min was 2.56. Patients with M1 stage on PET/CT had higher calcitonin (median of 5,372 vs 496.6 pg/ml; p = 0.005) and CEA concentrations (median of 95.8 vs 18.65 µg/l; p = 0.034) compared to patients with M0 disease. CONCLUSION: [18F]Fluorocholine PET/CT appears to be a promising radiotracer for primary staging of MTC by increasing diagnostic accuracy for N staging and detecting possible distant metastatic sites at initial presentation of disease.

Significance of nuclear factor - kappa beta activation on prostate needle biopsy samples in the evaluation of Gleason score 6 prostatic carcinoma indolence.

Background The goal of our study was to find out whether the immunohistochemical expression of nuclear factor-kappa beta (NF-κB) p65 in biopsy samples with Gleason score 3 + 3 = 6 (GS 6) can be a negative predictive factor for Prostate cancer (PCa) indolence. Patients and methods Study was conducted on a retrospective cohort of 123 PCa patients with initial total PSA ≤ 10 ng/ml, number of needle biopsy specimens ≥ 8, GS 6 on biopsy and T1/T2 estimated clinical stage who underwent laparoscopic radical prostatectomy and whose archived formalin-fixed and paraffin-embedded (FFPE) prostate needle biopsy specimens were used for additional immunohistochemistry staining for detection of NF-κB p65. Both cytoplasmic and nuclear NF-κB p65 expression in biopsy cores with PCa were correlated with postoperative pathological stage, positive surgical margins, GS and biochemical progression of disease. Results After follow-up of 66 months, biochemical progression (PSA ≥ 0.2 ng/ml) occurred in 6 (5.1%) patients, 3 (50%) with GS 6 and 3 (50%) with GS 7 after radical prostatectomy. Both cytoplasmic and nuclear NF-κB p65 expressions were not significantly associated with pathological stage, positive surgical margin and postoperative GS. Patients with positive cytoplasmic NF-kB reaction had significantly more frequent biochemical progression than those with negative cytoplasmic NF-kB reaction with PSA 0.2 ng/ml as cutoff point (p = 0.015) and a trend towards more biochemical progression with PSA ≥ 0.05 ng/ml as cutoff point (p = 0.068). Conclusions Cytoplasmic expression of NF-κB is associated with more biochemical progression and might be an independent prognostic factor for recurrence-free survival (RFS), but further studies including larger patient cohorts are needed to confirm these initial results.

Surgical options in treating patients with primary hyperparathyroidism.

Background Primary hyperparathyroidism is the third most common endocrine disorder for which surgical procedure called parathyroidectomy is the most effective treatment. Since the early 20th century, parathyroid surgery has improved extensively. With the advances in preoperative imaging and with understanding the causes of disease, new and minimally invasive surgical approaches overrode the standard bilateral exploratory operations. Directed parathyroidectomy is currently the standard technique for treatment of primary hyperparathyroidism worldwide. Conclusions Surgery is the only definitive treatment of primary hyperparathyroidism. The most appropriate type of surgical procedure depends on the number and localization of the hyperactive parathyroid glands, availability of modern imaging techniques, limitation of each type of procedure and expertise.

Completely resected stage III melanoma controversy - 15 years of national tertiary centre experience.

BACKGROUND: Two prospective randomized studies analysing cutaneous melanoma (CM) patients with sentinel lymph node (SLN) metastases and rapid development of systemic adjuvant therapy have changed our approach to stage III CM treatment. The aim of this study was to compare results of retrospective survival analysis of stage III CM patients' treatment from Slovenian national CM register to leading international clinical guidelines. PATIENTS AND METHODS: Since 2000, all Slovenian CM patients with primary tumour ≥ TIb are treated at the Institute of Oncology Ljubljana and data are prospectively collected into a national CM registry. A retrospective analysis of 2426 sentinel lymph node (SLN) biopsies and 789 lymphadenectomies performed until 2015 was conducted using Kaplan-Meier survival curves and log-rank tests. RESULTS: Positive SLN was found in 519/2426 (21.4%) of patients and completion dissection (CLND) was performed in 455 patients. The 5-year overall survival (OS) of CLND group was 58% vs. 47% of metachronous metastases group (MLNM) (p = 0.003). The 5-year OS of patients with lymph node (LN) metastases and unknown primary site (UPM) was 45% vs. 21% of patients with synchronous LN metastasis. Patients with SLN tumour burden < 0.3 mm had 5-year OS similar to SLN negative patients (86% vs. 85%; p = 0.926). The 5-year OS of patients with burden > 1.0 mm was similar to the MLNM group (49% vs. 47%; p = 0.280). CONCLUSIONS: Stage III melanoma patients is a heterogeneous group with significant OS differences. CLND after positive SLNB might still remain a method of treatment for selected patients with stage III.

18F-Fluorocholine PET/CT in Primary Hyperparathyroidism: Superior Diagnostic Performance to Conventional Scintigraphic Imaging for Localization of Hyperfunctioning Parathyroid Glands.

Primary hyperparathyroidism (PHPT) is a common endocrine disorder, definitive treatment usually requiring surgical removal of the offending parathyroid glands. To perform focused surgical approaches, it is necessary to localize all hyperfunctioning glands. The aim of the study was to compare the efficiency of established conventional scintigraphic imaging modalities with emerging 18F-fluorocholine PET/CT imaging in preoperative localization of hyperfunctioning parathyroid glands in a larger series of PHPT patients. Methods: In total, 103 patients with PHPT were imaged preoperatively with 18F-fluorocholine PET/CT and conventional scintigraphic imaging methods, consisting of 99mTc-sestamibi SPECT/CT, 99mTc-sestamibi/pertechnetate subtraction imaging, and 99mTc-sestamibi dual-phase imaging. The results of histologic analysis, as well as intact parathyroid hormone and serum calcium values obtained 1 d after surgery and on follow-up, served as the standard of truth for evaluation of imaging results. Results: Diagnostic performance of 18F-fluorocholine PET/CT surpassed conventional scintigraphic methods (separately or combined), with calculated sensitivity of 92% for PET/CT and 39%-56% for conventional imaging (65% for conventional methods combined) in the entire patient group. Subgroup analysis, differentiating single and multiple hyperfunctioning parathyroid glands, showed PET/CT to be most valuable in the group with multiple hyperfunctioning glands, with sensitivity of 88%, whereas conventional imaging was significantly inferior, with sensitivity of 22%-34% (44% combined). Conclusion:18F-fluorocholine PET/CT is a diagnostic modality superior to conventional imaging methods in patients with PHPT, allowing for accurate preoperative localization.

Plant protection product dose rate estimation in apple orchards using a fuzzy logic system.

In the process of applying a plant protection product mixed with water (spray mixture) at the prescribed concentration with conventional sprayers for chemical protection of tree canopies in an orchard, standard models are used to express the dose rate of the plant protection product. Characteristic properties of the tree canopy in an orchard are not taken into consideration. Such models result in fixed quantities of spray mixture being sprayed through individual nozzles into a tree canopy. In this research work, an autonomous system is presented, which ensures a controlled quantity of spray mixture sprayed through the nozzles onto different tree canopy segments. The autonomous system is based on a fuzzy logic system (FLS) that includes information about the estimated leaf area to ensure more appropriate control of the spray mixture. An integral part of the FLS is a fuzzy logic controller for three electromagnetic valves operating in the pulse width mode and installed on the axial sprayer prototype. The results showed that, with the FLS, it was possible to control the quantity of spray mixture in the specific range depending on the estimated value of the leaf area, with a quantitative spray mixture average saving of 17.92%. For the phenological growth stage BBCH 91, this method represents a powerful tool for reducing the quantity of spray mixture for plant protection in the future.

Cytology material is equivalent to tumor tissue in determining mutations of BRCA 1/2 genes in patients with tubo-ovarian high grade serous carcinoma.

BACKGROUND: High-grade serous ovarian cancer is a detrimental disease. Treatment options in patients with a recurrent disease are dependent on BRCA1/2 mutation status since only patients with known BRCA mutation are eligible for treatment with poly(ADP-ribose) polymerase inhibitors (PARPi). The aim of this study was to compare concordance of BRCA mutation analyses from cytological samples (CS) with BRCA mutation analyses from histological formalin fixed paraffin embedded (FFPE) samples. METHODS: Mutation analysis of BRCA1 and BRCA2 genes was performed in 44 women diagnosed with primary or recurrent high-grade ovarian cancer from three different samples: blood, cytological sample (ascites, pleural effusion and enlarged lymph nodes) and tumor tissue. Results from all three samples were compared. RESULTS: Among 44 patients, there were 15 germline mutations and two somatic mutations. A 100% concordance was found between cytological and histologic samples. CONCLUSION: There is a 100% concordance in BRCA mutation testing between cytological and histologic samples. BRCA mutation testing from CS could replace testing from FFPE tissue in clinical decision making in ovarian cancer patients. TRIAL REGISTRATION: The study was retrospectively registered at ISRCTN registry on 24/11/2015 - ISRCTN42408038 .

Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT.

BACKGROUND: Although rare in the general population, highly penetrant germline mutations in CDKN2A are responsible for 5%-40% of melanoma cases reported in melanoma-prone families. We sought to determine whether MELPREDICT was generalizable to a global series of families with melanoma and whether performance improvements can be achieved. METHODS: In total, 2116 familial melanoma cases were ascertained by the international GenoMEL Consortium. We recapitulated the MELPREDICT model within our data (GenoMELPREDICT) to assess performance improvements by adding phenotypic risk factors and history of pancreatic cancer. We report areas under the curve (AUC) with 95% confidence intervals (CIs) along with net reclassification indices (NRIs) as performance metrics. RESULTS: MELPREDICT performed well (AUC 0.752, 95% CI 0.730-0.775), and GenoMELPREDICT performance was similar (AUC 0.748, 95% CI 0.726-0.771). Adding a reported history of pancreatic cancer yielded discriminatory improvement (P < .0001) in GenoMELPREDICT (AUC 0.772, 95% CI 0.750-0.793, NRI 0.40). Including phenotypic risk factors did not improve performance. CONCLUSION: The MELPREDICT model functioned well in a global data set of familial melanoma cases. Adding pancreatic cancer history improved model prediction. GenoMELPREDICT is a simple tool for predicting CDKN2A mutational status among melanoma patients from melanoma-prone families and can aid in directing these patients to receive genetic testing or cancer risk counseling.