Sexual health in Belgian cervical cancer survivors: an exploratory qualitative study.

PURPOSE: To assess experiences of sexuality and of receiving sexual healthcare in cervical cancer (CC) survivors. METHODS: A qualitative phenomenological study using semistructured one-on-one interviews was conducted with 15 Belgian CC survivors recruited in 5 hospitals from August 2021 to February 2022. The interviews were audiotaped and transcribed verbatim. Data were analyzed using inductive thematic analysis. COREQ and SRQR reporting guidelines were applied. RESULTS: Most participants experienced an altered sexuality after CC treatment with often long-term loss/lack of sex drive, little/no spontaneity, limitation of positions to avoid dyspareunia, less intense orgasms, or no sexual activity at all. In some cases, emotional intimacy became more prominent. Physical (vaginal bleeding, vaginal dryness, dyspareunia, menopausal symptoms) and psychological consequences (guilt, changed self-image) were at the root of the altered sexuality. Treatment-induced menopause reduced sex drive. In premenopausal patients, treatment and/or treatment-induced menopause resulted in the sudden elimination of family planning. Most participants highlighted the need to discuss their altered sexual experience with their partner to grow together toward a new interpretation of sexuality. To facilitate this discussion, most of the participants emphasized the need for greater partner involvement by healthcare providers (HPs). The oncology nurse or sexologist was the preferred HP with whom to discuss sexual health. The preferred timing for information about the sexual consequences of treatment was at treatment completion or during early follow-up. CONCLUSION: Both treatment-induced physical and psychological experiences were prominent and altered sexuality. Overall, there was a need for HPs to adopt proactive patient-tailored approaches to discuss sexual health.

Robotic-Assisted Pelvic Exenteration for Cervical Cancer: A Systematic Review and Novel Insights into Compartment-Based Imaging.

Background: Patients with persistent or recurrent cervical cancer, following primary treatment with concurrent chemoradiation, represent a subgroup eligible for pelvic exenteration. In light of the substantial morbidity associated with open pelvic exenterations, minimally invasive surgical techniques have been introduced. This systematic review aims to analyze and discuss the current literature on robotic-assisted pelvic exenterations in cervical cancer. In addition, novel aspects of compartment-based magnetic resonance imaging (MRI) are highlighted. Methods: This systematic review followed the PRISMA guidelines, and a comprehensive literature search on robotic-assisted pelvic exenterations in cervical cancer was conducted to assess, as main objectives, early and late postoperative complications as well as oncological outcomes. Inclusion and exclusion criteria were applied to select eligible studies. Results: Among the reported cases of robotic-assisted pelvic exenterations in cervical cancer, 79.4% are anterior pelvic exenterations. Intraoperative complications are minimal and early/late major complications averaged between 30-35%, which is lower compared to open pelvic exenterations. Oncological outcomes are similar between robotic and open pelvic exenterations. Sensitivity for locoregional invasion increases up to 93% for compartment-based MRI in colorectal cancer. A refined delineation of the seven pelvic compartments for cervical cancer is proposed here. Conclusions: Robotic-assisted pelvic exenterations have demonstrated feasibility and safety, with reduced rates of major complications compared to open surgery, while maintaining surgical efficiency and oncological outcomes. Compartment-based MRI holds promise for standardizing the selection and categorization of pelvic exenteration procedures.

Robotic Staging of Cervical Cancer With Simultaneous Detection of Primary Pelvic and Secondary Para-Aortic Sentinel Lymph Nodes: Reproducibility in a First Case Series.

Objective: Discrepancies exist among international guidelines on the surgical staging of para-aortic lymph nodes in locally advanced cervical cancer (LACC), varying from considering a para-aortic lymph node dissection, at least up to the inferior mesenteric artery, to a complete para-aortic lymph node dissection. In this study, we aim to assess the reproducibility of our recently reported robotic technique using indocyanine green for identifying besides primary pelvic sentinel lymph nodes (SLNs), secondary para-aortic SLNs in a first case-cohort of cervical cancer patients. Methods: A retrospective case series of LACC patients with/without suspicious pelvic lymph nodes (LNs) on imaging (including two patients with an additional suspicious para-aortic LN) is reported. All patients underwent a robotic pelvic SLN and para-aortic sentinel/nonsentinel LN dissection using the da Vinci Xi platform. Indocyanine green was used as a fluorescent tracer, at a concentration of 1.9 mg/mL, and injected as 0.5 mL in each quadrant of the cervix. Results: In a total of 10 cases, primary pelvic SLNs (90% bilateral) with subsequent secondary para-aortic SLNs were identified in all cases. Lower para-aortic SLNs were present in all cases, and upper para-aortic SLNs were found in 9 out of 10 cases. The mean age of the cervical cancer patients was 49.8 years (SD ± 6.89), and the mean body mass index (BMI; kg/m2) was 23.96 (SD ± 4.60). The median total operative time was 105.5 min (range: 89-141 min). The mean numbers of primary pelvic SLNs and secondary lower and upper para-aortic SLNs were 3.10 (SD ± 1.10), 2.90 (SD ± 0.74), and 2.30 (SD ± 1.57), respectively. The median number of total para-aortic LNs (PALNs) dissected per patient was 11.5. Six patients had positive primary pelvic SLNs, and two had secondary positive para-aortic SLNs. The nonsentinel para-aortic LNs were negative in all cases. There were no intra- or postoperative complications. Conclusion: Our preliminary experience demonstrates the reproducibility of identifying, besides primary pelvic SLNs, secondary lower and upper para-aortic SLNs during robotic staging in LACC. A surgical approach limiting a complete para-aortic LN dissection could reduce the potential risks and morbidity associated with this procedure. To determine the sensitivity and negative predictive value of this new surgical approach, and whether the lower para-aortic SLNs under the inferior mesenteric artery are representative of the whole para-aortic region, large prospective observational studies are needed in LACC and/or those with suspicious pelvic LNs but apparent normal para-aortic LNs on imaging.

Pollinator loss causes rapid adaptive evolution of selfing and dramatically reduces genome-wide genetic variability.

Although selfing populations harbor little genetic variation limiting evolutionary potential, the causes are unclear. We experimentally evolved large, replicate populations of Mimulus guttatus for nine generations in greenhouses with or without pollinating bees and studied DNA polymorphism in descendants. Populations without bees adapted to produce more selfed seed yet exhibited striking reductions in DNA polymorphism despite large population sizes. Importantly, the genome-wide pattern of variation cannot be explained by a simple reduction in effective population size, but instead reflects the complicated interaction between selection, linkage, and inbreeding. Simulations demonstrate that the spread of favored alleles at few loci depresses neutral variation genome wide in large populations containing fully selfing lineages. It also generates greater heterogeneity among chromosomes than expected with neutral evolution in small populations. Genome-wide deviations from neutrality were documented in populations with bees, suggesting widespread influences of background selection. After applying outlier tests to detect loci under selection, two genome regions were found in populations with bees, yet no adaptive loci were otherwise mapped. Large amounts of stochastic change in selfing populations compromise evolutionary potential and undermine outlier tests for selection. This occurs because genetic draft in highly selfing populations makes even the largest changes in allele frequency unremarkable.

Differential regulation of a MYB transcription factor is correlated with transgenerational epigenetic inheritance of trichome density in Mimulus guttatus.

• Epigenetic inheritance, transgenerational transmission of traits not proximally determined by DNA sequence, has been linked to transmission of chromatin modifications and gene regulation, which are known to be sensitive to environmental factors. Mimulus guttatus increases trichome (plant hair) density in response to simulated herbivore damage. Increased density is expressed in progeny even if progeny do not experience damage. To better understand epigenetic inheritance of trichome production, we tested the hypothesis that candidate gene expression states are inherited in response to parental damage. • Using M. guttatus recombinant inbred lines, offspring of leaf-damaged and control plants were raised without damage. Relative expression of candidate trichome development genes was measured in offspring. Line and parental damage effects on trichome density were measured. Associations between gene expression, trichome density, and response to parental damage were determined. • We identified M. guttatus MYB MIXTA-like 8 as a possible negative regulator of trichome development. We found that parental leaf damage induces down-regulation of MYB MIXTA-like 8 in progeny, which is associated with epigenetically inherited increased trichome density. • Our results link epigenetic transmission of an ecologically important trait with differential gene expression states - providing insight into a mechanism underlying environmentally induced 'soft inheritance'.

Comparative analysis of remotely-sensed data products via ecological niche modeling of avian influenza case occurrences in Middle Eastern poultry.

BACKGROUND: Ecological niche modeling integrates known sites of occurrence of species or phenomena with data on environmental variation across landscapes to infer environmental spaces potentially inhabited (i.e., the ecological niche) to generate predictive maps of potential distributions in geographic space. Key inputs to this process include raster data layers characterizing spatial variation in environmental parameters, such as vegetation indices from remotely sensed satellite imagery. The extent to which ecological niche models reflect real-world distributions depends on a number of factors, but an obvious concern is the quality and content of the environmental data layers. METHODS: We assessed ecological niche model predictions of H5N1 avian flu presence quantitatively within and among four geographic regions, based on models incorporating two means of summarizing three vegetation indices derived from the MODIS satellite. We evaluated our models for predictive ability using partial ROC analysis and GLM ANOVA to compare performance among indices and regions. RESULTS: We found correlations between vegetation indices to be high, such that they contain information that overlaps broadly. Neither the type of vegetation index used nor method of summary affected model performance significantly. However, the degree to which model predictions had to be transferred (i.e., projected onto landscapes and conditions not represented on the landscape of training) impacted predictive strength greatly (within-region model predictions far out-performed models projected among regions). CONCLUSION: Our results provide the first quantitative tests of most appropriate uses of different remotely sensed data sets in ecological niche modeling applications. While our testing did not result in a decisive "best" index product or means of summarizing indices, it emphasizes the need for careful evaluation of products used in modeling (e.g. matching temporal dimensions and spatial resolution) for optimum performance, instead of simple reliance on large numbers of data layers.

The MicroRNA Landscape of Acute Beta Cell Destruction in Type 1 Diabetic Recipients of Intraportal Islet Grafts.

Ongoing beta cell death in type 1 diabetes (T1D) can be detected using biomarkers selectively discharged by dying beta cells into plasma. microRNA-375 (miR-375) ranks among the top biomarkers based on studies in animal models and human islet transplantation. Our objective was to identify additional microRNAs that are co-released with miR-375 proportionate to the amount of beta cell destruction. RT-PCR profiling of 733 microRNAs in a discovery cohort of T1D patients 1 h before/after islet transplantation indicated increased plasma levels of 22 microRNAs. Sub-selection for beta cell selectivity resulted in 15 microRNAs that were subjected to double-blinded multicenter analysis. This led to the identification of eight microRNAs that were consistently increased during early graft destruction: besides miR-375, these included miR-132/204/410/200a/429/125b, microRNAs with known function and enrichment in beta cells. Their potential clinical translation was investigated in a third independent cohort of 46 transplant patients by correlating post-transplant microRNA levels to C-peptide levels 2 months later. Only miR-375 and miR-132 had prognostic potential for graft outcome, and none of the newly identified microRNAs outperformed miR-375 in multiple regression. In conclusion, this study reveals multiple beta cell-enriched microRNAs that are co-released with miR-375 and can be used as complementary biomarkers of beta cell death.

The use of FDG-PET/CT and diffusion-weighted magnetic resonance imaging for response prediction before, during and after preoperative chemoradiotherapy for rectal cancer.

PURPOSE: To investigate the use of FDG-PET/CT before, during and after chemoradiotherapy (CRT) and diffusion-weighted magnetic resonance imaging (DW-MRI) before CRT for the prediction of pathological response (pCR) in rectal cancer patients. MATERIAL AND METHODS: Twenty-two rectal cancer patients treated with long course CRT were included. An FDG-PET/CT was performed prior to the start of CRT, after 10 to 12 fractions of CRT and five weeks after the end of CRT. The tumor was delineated using a gradient based delineation method and the maximal standardized uptake values (SUV(max)) were calculated. A DW-MRI was performed before start of CRT. Mean apparent diffusion coefficients (ADC) were determined. The ΔSUV(max) during and after CRT and the initial ADC values were correlated to the histopathological findings after total mesorectal excision (TME). RESULTS: ΔSUV(max) during and after CRT significantly correlated with the pathological response to treatment (during CRT: ΔSUV(max) = 59% ± 12% for pCR vs. 25% ± 27% if no pCR, p=0.0036; post-CRT: 90% ± 11 for pCR vs. 63% ± 22 if no pCR p=0.013). ROC curve analysis revealed an optimal threshold for ΔSUV(max) of 40% during CRT and 76% after CRT. The initial ADC value was also significantly correlated with pCR (0.94 ± 0.12 × 10(-3) mm(2)/s for pCR vs. 1.2 ± 0.24 × 10(-3) mm(2)/s, p=0.002) and ROC curve analysis revealed an optimal threshold of 1.06 × 10(-3) mm(2)/s. Combining the provided ΔSUV(max) thresholds during and after CRT increased specificity of the prediction (sensitivity 100% and specificity 94%). The combination of the thresholds for the initial ADC value and the ΔSUV(max) during CRT increased specificity of the prediction to a similar level (sensitivity of 100% and specificity of 94%). CONCLUSIONS: The combination of the different time points and the different imaging modalities increased the specificity of the response assessment both during and after CRT.

Combined Analysis of GAD65, miR-375, and Unmethylated Insulin DNA Following Islet Transplantation in Patients With T1D.

Aim: Several biomarkers have been proposed to detect pancreatic ß cell destruction in vivo but so far have not been compared for sensitivity and significance. Methods: We used islet transplantation as a model to compare plasma concentrations of miR-375, 65-kDa subunit of glutamate decarboxylase (GAD65), and unmethylated insulin DNA, measured at subpicomolar sensitivity, and study their discharge kinetics, power for outcome prediction, and detection of graft loss during follow-up. Results: At 60 minutes after transplantation, GAD65 and miR-375 consistently showed near-equimolar and correlated increases proportional to the number of implanted ß cells. GAD65 and miR-375 showed comparable power to predict poor graft outcome at 2 months, with areas under the curve of 0.833 and 0.771, respectively (P = 0.53). Using receiver operating characteristic analysis, we defined likelihood ratios (LRs) for rationally selected result intervals. In GADA-negative recipients (n = 28), GAD65 <4.5 pmol/L (LR = 0.15) and >12.2 pmol/L (LR = ∞) predicted good and poor outcomes, respectively. miR-375 could be used in all recipients irrespective of GAD65 autoantibody status (n = 46), with levels <1.4 pmol/L (LR = 0.14) or >7.6 pmol/L (LR = 9.53) as dual thresholds. The posttransplant surge of unmethylated insulin DNA was inconsistent and unrelated to outcome. Combined measurement of these three biomarkers was also tested as liquid biopsy for ß cell death during 2-month follow-up; incidental surges of GAD65, miR-375, and (un)methylated insulin DNA, alone or combined, were confidently detected but could not be related to outcome. Conclusions: GAD65 and miR-375 performed equally well in quantifying early graft destruction and predicting graft outcome, outperforming unmethylated insulin DNA.

Biological image-guided radiotherapy in rectal cancer: is there a role for FMISO or FLT, next to FDG?

PURPOSE: The purpose of this study is to investigate the use of PET/CT with fluorodeoxyglucose (FDG), fluorothymidine (FLT) and fluoromisonidazole (FMISO) for radiotherapy (RT) target definition and evolution in rectal cancer. MATERIALS AND METHODS: PET/CT was performed before and during preoperative chemoradiotherapy (CRT) in 15 patients with resectable rectal cancer. PET signals were delineated and CT images on the different time points were non-rigidly registered. Mismatch analyses were carried out to quantify the overlap between FDG and FLT or FMISO tumour volumes (TV) and between PET TVs over time. RESULTS: Ninety sequential PET/CT images were analyzed. The mean FDG, FLT and FMISO-PET TVs showed a tendency to shrink during preoperative CRT. On each time point, the mean FDG-PET TV was significantly larger than the FMISO-PET TV but not significantly larger than the mean FLT-PET TV. There was a mean 65% mismatch between the FMISO and FDG TVs obtained before and during CRT. FLT TVs corresponded better with the FDG TVs (25% mismatch before and 56% during CRT). During CRT, on average 61% of the mean FDG TV (7 cc) overlapped with the baseline mean TV (15.5 cc) (n=15). For FLT, the TV overlap was 49% (n=5) and for FMISO only 20% of the TV during CRT remained inside the contour at baseline (n=10). CONCLUSION: FDG, FLT and FMISO-PET reflect different functional characteristics that change during CRT in rectal cancer. FLT and FDG show good spatial correspondence, while FMISO seems less reliable due to the non-specific FMISO uptake in normoxic tissue and tracer diffusion through the bowel wall. FDG and FLT-PET/CT imaging seem most appropriate to integrate in preoperative RT for rectal cancer.

An analytical comparison of three immunoassay platforms for subpicomolar detection of protein biomarker GAD65.

A disproportional increase of circulating GAD65 within hours from an intraportal islet allotransplantation has been validated as biomarker of beta cell loss and poor functional outcome. More sensitive assays are, however, needed to allow detection of episodes of subtle beta cell loss during late-stage graft rejection or in the peri-onset period of type 1 diabetes. We applied the same sandwich monoclonal antibody couple reactive towards the C- and N-terminus of GAD65 on three advanced immunoassay platforms-the Cytometric Bead Array (CBA, Becton, Dickinson and Company), ElectroChemiLuminescence ImmunoAssay (ECLIA, Meso Scale Discovery) and digital ELISA technology (Single Molecule Array-SIMOA, Quanterix. We then compared analytical performance (linearity, imprecision, limit of detection and functional sensitivity), correlation of results, and practicality. All evaluated techniques showed linearity up to at least 500 ng/dL (76.9 pmol/L). SIMOA achieved the lowest imprecision. The 3 platforms correlate well with each other and could all detect subpicomolar concentrations of GAD65 in plasma, but only SIMOA and CBA could quantify down to that range. SIMOA can achieve the highest sample throughput. The three methods tested allow sensitive detection of GAD65, but SIMOA appears best suited for automated quantification of subpicomolar concentrations.

PET-based treatment planning in radiotherapy: a new standard?

Molecular imaging, in particular, PET, has brought an additional dimension to management for patients with cancer. 18F-FDG, which is the most widely available tracer, has been shown to be of value for the selection of target volumes in radiation oncology. Depending on its sensitivity and specificity, 18F-FDG has been shown to influence the selection of target volumes for non-small cell lung cancers (NSCLC) or for esophageal tumors. On the other hand, for tumors such as head and neck squamous cell carcinomas (HNSCC) and rectal carcinomas, convincing data on the value of 18F-FDG for target volume selection are still lacking. For target volume delineation, given that an adequate method is used for volume segmentation, the added value of 18F-FDG has been demonstrated for HNSCC and NSCLC. For both types of tumors, modifications in target volume delineation translated into differences in dose distribution compared with the results of CT scan-based plans. Studies are in progress for rectal tumors. Novel markers of tumor hypoxia or proliferation have the potential to modify the delineation of target volumes, allowing for "dose painting" in selected subvolumes. Finally, variations in tumor volume and viability during radiotherapy also are under intense investigation, potentially paving the way for so-called "theragnostic" or adaptive dose distribution during treatment. This review discusses how PET/CT might modify the current state of the art of radiotherapy planning.

Circulating microRNA-375 as biomarker of pancreatic beta cell death and protection of beta cell mass by cytoprotective compounds.

OBJECTIVE: Previous studies demonstrated that circulating microRNA-375 (miR-375) is a suitable plasma biomarker for real-time detection of beta cell death. The present study evaluated the use of this biomarker to assess the beta cytoprotective effect of phenylpropenoic acid glucoside (PPAG), which was previously demonstrated to protect beta cells against various types of injury, and of exendin-4, which is an established antidiabetic drug. METHODS: PPAG or exendin-4 were administered in mice treated with streptozotocin (STZ) to acutely induce beta cell death. Beta cell mass and apoptotic death were measured in pancreatic tissue sections. Circulating miR-375 was measured in blood plasma by RT-qPCR. The release of miR-375 was also measured in vitro by MIN-6 beta cells. RESULTS: Administration of STZ resulted in measurable circulating levels of miR-375, a decrease in beta cell mass and increase in frequency of apoptotic beta cells. In vitro, there was a good correlation between miR-375 release and the extent of beta cell death. Treatment of mice with PPAG or exendin-4 significantly attenuated STZ-induced loss of beta cell mass and beta cell apoptosis, and normalized the blood level of miR-375. CONCLUSIONS: These findings show the potential use of serological miR-375 measurements to evaluate the beta cytoprotective effect of (potential) antidiabetic drugs in vivo.

Definition and delineation of the clinical target volume for rectal cancer.

PURPOSE: Optimization of radiation techniques to maximize local tumor control and to minimize small bowel toxicity in locally advanced rectal cancer requires proper definition and delineation guidelines for the clinical target volume (CTV). The purpose of this investigation was to analyze reported data on the predominant locations and frequency of local recurrences and lymph node involvement in rectal cancer, to propose a definition of the CTV for rectal cancer and guidelines for its delineation. METHODS AND MATERIALS: Seven reports were analyzed to assess the incidence and predominant location of local recurrences in rectal cancer. The distribution of lymphatic spread was analyzed in another 10 reports to record the relative frequency and location of metastatic lymph nodes in rectal cancer, according to the stage and level of the primary tumor. RESULTS: The mesorectal, posterior, and inferior pelvic subsites are most at risk for local recurrences, whereas lymphatic tumor spread occurs mainly in three directions: upward into the inferior mesenteric nodes; lateral into the internal iliac lymph nodes; and, in a few cases, downward into the external iliac and inguinal lymph nodes. The risk for recurrence or lymph node involvement is related to the stage and the level of the primary lesion. CONCLUSION: Based on a review of articles reporting on the incidence and predominant location of local recurrences and the distribution of lymphatic spread in rectal cancer, we defined guidelines for CTV delineation including the pelvic subsites and lymph node groups at risk for microscopic involvement. We propose to include the primary tumor, the mesorectal subsite, and the posterior pelvic subsite in the CTV in all patients. Moreover, the lateral lymph nodes are at high risk for microscopic involvement and should also be added in the CTV.

Molecular responses of rectal cancer to preoperative chemoradiation.

BACKGROUND AND PURPOSE: Some rectal cancers respond well to preoperative neoadjuvant therapy while others are inherently resistant or develop resistance during the treatment. To understand the mechanism underlying these differences, several markers that might be prognostic or predictive of downstaging in response to chemoradiotherapy in patients with rectal cancer were evaluated. MATERIAL AND METHODS: Thirty patients were enrolled in this study. All were treated with preoperative chemoradiation (45Gy in 25 fractions+5-FU). Paraffin-embedded sections obtained before and after therapy were stained by H&E, for COX-2, and Ki67. In addition, osteopontin and IL-6 concentrations were determined in blood samples obtained before, during, and after therapy. RESULTS: COX-2 expression increased in 67% (n=8/12) of the patients from a median of 0% before to 74% after therapy (p=0.009). Ki67 median positivity diminished from 90% to 45% in 83% (n=10/12) of cases (p=0.007). Osteopontin expression showed no significant changes during therapy, whereas IL-6 expression levels increased in 70% (n=19/27) of all patients (p<0.001). For osteopontin and IL-6, patients with a complete response tended to have lower pre-therapy levels. Moreover, osteopontin was much higher before (p=0.02) and after therapy (p=0.01) in patients who later developed metastases. CONCLUSIONS: Chemoradiotherapy seems to affect expression of COX-2 and Ki67 which indicates that these proteins might be of importance in predicting long-term outcome. Moreover, osteopontin might be a marker of metastases.

Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project.

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice.

Detection and plant monitoring programs: lessons from an intensive survey of Asclepias meadii with five observers.

Monitoring programs, where numbers of individuals are followed through time, are central to conservation. Although incomplete detection is expected with wildlife surveys, this topic is rarely considered with plants. However, if plants are missed in surveys, raw count data can lead to biased estimates of population abundance and vital rates. To illustrate, we had five independent observers survey patches of the rare plant Asclepias meadii at two prairie sites. We analyzed data with two mark-recapture approaches. Using the program CAPTURE, the estimated number of patches equaled the detected number for a burned site, but exceeded detected numbers by 28% for an unburned site. Analyses of detected patches using Huggins models revealed important effects of observer, patch state (flowering/nonflowering), and patch size (number of stems) on probabilities of detection. Although some results were expected (i.e. greater detection of flowering than nonflowering patches), the importance of our approach is the ability to quantify the magnitude of detection problems. We also evaluated the degree to which increased observer numbers improved detection: smaller groups (3-4 observers) generally found 90 - 99% of the patches found by all five people, but pairs of observers or single observers had high error and detection depended on which individuals were involved. We conclude that an intensive study at the start of a long-term monitoring study provides essential information about probabilities of detection and what factors cause plants to be missed. This information can guide development of monitoring programs.

Value of diffusion-weighted magnetic resonance imaging for prediction and early assessment of response to neoadjuvant radiochemotherapy in rectal cancer: preliminary results.

PURPOSE: To evaluate diffusion-weighted magnetic resonance imaging (DWI) for response prediction before and response assessment during and early after preoperative radiochemotherapy (RCT) for locally advanced rectal cancer (LARC). METHODS AND MATERIALS: Twenty patients receiving RCT for LARC underwent MRI including DWI before RCT, after 10-15 fractions and 1 to 2 weeks before surgery. Tumor volume and apparent diffusion coefficient (ADC; b-values: 0-1000 s/mm(2)) were determined at all time points. Pretreatment tumor ADC and volume, tumor ADC change (∆ADC), and volume change (∆V) between pretreatment and follow-up examinations were compared with histopathologic findings after total mesorectal excision (pathologic complete response [pCR] vs. no pCR, ypT0-2 vs. ypT3-4, T-downstaging or not). The discriminatory capability of pretreatment tumor ADC and volume, ∆ADC, and ∆V for the detection of pCR was compared with receiver operating characteristics analysis. RESULTS: Pretreatment ADC was significantly lower in patients with pCR compared with patients without (in mm(2)/s: 0.94 ± 0.12 × 10(-3) vs. 1.19 ± 0.22 × 10(-3), p = 0.003), yielding a sensitivity of 100% and specificity of 86% for detection of pCR. The volume reduction during and after RCT was significantly higher in patients with pCR compared with patients without (in %: ΔV(during): -62 ± 16 vs. -33 ± 16, respectively, p = 0.015; and ΔV(post): -86 ± 12 vs. -60 ± 21, p = 0.012), yielding a sensitivity of 83% and specificity of 71% for the ΔV(during) and, respectively, 83% and 86% for the ΔV(post). The ∆ADC during (ΔADC(during)) and after RCT (ΔADC(post)) showed a significantly higher value in patients with pCR compared with patients without (in %: ΔADC(during): 72 ± 14 vs. 16 ± 12, p = 0.0006; and ΔADC(post): 88 ± 35 vs. 26 ± 19, p = 0.0011), yielding a sensitivity and specificity of 100% for the ΔADC(during) and, respectively, 100% and 93% for the ΔADC(post). CONCLUSIONS: These initial findings indicate that DWI, using pretreatment ADC, ΔADC(during), and ΔADC(post) may be useful for prediction and early assessment of pathologic response to preoperative RCT of LARC, with higher accuracy than volumetric measurements.