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Prostate rebiopsy is a poor surrogate of treatment efficacy in localized prostate cancer.

PURPOSE: Many investigators use prostate rebiopsy as an indicator of treatment efficacy and tumor response of localized prostate cancer for therapies in which the gland remains in situ. Because of the inherent sampling error of needle directed biopsies, however, some men will have a false-negative rebiopsy even if they have had no therapy or if the therapeutic intervention was unsuccessful in eradicating the malignancy. We evaluate the risk of a false-negative biopsy and the clinical factors that influence this risk. MATERIALS AND METHODS: A total of 90 patients undergoing radical prostatectomy for clinically localized disease underwent sextant biopsy of the prostate immediately after removal of the gland. Data collected included prostate specific antigen (PSA), hormonal status, age and biopsy core status. RESULTS: Of the total study population 67.8% received neoadjuvant hormonal therapy. While all patients had pathologically confirmed adenocarcinoma within the prostatectomy specimen, 45.6% demonstrated a false-negative rebiopsy. Within a combined predictive model, PSA and hormonal status demonstrated a statistically significant effect on the false-negative rebiopsy rate. Predictive power of this combined model was high across the spectrum of risk for a false-negative rebiopsy. CONCLUSIONS: This series demonstrates that the risk of a false-negative sextant biopsy in the presence of documented prostate cancer is high and is affected by several factors, including PSA and hormonal status. These data suggest that prostate sextant rebiopsy is an inaccurate method of assessing the therapeutic efficacy of treatments for carcinoma of the prostate in which the gland remains in situ following therapy.

Adenocarcinoma↗

Psychophysiological assessment of respiratory function in panic disorder: evidence for a hyperventilation subtype.

OBJECTIVE: Previous research has found differences in respiratory function between panic disorder and other anxiety disorder populations. These differences have been explained as reflecting either a) a specific feature of panic disorder, b) merely a sign of increased general arousal, or c) a result of population sampling error. The current study addressed the question of such differences by using improved methodology over previous research. A preliminary evaluation of respiratory symptoms during panic attacks was undertaken as a means of identifying a respiratory-sensitive subtype of the panic patient. METHOD: Seventeen panic disorder patients (PD), 18 patients with generalized anxiety disorder (GAD), and 20 normal control (NC) subjects were administered a psychophysiological evaluation composed of baseline, stressor, and recovery phases. Panic patients were measured for the severity of respiratory symptoms during panic attacks. End-tidal CO2 (EtCO2) and respiration rate were measured throughout the psychophysiological evaluation. RESULTS: PDs demonstrated significantly lower baseline EtCO2 levels than the GADs and NCs, in spite of being equivalent to GADs on baseline anxiety levels. Moreover, panic patients reporting a high level of respiratory symptoms during panic attacks seemed to account for the bulk of observed differences. CONCLUSIONS: These findings lend support to a group of studies showing differences in respiratory function between panic disorder and other anxiety disorder populations. In addition, this study provides preliminary support for the presence of a distinct "hyperventilation subtype" of panic disorder. The implications of these findings for future research and treatment are discussed.

Adult↗

An evaluation of rectal epithelial proliferation measurement as biomarker of risk for colorectal neoplasia and response in intervention studies.

Colorectal carcinogenesis is preceded by a phase of epithelial hyperproliferation. Detection and measurement of this hyperproliferation could be useful as a marker of risk for neoplasia or a measure of response to intervention therapy. Today, bromodeoxyuridine labelling and immunohistology is the easiest to perform and most standardized technique for evaluating proliferation in experimental and human studies. In general, measurement of proliferation has fulfilled expectation in experimental studies, however, in humans it has been less conclusive. The reasons are multifactorial and include: limitations in obtaining tissue samples and sampling error, the type of labelling technique used, lack of an objective method for quantifying proliferation and confounding factors influencing the degree of proliferation. The use of matched controls, sophisticated statistical analysis and the search for trends and not just statistical significance, is to be recommended. At present, evaluation of rectal epithelial proliferation is of limited value in assessing risk for colorectal neoplasia in the individual. On the other hand, it seems a useful biomarker of response within the context of a matched control intervention trial.

Biomarkers↗

Clonal analysis of colorectal tumors using K-ras and p53 gene mutations as markers.

Mutations to the K-ras oncogene and p53 tumor suppressor gene are two of the most common genetic lesions in human cancers. In the present study we examined the clonality of colorectal tumors with respect to each of these genetic alterations. Screening for mutations was carried out using the polymerase chain reaction-based technique of single-strand conformation polymorphism. Eleven primary colorectal adenocarcinomas and two secondary adenocarcinomas were analyzed at four different sites within the tumor. Involved pericolic lymph nodes were collected from nine of these cases, a metastatic deposit in the liver was obtained in one case, and adjacent adenomatous lesions were collected in two cases. Seven tumors contained mutations in either the K-ras or p53 genes. In all cases, DNA derived from multiple sites within an individual tumor or metastatic deposits arising from that tumor showed the same pattern of gene mutation. Immunohistochemical staining for p53 protein overexpression also showed similar patterns of reactivity within individual tumors and their metastatic deposits. These results suggest that the major clonal expansion of colorectal carcinomas occurs after the acquisition of mutations in these genes. Our results also indicate that sampling errors are unlikely to occur in molecular studies aimed at defining the role of these genes in colorectal cancer progression.

Carcinoma↗

Is immunostaining for Helicobacter pylori superior to the special stain thiazine in detecting small numbers of H. pylori in gastric biopsies?

Helicobacter pylori is implicated in the pathogenesis of gastritis and duodenal ulcers, gastric lymphoma of the mucosa-associated lymphoid tissue (MALT) type, and gastric adenocarcinoma. Eradication of H. pylori with antibiotic therapy therefore is essential, not only for the successful treatment of active gastritis, but also for the treatment and prevention of the MALT lymphoma. It has been suggested recently that immunostaining for H. pylori is more sensitive than special stains for the detection of the organism in the gastric biopsies after triple therapy. Fifty-five endoscopic mucosal biopsies from 38 patients, including 18 treated with H. pylori eradication therapy, were selected for immunostaining because they were either negative or contained rare H. pylori organisms by thiazine stain. Formalin-fixed, paraffin-embedded tissue sections were immunostained for H. pylori using a polyclonal antibody using standard immunoperoxidase technique. The results were compared with those obtained with the thiazine stain. Detection of H. pylori by immunostaining was easier and less time-consuming than by thiazine stain. There was complete agreement between immunostaining and thiazine stain in 48 (87%) cases. Of the 7 discordant cases, 3 (42%) were positive for H. pylori with thiazine only and 4 (48%) with immunostaining only. Given the nature of the selection of the study sample (absent to rare by thiazine stain), the discordance most likely represents a sampling error. The authors concluded that immunostaining for H. pylori did not appear to be more sensitive than special stains. Three cases with bacterial clumps were diagnosed previously as positive for H. pylori, but identified correctly as negative using both staining methods. Pathologists, however, should balance the added cost to patients of immunostaining against the time saved by the easier screening of the immunostained slides and the possibility of false positive results when special stains are interpreted by inexperienced pathologists.

Biopsy↗

The quality of community colposcopic practice.

OBJECTIVE: To estimate the quality of community colposcopic practice in British Columbia through an assessment of the degree of correlation between colposcopy, cytology, and histology. METHOD: We reviewed all new-patient colposcopies in British Columbia during 2001 by 37 gynecologists in 24 hospital-based clinics. RESULTS: Colposcopic impression closely mirrored the referral cytology diagnosis in 89.8% of cases. As with cytology-biopsy comparisons, discordant cases were more likely to be overestimates of disease rather than underestimates, 18.8% versus 1.8%. Overestimates were usually biopsy sampling errors rather than false positive cytology. The overall correlation between cytology and biopsy was considered satisfactory in 79.4% of cases. Satisfactory agreement between the colposcopic diagnosis and accompanying biopsies occurred in 86.8% of patients. Five colposcopists had performance scores below this standard. Colposcopy with a sensitivity of 90.3% and a specificity of 57.3% as practiced in this provincial program would appear to be of a satisfactory level. The rate of intraepithelial or invasive disease increased from 40.6% in patients with low-grade squamous intraepithelial changes to 91.9% in patients with suspicious or malignant cytology. The value of the colposcopic impression to identify disease correlated best with the higher the grade of disease predicted (64.6% to 92.6%). CONCLUSION: A measure of the colposcopic proficiency in the community can be estimated by comparing the level of agreement between the presenting cytology, colposcopic impression, and corresponding directed biopsies. The results of this study would indicate that 5 individuals had practice standards that were below average. An integrated cytology-colposcopy program facilitates the assessment and identification of below-average practice standards in a community.

Adult↗

Paracervical block in incomplete abortion using manual vacuum aspiration: randomized clinical trial.

OBJECTIVE: To estimate the effectiveness of paracervical block in controlling pain among women treated with manual vacuum aspiration for an incomplete abortion METHODS: A randomized clinical trial was conducted at Nuestra Señora de Altagracia, a maternal and perinatal referral hospital in the Dominican Republic. The sample size was based on a clinical difference of 1.5 points in the level of pain measured with the visual analog scale using 90% power and a sampling error of 0.04. Women who were at 12 weeks of gestation or less with an incomplete abortion were eligible to participate. They were randomly assigned to receive either the standard treatment of care (manual vacuum aspiration for uterine evacuation with psychological support but no paracervical block) or manual vacuum aspiration treatment with psychological support and paracervical block using 1.0% lidocaine. Patients with active infections, severe illnesses, psychiatric disorders, or allergies to lidocaine were excluded. Intraoperative pain as reported by the women and as documented by an external observer was measured. RESULTS: Although the paracervical block technique used showed a slight reduction in severe pain, there were no clinically or statistically significant differences in intraoperative pain between the 2 groups (relative risk 0.73; 95% confidence interval 0.43, 1.23) with 50% of all patients registering 7 or higher score on a visual analog pain scale of 0-10. However, statistically significant differences were found in each group when comparing the level of preoperative and intraoperative pain described by the patient (P <.001). The manual vacuum aspiration technique and the paracervical block were not accompanied by complications. CONCLUSION: The paracervical block technique used in this study along with psychological support was comparable with pain control using psychological support alone; neither pain management regimen provided sufficient pain control. It is recommended that randomized comparative studies be designed to determine the effectiveness of other paracervical block techniques and the efficacy of the use of analgesics in patients suffering from incomplete abortion treated with manual vacuum aspiration.

Abortion, Incomplete↗

The risk of false-positive results in orthopaedic surgical trials.

The risk of concluding that the results of a particular study are true, when, in fact, they really are attributable to chance (or random sampling error) is underappreciated by investigators. This erroneous false-positive conclusion is designated as a Type I or alpha error. The extent to which randomized trials in surgery risk Type I errors is unclear. The current authors hand-searched four orthopaedic journals, six general surgery journals, and five medical journals to identify recently published randomized trials (within the past 2 years). Information on outcomes and statistical adjustment for multiple outcomes was recorded for each study. The risk of a Type I error was calculated for each study that did not explicitly state a primary outcome measure for the main statistical comparison. One hundred fifty-nine studies met the inclusion criteria for the study: 60 studies from orthopaedic journals, 49 studies from nonorthopaedic surgical journals, and 50 studies from medical journals. Of the trials that did not state a primary outcome measure, the risk of Type I errors (false-positive results) in orthopaedic and nonorthopaedic surgery journals (mean 37.3% +/- 13.3% and 37.6% +/- 10.5%, respectively) were significantly greater than medical journals (10.1% +/- 1.9%). In the current review of randomized trials in surgery and medicine, the following is reported: (1) reporting of primary outcomes in trials was inadequate; (2) one in three trials in surgery and one in 10 trials in medicine risked false-positive results; and (3) few trials in surgery and medicine considered adjustment for multiple comparisons.

Humans↗

How to avoid false-negative dynamic sentinel node procedures in penile carcinoma.

PURPOSE: Evaluation of the false-negative dynamic sentinel node procedures in penile carcinoma at our institute. MATERIALS AND METHODS: Between January 1994 and February 2003, 123 patients with penile squamous cell carcinoma underwent dynamic sentinel node biopsy. RESULTS: The sentinel node revealed metastasis in 28 (23%) of 123 patients. Regional recurrence after excision of a tumor-negative sentinel node or after nonvisualization was seen in 6 patients resulting in a false-negative rate of 18% (6 of 34). We assume that 1 false-negative case was due to tumor blockage, 3 to tumor blockage and rerouting, 1 to a pathological sampling error and 1 to a low radioactivity level in the sentinel node during surgery. CONCLUSIONS: Based on the false-negative results, important adaptations have been made in the dynamic sentinel node biopsy procedure for penile carcinoma at our institute. Pathological analysis was extended by serial sectioning and immunohistochemical staining, and preoperative ultrasonography with fine needle aspiration cytology has been added. Furthermore, exploration of groin without visualized sentinel nodes and intraoperative palpation of the wound have been introduced.

Adult↗

The effects of 5alpha-reductase inhibitors on the natural history, detection and grading of prostate cancer: current state of knowledge.

PURPOSE: The Prostate Cancer Prevention Trial (PCPT) showed that the 5alpha-reductase inhibitor (5ARI) finasteride significantly decreased the 7-year period prevalence of prostate cancer vs placebo. However, Gleason score 7-10 tumors were significantly more common in the finasteride vs the placebo group. We considered data on the effects of 5ARIs on prostate cancer natural history and detection. MATERIALS AND METHODS: A detailed review was performed of the literature identified from the MEDLINE database examining the effects of 5ARIs on prostate cancer prevalence and tumor histopathology. RESULTS: In PCPT there were fewer biopsies performed for cause in the finasteride vs the placebo group and the proportion of high grade tumors in the treatment groups did not diverge with time. Given that finasteride has an effect on prostate specific antigen and prostate volume, which are key factors in triggering prostate biopsies, they may be significant confounders of Gleason score results. Prostate shrinkage in the finasteride treated group may minimize biopsy sampling error. Furthermore, histological studies have shown that 5ARIs have a significant effect on prostate architecture, which can make the interpretation of prostate specimens in men treated with 5ARIs difficult. Further evaluation of PCPT findings will help determine the true nature of these observations. CONCLUSIONS: 5ARIs decrease the risk of prostate cancer but also alter the detection of disease through effects on prostate specific antigen, and prostate volume and histology. The weight of evidence suggests an artifactual effect of finasteride on Gleason grading in the PCPT. The role of 5ARIs for prostate cancer chemoprevention needs further examination before it can be considered for wide recommendation.

Antineoplastic Agents↗

Discriminating vital tumor from necrotic tissue in human glioblastoma tissue samples by Raman spectroscopy.

Vital and necrotic glioblastoma tissues were studied by Raman microspectroscopy to identify possibilities for the development of an in vivo Raman method for real-time intraoperative brain biopsy guidance. The histologic malignancy grade of gliomas depends on the presence of parameters such as endothelial proliferation and necrosis, which are often not evenly distributed within the tumor. Because tissue samples obtained by stereotactic surgery are relatively small, sampling errors may easily occur by missing these crucial features. Although necrosis is important for grading, specimens containing only necrosis are diagnostically useless. Raman microspectroscopic mapping experiments were performed on unfixed cryosections of glioblastoma, obtained from 20 patients. After spectral acquisition, a clustering analysis was performed, resulting in groups of similar spectra. Each cluster was assigned a color, and pseudo-color Raman maps of the tissue sections were constructed. After the Raman experiments, the tissue sections were stained for histopathologic analysis, enabling identification of the histologic origin of the Raman spectra and assignment of the Raman spectral clusters to either vital or necrotic tissue. A classification model for discrimination between vital and necrotic tumor tissue based on linear discriminant analysis was developed. The classification model was evaluated using independent Raman data obtained from nine other tissue sections and yielded 100% accuracy. Information about the biochemical differences between necrosis and vital tumor was obtained by the analysis of difference spectra. Necrotic tissue was found to consistently contain higher levels of cholesterol (-esters). This in vitro result indicates that Raman spectra contain the information to distinguish vital glioblastoma from necrosis and makes Raman spectroscopy a powerful candidate for guidance of stereotactic brain biopsy.

Brain↗

Surveillance and screening for Barrett esophagus and adenocarcinoma.

Current recommendations for screening and surveillance of Barrett esophagus and related lesions are based on recent guidelines by the Practice Parameters Committee of the American College of Gastroenterology. The purpose of this review is to critically examine the rationale and evidence behind these recommendations. There is strong rationale for vigorous initial testing to document the baseline status and identify early adenocarcinoma, and for surveillance of high-grade dysplasia. Recommendations for esophagectomy in patients with high-grade dysplasia need to be individualized. However, recommendations for surveillance of low-grade dysplasia and specialized intestinal metaplasia without dysplasia are largely opinion statements not well supported by objective data. Although cancers identified by surveillance are at earlier stages than those diagnosed without prior endoscopic evaluation, surveillance failures are common. Recommendations for screening and surveillance are not evidence-based and unlikely to alter national mortality from esophageal adenocarcinoma. Their impact on individual patients depends on individual circumstances. Current recommendations are limited by inconsistent endoscopic findings and sampling errors, inconsistent histologic diagnoses of Barrett esophagus and dysplasia, and our poor understanding of the natural history of various histologic lesions. Future directions include validation of methods that reduce these inconsistencies by in vivo detection of abnormalities and by objective diagnostic markers besides grades of dysplasia, such DNA content analysis and molecular markers, and improved understanding of the disease progression. Effective screening programs depend on development of simple, inexpensive, and reliable methods to identify the small group of patients truly at high risk for adenocarcinoma for endoscopic screening.

Adenocarcinoma↗

The organizing pneumonias: an update and review.

PURPOSE OF REVIEW: Basic information as well as more recent concepts regarding cryptogenic organizing pneumonia and secondary forms of the disease. RECENT FINDINGS: More recently described and less well recognized illnesses associated with organizing pneumonia, such as organizing pneumonia associated with radiation, are enumerated. In vitro studies from separate laboratories are integrated to create a proposed model of the pathogenesis and repair mechanisms that occur in organizing pneumonias. Using current criteria, we note other interstitial lung processes, in addition to organizing pneumonia, are present in some earlier reports. SUMMARY: Cryptogenic organizing pneumonia has been reported to respond to corticosteroids with clinico-radiographic resolution in 70-80% of cases. Treatment duration is lengthy, and despite this, recurrences and late recurrences are common. Rapidly progressive, steroid resistant and poor prognostic forms of organizing pneumonia have been described and have been reported more frequently with secondary organizing pneumonia. Since other histologic interstitial patterns often coexist with organizing pneumonia, tissue sampling error or an incorrect morphologic diagnosis can be the reason for aggressive clinical behavior. Steroid nonresponsive patients have been treated with secondary non-steroidal agents. Good clinical outcomes have been reported. Inhaled antigens stimulate GM-CSF-mediated airway inflammation in organizing pneumonia. Repair requires the following: granulation tissue, upon which re-epithelialization occurs; a favorable stromal ratio of matrix metalloproteinase to tissue inhibitors of metalloproteinase; concurrent resolution of inflammation; and stromal fibroblast ingestion of collagen produced earlier in repair, reversing the initial fibrosis.

Bronchi↗

Significance of persistent mature rhabdomyoblasts in bladder/prostate rhabdomyosarcoma: Results from IRS IV.

Terminally differentiated rhabdomyoblasts are common after or during therapy for rhabdomyosarcoma (RMS). Case reports have suggested that their presence after therapy does not indicate a poor prognosis, but significance and relationship to outcome has not been systematically studied. Management of patients with this finding can cause confusion. Slides and pathology reports from 44 patients with bladder/prostate RMS treated on Fourth Intergroup Rhabdomyosarcoma Study were examined by a pathologist experienced in RMS, and findings compared with institutional reports. Details regarding patient characteristics, outcome, and management were reviewed. Outcome of patients with various pathologic findings was assessed. One of 10 patients with only mature rhabdomyoblasts at their last procedure recurred, versus 4 of 17 patients with viable tumor and 2 of 17 patients with no viable tumor and no rhabdomyoblasts. Sixteen of 42 cases reviewed had results differing from our review. Mature rhabdomyoblasts are a discrete entity which may not be predictive of recurrence, but should be evaluated by a pathologist experienced with this entity. The presence of mature rhabdomyoblasts at the end of therapy for bladder/prostate RMS does not justify radical surgery. Sequential biopsies are subject to sampling error and should only be performed in the context of protocol-directed therapy to avoid unnecessary radical surgeries.

Antineoplastic Agents↗

Characterization of micrometastatic disease in melanoma sentinel lymph nodes by enhanced pathology: recommendations for standardizing pathologic analysis.

Lymphatic mapping and sentinel lymph node (SLN) biopsy are widely used as a staging technique for patients with cutaneous malignant melanoma who are at risk for metastases. SLN status has been shown to be a strong predictor of prognosis, and a variety of techniques have been used to identify minimal metastatic disease in SLNs. However, there is no validated consensus method for the optimal histologic analysis of SLNs harvested from melanoma patients. This study was conducted: 1) to assess the yield of metastatic melanoma detected in SLNs deemed negative by initial routine pathologic analysis (RPA) by subjecting them (after review of the original slides) to enhanced pathologic analysis (EPA) that included complete step-sectioning and immunohistochemistry (IHC); 2) to characterize the distribution of metastatic melanoma deposits within the SLNs; 3) to determine a preferred method of pathologic analysis applicable to daily practice; and 4) to attempt to assess the clinical significance of disease detected by EPA. A total of 105 SLNs were harvested from 49 patients who underwent successful SLN biopsy procedures during the period of study. Ten SLNs from 10 patients were positive on initial RPA and were not analyzed further. Ninety-five SLNs from the remaining 39 patients were reviewed and processed with additional hematoxylin and eosin, S-100 protein, and HMB-45 stains at 50-microm intervals for 20 levels or until the SLN tissue was exhausted. A single pathologist reviewed all sections without knowledge of the results of the other stains. Overall, metastatic melanoma was discovered in SLNs from 20 of the 39 patients: SLNs from 6 patients were found to have melanoma on review of the original hematoxylin and eosin slides, and SLNs from 14 patients were positive only after EPA. Twenty-one individual positive SLNs from these 14 patients were detected by EPA; of these, 10 positive SLNs were identified solely by IHC, representing 12% of the patient cohort and 10% of all SLNs studied by EPA. Detection rates were significantly associated with the staining method and the number of levels performed (P < 0.01). S-100 protein staining resulted in the highest yield of SLN positivity (86%), followed by HMB-45 (81%) and hematoxylin and eosin (52%). No single method detected all of the micrometastases. A detailed topographic mapping of metastatic deposits in SLNs was carried out. When using all three staining techniques, all 20 levels were required to identify 100% of the micrometastases; 95% of positive SLNs were identified with 17 levels, 90% with 15 levels, 75% with 10 levels, and 42% with 3 levels. Projected rates of detection for various different sectioning strategies were determined, with alteration of either the number of levels examined, the interval between the levels, or both. Detection of SLN positivity can be increased to 71% by performing three levels at 250-mum intervals, each level being composed of a set of three sections stained with hematoxylin and eosin, S-100 protein, and HMB-45, respectively. Therefore, this is the methodology we propose for the study of SLNs in melanoma patients. After a median follow-up of 87 months (range, 9-134 months), patients with EPA-detected disease and those with negative SLNs by EPA demonstrated improved recurrence-free and disease-specific survival compared with patients with RPA-detected disease in SLNs. Sampling error introduced by variations in pathologic processing should be addressed by standardization of pathologic methods, and the clinical significance of minimal SLN disease should be addressed in prospective studies of homogeneously staged patients.

Adult↗

Follow-up surgical excision is indicated when breast core needle biopsies show atypical lobular hyperplasia or lobular carcinoma in situ: a correlative study of 33 patients with review of the literature.

Atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) diagnosed in core needle biopsy (CNB) are generally regarded as risk indicators for developing invasive ductal or lobular carcinoma in either breast. Currently, there are no well-established guidelines for management of these patients. The most common management options are careful observation and endocrine chemoprophylaxis for high-risk patients. Previous studies had contradicting recommendations regarding follow-up surgical excision (FSE) of CNB yielding ALH or LCIS. These studies, unfortunately, have been limited by their retrospective nature, small number of patients examined, and association with other high-risk lesions. Only CNB diagnosed as pure LCIS or ALH (not associated with other high-risk lesions such as ADH, radial scar, or papilloma) were included in the study. We reviewed 33 CNB (20 ALH and 13 LCIS) with subsequent FSE from 33 patients (age range, 30-83 years; mean, 58 years). Eighteen of these patients were prospectively analyzed, where FSE was performed in an unselected fashion. All CNBs were obtained by mammotome (11-gauge, 30 cases; and 14-gauge, 3 cases). Mammography identified calcifications in 29 cases (88%) and a mass in 4 cases (12%). FSE revealed infiltrating ductal and/or lobular carcinoma in 4 of 13 LCIS (31%). FSE of 20 ALH revealed cancer in 5 cases (25%), including 4 ductal carcinoma in situ (DCIS) and 1 invasive lobular carcinoma. Seven of these nine cancers were associated with calcifications, and two presented as masses. Sampling error and underestimation of cancer (DCIS or invasive carcinoma) was associated with CNB diagnosis of LCIS or ALH in 27% of all cases. Underestimation of cancer was seen in 28% of prospectively examined patients, including 20% of ALH and 38% of LCIS. CNB associated with mass lesions or that showed histologic features of pleomorphic LCIS or extensive classic LCIS had a higher rate of cancer underestimation. Despite removal of all abnormal mammographic calcifications by CNB in 6 patients, one cancer was detected on FSE. To the best of our knowledge, this is the largest study reported to date, and the only one to include prospectively examined patients with no pre-selection bias. Our data strongly suggests that subsequent FSE is warranted in all patients with CNB diagnoses of LCIS or ALH, to exclude the presence of cancer.

Adult↗

Mucinous cystic neoplasms of the pancreas.

Mucinous cystic neoplasms of the pancreas (MCNP) are rare tumors with presentation and findings that differ in most cases from pancreatic pseudocysts. A simple pancreatic cystic lesion in a younger-aged patient with a history of pancreatitis and endoscopic retrograde cholangiopancreatography (ERCP) demonstration of ductal communication with the cyst strongly suggests the diagnosis of a benign pseudocyst. MCNP may have extensive areas without an epithelial lining, adding histologic sampling error to the potential for confusing these two entities. Pancreatic pseudocysts are benign lesions treated by enteric drainage procedures, while MCNP have significant malignant potential, and resection is advised. Even when clinical presentation and imaging are persuasive for a benign cyst, MCNP of the pancreas should be considered in planning, evaluation, and treatment.

Adult↗

Facultative primary sex ratio variation: a lack of evidence in birds?

The facultative control of primary sex ratio by breeding birds has become a major focus in evolutionary biology in recent years. A combination of well-developed theoretical literature and rapid publication of empirical results has created considerable confusion, with controversial claims for both extreme control of primary sex ratio versus no control around inherent random variability. We present a robust and quantitative summary of published empirical literature to assess clearly the body of evidence for female birds to control sex assignment in their offspring. Our meta-analytical approach reveals that published studies do not exhibit any variability beyond that which could be expected owing to sampling error. Therefore, we conclude that facultative control of offspring sex is not a characteristic biological phenomenon in breeding birds.

Animals↗