US and Digital Breast Tomosynthesis in Women with Focal Breast Complaints: Results of the Breast US Trial (BUST).

Background Digital breast tomosynthesis (DBT) followed by targeted US is commonly performed to evaluate women with localized breast complaints. However, the added value of DBT in addition to targeted US is unknown. Omitting DBT may be cost-effective and improve patient comfort but may miss potential breast cancer. Purpose To assess whether an imaging protocol consisting of targeted US alone may be feasible for the diagnostic work-up of women with localized symptoms and to assess the supplemental value of DBT in this reversed setting. Materials and Methods This prospective study enrolled consecutive women aged 30 years or older with focal breast complaints in three hospitals in the Netherlands between September 2017 and June 2019. In all participants, first, targeted US was evaluated, and if needed, biopsy was performed, followed by DBT. The primary outcome was the frequency of breast cancer detected with DBT when US was negative. Secondary outcomes were frequency of cancer detected with DBT elsewhere in the breast and combined overall sensitivity of US plus DBT. The reference standard was 1 year follow-up or histopathologic examination. Results There were 1961 women (mean age ± SD, 47 years ± 12) enrolled. Based on initial US alone, 1587 participants (81%) had normal or benign findings and 1759 (90%) had a definitive accurate diagnosis. In total, 204 breast cancers were detected during initial work-up. The frequency of malignancy was 10% (192 of 1961 participants) with US (US sensitivity, 98.5% [95% CI: 96, 100]; US specificity, 90.8% [95% CI: 89, 92]). DBT depicted three unobserved malignant lesions at the complaint site and 0.41% (eight of 1961 participants) of incidental malignant findings in participants without symptomatic cancer. Conclusion Compared with combined US and DBT, US was accurate as a stand-alone breast imaging modality in the assessment of focal breast complaints. The rate of cancer detection of cancers elsewhere in the breast with DBT is comparable to cancer detection rate of screening mammography. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Newell in this issue.

The value of mammography in women with focal breast complaints in addition to initial targeted ultrasound.

PURPOSE: To determine the added value of mammography in women with focal breast complaints and the utility of initial targeted ultrasound in this setting. METHODS: Women with symptomatic breast disease who were evaluated by breast imaging (mammography/digital breast tomosynthesis and ultrasound) between January 2016 and December 2016 in the Radboud University Medical Centre were included. We retrospectively collected the following data: date of birth, indication of imaging, visibility on mammography/ultrasound, whether biopsy was taken, additional findings, BI-RADS-classification, pathology and follow-up results. RESULTS: A total of 494 women were included (mean age 46.5, range 30 to 93). In 49 women (9.9%), symptomatic breast cancer was diagnosed, all visible during targeted ultrasound. The negative predictive value of targeted ultrasound was very high (99.8%). Additional findings on mammography were significantly more often malignant when the symptomatic lesion was also malignant (3.8% vs 70%, P < 0.05). In only one patient with symptoms caused by a benign finding, an incidental malignancy was detected on mammography outside the area of complaint (detection rate 2.2/1000 examinations). CONCLUSIONS: The contribution of mammography for cancer detection in women with focal breast complaints is very low when targeted ultrasound is performed. Additional findings are most common in patients with symptomatic breast cancer. Our results suggest that initial targeted ultrasound is a more appropriate initial tool for the evaluation of focal breast complaints. Mammography could be performed on indication only.

Modification of The Paris System for urinary tract washing specimens using diagnostic cytological features.

OBJECTIVE: The Paris System (TPS), which was recently introduced, emphasised the key features of malignant urine cytology: a high nuclear to cytoplasmic ratio, nuclear hyperchromasia, irregular nuclear membranes and coarse chromatin. Although other diagnostic features have been described, the diagnostic significance of such features and their application to TPS have not been fully defined for urinary tract washing specimens. METHODS: A total of 142 cases of urinary tract washing specimens with corresponding surgical pathology samples were examined for the key features of TPS and 13 previously described features. The diagnostic performance of TPS and our proposed modification of TPS was compared with that of the current system. RESULTS: In addition to the key features of TPS, in the present study, high-grade urothelial carcinoma (HGUC) frequently exhibited tumour diathesis, a ragged edge of urothelial cell groups, anisonucleosis, India ink nuclei, apoptotic bodies and pleomorphism. As anisonucleosis and India ink nuclei remained independent predictors of HGUC for the multivariate analysis, they were used to modify TPS. The reporting rate of the atypical urothelial cell (AUC) category decreased from 25.3% in the current system to 14.8% in TPS and 11.3% in our proposed modification of TPS. The sensitivity increased from 59.4% in the current system to 70.8% in TPS and 90.0% in this study. The diagnostic accuracy increased from 0.786 in the current system and 0.754 in TPS to 0.859 in this study. CONCLUSIONS: TPS is a useful diagnostic system for urinary tract washing specimens by decreasing the number of AUC cases and increasing sensitivity. In this study, anisonucleosis and India ink nuclei improved the diagnostic accuracy of HGUC.

Is ultrasound-guided fine-needle aspiration cytology of adequate value in detecting breast cancer patients with three or more positive axillary lymph nodes?

This study evaluated the accuracy of ultrasound-guided fine-needle aspiration cytology of the sonographically most suspicious axillary lymph node (US/FNAC) to select early breast cancer patients with three or more tumour-positive axillary lymph nodes. Between 2004 and 2014, a total of 2130 patients with histologically proven early breast cancer were evaluated and treated in the Noordwest Clinics Alkmaar. US/FNAC was performed preoperatively in all these patients. We analysed the results of US/FNAC retrospectively. Pathological axillary node status (sentinel node biopsy and/or axillary lymph node dissection) was used as reference standard. A total of 634 (29.8 %) of 2130 patients had axillary lymph node metastases on final histology. 248 node positive patients (11.6 %) had three or more positive lymph nodes. The accuracy of US/FNAC to detect three or more positive lymph nodes was 89.8 %, sensitivity was 44.8 %, specificity was 95.7 %, PPV was 58.1 %, and NPV was 92.9 %. This study shows a more than adequate accuracy of preoperative US/FNAC to detect three or more positive lymph nodes (89.8 %). However, when US/FNAC was chosen as the only axillary staging method, 6.4 % of all patients (false negative group) would have been undertreated and 3.8 % of all patients (false positive group) would have been overtreated according to the ACOSOG Z0011 criteria.

Effect of proanthocyanidin-rich extract from Pinus radiata bark on immune response of specific-pathogen-free White Leghorn chickens.

Proanthocyanidins are naturally occurring compounds that are widely found in fruits, vegetables, nuts, seeds, flowers, and bark. We evaluated the immunomodulatory effects of proanthocyanidin-rich extract (PAE) from Pinus radiata bark in specific-pathogen-free White Leghorn chickens. Proliferation of peripheral blood mononuclear cells was significantly enhanced in chickens treated for 2 wk with 20 mg/kg of PAE. Proliferation of splenocytes and bursal cells was significantly enhanced in chickens treated for 5 wk with 5, 10, and 20 mg/kg of PAE. Thymocyte proliferation was significantly enhanced in chickens treated for 5 wk with 5 and 10 mg/kg of PAE. These effects were markedly enhanced by the presence of lipopolysaccharide, which acted on B cells responsible for humoral immunity, and concanavalin A, which acted directly on T cells involved in cell-mediated immunity. The PAE significantly promoted the expression of T helper 1 cytokine (interferon-γ) and decreased the expression of T helper 2 cytokine (IL-6). Thus, P. radiata PAE has immunomodulatory effects in specific-pathogen-free White Leghorn chickens.

Serum cytokine profiling in neonates with hypoxic ischemic encephalopathy.

BACKGROUND: The fetal brain is vulnerable to severe and sustained hypoxia during and after birth, which can lead to hypoxic-ischemic encephalopathy (HIE). HIE is characterized by clinical and laboratory evidence of acute or subacute brain injury. The role of cytokines in the pathogenesis of brain injury and their relation to neurological outcomes of asphyxiated neonates are not fully understood. In this study, we investigated cytokine profile related to cerebral palsy (CP) with neonatal hypoxic ischemic encephalopathy (HIE) and HIE severity. METHODS: Eligible subjects were HIE newborns with a gestational age between 36 and 42 weeks. We included newborns who was born at our NICU and did not admit to NICU as healthy controls. The study comprised 52 newborns, including 13 with mild to severe HIE and 39 healthy control. Serum cytokine profiles were performed using a LUMINEX cytokine kit (R&D Systems). RESULTS: VEGF, MCP-1, IL-15, IL-12p70, IL-12p40, IL-1Ra, IL-2, IL-6, IL-7, IL-8, IL-10, IFN-γ, G-CSF and eotaxin in the HIE patients were significantly increased compared with the healthy neonates. In the subgroup analysis, IL-6 and G-CSF were significantly increased in CP infants (n = 5) compared with non-CP infants (n = 8). Five and eight HIE patients were classified into the mild HIE and moderate-severe HIE groups, respectively. IL-6, 10, 1Ra, and G-CSF in the moderate-severe HIE group were significantly higher than those in the mild HIE group. CONCLUSION: We demonstrated that higher serum IL-6 and G-CSF at birth in HIE patients were associated with CP and moderate-severe HIE.

Two patients with focal segmental glomerulosclerosis complicated by cyclosporine-induced reversible posterior leukoencephalopathy syndrome.

Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity observed in a variety of clinical settings. Cyclosporine (CyA)-RPLS has been reported in a few patients with focal segmental glomerulosclerosis (FSGS); however, there had been no reports on developed RPLS after the re-administration of CyA treatment. We report two patients with FSGS who developed CyA-induced RPLS and summarize the results of a literature review for similar patients. The two patients with FSGS presented here were a 4-year-old boy and a 9-year-old boy, who presented with steroid-resistant nephrotic syndrome (NS) and were treated with CyA. The first patient developed CyA-induced RPLS at the 7th day after the start of CyA treatment, and the second patient at the 16th day after the re-start of CyA treatment. The two patients complained of a visual disorder and exhibited signs of a disturbance in consciousness and hypertension. Electroencephalography (EEG) examinations revealed a generalized slow wave pattern, and magnetic resonance imaging (MRI) disclosed an area of high signal intensity in the white matter. Subsequently, CyA was discontinued and neurological symptoms improved and recrudescence of RPLS did not occur. Our findings suggest that patients with FSGS and NS who are treated with CyA should be closely monitored for the possible onset of RPLS, presenting as a disturbance in consciousness, visual disturbances and/or convulsions.

A comparative study to validate the use of ultrasonography and computed tomography in patients with post-operative intra-abdominal sepsis.

PURPOSE: To validate abdominal ultrasonography and helical computed tomography in detecting causes for sepsis in patients after abdominal surgery and to determine improved criteria for its use. MATERIALS AND METHODS: Eighty-five consecutive surgical patients primarily operated for non-infectious disease were included in this prospective study. Forty-one patients were admitted to the intensive care unit. All patients were suspected of an intra-abdominal sepsis after abdominal surgery. Both ultrasonography (US) and helical abdominal computed tomography (CT) were performed to investigate the origin of an intra-abdominal sepsis. The images of both US and CT were interpreted on a four-point scale by different radiologists or residents in radiology, the investigators were blinded of each other's test. Interpretations of US and CT were compared with a reference standard which was defined by the result of diagnostic aspiration of suspected fluid collections, (re)laparotomy, clinical course or the opinion of an independent panel. Likelihood ratios and post-test probabilities were calculated and interobserver agreement was determined using kappa statistics. RESULTS: The overall prevalence of an abdominal infection was 0.49. The likelihood ratio (LR) of a positive test-result for US was 1.33 (95% CI: 0.8-2.5) and for CT scan 2.53 (95% CI: 1.4-5.0); corresponding post-test probabilities for US 0.57 (95% CI: 0.42-0.70) and for CT 0.71 (95% CI: 0.57-0.83). The LR of a negative test-result was, respectively, 0.60 (95% CI: 0.3-1.3) and 0.18 (95% CI: 0.06-0.5); corresponding post-test probabilities for US 0.37 (95% CI: 0.20-0.57) and for CT 0.15 (95% CI: 0.06-0.32) were calculated. CONCLUSION: Computed tomography can be used as the imaging modality of choice in patients suspected of intra-abdominal sepsis after abdominal surgery. Because of the low discriminatory power ultrasonography should not be performed as initial diagnostic test.

In vitro platelet-activating factor receptor binding inhibitory activity of pinusolide derivatives: a structure-activity study.

Pinusolide, a labdane-type diterpene lactone isolated from Biota orientalis, was found to be a potent platelet-activating factor (PAF) receptor binding antagonist. To investigate the structure-activity relationship and find derivatives with improved pharmacological profiles, 17 pinusolide derivatives were prepared and tested for their ability to inhibit the PAF receptor binding. The results demonstrated that the carboxymethyl ester group at C-19, the integrity of the alpha,beta-unsaturated butenolide ring, and the exocyclic olefinic function of pinusolide are all necessary for its maximum PAF receptor binding inhibitory activity. Among the derivatives, the 17-nor-8-oxo derivative 8 was found to be as potent as pinusolide. The results also suggested that several derivatives warrant further pharmaceutical and pharmacological studies due to their improved water solubility (8 and 11) and apparent lack of susceptibility to Michael-type nucleophilic addition (13 and 18).

Effect of (-)-epigallocatechin gallate, the main constituent of green tea, on lung metastasis with mouse B16 melanoma cell lines.

(-)-Epigallocatechin gallate (EGCG), the main polyphenolic constituent of green tea, inhibits tumor promotion and chemical carcinogenesis in animal experimental systems. Here we report that the peroral administration of EGCG inhibited metastasis of B16 melanoma cell lines, such as B16-F10 and BL6, in both experimental and spontaneous systems.

Effect of total sleep deprivation on the dimensional complexity of the waking EEG.

STUDY OBJECTIVES: Sleep deprivation can affect the waking EEG that may reflect information processing of the brain. We examined the effect of total sleep deprivation (TSD) on nonlinear dynamics of the waking EEG. DESIGN: Paired-group design. SETTING: A sleep disorders laboratory in a hospital. PARTICIPANTS: Twenty healthy male volunteers. INTERVENTIONS: Waking EEG data were recorded from subjects with eyes closed after (a) an 8-hour night's sleep and (b) TSD for 24 hours. The dimensional complexity (D2), as a nonlinear measure of complexity, of the EEG after a full night sleep were compared with those of the EEG after TSD. MEASUREMENTS AND RESULTS: The sleep-deprived states had lower D2 values at three channels (P4, O2, and C3) than normal states. CONCLUSIONS: TSD results in the decrease of complexity in the brain, which may imply sub-optimal information processing of the cerebral cortex. We suggest that the investigation of the relation between nonlinear dynamics of the waking EEG induced by TSD and cognitive performance may offer fruitful clues for understanding the role of sleep and the effects of sleep deprivation on brain function.

Laparoscopic adrenalectomy for primary aldosteronism: report of initial ten cases.

BACKGROUND: Although laparoscopic technique has become popular in the surgical field, the value of laparoscopy in the removal of adrenal gland is unknown. The objective of this study was to examine the feasibility of laparoscopic adrenalectomy. METHODS: Between January 17, 1992, and March 16, 1993, 10 patients (four men, six women; mean, 48.2 years of age) with primary aldosteronism underwent laparoscopic adrenalectomy (seven of left adrenal gland and three of right adrenal gland) with almost the same devices as laparoscopic cholecystectomy. RESULTS: Adrenal tumors were successfully removed with adjacent normal adrenal gland in every patient. The operative time ranged from 165 to 572 minutes (mean, 295 minutes), and the operative bleeding ranged from 50 to 920 ml (mean, 270.5 ml) without requiring blood transfusion. Only one patient required open hemostasis because of uncontrollable bleeding complicated by dislocation of vascular clip in spite of successful laparoscopic removal of adrenal tumor. There was no major complication except for this case. CONCLUSIONS: Laparoscopic adrenalectomy is a relatively safe, alternative operative method for primary aldosteronism, but application of this technique to other types of adrenal lesions remains to be studied.

Laparoscopic adrenalectomy for Cushing's syndrome: comparison with primary aldosteronism.

BACKGROUND: Removal of adrenal adenoma of Cushing's syndrome is believed to be more troublesome than primary aldosteronism because of large amount of retroperitoneal adipose tissue and bleeding from the fat. The objective of the present study was to evaluate the feasibility of laparoscopic adrenalectomy for Cushing's syndrome and comparison of the results of laparoscopic adrenalectomy between primary aldosteronism and Cushing's syndrome. METHODS: From January 17, 1992, to July 31, 1993, laparoscopic adrenalectomies for functioning adrenal lesions were performed in 14 patients (five men, nine women), three of whom had Cushing's syndrome and 11 of whom had primary aldosteronism. RESULTS: Operative times (mean +/- SD) for primary aldosteronism and Cushing's syndrome were 269.0 +/- 100.9 minutes and 253.7 +/- 57.9 minutes, respectively. No difference was noted in operative time, operative bleeding, and postoperative recovery between them. However, the weight of removed tissue from patients with Cushing's syndrome (20.00 +/- 8.17 gm) was greater than that from those with primary aldosteronism (6.64 +/- 2.01 gm). No operative complications occurred in patients with Cushing's syndrome. Ultrasonic aspiration and argon-beam coagulation were useful for laparoscopic adrenalectomy in patients with Cushing's syndrome. CONCLUSIONS: Cushing's syndrome may be a good indication for laparoscopic operation.

Retroperitoneal and pelvic extraperitoneal laparoscopy: an international perspective.

OBJECTIVES: To assess technical preferences and current practice trends of retroperitoneal and pelvic extraperitoneal laparoscopy. METHODS: A questionnaire survey of 36 selected urologic laparoscopic centers worldwide was performed. RESULTS: Twenty-four centers (67%) responded. Overall, 3988 laparoscopic procedures were reported: transperitoneal approach (n = 2945) and retroperitoneal/extraperitoneal approach (n = 1043). Retroperitoneoscopic/extraperitoneoscopic procedures included adrenalectomy (n = 74), nephrectomy (n = 299), ureteral procedures (n = 166), pelvic lymph node dissection (n = 197), bladder neck suspension (n = 210), varix ligation (n = 91), and lumbar sympathectomy (n = 6). Mean number of total laparoscopic procedures performed in 1995 per center was 41 (range 5 to 86). Major complications occurred in 49 (4.7%) patients and included visceral complications in 26 (2.5%) patients and vascular complications in 23 (2.2%). Open conversion was performed in 69 (6.6%) patients, electively in 41 and emergently in 28 (visceral injuries, n = 16; vascular injuries, n = 1 2). Retroperitoneoscopy/extraperitoneoscopy is gaining in acceptance worldwide: in 1993, the mean estimated ratio of transperitoneal laparoscopic cases versus retroperitoneoscopic/ extraperitoneoscopic cases per center was 74:26; however, in 1996 the ratio was 49:51. CONCLUSIONS: Retroperitoneoscopy and pelvic extraperitoneoscopy are important adjuncts to the laparoscopic armamentarium in urologic surgery. The overall major complication rate associated with retroperitoneoscopy/extraperitoneoscopy was 4.7%.

An estimation of the first positive Lyapunov exponent of the EEG in patients with schizophrenia.

We studied the complexity of the electroencephalogram (EEG) in schizophrenic patients by estimating the first Lyapunov exponent (L1), which might serve as an indicator of the specific brain function in schizophrenia. We recorded the EEG from 25 schizophrenic patients (12 male, 13 female; age=25.1+/-7.0 years) fulfilling DSM-IV criteria and 15 healthy controls (9 male, 6 female; age=27. 8+/-4.2 years) at 16 electrodes, different from previous studies which recorded the EEGs at limited electrodes. We employed a method with an optimal embedding dimension to calculate the L1s. For limited noisy data, this algorithm was strikingly faster and more accurate than previous ones. Our results showed that the schizophrenic patients had lower values of the L1 at the left inferior frontal and anterior temporal regions compared with normal controls. These results for L1 in non-linear analysis have some differences from those for power ratios in linear analysis. These suggest that the non-linear analysis of the EEGs such as the estimation of the L1 might be a useful tool in analyzing EEG data to explore the neurodynamics of the brains of schizophrenic patients.

Mite antigen and allergen contents of house dust samples.

The house dust mite (Dermatophagoides pteronyssinus) antigen and allergen contents were measured by enzyme-linked immunosorbent assay (ELISA) with enzyme-labelled anti-human IgE and anti-mite rabbit IgG antibodies. Antigen content was high in dust samples from homes of patients with allergy but not in samples from homes of patients with Kawasaki disease or of normal control subjects. Allergen content was high in dust samples from homes of Kawasaki disease patients. However, the values overlapped, and we considered these differences to be of little ecological significance, although the assay method itself is useful.

[A clinical survey of 7 cases with primary ureteral tumor: experiences in a year].

Seven cases of primary ureteral tumors treated at Nagaoka Koseiren Chuo General Hospital in 1983 were reviewed retrospectively. The incidence of primary ureteral tumors among the out-patients in the urologic clinic of the hospital was 0.22% and the incidence among the in-patients was 1.65%. The patient's age ranged from 45 to 83 years (average: 59.14 years old). The ratio of male to female was 2.5: 1.0. The left ureter and the lower third of the ureter were involved more frequently than the others. The most common symptom was colicky flank pain (57% of the cases), which was followed by macroscopic hematuria. On IVP, 5 of the 7 cases showed a non-functioning kidney or hydronephrosis, but the others showed filling defects in the ureteral lumen without hydronephrosis. Diagnostic accuracy of CT was 14.3%. Diagnostic accuracy of urine cytology was 42.9% and the false negative rate was the same. Six of the 7 cases underwent total nephroureterectomy with bladder cuff excision. The higher the grade and stage of the tumor, the poorer the prognosis tended to be.

[Examination of the risk factors for infectious urolithiasis formation in patients receiving urinary diversion or urinary reconstruction using intestine--comparison of reservoir and ileal conduit].

Urinary risk factors and preventive factors for infectious calcium (Ca) urolithiasis formation, such as citrate, oxalate, Ca, phosphate, magnesium, and uric acid were examined more than 2 months after performing a urinary reservoir in 12 patients (R group) and ileal conduit in 10 patients (C group). There was no difference in the positive rate of risk factors between the two groups and also no difference in the positive rate of more than two risk factors between the two groups. Although four patients with more than two risk factors in the R group suffered from reservoir stones all of which included Ca-urolithiasis, none in the C group did. In the R group, the incidence of stone formation in patients with 2 or more risk factors was significantly higher than those in patients with 1 or no risk factor. In conclusion, the urinary reservoir operation should not be carried out in patients with more than two risk factors for urolithiasis formation, and urinary risk factors should be examined before reservoir operation.

Subcostal transabdominal incision with midline extension for tumors of the kidney, adrenal gland or retroperitoneal cavity.

Subcostal transabdominal incision with midline extension is excellent for removal of large renal or adrenal tumors, or bilateral or retroperitoneal tumors. This incision is simple and gives a wide surgical field without involving the pleural cavity. No troublesome complications resulting from this approach have occurred.

[Long-term results and indications of intraurethral stents in elderly patients with prostatic hypertrophy complaining of urinary retention].

Thirty-two elderly male patients with benign prostatic hypertrophy complaining of urinary retention were treated by polyurethane intraurethral stents. All of them were unfit for prostatic surgery due to the presence of several complications, and had been indwelt with a urethral balloon catheter. Cystometry before stent insertion was performed in 23 of the 32 patients. Eleven patients showed overactive bladder, 5 patients normal bladder, and 7 patients underactive bladder. Duration of stent indwelling ranged from 2 days to 22 months (mean 6.7 months), and stent could successfully function for more than 6 months in 20 of the 32 patients (62.5%). Nine of these 20 patients (45%) could keep continence of urine, and urinary tract infections improved in 7 of these 20 patients (35%). The stent failed in 4 of the 5 patients who had had previous operations for prostatic hypertrophy. In a comparison of the findings of urodynamic study prior to insertion of stent with the results of the stent, the results were significantly better in the patients with overactive or normal bladder than in those with underactive bladder (p < 0.05, chi-square test). Bladder stone formation was found in one patient and was the only complication among the 32 patients. In conclusion, stent placement without incontinence or urinary tract infection can be successful for more than 6 months in patients who do not have an underactive bladder and who had not had a previous prostatic operation.