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.

Ultrasound and fine needle aspiration cytology of axillary lymph nodes in breast cancer. To do or not to do?

AIM: The purpose of our study was to evaluate the accuracy of axillary ultrasound and ultrasound-guided fine needle aspiration cytology (FNAC) in the preoperative diagnosis of axillary metastases. METHODS: Between 2004 and 2009, 1132 female patients were evaluated and treated in our clinic for histologically proven breast carcinoma. Preoperative axillary ultrasound with subsequent FNAC in case of suspicious lymph nodes was performed in 1150 axillae (18 bilateral breast carcinomas). We analyzed the results of axillary ultrasound and FNAC retrospectively. Pathological node status was used as the reference standard (based on axillary dissection or sentinel node biopsy). RESULTS: Axillary ultrasound showed suspicious lymph nodes in 327 axillae (28.4%). FNAC showed axillary metastases in 107 of these 327 axillae. Final histological analysis confirmed 106 metastases (one false positive). Histological analysis showed metastatic disease in 429 of 1150 axillae (37.3%). Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of axillary ultrasound alone were 43.8% (188/429), 80.7% (582/721), 57.5% (188/327) and 70.7% (582/823), respectively. When combining axillary ultrasound with FNAC of suspicious lymph nodes, sensitivity was 24.7% (106/429), specificity was 99.9% (720/721), PPV was 99.1% (106/107) and NPV was 69.0% (720/1043). CONCLUSIONS: 106/429 (24.7%) Node-positive axillae were identified by ultrasound-guided FNAC and spared unnecessary sentinel node biopsy. Unfortunately, the percentage of false negative results of ultrasound-guided FNAC (28.1%, 323/1150) was very high.

Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation.

Telomere length is critical for chromosome stability that affects cell proliferation and survival. Telomere elongation by telomerase is inhibited by the telomeric protein, TRF1. Tankyrase-1 (TNKS1) poly(ADP-ribosyl)ates TRF1 and releases TRF1 from telomeres, thereby allowing access of telomerase to the telomeres. TNKS1-mediated poly(ADP-ribosyl)ation also appears to be crucial for regulating the mitotic cell cycle. In searching for proteins that interact with polo-like kinase-1 (Plk1) by using complex proteomics, we identified TNKS1 as a novel Plk1-binding protein. Here, we report that Plk1 forms a complex with TNKS1 in vitro and in vivo, and phosphorylates TNKS1. Phosphorylation of TNKS1 by Plk1 appears to increase TNKS1 stability and telomeric poly(ADP-ribose) polymerase (PARP) activity. By contrast, targeted inhibition of Plk1 or mutation of phosphorylation sites decreased the stability and PARP activity of TNKS1, leading to distort mitotic spindle-pole assembly and telomeric ends. Taken together, our results provide evidence of a novel molecular mechanism in which phosphorylation of TNKS1 by Plk1 may help regulate mitotic spindle assembly and promote telomeric chromatin maintenance.

CT appearance of primary peritoneal serous borderline tumour: a rare epithelial tumour of the peritoneum.

Primary peritoneal serous borderline tumour (PPSBT) is a rare epithelial neoplasm which is histologically identical to serous borderline tumour of the ovary. PPSBT is distinguishable from primary peritoneal serous carcinoma because the tumour cells do not invade the underlying tissue and affected patients have a good prognosis. We report the CT findings of surgically proven PPSBT in which multiple peritoneal cysts were seen. Although rare, PPSBT should be considered in the differential diagnosis of primary peritoneal tumours. Since the prognosis of the disease is good, conservation of the uterus and ovaries should be a consideration in young female patients during surgery.

Green tea consumption, abdominal obesity as related factors of lacunar infarction in Korean women.

OBJECTIVES: Our purpose was to evaluate interaction of green tea consumption and abdominal obesity as related factors for lacunar infarction in Korean women. DESIGN: A hospital-based, incident case-control study. SETTINGS: The Prevention and Managements of Stroke in Women study. PARTICIPANTS: Cases (n=233) of first incident lacunar infarction were enrolled and matched by age to stroke-free hospital controls (n=204). MEASUREMENTS: The data were collected through face-to-face interviews by well trained research assistants to assess demographic, medical, lifestyle, marital status, religions status, green tea consumptions, family history of stroke, smoking status, alcohol consumption, meat and vegetable intake frequency, and past history of hypertension. Biochemical analysis, fasting blood specimens for lipid, glucose, and cholesterol level were acquired. RESULTS: Compared with the non green tea consumer and obese women group, only the green tea consumption and non obese women group had a protective effect of lacunar infarction when adjusted for age, and age plus diet factors (OR, 0.23; 95% CI, 0.09, 0.59; OR, 0.21; 95% CI, 0.08, 0.56 respectively), but lost their significance after adjustment for age, diet factors, vascular risk factors and full model included atherogenic index factors (OR, 0.32; 95% CI, 0.09 to 1.01; OR, 0.49; 95% CI, 0.12, 1.89 respectively). CONCLUSIONS: The interaction of green tea consumption and non obesity have reduced risk of lacunar infarction, but not after adjustment for age, diet factors, vascular risk factors and atherogenic index. Also individually green tea consumption and abdominal obesity have failed to find an independent relationship with lacunar infarction after adjustment by all risk factors. Green tea consumption and green tea consumption with non obese group seemed to have a protective effect for lacunar infarction. In the results of our study, these results still remain controversial, and then we need further and larger study to get at the root of real causal effect of both relationships.

Sentinel lymph node biopsy in thin melanoma patients.

BACKGROUND: We sought to determine the incidence of positive sentinel lymph nodes in thin melanoma (or= III and thicker lesions (mean 0.77 mm vs. 0.47 mm), but were not different in regards to age, sex, or lesion location. Eight percent and 58% of sentinel nodes were positive by routine histology and RT-PCR, respectively. Among mapped patients, younger age was the only significant prognostic factor for node positivity. With a median follow-up of 18 months among all patients, one regional recurrence (at 2 years) has been identified. CONCLUSIONS: Given the low morbidity of sentinel lymph node biopsy, this procedure should be discussed with selected thin melanoma patients to detect microscopic disease, however PCR positivity by our methods is too commonly seen to be clinically significant in thin melanoma patients and requires additional study.

The use of a percutaneous closure device for closure of an accidental puncture of the aortic arch; a simple solution for a difficult problem.

Percutaneous closure devices are now often used for closure of the femoral puncture site after percutaneous vascular interventions. We describe a case were an accidental puncture in the aortic arch during placement of a central venous catheter is successfully closed with a closure device.

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.

Bladder neck suspension using percutaneous bladder neck stabilization to the pubic bone with a bone-anchor suture fixation system: A new extraperitoneal laparoscopic approach.

A 39-year-old woman with type 1 genuine stress urinary incontinence was treated using a novel extraperitoneal laparoscopic bladder neck suspension procedure with a bone-anchor suture fixation system. Operative time and blood loss were 2.5 and 50 g, respectively. The patient showed a remarkable improvement on chain cystography and in subjective and objective well-being with no complications, even 12 months after surgery. Extraperitoneal laparoscopic bladder neck suspension using the bone-anchor suture fixation system is an easy and feasible procedure.

Augmentation in the expression of a ribosomal protein associated with transformation.

Using differential hybridization technique, cDNA that was a partial sequence of rat ribosomal protein L41 was isolated from fos- and src-transfected rat fibroblast 3Y1. The cDNA was named #31. Subsequently, the human counterpart(named hm3168) was cloned from a human melanoma cell line(M14) and the amino acid sequence deduced from the cDNA proved to be identical to that of HG-12. The gene expression of hm3168 was inducible by serum-stimulation. It reveals the possible up-regulation of the transcription via fos-mediated signal transduction. Northern-blot and Western-blot analyses showed a large expression of the #31 gene in the rat transformed cell lines.

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%.

Learning curve and conversion to open surgery in cases of laparoscopic adrenalectomy and nephrectomy.

PURPOSE: We examine how the level of experience acquired by the laparoscopist affects the outcome of laparoscopic adrenalectomy and nephrectomy, and what is necessary to avoid complications in these surgeries. MATERIALS AND METHODS: We retrospectively evaluated the experience levels of 8 urological laparoscopists between 1991 and 1995. In addition, other cases that were converted to open surgery were collected from the institutes with which the 8 laparoscopists were affiliated. RESULTS: The rates of conversion to open surgery were 6.4% in 204 cases of adrenalectomy and 14.3% in 63 of nephrectomy. Conversion rates were related to blood loss volume but not operative time. The major causes of conversion were bleeding in 45% of cases and adhesion in 34%. There were no mortalities. Mean operative time decreased significantly, reaching that of open surgery as the number of procedures increased up to 20 adrenalectomies and 10 nephrectomies. The volume of blood lost remained low from the early experience. Blood transfusion rates were 4.4% for adrenalectomy and 11.1% for nephrectomy. CONCLUSIONS: Operative time of these procedures decreased significantly with surgeon experience and reached that of open surgery. Cases in which adhesion is anticipated should be restricted to avoid conversion. These laparoscopic procedures are acceptable as a standard operative techniques for adrenal and renal diseases.

Efficient induction of antitumor cytotoxic T lymphocytes from a healthy donor using HLA-A2-restricted MAGE-3 peptide in vitro.

The antigenic peptides encoded by tumor-rejection antigen genes, MAGE-1 and -3, have been identified, and various methods have been utilized for the in vitro induction of MAGE-specific, cytotoxic T lymphocytes (CTL) from peripheral blood mononuclear cells (PBMC) using synthetic peptides. However, all of these methods are technically demanding and thus have a relatively limited usefulness. We herein report a simple and efficient method for the vitro induction of specific CTL by using the HLA-A2-restricted MAGE-3 peptide from the PBMC of a healthy donor. CTL responses could thus be efficiently induced from unseparated PBMC by stimulation with freshly isolated, peptide-pulsed PBMC as antigen-presenting cells and by using interleukin-7 and keyhole limpet hemocyanin for the primary culture. The induced CTL could thus recognize and lyse not only HLA-A2 target cells pulsed with the peptide but also HLA-A2 tumor cells expressing MAGE-3, in an HLA-class-I-restricted manner. This simple method may, therefore, become a useful tool for investigating the potential peptides for tumor antigens as well as for developing various immunotherapeutic approaches for human malignant tumors.

Retroperitoneal laparoscopic adrenalectomy for functioning adrenal tumors: comparison with conventional transperitoneal laparoscopic adrenalectomy.

PURPOSE: We attempted to confirm the possibility and feasibility of laparoscopic adrenalectomy via the retroperitoneal approach, and to compare results of the transperitoneal and retroperitoneal approaches. MATERIALS AND METHODS: Three men and 8 women (mean age 39.6 years) with functioning adrenocortical tumors (primary aldosteronism in 5 and Cushing's syndrome in 6) underwent laparoscopic adrenalectomy via the retroperitoneal approach using a balloon dissection technique and a newly developed ultrasonic aspirator. Results were compared to those of 27 cases of transperitoneal laparoscopic adrenalectomy. RESULTS: Although the retroperitoneal approach was successful in all 5 patients with primary aldosteronism, it succeeded in only 2 of the 6 cases of Cushing's syndrome. In 3 Cushing's syndrome cases the retroperitoneal approach was changed to the transperitoneal laparoscopic approach due to difficulty in exploration. Open laparotomy was required in 1 case of left Cushing's syndrome because of an inadvertent pancreatic injury. Subcutaneous emphysema developed in 6 patients without hypercapnia or prolonged postoperative symptoms. Mean operative time and blood loss, and time to oral intake and ambulation were 248.3 minutes, 151.4 ml., and 1.55 and 2 days, respectively. There was no difference between retroperitoneal and conventional transperitoneal laparoscopic adrenalectomy in regard to these factors or to convalescence. CONCLUSIONS: Retroperitoneal laparoscopic adrenalectomy is feasible for primary aldosteronism. However, Cushing's syndrome is presently a much more difficult indication than primary aldosteronism for this new operative technique.

Neoadjuvant chemoimmunotherapy with cisplatin and low-dose interleukin-2 for locally advanced esophageal carcinoma

After a single dose of cisplatin, the ability of peripheral blood mononuclear cells (PBMC) to generate lymphokine-activated killer (LAK) cells was significantly augmented in cancer patients. Based on this clinical finding, the patients with locally advanced esophageal carcinoma were thus treated with a combination of cisplatin and low-dose interleukin-2 (IL-2) in a neoadjuvant setting. Four patients with squamous cell carcinoma of the esophagus (T3 or T4 disease) were preoperatively treated with a regimen consisting of 50 mg/m2 cisplatin on day 1, followed by IL-2 from day 4 through day 8, when the ability of PBMC to generate LAK cells had been shown to be significantly augmented. After two to four courses of the preoperative therapy, one patient achieved a histologic CR, one showed PR and one MR. No severe toxicity was encountered. All patients thereafter underwent surgery. The median survival of these patients was 47.5 months and three of the patients had been disease free for 43 to 62 months after the initiation of the therapy. The combination of cisplatin and low-dose IL-2 administered in a neoadjuvant setting seems to result in an improved survival of locally advanced squamous cell carcinoma of the esophagus.

Spontaneous hemorrhage of an adrenal cortical adenoma causing Cushing's syndrome.

We report the case of a spontaneously ruptured adrenal adenoma which caused Cushing's syndrome. The 34-year-old female patient had severe left-side back pain and anemia. Computerized tomography disclosed a retroperitoneal hemorrhage and a 4-cm mass on the left which was considered to be an adrenal tumor. An operation was successfully performed, and the patient is well 12 months after surgery.