Variations in clinical course and surgical outcomes of acute appendicitis during COVID-19 Pandemic: a multicenter cohort study.

BACKGROUND: COVID-19 pandemic has led to changes in the presentation and treatment of surgical pathologies. Therefore, we aim to describe the influence of the COVID-19 pandemic on the clinical presentation and management of acute appendicitis (AAp) and its surgical outcomes. STUDY DESIGN: A multicenter cohort study with prospectively collected databases. Three high-volume centers were included and all patients over 18 years of age who underwent appendectomy for AAp were included. Multiple logistic regression and multinomial logistic regression were performed, and odds ratio, relative risk, and B-coefficient were reported when appropriate, statistical significance was reached with p-values < 0.05. RESULTS: 1.468 patients were included (709 in the pre-pandemic group and 759 in the COVID-19 group). Female patients constituted 51.84%. Mean age was 38.13 ± 16.96 years. Mean Alvarado's score was 7.01 ± 1.59 points. Open surgical approach was preferred in 90.12%. Conversion rate of 1.29%. Mortality rate was 0.75%. There was an increase of perforated and localized peritonitis (p 0.01) in the COVID-19 group. Presence of any postoperative complication (p 0.00), requirement of right colectomy and ileostomy (p 0.00), and mortality (p 0.04) were higher in the COVID-19 group. Patients in the pre-pandemic group have a lesser risk of mortality (OR 0.14, p 0.02, 95% CI 0.02-0.81) and a lesser relative risk of having complicated appendicitis (RR 0.68, p 0.00, 95% CI 0.54-0.86). CONCLUSION: Complicated appendicitis was an unexpected consequence of the COVID-19 pandemic, due to surgical consultation delay, increased rates of morbidity, associated procedures, and mortality, influencing the clinical course and surgical outcomes of patients with AAp.

Clinical experience of thoracoplasty with absorbable rib substitutes.

PURPOSE: Malignant chest wall tumors are rare in pediatrics. They require multimodal oncological treatment and local surgical control. Resections are extensive; therefore, thoracoplasty should be planned to protect intrathoracic organs, prevent herniation, future deformities, preserve ventilatory dynamics, and enable radiotherapy. METHODS: We present a case series of children with malignant chest wall tumors and our surgical experience with thoracoplasty using absorbable rib substitutes (BioBridge®), after local surgical control. BioBridge® is a copolymer made of a polylactide acid blend (70% L-lactic acid y 30% DL-lactide). RESULTS: In 2 years, we had three patients with malignant chest wall tumors. Resection margins were negative, without recurrence at follow-up. We achieved good cosmetic and functional results, and no postoperative complications. CONCLUSION: Alternative reconstruction techniques such as absorbable rib substitutes provide protection, guarantee a flexible chest wall, and do not interfere with adjuvant radiotherapy. Currently, there are no management protocols in thoracoplasty. This option represents an excellent alternative for patients with chest wall tumors. Knowledge of different approaches and reconstructive principles is essential to offer children the best onco-surgical option.

Uroplakin II as a single marker for luminal versus basal molecular subtypes in muscle invasive urothelial carcinoma.

Bladder cancer is a heterogeneous disease classified into two broad molecular subtype categories, basal and luminal, with critical treatment and prognostic implications. Recent studies have shown the utility of immunohistochemistry in predicting bladder cancer molecular subtypes, with a two-marker approach using GATA3 and CK5/6 showing over 80% reliability. In the current study, we calculated the accuracy of uroplakin II (UPII), a marker of urothelial differentiation, with different scores (0: <1%, 1+: 1-10%, 2+: 10-50%, 3+: >50%) to predict RNA-based luminal versus basal subtypes in a cohort of muscle-invasive bladder cancer-received neoadjuvant chemotherapy followed by radical cystectomy. The 1% cutoff of the UPII stain predicts the luminal subtype with the sensitivity and specificity of 95% and 56%, respectively. With a UPII cutoff of 10%, the sensitivity and specificity were 93% and 81%, respectively, and with a UPII cutoff of 50%, the sensitivity and specificity were 91% and 96%, respectively. The prediction performance of UPII was better than either GATA3 or CK5/6. There was no significant difference in prognoses between UPII 0-2+ and UPII 3+ patients in this cohort. The current study shows that evaluating the staining proportion score of UPII can accurately predict basal and luminal subtypes of muscle-invasive bladder cancer.

Classifying Pulmonary and Urinary High-grade Neuroendocrine Carcinoma by CK7 Immunohistochemistry.

High-grade neuroendocrine carcinoma (HGNEC) is subclassified into small cell carcinoma (SmCC) and large cell neuroendocrine carcinoma (LCNEC). Although both are clinically aggressive, the SmCC and LCNEC need to have different treatment strategies, and accurate pathologic diagnosis is challenging. We studied a large retrospective cohort (186 cases) of HGNEC of bladder and lung to investigate the abundance of cytokeratin (CK) 7 expression and staining pattern in SmCC and LCNEC. Overall, the pulmonary and urinary HGNEC exhibited several different CK7 staining patterns, including negative staining (n=28), dot-like staining (n=73), partial membranous staining (n=26), and complete membranous staining (n=60). Overall, 88.9% (44/49) of pulmonary SmCC and 88.0% (44/50) of urinary SmCC showed negative or dot-like patterns for CK7, while 90.8% (59/65) of pulmonary LCNEC and 72.7% (16/22) of urinary LCNEC showed partial or complete membranous patterns for CK7 (χ 2 =105.05, P <0.0001). The distinct staining patterns were also present in those mixed SmCC and LCNEC. In addition, the specimen types or fixation did not affect CK7 staining patterns. In conclusion, CK7 has a high differential value for SmCC and LCNEC and could help guide personalized treatment for patients.

Cholecystogastric fistula in Bouveret syndrome: Case report and literature review.

INTRODUCTION AND IMPORTANCE: Cholelithiasis is the benign bile pathology with major prevalence. A rare condition has been described, when a stone migrates through the duodenum causing small bowel obstruction (SBO), it's known as Bouveret syndrome, and it's attributed to almost 5% of SBO. Just 2% of the cases present with the migration of the stone through a fistula between gastric chamber and gallbladder, with limited reports in the literature. CLINICAL FINDINGS: We present a case of an 87-year-old male with Bouveret syndrome and a cholecystogastric fistula with a stone in the gastric chamber who underwent laparoscopic gastrotomy to resolve the clinical case. CONCLUSION: Bouveret syndrome remains to be a rare condition in benign bile pathology. Individualized treatment should be performed and multidisciplinary approach leads to improved outcomes for the patient.

Small cell carcinoma of the bladder: A population-based analysis of long-term outcomes after radical cystectomy and bladder conservation with chemoradiotherapy.

INTRODUCTION: We aimed to describe the oncological outcomes after radical cystectomy and chemo-radiation for localized small cell bladder cancer (SCBC). METHODS: This population-based analysis of localized SCBC from 1985-2018 in British Columbia included an analysis (analysis 1) of cancer-specific survival (CSS) and overall survival (OS) of patients treated with curative-intent radical cystectomy (RC) and radiation (RT), and an analysis (analysis 2) of CSS and OS in patients treated with RC and chemoRT consistent with the SCBC Canadian consensus guideline. RESULTS: Seventy-seven patients who were treated with curative intent were identified: 33 patients had RC and 44 had RT. For analysis 1, five-year OS was 29% and 39% for RC and RT, respectively (p=0.51), and five-year CSS was 35% and 52% for RC and RT, respectively (p=0.29). On multivariable analysis, higher Charlson comorbidity index (CCI) and the lack of neoadjuvant chemotherapy (NAC) were associated with worse OS, while higher CCI and Eastern Cooperative Oncology Group (ECOG) were associated with worse CSS. For analysis 2, five-year OS was 56% and 58% for the RC and chemoRT groups, respectively (p=0.90), and five-year CSS was 56% for RC and 71% for chemoRT (p=0.71). Four of 42 (9.5%) chemoRT patients had RC at relapse. CONCLUSIONS: SCBC is a rare entity with a poor prognosis. RC and chemoRT offer similar CSS and OS for localized SCBC, even when focusing the analysis on patients treated according to the modern consensus guidelines. NAC should be considered for eligible patients. Both chemoRT and RC treatment options should be discussed with patients with SCBC.

Evaluation of 18F-EF5 for detection of hypoxia in localized adenocarcinoma of the prostate.

BACKGROUND: A common feature of solid tumours that are resistant to therapy is the presence of regions with low oxygen content (i.e., hypoxia). Oxygen electrode studies suggest that localized prostate adenocarcinoma is commonly hypoxic, although conflicting data have been reported between immunohistochemical detection of hypoxia-induced proteins in biopsy specimens and positron emission tomography (PET) imaging of 18F-labeled hypoxia reporters. Although the 2-nitroimidazole 18F-EF5 is well-established to label hypoxic tumour cells in pre-clinical tumour models and clinical trials of multiple primary tumour sites, it has yet to be tested in prostate cancer. The purpose of this study was to evaluate the feasibility of using 18F-EF5 to detect hypoxia in clinical prostate tumours. MATERIAL AND METHODS: Patients with localized adenocarcinoma of the prostate were recruited for pre-treatment 18F-EF5 PET scans. Immunohistochemistry was conducted on diagnostic biopsies to assess the expression of glucose transporter 1 (GLUT1), osteopontin (OPN), and carbonic anhydrase IX (CAIX). Immunoreactivity scores of staining intensity and frequency were used to indicate the presence of tumour hypoxia. RESULTS: We found low tumour-to-muscle ratios of 18F-EF5 uptake that were not consistent with tumour hypoxia, causing early termination of the study. However, we observed GLUT1 and OPN expression in all prostate tumour biopsies, indicating the presence of hypoxia in all tumours. CONCLUSION: Our data do not support the use of 18F-EF5 PET to detect hypoxia in prostate adenocarcinoma, and suggest the use of immunohistochemistry to quantify expression of the hypoxia-inducible proteins GLUT1 and OPN as indications of prostate tumour hypoxia.

Urinary Large Cell Neuroendocrine Carcinoma: A Clinicopathologic Analysis of 22 Cases.

Large cell neuroendocrine carcinoma (LCNEC) of the urinary tract is a rare disease. We present a relatively large retrospective cohort of urinary LCNEC, 20 from the urinary bladder, and 2 from the ureter, from a single institution. The patients included 16 men and 6 women with a median age of 74.5 years. Most LCNEC presented at an advanced stage with tumors invading the muscularis propria and beyond (21/22). Eight cases were pure LCNEC, while 14 cases were mixed with other histologic types, including conventional urothelial carcinoma (n=9), carcinoma in situ (n=7), small cell carcinoma (n=6), and urothelial carcinoma with glandular (n=3) features. Most LCNEC expressed neuroendocrine markers synaptophysin (22/22), chromogranin (13/16), CD56 (7/7), TTF1 (8/8), and INSM1 (2/3). They were negative for common urothelial markers including HMWCK (0/3), p40/p63 (0/6), CK20 (0/10), and had variable GATA3 staining (4/8). Ki-67 stained 25% to nearly 100% tumor cell nuclei. Patient survival was associated with cancer stage, and pure LCNEC showed worse survival than mixed LCNEC. Compared with small cell carcinoma at similar stages from a prior study, LCNEC had a worse prognosis only when patients developed metastatic disease. For organ-confined LCNEC, neoadjuvant chemotherapy followed by radical resection is the treatment option to achieve long-term survival.

Impact of breed on canine humeral condylar fracture configuration, surgical management, and outcome.

OBJECTIVE: To report the prevalence, configuration, risk factors, fixation methods and outcomes after repair of humeral condylar fractures (HCF) in dogs. STUDY DESIGN: Retrospective nested cohort study. SAMPLE POPULATION: One hundred twelve dogs. METHODS: Medical records of dogs referred between January 2010 and August 2018 were searched for HCF. Demographics, fracture configuration, repair, and complications were obtained from medical records. Radiographs were assessed for fracture reduction, implant positioning, and bone healing. Short-term radiographic and clinical outcomes, and long-term owner-assessed outcome was determined. Associations between these variables were statistically analyzed. RESULTS: Dogs with HCF represented 112 of 43 325 (0.26%, 95% CI 0.22-0.31) referrals. French bulldogs and spaniel breeds were predisposed to HCF (P < .02). French bulldogs were 6.58 times (95% CI 1.62-26.7) more likely than other breeds to have a medial HCF (P = .008). Epicondylar plate fixation was associated with reduced complications compared with lag screws and Kirschner wires (P = .009). Lameness was scored as 1 of 5 (median) in the 85 dogs with initial follow-up (median 6 weeks) after HCF repair. Outcome was considered excellent in 26 of 31 dogs with long-term follow-up (median 36 months). CONCLUSION: French bulldogs and spaniels were predisposed to HCF, and medial HCF were more common in French bulldogs. Epicondylar plate fixation was associated with reduced complications. CLINICAL SIGNIFICANCE: French bulldogs are predisposed to HCF, including medial HCF. Epicondylar plate fixation is recommended over other epicondylar fixation methods to reduce complications.

Prognostic factors for short-term survival of dogs that experience postattenuation seizures after surgical correction of single congenital extrahepatic portosystemic shunts: 93 cases (2005-2018).

OBJECTIVE: To identify prognostic factors for short-term survival of dogs that experience seizures within 7 days after surgical correction of single congenital extrahepatic portosystemic shunts (cEHPSS). STUDY DESIGN: Multi-institutional retrospective study. SAMPLE POPULATION: Ninety-three client-owned dogs. METHODS: Medical records at 14 veterinary institutions were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 1, 2005 through February 28, 2018 and experienced postattenuation seizures (PAS) within 7 days postoperatively. Logistic regression analysis was performed to identify factors associated with 1-month survival. Factors investigated included participating institution, signalment, shunt morphology, concurrent/historical conditions, presence of preoperative neurologic signs, presence of preoperative seizures, aspects of preoperative medical management, surgical details including method and degree of shunt attenuation, type of PAS (focal only or generalized ± focal), drugs administered as part of the treatment of PAS, and development of complications during treatment of PAS. RESULTS: Thirty (32.3%) dogs survived to 30 days. Seventy-six (81.7%) dogs experienced generalized PAS. Factors positively associated with short-term survival included having a history of preoperative seizures (P = .004) and development of focal PAS only (P = .0003). Most nonsurvivors were humanely euthanized because of uncontrolled or recurrent seizures. CONCLUSION: Dogs that experienced PAS that had a history of preoperative seizures and those that experienced focal PAS only had significantly improved short-term survival. CLINICAL SIGNIFICANCE: The results of this study provide information that will help in the counseling of owners who seek treatment for PAS after surgical correction of cEHPSS. © 2020 The American College of Veterinary Surgeons.

Metastatic Renal Cell Carcinoma to the Testis: A Clinicopathologic Analysis of Five Cases.

The testicular spread of renal cell carcinoma is extremely rare. Five cases of renal cell carcinoma metastatic to the testis are described. The patients ranged from 45 to 81 years of age. Four of the five patients had known renal cell carcinoma. The time intervals between the partial and radical nephrectomies for the primary kidney tumors and the occurrence of testicular metastases ranged from 29 to 34 months. In one patient, the testicular mass was the initial presentation leading to a diagnosis of renal cell carcinoma. There were three ipsilateral metastases, one contralateral metastasis, and one bilateral metastasis. The metastatic deposits ranged in size from 2.0 to 5.7 cm. One case had multiple metastatic tumor nodules. All of the metastatic tumors had clear cell histological features, microscopically concordant with the primary renal cell carcinoma subtype. Three patients died of the disease 17 to 42 months after orchiectomy. One patient is alive with additional metastatic lesions 13 months after orchiectomy. One patient had been free of disease at 87 months after orchiectomy but is now on targeted therapy for an additional metastasis at 93 months after orchiectomy. To date, this report is one of the largest single series of patients with renal cell carcinoma metastatic to the testis, and it has the longest follow-up and survival among all the reported cases.

Clinical and pathological characteristics of bladder cancer in post brachytherapy patients.

The long-term risk of secondary malignancy is a potential late effect of brachytherapy. However, the time interval, anatomic site and histopathology are not well studied. We sought to characterize the bladder cancers that developed following treatment of prostate cancer with brachytherapy. Between 1998 and 2014, 4570 patients were treated with brachytherapy at the BC Cancer Agency. Out of those, 69 patients subsequently developed bladder cancer, some of which could have been radiation induced. Histology slides were reviewed for all cases, and site and pathologic features were recorded. Cases were classified as luminal and basal subtypes based on GATA3 and CK5/6 immunohistochemistry. Bladder neck and trigone were among the common sites of involvement. Pathologic review of cases showed that 68 % were high-grade, 25 % were muscle-invasive, and 20 % showed variant histology, including small cell carcinoma, sarcomatoid carcinoma, squamous cell carcinoma, and adenocarcinoma. A subgroup of cases more likely to be radiation-induced, based on site and time interval, was associated with increased pathologic stage (pT1 or higher) compared to the other cases (70 % vs 34 %, p = 0.01). In conclusion, the majority of bladder cancers following brachytherapy in this cohort were of high grade and low stage at diagnosis, most of them demonstrating luminal immunophenotype. A significant number of variant histologies are seen, each demonstrating a specific immunophenotype.

Cytologic features and diagnostic value of PeriView FLEX transbronchial needle aspiration targeting pulmonary nodules.

BACKGROUND: Transbronchial needle aspiration (TBNA) of peripheral lung nodules can be difficult with conventional devices due to their limited flexibility. A promising new technology for accessing these lesions is the PeriView FLEX TBNA device, which has a flexible spiral-grooved needle. The present study reports the unique cytologic features, diagnostic value, and potential pitfalls of PeriView FLEX TBNA specimens. METHODS: This study retrospectively evaluates 113 consecutive cases of lung nodules sampled using the PeriView FLEX device with radial endobronchial ultrasound guidance. RESULTS: PeriView FLEX specimens were satisfactory for evaluation in 111 of 113 cases (98%). A diagnosis of malignancy was made on 64 specimens (57%), with 100% specificity and 70% sensitivity for malignancy. In 4 cases, the PeriView FLEX sample was the only specimen from bronchoscopy that was diagnostic of malignancy. Of the 64 PeriView FLEX specimens with malignant cells, 58 (91%) were adequate for immunohistochemistry and 44 (69%) were adequate for molecular genetic testing. Potential pitfalls were largely ameliorated through education regarding the unique features of PeriView FLEX samples, such as the expected abundance of anthracotic pigment and the paucity of lymphocytes. CONCLUSIONS: TBNA using the PeriView FLEX device to sample pulmonary nodules contributed to the diagnostic value of bronchoscopy and tended to provide sufficient tissue for ancillary studies. Many of the possible pitfalls may be avoided through consideration of the unique cytologic features associated with this novel sampling method.

Comparison of Artificial Intelligence Techniques to Evaluate Performance of a Classifier for Automatic Grading of Prostate Cancer From Digitized Histopathologic Images.

Importance: Proper evaluation of the performance of artificial intelligence techniques in the analysis of digitized medical images is paramount for the adoption of such techniques by the medical community and regulatory agencies. Objectives: To compare several cross-validation (CV) approaches to evaluate the performance of a classifier for automatic grading of prostate cancer in digitized histopathologic images and compare the performance of the classifier when trained using data from 1 expert and multiple experts. Design, Setting, and Participants: This quality improvement study used tissue microarray data (333 cores) from 231 patients who underwent radical prostatectomy at the Vancouver General Hospital between June 27, 1997, and June 7, 2011. Digitized images of tissue cores were annotated by 6 pathologists for 4 classes (benign and Gleason grades 3, 4, and 5) between December 12, 2016, and October 5, 2017. Patches of 192 µm2 were extracted from these images. There was no overlap between patches. A deep learning classifier based on convolutional neural networks was trained to predict a class label from among the 4 classes (benign and Gleason grades 3, 4, and 5) for each image patch. The classification performance was evaluated in leave-patches-out CV, leave-cores-out CV, and leave-patients-out 20-fold CV. The analysis was performed between November 15, 2018, and January 1, 2019. Main Outcomes and Measures: The classifier performance was evaluated by its accuracy, sensitivity, and specificity in detection of cancer (benign vs cancer) and in low-grade vs high-grade differentiation (Gleason grade 3 vs grades 4-5). The statistical significance analysis was performed using the McNemar test. The agreement level between pathologists and the classifier was quantified using a quadratic-weighted κ statistic. Results: On 333 tissue microarray cores from 231 participants with prostate cancer (mean [SD] age, 63.2 [6.3] years), 20-fold leave-patches-out CV resulted in mean (SD) accuracy of 97.8% (1.2%), sensitivity of 98.5% (1.0%), and specificity of 97.5% (1.2%) for classifying benign patches vs cancerous patches. By contrast, 20-fold leave-patients-out CV resulted in mean (SD) accuracy of 85.8% (4.3%), sensitivity of 86.3% (4.1%), and specificity of 85.5% (7.2%). Similarly, 20-fold leave-cores-out CV resulted in mean (SD) accuracy of 86.7% (3.7%), sensitivity of 87.2% (4.0%), and specificity of 87.7% (5.5%). Results of McNemar tests showed that the leave-patches-out CV accuracy, sensitivity, and specificity were significantly higher than those for both leave-patients-out CV and leave-cores-out CV. Similar results were observed for classifying low-grade cancer vs high-grade cancer. When trained on a single expert, the overall agreement in grading between pathologists and the classifier ranged from 0.38 to 0.58; when trained using the majority vote among all experts, it was 0.60. Conclusions and Relevance: Results of this study suggest that in prostate cancer classification from histopathologic images, patch-wise CV and single-expert training and evaluation may lead to a biased estimation of classifier's performance. To allow reproducibility and facilitate comparison between automatic classification methods, studies in the field should evaluate their performance using patient-based CV and multiexpert data. Some of these conclusions may be generalizable to other histopathologic applications and to other applications of machine learning in medicine.

Effect of prophylactic treatment with levetiracetam on the incidence of postattenuation seizures in dogs undergoing surgical management of single congenital extrahepatic portosystemic shunts.

OBJECTIVE: To report the incidence of postattenuation seizures (PAS) in dogs that underwent single congenital extrahepatic portosystemic shunt (cEHPSS) attenuation and to compare incidence of PAS in dogs that either did or did not receive prophylactic treatment with levetiracetam (LEV). STUDY DESIGN: Multi-institutional retrospective study. POPULATION: Nine hundred forty dogs. METHODS: Medical records were reviewed to identify dogs that underwent surgical attenuation of a single cEHPSS from January 2005 through July 2017 and developed PAS within 7 days postoperatively. Dogs were divided into 3 groups: no LEV (LEV-); LEV at ≥15 mg/kg every 8 hours for ≥24 hours preoperatively or a 60 mg/kg intravenous loading dose perioperatively, followed by ≥15 mg/kg every 8 hours postoperatively (LEV1); and LEV at <15 mg/kg every 8 hours, for <24 hours preoperatively, or continued at <15 mg/kg every 8 hours postoperatively (LEV2). RESULTS: Seventy-five (8.0%) dogs developed PAS. Incidence of PAS was 35 of 523 (6.7%), 21 of 188 (11.2%), and 19 of 228 (8.3%) in groups LEV-, LEV1, and LEV2, respectively. This difference was not statistically significant (P = .14). No differences between groups of dogs that seized with respect to investigated variables were identified. CONCLUSION: The overall incidence of PAS was low (8%). Prophylactic treatment with LEV according to the protocols that were investigated in our study was not associated with a reduced incidence of PAS. CLINICAL SIGNIFICANCE: Prophylactic treatment with LEV does not afford protection against development of PAS. Surgically treated dogs should continue to be monitored closely during the first 7 days postoperatively for seizures.

Prostatic ductal adenocarcinoma with cribriform architecture has worse prognostic features than non-cribriform-type.

Prostatic ductal adenocarcinoma (PDA) is a rare histologic subtype of prostate cancer characterized by large glands lined with tall columnar pseudostratified epithelium. PDA has several architectural patterns, with papillary and cribriform being the most common. The cribriform pattern of acinar carcinoma has shown to be associated with a worse prognosis in terms of disease progression and disease-specific mortality. However, the significance of cribriform pattern in PDA is unknown. In this study, we sought to compare the adverse pathologic features between cribriform-type and non-cribriform-type PDA, and between PDA and acinar carcinoma with Gleason scores 8-10. We identified PDA cases diagnosed between 2008 and 2018 and 428 radical prostatectomy (RP) specimens containing Gleason 8-10 acinar carcinoma. The slides of all PDA cases were reviewed, and pathologic features were recorded. We found that the vast majority of PDA contained admixed acinar carcinoma, with a median percentage of the ductal component of 50% (range 5-100). 29% of PDA was graded as Grade Group 4 and 35.5% as Grade Group 5. At the time of RP, 45.2% of cases presented as pathologic stage T3a and 29% as T3b. Cribriform-type PDA demonstrated a significantly higher likelihood of extraprostatic extension (84% vs 33.3%, p = 0.01), seminal vesical invasion (36% vs 0%, p = 0.04), lymphovascular invasion (40% vs 0%, p = 0.03) and advanced pathologic stage (84% vs 33.3%, p = 0.01) compared to PDA without cribriform architecture. The proportion of stage ≥pT3 tumors in PDA was similar compared to that in Gleason 8-10 acinar carcinoma (74.2% vs 70.8%, p = 0.68).

Metastatic breast carcinoma to the urinary bladder-a report of 11 cases including a tumor to tumor metastasis.

Metastatic breast carcinoma to the urinary bladder is rare. Eleven cases of metastatic breast carcinoma to the bladder are described in this report, including one case with a tumor to tumor metastasis. The patients ranged from 51 to 83 years of age. The time intervals between the diagnosis of primary breast cancer and the occurrence of bladder metastases ranged from 41 to 336 months. There were seven cases of invasive ductal carcinoma and four cases of invasive lobular carcinoma. In one case, a lobular carcinoma of the breast metastasized to a concurrent squamous cell carcinoma of the bladder. The immunophenotypic status of estrogen receptor and Her2 expression of the metastatic carcinomas were all concordant with the primary tumors. In nine patients with follow-up available, seven patients died of the disease ranging from 1 to 23 months after the diagnosis of the bladder metastasis and two patients were alive at 5 months of follow-up. To date, this report is the largest single series of patients with breast carcinoma metastatic to the bladder. It is the first reported instance of lobular carcinoma of the breast metastasizing to a squamous cell carcinoma of the bladder.

Automatic grading of prostate cancer in digitized histopathology images: Learning from multiple experts.

Prostate cancer (PCa) is a heterogeneous disease that is manifested in a diverse range of histologic patterns and its grading is therefore associated with an inter-observer variability among pathologists, which may lead to an under- or over-treatment of patients. In this work, we develop a computer aided diagnosis system for automatic grading of PCa in digitized histopathology images using supervised learning methods. Our pipeline comprises extraction of multi-scale features that include glandular, cellular, and image-based features. A number of novel features are proposed based on intra- and inter-nuclei properties; these features are shown to be among the most important ones for classification. We train our classifiers on 333 tissue microarray (TMA) cores that were sampled from 231 radical prostatectomy patients and annotated in detail by six pathologists for different Gleason grades. We also demonstrate the TMA-trained classifier's performance on additional 230 whole-mount slides of 56 patients, independent of the training dataset, by examining the automatic grading on manually marked lesions and randomly sampled 10% of the benign tissue. For the first time, we incorporate a probabilistic approach for supervised learning by multiple experts to account for the inter-observer grading variability. Through cross-validation experiments, the overall grading agreement of the classifier with the pathologists was found to be an unweighted kappa of 0.51, while the overall agreements between each pathologist and the others ranged from 0.45 to 0.62. These results suggest that our classifier's performance is within the inter-observer grading variability levels across the pathologists in our study, which are also consistent with those reported in the literature.

Formation of new stimulus equivalence classes by exclusion.

This study presents three experiments that aimed to show the formation of stimulus equivalence relations among stimuli that had been previously related only by exclusion. In Experiment 1, participants were trained on baseline conditional discriminations to establish two 3-member equivalence classes. Then, they were exposed to exclusion trials, without feedback, in which undefined stimuli had to be matched by rejecting the defined baseline stimuli. Finally, participants responded to test trials evaluating the emergence of symmetry and transitivity among the undefined stimuli from the exclusion trials. For half of the participants, the stimuli related by exclusion were introduced as S- stimuli in the baseline trials, whereas for the other half they were not. Further, half of the participants were assessed for emergent relations with stimuli from all the classes, whereas the other half was assessed for emergent relations with only the stimuli related by exclusion. In Experiment 2, the S- comparisons in the emergent relations test trials with stimuli only related by exclusion were stimuli from a null class. In Experiment 3, the number of exclusion trials was doubled. Across experiments, most participants showed emergence of equivalence relations among the stimuli related by exclusion. Some conditions of stimulus control associated with exclusion learning and the emergence of equivalence relations are discussed.

Usefulness of Urinoculture to Patients With Dementia and Femoral Neck Fracture at Admission to Hospital: Preliminary Results.

INTRODUCTION: While preoperative urinary tract infection (UTI) has the potential to cause bacteremia and postsurgical acute prosthetic joint infections (APJIs), the influence of asymptomatic bacteriuria (AB) in these infections remains unclear. So the majority of guidelines not recommend the treatment of AB prior to the surgery. However, as patients with dementia usually cannot explain the symptoms of dysuria, the differential diagnosis between AB and UTI may be very difficult in this group of patients. The principal aim of the study was to compare the rate of positive urine culture at admission in patients with femoral neck fracture with and without dementia and secondarily try to assess the connection of positive urinoculture and postoperative acute gram-negative PJI. METHODS: All patients with a femoral neck fracture underwent a urine culture on hospital admission and were prospectively recorded. Variables such as sex, age, institutionalization, dementia and other comorbidities, PJI rate, and in-hospital death were collected. The results of cultures were retrospectively revised. Patients who received postoperative antibiotics or had been diagnosed with UTI during hospital stay were excluded. Statistical comparisons between patients with and without dementia were performed using SPSS software version 17. RESULTS: A total of 148 patients were included (52 with dementia). The rate of positive urine culture was 32% (n = 16) in patients with dementia and 11.5% in patients without dementia (P = .003). Of these 16 patients with dementia and positive urine culture, 2 (12.5%) developed an acute gram-negative PJI, whereas there were no cases in the group without dementia (P = .011). DISCUSSION: The only difference between UTI and AB is the expression of symptoms by the patient. However, as patients with dementia have difficulties to explain UTI symptoms, some UTI may be underdiagnosed. CONCLUSION: Patients with dementia have a statistically higher rate of presurgical positive urine culture compared with patients without dementia.