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A 61-year-old woman was diagnosed with an incidental liver lesion with a satellite lesion that had features of a secondary liver metastasis. Investigations for primary sites did not reveal a primary tumour. The lesion was not amenable to biopsy due to location. Intraoperatively, the two lesions were adjacent, but the first was on the diaphragm and the lesion was in segment 7 of the liver. The liver lesion underwent non-anatomical resection and the diaphragmatic lesion was resected separately. The histopathology diagnosed peritoneal mesothelioma in the lesion removed from diaphragm and the liver lesion to be local metastatic spread to an area of liver that was in close contact (a ‘kissing’ lesion). This report portrays a rare occurrence of liver metastases from peritoneal mesothelioma and discusses the current evidence for diagnosis and treatment.

Metastatic spread to the oral cavity is a rare entity, comprising 1% of oral malignancies. However, 25% of oral metastases are found to be the initial sign of metastatic spread; therefore, initial presentation in the oral cavity may indicate significant underlying disease. Common primary sites for men include the prostate, lung, kidney and liver. For women, it is the breast, kidney, colon and genital organs. General dental practitioners are in a unique position to identify and instigate rapid referrals as gatekeepers of primary care whereby patients commonly present to them with symptoms. This clinical review article aims to educate dental practitioners on appropriate recognition of oral metastatic pathology and referral to secondary care.

PURPOSE: The significant pathogens associated with paediatric cervical suppurative lymphadenitis (CSL) are unclarified, and there is a lack of clinical evaluations of antibiotic regimens in paediatric CSL. We aimed to (1) explore the bacterial findings and the associated primary sites of infection in paediatric cases of CSL and (2) evaluate the clinical outcomes in patients treated with different antibiotic regimens.METHODS: All children (RESULTS: Eighty-five patients were included in the study. The prevalent isolates were S. aureus (57%), S. pyogenes (17%), non-haemolytic streptococci (11%), and F. necrophorum (3%). The primary sites of infection were identified in 30 (35%) patients. The most common sites were the oropharynx (n = 15), the middle ear (n = 10), and the skin (n = 5). All patients were treated with surgical incision and antibiotics. No statistically significant differences were found between patients treated with antibiotics covering streptococci (n = 60) versus antibiotics covering streptococci and S. aureus (n = 25) in terms of duration of hospitalisation (median 4 vs 4 days, p = 0.26), altered antibiotic treatment because of insufficient clinical or biochemical progress (7% vs 12%, p = 0.41), and abscess recurrence (8% vs 12%, p = 0.69).CONCLUSION: S. aureus was the predominant pathogen in paediatric CSL at all cervical levels, and even in cases with evidence of primary site infection not normally associated with S. aureus. We were unable to underscore the importance of antibiotic treatment covering S. aureus based on evaluation of the clinical outcomes.

The aims of the present study were to describe atraumatic proximal radial nerve entrapment (PRNE) and potential strategies for management. We performed a comprehensive search of 4 electronic databases for studies pertaining to patients with atraumatic PRNE. Studies published between 1930 and 2020 were included. Clinical presentation, nerve conduction studies, electromyography, and treatment methods were reviewed. In order to outline management strategies, 2 illustrative cases of acute PRNE were presented. We analyzed 12 studies involving 21 patients with 22 PRNE (15 acute and 7 progressive). Sudden or repetitive elbow extension with forceful muscle contraction (n = 16) was the primary mechanism of injury. The two main sites of entrapment were the fibrous arch (n = 7) and hiatus of the lateral intermuscular septum (n = 7). Conservative treatment was performed in 4 patients and allowed for complete clinical recovery in all cases. The remaining 18 patients underwent epineurolysis (n = 16) or resection/repair of hourglass-like constriction (n = 2) between 1.5- and 120-months following diagnosis. Twelve patients experience complete recovery, while partial or no clinical recovery was reported in 1 and 4 cases, respectively; the outcome was unknown in 1 case. Atraumatic PRNE is rare and remains challenging with respect to diagnosis and treatment. Current literature suggests that primary sites of entrapment are the fibrous arch and hiatus of the radial nerve at the time of forceful elbow extension. Case series (IV) & systematic review (I)

In major/life-threatening bleeding, administration of timely and appropriate reversal agents is imperative to reduce morbidity and mortality. Due to complexities associated with the use of reversal agents, a clinical pharmacist-driven anticoagulation reversal program (ARP) was developed. The goal of this program was to ensure appropriateness of reversal agents based on the clinical scenario, optimize selection and avoid unintended consequences. This study describes the impact of a pharmacist-driven anticoagulation program on patient outcomes and cost. A single center retrospective chart review of adult patients whom the ARP was consulted from October 2018 to January 2020 was performed. Patients were included in the efficacy analysis if they were > 18 years of age and presented with acute bleeding. Patients were excluded from the efficacy analysis if the recommended reversal agent was not administered, if a repeat head CT was not available for patients who presented with intracranial hemorrhage (ICH), or if the patient was not bleeding. All patients were included in the economic evaluation. The primary outcome was the percentage of patients who achieved effective hemostasis within 24 h of anticoagulation reversal. Secondary outcomes include incidence of thromboembolic events, in-hospital mortality, and cost avoidance. One hundred twenty-one patients were evaluated by the ARP with 92 patients included in the efficacy analysis. The primary sites of bleeding were ICH in 46% and gastrointestinal (GI) in 29%. Hemostasis was achieved in 84% of patients. Thrombotic events occurred in 7.4% of patients and in-hospital mortality was 26.4%. Total cost avoidance was $1,005,871.78. To our knowledge, this is the first study to evaluate the impact of a pharmacist-driven ARP on clinical and economic outcomes. Implementation of a pharmacist-driven ARP was associated with favorable outcomes and cost savings.

Background Soft tissue sarcomas (STS) are a heterogeneous group of rare tumours that represent less than 1% of all malignant, solid tumours in adults. There is limited epidemiological information regarding STS in Latin America. Therefore, the objective of this study is to present an epidemiological profile of these tumours observed at a single reference centre. Methods A retrospective study was carried out based on hospital records obtained from a registry of 879 patients with STS of the extremities who were treated at the National Cancer Institute of Mexico from January 1, 1994 to December 31, 2017. Epidemiological variables and relevant clinical data were collected. Five-year survival rates were analysed using Kaplan-Meier estimates, and a multivariate Cox proportional-hazards model measured associations. Results A total of 879 records were collected. The median age was 45 years (15–95 years), and the ratio of men to women was 1:1, with 433 men (49.3%), and 446 women (50.7%). The median tumour size was 11.4 cm (2–49 cm). The most prevalent histological variants were liposarcomas and synovial sarcomas. The lower limb was the most frequently affected extremity, with the thigh being the most common site followed by the leg. A majority of the patients were diagnosed at clinical stages IIIA-IV. Conclusions The data collected from the present cohort provides an overview of the epidemiological profile of STS at a single reference centre in Latin America, and allow comparison with global data.

To assess the survival benefits associated with epidermal growth factor receptor (EGFR) inhibitors in head and neck squamous cell carcinoma (HNSCC) according to the primary site.A systematic review and meta-analysis were conducted for randomized phase III trials comparing treatment with or without EGFR inhibitors in locoregionally advanced, recurrent, or metastatic HNSCC. The primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS), respectively. Data were pooled using a random-effects model.Seven trials with a total of 3391 patients were included. The addition of EGFR inhibitors improved OS in patients with oral cavity-oropharyngeal carcinoma (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.67-0.87, P 0.001) but not in patients with hypopharyngeal-laryngeal carcinoma (HR 0.94, 95% CI 0.82-1.08, P = 0.398). A significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.029). The addition of EGFR inhibitors increased PFS in both patients with oral cavity-oropharyngeal carcinoma (HR 0.67, 95% CI 0.52-0.85, P = 0.001) and patients with hypopharyngeal-laryngeal carcinoma (HR 0.81, 95% CI 0.69-0.94, P = 0.005). A trend towards significant interaction was found in favor of oral cavity-oropharyngeal carcinoma (P = 0.161). Comparable results were observed in the pre-specified subgroup analyses. Meta-regression analyses suggested that the primary site appeared to be a predictor of survival benefits in HNSCC patients who received treatment with EGFR inhibitors over those who did not.Our meta-analysis suggests that the survival benefits of EGFR inhibitors might depend on primary sites in HNSCC. Further studies are needed to confirm this finding.

The identification of gene fusions is a cornerstone of diagnosis and treatment decision making for tumors of many forms and primary sites. Diverse molecular approaches are currently used for the molecular diagnosis of fusions, but few permit broad, partner agnostic detection of fusions over multiple potential targets. We previously described the combination of nanopore sequencing with the anchored multiplex PCR technique to permit a rapid testing paradigm. Recently, a new platform for nanopore sequencing has become publicly available, the Flongle flow cell from Oxford Nanopore Technologies, which offers lower throughput, but lower price testing. Here, we describe the results of retesting of 15 specimens previously tested with both Illumina and Oxford Nanopore Technologies MinION sequencing. Furthermore, we additionally blindly tested 13 specimens that had undergone clinical Illumina-based sequencing. The Flongle sequencing pipeline removed key complexities of a multiplexed nanopore sequencing protocol, reduced sequencing turnaround time, and showed excellent concordance with Illumina results. It was particularly strong in identifying notoriously difficult to detect CIC-DUX4 translocations. The Flongle sequencing pipeline may be the assay of choice for deployment in small- to medium-sized molecular laboratories.

Regions remain in flux. Their status as primary sites of governance and government is an ongoing negotiation between multiple endogenous and exogenous actors. The role of regions as drivers of econ...

Parotid lymph node (PLN) metastasis greatly worsens the prognosis of patients with oral squamous cell carcinoma (OSCC) and poses a great challenge for further treatment of OSCC. The clinicopathological characteristics and treatment strategies for PLN metastasis from OSCC need to be comprehensively elucidated. A retrospective review of OSCC patients who experienced postoperative PLN metastasis in our department between 2000 and 2018 was performed in this study. A total of 47 OSCC patients with postoperative PLN metastasis were identified. PLN with metastasis were divided into three groups based on the location: parotid tail (PLN-t), superficial lobe (PLN-sl), and deep lobe (PLN-dl). Most of the patients experienced PLN metastasis within less than 12 months after the primary surgery for OSCC. Comparatively, patients with PLN-sl metastasis were more prone to have infiltration of the facial nerve. The tongue and buccal mucosa were the most frequent primary sites associated with PLN metastasis from OSCC. PLNs in the parotid tail were most commonly affected by the metastasized OSCC. Consequently, we recommend a series of strategies for the prevention and treatment of PLN metastasis for OSCC patients. In conclusion, PLNs should not be overlooked during preoperative evaluation and postoperative follow-up examinations for OSCC patients.

Plectranthus edulis (Vatke) Agnew is an underutilized and neglected ancient Ethiopian indigenous annual tuber crop. Very limited research has been done to improve this crop especially in the area of molecular genetic diversity. Therefore, this study was aimed to assess the genetic diversity of this crop using ISSR markers. Fourteen ISSR primers were screened, and four polymorphic and reproducible primers were selected. These primers generated a total of 46 scorable bands of which 42 were polymorphic. Primer UBC-880 showed 100% polymorphism, and a unique band in some individuals was observed. Within-population diversity ranged from 41.30% to 65.22% with overall percentage of polymorphic loci of 91.30%, Nei’s gene diversity of 0.18–0.30 with overall diversity of 0.33, Shannon information index of 0.25–0.39 with overall index of 0.48, and 74.23% within-population variation was detected. Sodo Zuria, Gojam-II and Areka populations showed the highest diversity, whereas the lowest was exhibited by Nekemte. According to Jaccard’s pairwise similarity coefficient, Ambo and Sodo Zuria were most related populations exhibiting 0.648 similarity coefficient, and Gojam-I and Sodo Zuria were the most distantly related populations with similarity coefficient of 0.489. Wolaita and Wollega populations showed the highest genetic diversity so that these populations should be considered as the primary sites in designing conservation strategies for this crop.

Peritoneal carcinomatosis (PC) is defined as a metastatic involvement of the peritoneum by several other primary sites and it is characterized by a marked worsening of prognosis, with limited treatment opportunities. Subsequently, PC should be ruled out before any invasive treatment is administered. A new through-the-needle micro-biopsy forceps (MF) was recently introduced that permits micro-histology cores. In this case series, we evaluated the feasibility of MF in the assessment of PC to complete patient diagnostic work-ups. Five consecutive patients referred for endoscopic ultrasound staging were sampled using MF. Sampling was feasible in all patients with a technical success of 100%. No adverse events were reported in any cases. This technique was feasible and safe with a technical success rate of 100%. It permitted sampling of peritoneal irregularity, obtained high-quality tissue fragments in all cases, and enabled an additional assessment, i.e., immunohistochemical staining.

The correlates of dual tracer positron emission tomography and computed tomography (PET-CT) (18F-fluorodeoxyglucose [18F-FDG] and 68Ga-DOTATATE) in patients of Grade 3 neuroendocrine neoplasms (NENs) are presented. The first, a patient of gall bladder NEN, operated, with histopathology suggestive of high-grade well-differentiated neuroendocrine tumors with MiB-1 labeling index of 35%, showed uptake with both 18F-FDG and 68Ga-DOTATATE, including an uptake equivalent to Krenning score of 3–4 on 68Ga-DOTATATE PET-CT; in the second, a patient of esophageal NEN, Grade 3 with poor differentiation features, with MiB-1 labeling index of 70%, thereby qualifying for Grade 3 neuroendocrine carcinoma, the FDG uptake was high with minimal uptake on 68Ga-DOTATATE PET-CT. The illustrations reiterate the impression that relative uptake of 68Ga-DOTATATE/FDG in the NEN lesions forms a valuable parameter for assessing the dynamic tumor biology in continuum and thus personalizing the treatment strategies.

Context.— Mutational signatures have been described in the literature and a few centers have implemented pipelines for clinical reporting. Objective.— To describe the performance of a mutational signature caller with clinical samples sequenced on a targeted next-generation sequencing panel with a small genomic footprint. Design.— One thousand six hundred eighty-two clinical samples were analyzed for the presence of mutational signatures using deconstructSigs on variant calls with at least 20 variant reads. Results.— Signature 10 (associated with POLe mutation) achieved separation of cases and controls in hypermutated samples. Signatures 4 (associated with tobacco smoking) and 7 (associated with ultraviolet radiation) as an indicator of pulmonary or cutaneous primary sites showed moderate sensitivity and high specificity at optimal cutpoints. Mutational signatures in malignancies with unknown primaries were somewhat consistent with the clinically suspected primary site, with an apparent dose-response relationship between the number of variants analyzed and the ability of mutational signature analysis to correctly suggest a primary site. Conclusions.— Mutational signatures represent an opportunity for orthogonal testing of primary site, which may be particularly useful in supporting cutaneous or pulmonary sites in poorly differentiated neoplasms. Tobacco smoking, ultraviolet radiation, and POLe mutational signatures are the most appropriate signatures for implementation. Even relatively small numbers of variants appear capable of supporting a clinically suspected primary.

Museums are primary sites of exchange between diverse publics and disciplinary experts As museums' missions have shifted toward public service over the last 40 years, public access has been partially digital Here, they survey ways museums have recently brought their ancient Mediterranean and Middle Eastern resources to online audiences, in both long-term projects and COVID-19 pandemic efforts Focusing on virtual galleries, digitized collections, and social media activities, we offer a critical museum studies perspective as we highlight notable digital practices, challenges, and opportunities in the current digital museum landscape

Hydatid disease is a common health problem in sheep-farming countries including Iran. The liver and lungs are the most frequent primary sites of hydatid cysts in humans. Cardiac involvement is an uncommon manifestation and the right ventricle outflow tract is rarely involved. This is a case report of a 34-year-old man who presented to the Heart Clinic, Tehran, Iran, in 2019 with a history of dyspnea and fatigue. Following imaging study, the patient was diagnosed with a right ventricular outflow tract hydatid cyst. He underwent surgical resection of the cyst. The post-operative course was uneventful.Keywords: Hydatid cyst; Right ventricular; Outflow obstruction; case report; Iran.

Purpose The study aims to investigate and compare the efficacy and safety of intraoperative 125I implantation and postoperative irradiation after surgical decompression and stabilization in the treatment of patients with metastatic epidural spinal cord compression (MESCC). Methods The study retrospectively enrolled 122 MESCC patients treated with surgical decompression and pedicle stabilization combined with 125I brachytherapy (the brachytherapy group) or postoperative radiotherapy (the irradiation group). Operation time, intraoperative blood loss, pain relief, postoperative ambulatory status, postoperative survival outcome, complications, and length of hospitalization were collected and compared between the two groups. Ten potential risk factors were analyzed for postoperative survival outcome. Results No significant difference was found in baseline characteristics between the two groups (P>0.05). Postoperative VAS score was significantly decreased, as compared with preoperative scores in both groups (P˂0.001). The VAS in the brachytherapy group was significantly lower than that in the irradiation group at postoperative 1 month, 3 months, and 6 months (P˂0.05). The postoperative ambulatory rates were 90.0% (54/60) in the brachytherapy group and 83.9% (52/62) in the irradiation group (P=0.32). The median overall survival time was similar between the two groups (7.43 months vs 7.27 months, P=0.37). Of all patients in the brachytherapy group, 25.0% (15/60) of patients suffered from complications, while 46.8% (29/62) of patients had complications in the irradiation group (P=0.0086). According to the multiple Cox regression, primary sites (P=0.038), ECOG performance status (P=0.014), and visceral metastases (P=0.0016) showed significance for postoperative survival outcome. Conclusion Surgical decompression and spine stabilization combined with 125I brachytherapy is a relatively safe and useful method in MESCC patients.

Active centers in porous solid catalysts are multifaceted in structure, comprised of primary sites that bind intermediates, secondary environments that confine intermediates and transition states, ...

Objective We investigated the role of Ga-68 DOTATATE PET/CT in comparison to F-18 FDG PET/CT in patients with low and intermediate versus high-grade neuroendocrine tumors (NETs). Methods We identified 81 patients who underwent Ga-68 DOTATATE PET/CT at our institution between May 2017 and December 2018 and met inclusion criteria of biopsy-proven NET with known Ki-67 index, histologic grade, or differentiation. Patients were divided into two groups. Control group included Ki-67 ≤20%, grade 1 or 2, or well-differentiated tumors. Experimental group included Ki-67 >20%, grade 3, or poorly-differentiated tumors. Results Mean age was 57 years, with 36 males and 45 females. Most common primary sites were small bowel, pancreas, and lung. Most common distant metastatic sites were liver and bone. In the control group (n = 67), median Ki-67 was 4% (range 1-30%). 55/67 (82.1%) DOTATATE and 6/11 (54.5%) FDG scans were positive (P = 0.04). Positive scans showed >10 lesions in 25/55 (45.5%) DOTATATE and 1/6 (16.7%) FDG scans (P = 0.18). 40/55 (72.7%) positive DOTATATE and 3/6 (50%) FDG scans showed distant disease (P = 0.25). In the experimental group (n = 14), median Ki-67 was 68% (range 25-95%). All 14 DOTATATE and all nine FDG scans were positive. Positive scans showed >10 lesions in 4/14 (28.6%) DOTATATE and 5/9 (55.6%) FDG scans (P = 0.20). 10/14 (71.4%) positive DOTATATE and 7/9 (77.8%) FDG scans showed distant disease (P = 0.74). Conclusion All patients with high grade, poorly-differentiated NETs had positive DOTATATE PET/CTs. In these patients, DOTATATE PET/CT did not significantly differ from FDG PET/CT in identifying >10 lesions or distant disease.

PURPOSE: MYCN amplification (MNA) is associated with poor outcomes in neuroblastoma. Less is known about heterogeneous MNA within a tumor. We compared clinical characteristics, biologic features, and clinical outcomes of patients with heterogeneous MNA to patients with either homogeneous MNA or MYCN wild-type tumors. PATIENTS AND METHODS: In this retrospective cohort study, we categorized patients as having tumors with MYCN wild-type, homogeneous MNA (>20% amplified tumor cells) or heterogeneous MNA (≤20% amplified tumor cells). We used chi-squared or Fisher’s exact tests to compare features between groups. We used log-rank tests and Cox models to compare event-free survival (EFS) and overall survival (OS) between groups. RESULTS: MYCN status and heterogeneity status (if amplified) could be ascertained in diagnostic tumor samples from 5,975 patients, including 57 (1%) with heterogeneous MNA, 981 (16.4%) with homogeneous MNA, and 4,937 (82.6%) with MYCN wild-type tumors. Multiple clinical and biological features differed between patients with heterogeneous vs. homogeneous MNA, including enrichment for thoracic primary sites and paucity of 1p LOH with heterogeneous MNA (p

Background In the CheckMate-141 trial, nivolumab conferred a survival benefit in patients with recurrent or metastatic refractory squamous cell carcinoma (SCC) head and neck cancer (HNC). Here, we examined the efficacy of nivolumab in patients with histological subtypes or primary sites of HNC not included in the CheckMate-141 trial. Methods This was a retrospective analysis of data collected prospectively from 97 patients who were treated with nivolumab for recurrent or metastatic HNC at our institution. The patients were assigned to three groups based on HNC primary site: 1) oral cavity, pharynx, and larynx, which were included in CheckMate-141 (n = 68), 2) nasopharynx (excluded in CheckMate-141, n = 7) and 3) other primary sites excluded in CheckMate-141 (n = 22) and assigned to two groups according to histological subtype: 1) SCC (included in CheckMate-141, n = 83) and 2) non-SCC (all sites excluded in CheckMate-141, n = 14). Survival outcomes and nivolumab treatment response were compared between the primary site and histological subgroups. Results The median number of nivolumab treatments was 7 cycles (range, 1-53 cycles) and the median follow-up time was 9.1 months (range, 0.66-33.0 months). There were no significant differences in response rates between the three primary site subgroups (CheckMate-141 sites 22%, nasopharynx 43%, others 18%; p=0) or the two histological subtype subgroups (SCC 25%, non-SCC 7%, p=0). Similarly, overall survival and progression-free survival were comparable for patients stratified by primary site or histological subtype. Conclusion No significant difference in response rates or survival outcomes was detected between nivolumab-treated HNC patients with primary sites and histological subtypes that were included versus excluded in the CheckMate-141 trial. These data provide a potential rationale for nivolumab therapy for all HNC patients in clinical practice.

Background Diffuse large B-cell lymphomas (DLBCL) are fast-growing non-Hodgkin lymphomas that affect B-lymphocytes. Double expressor DLBCL is the concomitant expression of Myc and Bcl-2 proteins during lymphomas which results in poor prognosis of patients. This study aimed to determine the frequency of double expresser in high grade diffuse large B-cell lymphomas. Materials and methods The study was conducted on 74 cases (54 males (68.4%) and 20 females (25.3%)) of DLBCL between August 2018 to January 2019. The mean age of the 74 patients was 51.7 years + 18.5. Expression of proteins c-Myc, Bcl-2 and Bcl-6 were evaluated by immunohistochemistry. The involvement of primary lymph node was reported in 38 cases (51.3%) whereas, extra nodal site was observed in 22 cases (29.7%). Among the primary sites, the cervical lymph node enlargement was the most frequent site of presentation. Results The rearrangement pattern was studied among 74 patients, 35 (47%) were found to have either one of the rearrangements i.e. Myc, Bcl-2, or Bcl-6. On the other hand, 14 (18.9%) had shown double rearrangements i.e. Bcl-2 and c-Myc (11 cases) and Bcl-6 and c-Myc (3 cases). The Bcl-2 and Bcl-6 rearrangements were demonstrated by 12 cases whereas 2 cases (2.7%) indicated all three types of rearrangements i.e. c-Myc, Bcl-2, and Bcl-6. In 11 cases the Bcl-2 and c-Myc rearrangements were found to be Bcl-2 > 50% and c-Myc > 40% and demonstrating the overall frequency of double expressers as 14.8%. The prognosis of the mentioned cases was extremely poor, median survival of 10 months. Conclusion The concurrent expression of Bcl-2 and c-Myc was found to be 14% (level of expression for Bcl-2 > 50% and c-Myc > 40%) which is potentially a significant health burden and an emerging threat.

Background Invasive solid cancers originating from diverse organs like breast, ovary and lung metastasize to distant sites. The structural changes at the primary sites of these high-grade tumors have not been well characterized. The main aim of the current study was to examine if there is any morphological overlap of metastasizing tissues of different invasive tumors. Methods Whole slide hematoxylin and eosin (H&E) stained images from web repository of multiple tumor specimens were used for this study. ImageJ was used for image processing and analysis. Results The metastatic tissue(s) at the primary sites of different examined high-grade tumors appeared similar, irrespective of the organ of origin of the primary tumor. Numerous cellular excrescences with the repetitive appearance of a bulb-like projection with a narrowed-off trailing end were seen emanating from the tumor cell membrane. Many of them contained nuclei, while others were empty vesicles. Although these structures were not exactly equal in their dimensions, the rubrics of architectural distortion in different high-grade tumors were conserved. Conclusions The preliminary observations suggest for the first time that there is structural similarity of the epithelial dysmorphia in many high-grade invasive tumors irrespective of their parental tissue of origin. This commonality of morphological prints of metastases suggests that common pathways of cytosolic force generation are activated during temporal progression of cancer, resulting in the conserved mushroom-shaped appearance of the dismantling individual cell or cell clusters from the parental epithelium. The conserved genomic mechanisms underlying these fascinating observations merit testing and validation in future studies.

Primary cutaneous mucinous carcinoma (PCMC) is a rare malignant adnexal tumor of eccrine origin with a higher incidence in the head and neck region of the body while scrotal skin involvement is rare. We report a case of a 72-year-old man with ulceration of painless scrotal lesions of 10 years' duration. Histology of the wedge biopsies of the lesions was mucinous carcinoma. Clinical workup excluded noncutaneous primary sites of mucinous carcinoma and distant metastasis. He had wide excision of the scrotal skin lesions with histological findings of nests of malignant cells separated from pool of mucin by fibrocollagenous septae. Periodic acid-Schiff stain was positive; however, immunohistochemical stains for estrogen and progesterone receptors were negative. No local recurrence was observed after 12 months of follow-up. Scrotal PCMC is a rare tumor; this may probably be the first reported case of this tumor in the scrotum. Prognosis was good following surgical excision.

Background/aim Solitary extramedullary plasmacytoma (SEP) is a rare, malignant plasma-cell tumor, which mainly occurs in the head and neck regions. Globally the disease has been rarely happening up to 2019, with only about ten papers focused on SEP cases reported in English. Thus, a literature collectively reviewing the characteristics of the patients would be valuable. Patients and methods We enrolled 10 SEP patients, and recorded their primary sites and the treatment modality, and analyzed their survival rates and outcomes. We also reviewed previous studies and compared their findings with ours. Results No gender or age disparity has been observed, and younger patients had a better local control with RT compared to surgery among our patients. Conclusion Further investigations with more patients and long-time follow-up may provide more information for treatment determination and the recurrence and progression from SEP to MM.

Today’s immigrant rights movements bring attention to jails—some cities’ largest public safety expenditures—as primary sites for deportation operations. This article examines how these movements push for sanctuary while challenging jails’ political and economic place in cities. With qualitative and archival data from a case study in Santa Ana, California, this research finds that by ending U.S. Immigration and Customs Enforcement (ICE) contracts, exposing the economic and political interests invested in jails, and pushing for jail reuse alternatives, sanctuary planning threatens public investment in police and security infrastructure. Challenges to these movements include jurisdictional fragmentation with diverse approaches to detention.

Evaluating wildlife population trends is necessary for the development of effective management strategies, which are particularly relevant for highly threatened species. Hawksbill marine turtles (Eretmochelys imbricata) are considered endangered globally and are rare in Hawai‘i. Remnant hawksbill nesting beaches were identified in Hawai‘i in the late 1980s and the primary sites have been monitored since that time. In this study we summarize all available hawksbill nesting activity around the Hawaiian Islands between 1988 and 2018, highlighting relevant demographic and geographic data for the species. Because monitoring effort varied substantially across space and time, we implemented a predictive modeling approach that accounted for varying effort to explore potential trends in annual number of nesting females and nests over time. Field monitoring efforts documented an annual average of 14 ± 4.3 (range: 5–26) nesting females and 48 ± 19.0 (range: 12–93) nests, with a cumulative total of 178 individual nesting females and 1,280 nests recorded across all years. Nesting has been documented on four Hawaiian Islands, with the overwhelming majority of nesting females (78.4%) and nests (86.5%) recorded at four beaches along the southern coast of Hawai‘i Island. Recent monitoring (2018) at a beach on Moloka‘i Island revealed numbers similar to the most important beaches on Hawai‘i Island. Despite difficulty discerning obvious trends when looking solely at the raw tabulated numbers from field monitoring, our analysis suggests both the number of nesting females and nests have been positively trending since 2006, and this is supported by a higher percentage (57.1% of annual cohorts) of neophyte (vs. remigrant) nesters over the second half of the monitoring timeframe. The masking of obvious trends in the tabulated numbers is likely due to decreased overall monitoring effort as a result of reduced funding in recent years, coupled with a shift in focal monitoring effort from the historical primary nesting site of Kamehame, to the more recently established nesting site of Pōhue. Although the positive trend is encouraging, our findings highlight the precarious state of hawksbills in Hawai‘i and the need to enhance monitoring across all sites to support more robust population assessments and management decision making.

Background: Fine needle aspiration cytology is an indispensible technique, both as a modality of pre-therapeutic investigation and also in diagnosing recurrences. The role of fine needle aspiration cytology (FNAC) in the diagnosing malignant tumours is recorded. Yet it is not always possible to arrive at a definitive diagnosis based on FNAC alone. Certain pitfalls are there in conventionally assessed FNA smears. Often, they contain very less quantity of tissue material and the relative absence of recognizable tissue architecture in cytology smears often makes diagnosis very difficult.Fine needle aspiration (FNA) smears prepared through conventional method, often contain well preserved viable tissue fragments which are intact (tissue microbiopsies). Micro biopsies are defined as well preserved viable tissue fragments obtained on cytology smears. They will provide information on the tissue architecture and thereby contribute to the tumour ontogeny. This study was done to assess the significance of the presence of microbiopsies in conventional/guided FNAC in giving a more precise diagnosis. Aim: To Study the Significance of Tissue Microbiopsies in Conventional/Guided Fine needle aspiration Cytology preparation and to assess the utility of the microbiopsy fragments in giving a precise cytological diagnosis. Methods: A prospective study of significance of tissue microbiopsies in fine needle aspiration cytology were studied and interpreted during the period from June 2014 to June 2015 in the Cytopathology laboratory of the Department of Pathology, Tirunelveli Medical College, Tirunelveli. 100 cases with clinically palpable Swellings were studied. Results: Out of 100 cases, 82% of cases were coming under the category of conventional FNAC, 10% of the cases were USG guided and 8% were falling under CT guided FNAC. Lymph nodes had the highest yield of microbiopsies, with 34 cases (34%), followed by breast 24 cases, thyroid 11 cases, lung 8 cases, salivary gland 7 cases, liver and bone and soft tissue 4 cases each, abdominal mass 3 cases, pancreas 2 cases, and ovary, spleen, and anterior mediastinum 1 case each. There were 56 percent malignant cases and 44 percent benign instances out of a total of 100 cases. There were 56 malignant tumours in total, with 41 (73.2%) being primary tumours and 15 (26.8%) being metastatic tumours. Conclusion: FNA smears containing microbiopsies are of more help in establishing confirm diagnosis, typing of tumour, and predicting possible primary sites in cases of metastatic tumors which were not possible by cytology alone. Hence, this technique can be used to increase the diagnostic accuracy of FNAC, if put into practice in evaluation of routine cytology sample. Whatever be the types of FNAC, conventional, CT or USG guided, fine needle aspiration cytology aspirate with tissue microbiopsy is an effective tool in evaluating and diagnosing suspected lumps or masses.

OBJECTIVES: Post-amputation, clinical markers of pain-related peripheral and central nervous system hypersensitivity remain understudied. This study aimed to identify whether adults with post-amputation pain demonstrate greater pain sensitivity in primary (i.e., amputated-region) and secondary (i.e., non-amputated-region) sites, as compared to pain-free peers and controls with intact limbs. METHODS: Ninety-four participants post-unilateral, transtibial amputation (59 with pain, 35 pain-free) and 39 controls underwent pain-pressure threshold testing at 10 sites. Pain pressure-thresholds were normalized to sex-specific control data using z-score conversions. Normalized primary- and secondary-site pain-pressure thresholds were compared between groups using multivariate analysis of variance (p

Background The objective of this study was to evaluate the efficiency and safety of microwave thermal ablation in the treatment of skip metastases in extremity osteosarcomas. Osteosarcoma of extremities with skip metastases has a poor prognosis, and thus, microwave thermal ablation presents an attractive minimally invasive option in this patient group. Methods A retrospective review included a cohort of 76 patients with extremity osteosarcoma in one institute, of which five cases (6.6%) showed skip metastases. Skip lesions located in proximal femur and primary sites were distal femur in all five patients. The authors treated skip lesions using microwave thermal ablation after primary tumors were removed at wide margins. Procedural efficacy and safety were determined with postoperative MSTS score and follow-ups of 12-62 months (median 22 months). Results The ablation time was five to nine minutes (mean seven minutes). Taking advantage of Microwave-induced hyperthermia, wide resections of distal femur and endoprosthesis reconstructions were performed instead of total femoral resection and replacement in four patients, and above-knee amputation was performed instead of hip disarticulation in one patient. The postoperative hip functions were intact and the mean lower extremity MSTS score was 26. Three patients died at 12-22 months after definitive surgery because of pulmonary metastases, and two patients remained disease-free at 44 and 62 months after surgery, respectively. No local recurrence either at sites of primary tumors or skip lesions was found at time of the latest follow up. Conclusion Microwave thermal ablation is efficacious in treating skip metastases of osteosarcoma in extremities. The modality has promise for good local control of tumors, less invasive surgeries, and intact and satisfied lower extremity functions in these relatively poor prognosis patients. Level of evidence Therapeutic Level III.

Summary Urothelial carcinoma with an inverted/endophytic growth pattern can occasionally mimic inverted urothelial papilloma and pose diagnostic challenges when assessing the presence or absence of invasion. Making these distinctions is critical for guiding appropriate treatment and improving patient outcomes. Here we conducted one of the largest studies to date of invasive high-grade urothelial carcinoma arising in a background of urothelial carcinoma with an inverted growth pattern. Primary sites examined included bladder, renal pelvis, ureter, and prostatic urethra. Clinicopathological parameters including extent of invasion, variant histology, presence of urothelial carcinoma in situ, and clinical follow-up were obtained. Ninety-one cases from 82 patients were included in the study. Lamina propria invasion was present in 81% of bladder, 60% of ureter, 20% of renal pelvis, and 100% of prostatic urethra cases. Muscularis propria invasion was identified in 19% of bladder, 14% of ureter, and 20% of renal pelvis cases. Urothelial carcinoma invaded periureteric fat in 29% of ureter cases and invaded the renal parenchyma in 60% of renal pelvis cases. Clinical follow-up was available for 77 of 82 (94%) patients with a mean duration of 18 months. Recurrent urothelial carcinoma persisted in 63 of 82 (77%) patients, 16 of 82 (19%) progressed with metastatic disease, and 20 of 77 (26%) patients with bladder involvement died of disease. This study further emphasizes the importance of distinguishing these tumors from benign mimickers of urothelial carcinoma. Recognition of invasive foci is also critical in view of the potentially high frequency of recurrence and the possibility of advanced disease in a subset of these patients.

The mechanisms leading to aggregation of the crystallin proteins of the eye lens remain largely unknown. We use atomistic multiscale molecular simulations to model the solution-state conformational dynamics of γD-crystallin and its cataract-related W42R variant at both infinite dilution and physiologically relevant concentrations. We find that the W42R variant assumes a distinct conformation in solution that leaves the Greek key domains of the native fold largely unaltered but lacks the hydrophobic interdomain interface that is key to the stability of wild-type γD-crystallin. At physiologically relevant concentrations, exposed hydrophobic regions in this alternative conformation become primary sites for enhanced interprotein interactions leading to large-scale aggregation.

Tuberculous pleurisy is one of the primary sites of extrapulmonary tuberculosis, but clinicians currently lack the diagnostic tools necessary for early recognition in the absence of typical signs and symptoms. With this study, we aimed to test the association between internal mammary adenopathies and tuberculous pleurisy (TP). 60 patients with a post-thoracoscopic histological diagnosis of granulomatosis or acute infective pleurisy were retrospectively enrolled. All of them had chest sonography and/or CT scan data available. At least two expert chest sonography physicians re-analyzed the sonography images to look for any internal mammary adenopathy. Such findings were compared to the CT data. Chest sonography showed internal mammary adenopathy ipsilateral to the pleural effusion in 97 % of 29 patients who had a diagnosis of TP, and in 13 % of those with an acute infective pleurisy (p 0.001). Receiver operator characteristic analysis revealed 97 % sensitivity and 87 % specificity for this technique in predicting TP (area under curve 0.92 ± 0.04, p 0.001). CT detection power and node measures were significantly similar (p 0.001). Sonographic internal mammary node visualization ipsilateral to the pleural effusion may become a sentinel sign for TP, contributing to early diagnosis or orienting the diagnostic management towards invasive procedures in uncertain cases. Die tuberkulöse Pleuritis ist eine der primären Stellen der extrapulmonalen Tuberkulose. Derzeit fehlt es den Ärzten jedoch an diagnostischen Mitteln für die Früherkennung, wenn typische Anzeichen und Symptome fehlen. Mit dieser Studie wollten wir den Zusammenhang zwischen interner Mamma-Adenopathie und tuberkulöser Pleuritis (TP) untersuchen. 60 Patienten mit der post-thorakoskopischen histologischen Diagnose einer Granulomatose oder akuten infektiösen Pleuritis wurden retrospektiv aufgenommen. Bei allen wurde eine Thorax-Sonografie durchgeführt und/oder es lagen CT-Aufnahmen vor. Mindestens 2 auf Thorax-Sonografie spezialisierte Ärzte reanalysierten die sonografischen Aufnahmen im Hinblick auf interne Mamma-Adenopathien. Entsprechende Befunde wurden mit den CT-Daten verglichen. Die Thorax-Sonografie zeigte eine interne Mamma-Adenopathie ipsilateral zum Pleuraerguss bei 97 % der 29 Patienten mit diagnostizierter TP und bei 13 % der Patienten, die eine akute infektiöse Pleuritis hatten (p 0,001). Die ROC-Analyse („receiver operator characteristic“) ergab für diese Methode eine Sensitivität von 97 % und eine Spezifität von 87 % für die Vorhersage einer TP („area under the curve“ 0,92 ± 0,04, p 0,001). Die CT-Detektionsleistung und die Knotenmessungen waren signifikant ähnlich (p 0,001). Die sonografische Darstellung der inneren Brustknoten ipsilateral zum Pleuraerguss kann zu einem Sentinelmarker für TP werden, der zur Frühdiagnose beiträgt oder bei fraglichen Fällen das diagnostische Management in Richtung invasiver Verfahren lenkt.

Purpose: In patients with neuroendocrine neoplasm (NEN), the diagnostic role of positron-emission tomography (PET) using somatostatin receptor-targeted tracers, such as 68Ga-DOTATOC and 68Ga-DOTATATE in combination with 18F-FDG to assess glucose metabolism, is still a matter of debate. This systematic review aims to examine all published data on the role ofcombined 68Ga DOTA-peptides and 18F-FDG PET in the diagnosis and management of patients with NEN. Methods: A systematic search of studies assessing the use of dual-tracer PET in patients with NEN has been carried out on PubMed, Web of Science and Scopus databases. PRISMA guidelines have been used to screen the suitable studies. Results: Overall, 13 articles (658 patients in total) were considered for the analysis. All but three studies included patients with NEN of different primary sites of origin and different histologic grades. Seven studies included patients at initial diagnosis, whereas the remaining six considered patients at first diagnosis and at restaging after therapy. The median sensitivity of 68Ga DOTA-peptide PET (68Ga-DOTATOC, 68Ga-DOTATATE and 68Ga-DOTANOC) and 18F-FDG PET was 93% (range 82–100%) and 58% (range 37–75%), respectively. The median sensitivity of combined examinations was 94% (range 92–100%). Conclusions: There is still very limited evidence supporting the role of a routine use of combined 68Ga DOTA-peptide and 18F-FDG PETs in the diagnostic work-up of NEN.

Background Adrenal metastases can arise from different primary sites. Surgical resection of the adrenal gland in patients with isolated metastases may offer improved survival in many of these patients. However, the benefit of surgery in this heterogenous group is often disputed. The aim of this study was to identify patients undergoing adrenalectomy for isolated metastases and to describe survival outcomes based on origin of the primary malignancy. Methods Patients undergoing surgery for isolated adrenal metastases were retrospectively analysed from a prospectively kept database. Data collected included the age of the patient, gender, size and functional status of the tumour and the site of the primary malignancy. Overall survival and survival based on the primary tumour were calculated using Kaplan-Meier survival analyses. Results 42 patients were included for analysis. The median tumour size was 40 mm. 91% (n = 38) of operations were performed laparoscopically. Metastases were from the following primary organs: kidney (n = 22), lung (n = 11), breast (n = 2), gastric (n = 1), skin (n = 3), liver (n = 2) and neuroendocrine (n = 1). Overall median survival was 56 (19–93) months with 95% of patients followed up for >6 months. There was a significant difference in median survival between primary organs of origin: 83(42–123), 14(9–18), 15 and 12(3–20) months (p Conclusion There is a potential survival benefit for patients undergoing surgery for isolated adrenal metastases; however this survival benefit is greater in patients undergoing resection for metastases arising from kidney primaries. A selective approach should be adopted to identify patients that will clearly benefit from surgery.

Metastasis to the breast from all other primary sites is unusual. Twelve patients were diagnosed between 2007 and 2017 at National Cancer Institute, Mexico. Solitary or multiple masses, round or oval, and hypoechoic and solid lesions with posterior acoustic shadowing were patterns commonly reported in these patients; other arrangements include diffuse involvement of the breast simulating an inflammatory carcinoma. The development of a breast metastasis is revealed, in our experience, as a negative prognostic factor. Thus, the radiologist should know about the varied appearance of metastatic breast lesions and provide radiopathological correlations when available.

Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis., Failure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Here, the authors show that a systemic metastasis-targeted nanotherapeutic may offer a powerful adjunct therapy for suppressing tumor metastasis.

Aim: This retrospective analysis of the scintimetric characterization of the primary tumors of various cancers using the dual phase PETCT scans thrives to establish the utility of the Rong's Retention ratio and the Dr. V. Siva's modification of RRI. Methods: In the proven cases of various cancers the SUV max values were obtained in the Early and Delayed PETCT scans using the ROI method over the FDG avid primary sites. The PETCT scans were done using the GE Discovery IQ unit one and 4 hours after the I.V injection of 5 to 10 mCi of F18- FDG after overnight Fasting. The image analysis and the SUV were calculated using the Advantage 4.7 software provided by GE. Total of 19 primary sites at various locations were included and the calculated SUV max were used to arrive at the Rongs Retention Index (RRI) and Dr. V. Siva's modification of RRI. The values were tabulated and analyzed. Results: The Rong's retention ratio had a very narrow range with wide overlapping. However the Dr. V. Siva's modification of RRI showed much wider values with a definite cut off level. The statistical evaluation of the data confirm that the Dr. V. Siva's modification of RRI significantly correlates well with the Rong's Retention Index (RRI). Conclusion: It can be concluded that the scintimetric characterization of the primary tumors of various cancers is possible and might be useful in the identification of the primary malignancies.

Introduction Haemangiosarcoma (HSA) is a malignant neoplasm of dogs and cats that is suspected to originate from a pluripotent bone marrow progenitor with a complex and multifactorial pathogenesis. Approach Pertinent literature was identified, reviewed, and summarized for inclusion in the manuscript. Results/interpretation Dogs are more frequently diagnosed with HSA than cats, and primary sites of this disease include dermal, subcutaneous/intramuscular, and visceral (most commonly the spleen). Dogs and cats with HSA generally have a poor prognosis owing to the rapid and widespread metastasis typically associated with this disease. However, some forms such as cutaneous HSA behave in a less aggressive fashion with improved outcomes. Surgical excision and anthracycline-based chemotherapy remain the mainstays of treatment, although novel treatment modalities are currently under investigation for potential roles in treatment of this disease. Conclusion This review aims to describe the clinical presentation and progression of the various forms of HSA in dogs and cats as well as to provide a systematic review of the veterinary literature with a focus on the various published treatment options and associated outcomes.

Emergence of malignant ureteral obstruction (MUO) has been reported as a sign of poor prognosis; however, the distribution of survival time in patients with MUO is considerably wide, and no risk classification score has been constructed. To evaluate whether a novel risk classification score for overall survival that we previously developed, is effective in a large cohort. Investigator-initiated, prospective, multicenter diagnostic/prognostic study was conducted. Patients with MUO were divided into three risk groups based on the score calculated using four prognostic factors (PLaCT: Primary site, Laterality, serum Creatinine level, and Treatment for primary site) at the first visit, and prospective follow-up was performed. Overall survival and ureteral stent failure-free survival of each risk group were compared. In total, 300 patients with 21 different primary sites were enrolled. The numbers of patients in good, intermediate, and poor risk groups were 105, 106, and 89, respectively. Median survival times of patients in good, intermediate, and poor risk groups were 406, 221, and 77 days, respectively (P P

Background Extra-appendicular neuroendocrine tumors (NETs) are very rare tumors. While diagnostic and therapeutic guidelines are well established for adults, data on children and adolescents are lacking. Patients and methods Patients with a diagnosis of extra-appendicular NET registered on the Tumori Rari in Eta Pediatrica - Rare Tumors in Pediatric Age (TREP) from 2000 to 2020 were analyzed. Clinical characteristics including patients' presentation, tumor features, treatment, and outcome were reviewed. Results Twenty-seven patients with extra-appendicular NET registered on TREP with a median age of 173 months. The primary site was the pancreas (12) or bronchi (10) in the majority of cases. Other primary sites included the thymus, Meckel's diverticulum, and liver. Thirteen (48%) of tumors extended beyond the organ of origin: four invaded neighboring organs and/or regional nodes and nine involved distant metastases. The 3-year event-free survival (EFS) for those with localized disease was superior to those with metastatic disease (66.6% 95% CI 5-95% vs 33% 95% CI 5-68%, respectively; P = .005). A complete resection was feasible in 17 patients. The 3-year EFS in these patients was superior to those with no or incomplete resection (R0 vs R1/R2, respectively; P = .007). Overall, 16 children had no evidence of disease at follow-up, and one is alive with disease; five died, and five were lost to follow-up. Conclusions Data from our experience demonstrated a wide heterogeneity of presentation and outcome of these tumors. Localized disease and complete surgical resection were the main prognostic factors of good outcome. Other therapies may have a role in prolonging survival in metastatic disease.

Small-diameter dendrites are the primary sites of synaptic input integration and plasticity in hippocampal principal cells. Recent work has begun to characterize the dynamics of these compartments in vivo, but the extent to which dendrites are modulated by network states, behavior, and learning remains enigmatic. Here we monitored somatic and basal dendritic activity in hippocampal CA1 pyramidal cells (CA1 PCs) using longitudinal, multi-plane two-photon calcium imaging coupled with simultaneous local field potential recordings. We found that immobility was associated with a transient increase in dendritic activity, particularly during awake sharp-wave ripple (SWR) events. During exploration of a novel context, dendritic activity during somatic SWR recruitment predicted the stability of dendritic activity patterns. Distinct soma-dendrite dynamics arose also during spatially-guided reward learning. Together, these results indicate that network state- and task-dependent reorganization of CA1 PCs' dendritic activity support navigation- and learning-related hippocampal computations.