Rapid clearing and imaging of Mohs and melanoma surgical margins using a low-cost tissue processor.

Tissue clearing methods render biological tissues transparent while maintaining tissue structure, enabling visualization of entire tissues. Recent developments in tissue clearing have predominantly emphasized preserving intrinsic fluorescent proteins or aqueous-based tissue clearing and so typically involve complex procedures and long processing times. The utilization of tissue clearing protocols in standard of care histology settings has been less well explored, and protocols for rapid clearing of human tissue specimens are limited.

The impact of time to death in donors after circulatory death on recipient outcome in simultaneous pancreas-kidney transplantation.

The time to arrest donors after circulatory death is unpredictable and can vary. This leads to variable periods of warm ischemic damage prior to pancreas transplantation. There is little evidence supporting procurement team stand-down times based on donor time to death (TTD).

SWI/SNF chromatin remodeling complex in pancreatic ductal adenocarcinoma: Clinicopathologic and immunohistochemical study.

The SWItch/Sucrose Non-Fermentable (SWI/SNF) complex is a multimeric protein involved in transcription regulation and DNA damage repair. SWI/SNF complex abnormalities are observed in approximately 14-34 % of pancreatic ductal adenocarcinomas (PDACs). Herein, we evaluated the immunohistochemical expression of a subset of the SWI/SNF complex proteins (ARID1A, SMARCA4/BRG1, SMARCA2/BRM, and SMARCB1/INI1) within our PDAC tissue microarray to determine whether SWI/SNF loss is associated with any clinicopathologic features or patient survival in PDAC.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide.

Youngest pancreas transplantation alone in the UK for type 1 diabetes and severe subcutaneous insulin resistance.

A child diagnosed with type 1 diabetes mellitus during her middle childhood developed severe subcutaneous insulin resistance as her illness progressed. This resulted in recurrent episodes of diabetic ketoacidosis and hypoglycaemia, eventually leading to intravenous insulin dependence. Despite intensive investigations, an organic cause was not found.

The UK kidney donor risk index poorly predicts long-term transplant survival in paediatric kidney transplant recipients.

Background: The UK kidney offering scheme introduced a kidney donor risk index (UK-KDRI) to improve the utility of deceased-donor kidney allocations. The UK-KDRI was derived using adult donor and recipient data. We assessed this in a paediatric cohort from the UK transplant registry.

New insights into the responder/nonresponder divide in rectal cancer: Damage-induced Type I IFNs dictate treatment efficacy and can be targeted to enhance radiotherapy.

Rectal cancer ranks as the second leading cause of cancer-related deaths. Neoadjuvant therapy for rectal cancer patients often results in individuals that respond well to therapy and those that respond poorly, requiring life-altering excision surgery. It is inadequately understood what dictates this responder/nonresponder divide.

Radiation Therapy Exacerbates Tumor-Promoting Innervation and Nerve Signaling in Rectal Cancer.

Purpose: Many solid tumors present with perineural invasion (PNI), and innervation correlates with worsened prognosis. The effects that commonly administered therapies such as radiation therapy (RT) have on PNI status remain unknown. We investigated the contribution of RT on the nervous system and elucidated the implications that increased nerve signaling can have on tumor burden using our previously developed orthotopic murine model of rectal cancer (RC) and our targeted and clinically relevant short-course RT (SCRT) regimen.

Gluten Induces Subtle Histological Changes in Duodenal Mucosa of Patients with Non-Coeliac Gluten Sensitivity: A Multicentre Study.

Background: Histological changes induced by gluten in the duodenal mucosa of patients with non-coeliac gluten sensitivity (NCGS) are poorly defined. Objectives: To evaluate the structural and inflammatory features of NCGS compared to controls and coeliac disease (CeD) with milder enteropathy (Marsh I-II). Methods: Well-oriented biopsies of 262 control cases with normal gastroscopy and histologic findings, 261 CeD, and 175 NCGS biopsies from 9 contributing countries were examined.

Characterization of naked mole-rat hematopoiesis reveals unique stem and progenitor cell patterns and neotenic traits.

Naked mole rats (NMRs) are the longest-lived rodents yet their stem cell characteristics remain enigmatic. Here, we comprehensively mapped the NMR hematopoietic landscape and identified unique features likely contributing to longevity. Adult NMRs form red blood cells in spleen and marrow, which comprise a myeloid bias toward granulopoiesis together with decreased B-lymphopoiesis.

Presence of Tim3 and PD-1 CD8 T cells identifies microsatellite stable colorectal carcinomas with immune exhaustion and distinct clinicopathological features.

Colorectal carcinoma (CRC) is the second leading cause of cancer mortality worldwide. CRC is stratified into two major groups: microsatellite stable (MSS) and microsatellite instability-high (MSI-H). MSS CRC constitutes the majority of cases, has worse overall prognosis, and thus far has failed to respond to immunotherapies targeting the immune checkpoint receptors PD-1, PD-L1, and CTLA-4.

Development of an Orthotopic Murine Model of Rectal Cancer in Conjunction With Targeted Short-Course Radiation Therapy.

Purpose: Orthotopic tumors more closely recapitulate human cancers than do ectopic models; however, precision targeting of such internal tumors for radiation therapy (RT) without inducing systemic toxicity remains a barrier. We developed an innovative murine orthotopic rectal tumor model where the insertion of clinical grade titanium fiducial clips on opposing sides of the rectal tumor allowed for targeted administration of short-course radiation therapy (SCRT). With this novel approach, clinically relevant RT regimens can be administered to orthotopic tumors to explore the biology and efficacy of radiation alone or as a combination therapy in a murine model that closely recapitulates human disease.

Modulation of the Human Pancreatic Ductal Adenocarcinoma Immune Microenvironment by Stereotactic Body Radiotherapy.

Purpose: Stereotactic body radiotherapy (SBRT) is an emerging treatment modality for pancreatic ductal adenocarcinoma (PDAC), which can effectively prime cytotoxic T cells by inducing immunogenic tumor cell death in preclinical models. SBRT effects on human PDAC have yet to be thoroughly investigated; therefore, this study aimed to characterize immunomodulation in the human PDAC tumor microenvironment following therapy.

Experimental Design: Tumor samples were obtained from patients with resectable PDAC.

Interobserver agreement in the diagnosis of anal dysplasia: comparison between gastrointestinal and gynaecological pathologists and utility of consensus conferences.

Aims: Management of anal dysplasia relies upon the accurate diagnosis of anal biopsy specimens. As institutions move towards subspecialty signout (SSSO), decisions must be made regarding whether to assign anal biopsies to the gastrointestinal (GI) or gynaecological (GYN) pathology service.

Materials And Results: We identified 200 archival tissue biopsies of anal mucosa and circulated them among three GI pathologists and three GYN pathologists.

Ectopic cervical thymi and no thymic involution until midlife in naked mole rats.

Immunosenescence is a hallmark of aging and manifests as increased susceptibility to infection, autoimmunity, and cancer in the elderly. One component of immunosenescence is thymic involution, age-associated shrinkage of the thymus, observed in all vertebrates studied to date. The naked mole rat (Heterocephalus glaber) has become an attractive animal model in aging research due to its extreme longevity and resistance to disease.

Phosphomannose Isomerase High Expression Associated with Better Prognosis in Pancreatic Ductal Adenocarcinoma.

Introduction: Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer-related death in the United States. The need for increased patient survival has not been met for PDAC. The addition of mannose to conventional chemotherapy leads to accumulation of mannose metabolite in cancer cells and increases subsequent cell death.

Evidence for Roux-en-Y Pancreatic Duct Drainage Versus Standard Anastomosis in Pancreatic Transplantation.

Objectives: Pancreatic transplantation is usually performed simultaneously with renal transplantation in the setting of end-stage nephropathy and type 1 diabetes. Surgical methods for dealing with exocrine secretions include bladder drainage, direct duodenojejunostomy and Roux-en-Y (ReY) enteric drainage. Roux-en-Y may confer an advantage over duodenojejunostomy because it distances enteric content from the transplant duodenal anastomosis.

Inhibin-positive hepatic carcinoma: proposal for a solid-tubulocystic variant of intrahepatic cholangiocarcinoma.

Inhibin-positive hepatic carcinoma is a rare primary liver neoplasm that resembles sex cord-stromal tumor and thyroid follicular tumors. The term "cholangioblastic variant of intrahepatic cholangiocarcinoma" has been proposed. This study describes the clinicopathologic, immunophenotypic, and molecular features of a small series (n = 6) of this rare tumor.

Outcomes of pregnancy in simultaneous pancreas and kidney transplant recipients: A single-center retrospective study.

Simultaneous pancreas and kidney (SPK) transplantation, in uremic women with insulin-dependent diabetes, increases the chance of a successful pregnancy and minimizes the risk to infants. The aim of this study was to document pregnancy and explore the challenges in this cohort of women. Retrospective analysis of women who underwent pancreas transplantation between January 1, 1998 and 8 January, 2019 was conducted.

Hypermucinous, Goblet Cell-Deficient and Crypt Cell Dysplasias in Inflammatory Bowel Disease are Often Associated with Flat/Invisible Endoscopic Appearance and Advanced Neoplasia on Follow-Up.

Background And Aims: Several different types of non-conventional dysplasia have been recently described in inflammatory bowel disease [IBD]. Hypermucinous, goblet cell-deficient and crypt cell dysplasias have received most attention, but there is limited information regarding their clinicopathological features and clinical outcomes.

Methods: A total of 126 cases of hypermucinous [n = 55], goblet cell-deficient [n = 26] and crypt cell [n = 45] dysplasias from 97 IBD patients were collected from seven different institutions and analysed.