OBJECTIVE:To test whether frailty, a novel measure of physiologic reserve, is associated with longer kidney transplant (KT) length of stay (LOS), and modifies the association between LOS and ...mortality.
BACKGROUND:Better understanding of LOS is necessary for informed consent and discharge planning. Mortality resulting from longer LOS has important regulatory implications for hospital and transplant programs. Which recipients are at risk of prolonged LOS and its effect on mortality are unclear. Frailty is a novel preoperative predictor of poor KT outcomes including delayed graft function, early hospital readmission, immunosuppression intolerance, and mortality.
METHODS:We used registry-augmented hybrid methods, a novel approach to risk adjustment, to adjust for LOS risk factors from the Scientific Registry of Transplant Recipients (n = 74,859) and tested whether (1) frailty, measured immediately before KT in a novel cohort (n = 589), was associated with LOS (LOSnegative binomial regression; LOS ≥2 weekslogistic regression) and (2) whether frailty modified the association between LOS and mortality (interaction term analysis).
RESULTS:Frailty was independently associated with longer LOS relative risk = 1.15, 95% confidence interval (CI)1.03–1.29; P = 0.01 and LOS ≥2 weeks (odds ratio = 1.57, 95% CI1.06–2.33; P = 0.03) after accounting for registry-based risk factors, including delayed graft function. Frailty also attenuated the association between LOS and mortality (nonfrail hazard rate = 1.55 95% CI1.30–1.86; P < 0.001; frail hazard rate = 0.97, 95% CI0.79–1.19, P = 0.80; P for interaction = 0.001).
CONCLUSIONS:Frail KT recipients are more likely to experience a longer LOS. Longer LOS among nonfrail recipients may be a marker of increased mortality risk. Frailty is a measure of physiologic reserve that may be an important clinical marker of longer surgical LOS.
The omega-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA) and aspirin both have proof of concept for colorectal cancer chemoprevention, aligned with an excellent safety profile. Therefore, ...we aimed to test the efficacy of EPA and aspirin, alone and in combination and compared with a placebo, in individuals with sporadic colorectal neoplasia detected at colonoscopy.
In a multicentre, randomised, double-blind, placebo-controlled, 2 × 2 factorial trial, patients aged 55–73 years who were identified during colonoscopy as being at high risk in the English Bowel Cancer Screening Programme (BCSP; ≥3 adenomas if at least one was ≥10 mm in diameter or ≥5 adenomas if these were <10 mm in diameter) were recruited from 53 BCSP endoscopy units in England, UK. Patients were randomly allocated (1:1:1:1) using a secure web-based server to receive 2 g EPA-free fatty acid (FFA) per day (either as the FFA or triglyceride), 300 mg aspirin per day, both treatments in combination, or placebo for 12 months using random permuted blocks of randomly varying size, and stratified by BCSP site. Research staff and participants were masked to group assignment. The primary endpoint was the adenoma detection rate (ADR; the proportion of participants with any adenoma) at 1 year surveillance colonoscopy analysed in all participants with observable follow-up data using a so-called at-the-margins approach, adjusted for BCSP site and repeat endoscopy at baseline. The safety population included all participants who received at least one dose of study drug. The trial is registered with the International Standard Randomised Controlled Trials Number registry, number ISRCTN05926847.
Between Nov 11, 2011, and June 10, 2016, 709 participants were randomly assigned to four treatment groups (176 to placebo, 179 to EPA, 177 to aspirin, and 177 to EPA plus aspirin). Adenoma outcome data were available for 163 (93%) patients in the placebo group, 153 (85%) in the EPA group, 163 (92%) in the aspirin group, and 161 (91%) in the EPA plus aspirin group. The ADR was 61% (100 of 163) in the placebo group, 63% (97 of 153) in the EPA group, 61% (100 of 163) in the aspirin group, and 61% (98 of 161) in the EPA plus aspirin group, with no evidence of any effect for EPA (risk ratio RR 0·98, 95% CI 0·87 to 1·12; risk difference −0·9%, −8·8 to 6·9; p=0·81) or aspirin (RR 0·99 (0·87 to 1·12; risk difference −0·6%, −8·5 to 7·2; p=0·88). EPA and aspirin were well tolerated (78 44% of 176 had ≥1 adverse event in the placebo group compared with 82 46% in the EPA group, 68 39% in the aspirin group, and 76 45% in the EPA plus aspirin group), although the number of gastrointestinal adverse events was increased in the EPA alone group at 146 events (compared with 85 in the placebo group, 86 in the aspirin group, and 68 in the aspirin plus placebo group). Six upper-gastrointestinal bleeding events were reported across the treatment groups (two in the EPA group, three in the aspirin group, and one in the placebo group).
Neither EPA nor aspirin treatment were associated with a reduction in the proportion of patients with at least one colorectal adenoma. Further research is needed regarding the effect on colorectal adenoma number according to adenoma type and location. Optimal use of EPA and aspirin might need a precision medicine approach to adenoma recurrence.
Efficacy and Mechanism Evaluation Programme, a UK Medical Research Council and National Institute for Health Research partnership.
Barrett's esophagus (BE) is a major risk factor for the development of esophageal adenocarcinoma (EAC). BE patients undergo periodic endoscopic surveillance with biopsies to detect dysplasia and EAC, ...but this strategy is imperfect owing to sampling error and inconsistencies in the diagnosis and grading of dysplasia, which may result in an inaccurate diagnosis or risk assessment for progression to EAC. The desire for more accurate diagnosis and better risk stratification has prompted the investigation and development of potential biomarkers that might assist pathologists and clinicians in the management of BE patients, allowing more aggressive endoscopic surveillance and treatment options to be targeted to high-risk individuals, while avoiding frequent surveillance or unnecessary interventions in those at lower risk. It is known that progression of BE to dysplasia and EAC is accompanied by a host of genetic alterations, and that exploration of these markers could be potentially useful to diagnose/grade dysplasia and/or to risk stratify BE patients. Several biomarkers have shown promise in identifying early neoplastic transformation and thus may be useful adjuncts to histologic evaluation. This review provides an overview of some of the currently available biomarkers and assays, including p53 immunostaining, Wide Area Transepithelial Sampling with Three-Dimensional Computer-Assisted Analysis (WATS3D), TissueCypher, mutational load analysis (BarreGen), fluorescence in situ hybridization, and DNA content abnormalities as detected by DNA flow cytometry.
Patients with inflammatory bowel disease (IBD) are at an increased risk for colorectal cancer. Currently, dysplasia is the best marker of CRC risk. Assessing dysplasia is a challenging task for ...pathologists as the longstanding inflammation causes marked reactive cytologic changes and architectural distortion. Recent descriptions of nonconventional types of dysplasia in IBD have added to the complexity. In this review, we focus on the clinical, endoscopic, histologic, and molecular findings in lesions with serrated epithelium. Serrated epithelial change (SEC), sessile serrated lesion (SSL)-like, serrated lesion-not otherwise specified (SL-NOS), and traditional serrated adenoma (TSA)-like lesions all typically occur in patients with longstanding IBD with mean ages in the fifth-sixth decade. SEC is often encountered in nontargeted biopsies while the others form visible polyps. While serrated lesions have significant histologic overlap, subtle differences can help pathologists separate them. SEC has markedly distorted architecture with crypts losing perpendicular orientation to the muscularis mucosae. The crypts are goblet cell–rich and have irregular serrations that involve the full length of the crypt. SSL-like lesions are goblet cell poor and have microvesicular cytoplasm. Like their sporadic counterpart in non-IBD patients, these lesions have lateral growth at the crypt bases. TSA-like lesions are characterized by their villous architecture, ectopic crypts, pink cytoplasm, and hyperchromatic elongated nuclei. We also explore molecular findings that help in distinguishing these lesions, current knowledge on the association of each of these lesions with dysplasia and CRC, and future research needed to better characterize these entities.
•Colon biopsies from inflammatory bowel disease (IBD) patients can show several types of serrated epithelium (flat or endoscopically visible).•Sessile serrated lesion-like and traditional serrated adenoma-like lesions arising in IBD patients are probably the same as sporadic ones.•Serrated epithelial change, when defined based on strict morphologic criteria, differs from those above, harboring TP53 mutations.
NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Although most studies have shown that staining for NKX3.1 protein is positive in the majority of primary prostatic ...adenocarcinomas, it has been shown to be downregulated in many high-grade prostate cancers, and completely lost in the majority of metastatic prostate cancers (eg, in 65% to 78% of lesions). A recent study showed that NKX3.1 staining with a novel antibody was highly sensitive and specific for high-grade prostatic adenocarcinoma when compared with high-grade urothelial carcinoma. This raised the question that this antibody may perform better than earlier used antibodies in metastatic prostate tumors. However, the sensitivity and specificity for prostate carcinomas for this antibody in metastatic lesions was not determined. Although prostate-specific antigen (PSA) and prostatic-specific acid phosphatase (PSAP) are excellent tissue markers of prostate cancer, at times they may be expressed at low levels, focally, or not at all in poorly differentiated primary and metastatic prostatic adenocarcinomas. The purpose of this study was to determine the performance of NKX3.1 as a marker of metastatic adenocarcinoma of prostatic origin. Immunohistochemical staining against NKX3.1, PSA, and PSAP was carried out on a tissue microarray (TMA) (0.6-mm tissue cores) of hormone naïve metastatic prostate adenocarcinoma specimens from lymph nodes, bone, and soft tissue. To determine the specificity of NKX3.1 for prostatic adenocarcinoma, we used TMAs that contained cancers from various sites including the urinary bladder, breast, colon, salivary gland, stomach, pancreas, thyroid, and central nervous system, and standard paraffin sections of cancers from other sites including the adrenal cortex, kidney, liver, lung, and testis. Overall 349 nonprostatic tumors were evaluated. Any nuclear staining for NKX3.1 was considered positive and the percentage of cells with nuclear staining and their mean intensity level were assessed visually. Sensitivity was calculated by considering a case positive if any TMA core was positive. The sensitivity for identifying metastatic prostatic adenocarcinomas overall was 98.6% (68/69 cases positive) for NKX3.1, 94.2% (65/69 cores positive) for PSA, and 98.6% (68/69 cores positive) for PSAP. The specificity of NKX3.1 was 99.7% (1/349 nonprostatic tumors positive). The sole positive nonprostatic cancer case was an invasive lobular carcinoma of the breast. NKX3.1 seems to be a highly sensitive and specific tissue marker of metastatic prostatic adenocarcinoma. In the appropriate clinical setting, the addition of IHC staining for NKX3.1, along with other prostate-restricted markers, may prove to be a valuable adjunct to definitively determine prostatic origin in poorly differentiated metastatic carcinomas.
Familial adenomatous polyposis is an autosomal dominant disorder characterized by the development of hundreds of colorectal adenomas and eventually colorectal cancer. Oral administration of the spice ...curcumin has been followed by regression of polyps in patients with this disorder. We performed a double-blinded randomized trial to determine the safety and efficacy of curcumin in patients with familial adenomatous polyposis.
This study included 44 patients with familial adenomatous polyposis (18–85 years old) who had not undergone colectomy or had undergone colectomy with ileorectal anastomosis or ileal anal pouches, had at least 5 intestinal adenomatous polyps, and had enrolled in Puerto Rico or the United States from September 2011 through November 2016. Patients were randomly assigned (1:1) to groups given 100% pure curcumin (1,500 mg orally, twice per day) or identical-appearing placebo capsules for 12 months. The number and size of lower gastrointestinal tract polyps were evaluated every 4 months for 1 year. The primary outcome was the number of polyps in the curcumin and placebo groups at 12 months or at the time of withdrawal from the study according to the intention-to-treat principle.
After 1 year of treatment, the average rate of compliance was 83% in the curcumin group and 91% in the placebo group. After 12 weeks, there was no significant difference in the mean number of polyps between the placebo group (18.6; 95% CI, 9.3–27.8) and the curcumin group (22.6; 95% CI, 12.1–33.1; P = .58). We found no significant difference in mean polyp size between the curcumin group (2.3 mm; 95% CI, 1.8–2.8) and the placebo group (2.1 mm; 95% CI, 1.5–2.7; P = .76). Adverse events were few, with no significant differences between groups.
In a double-blinded randomized trial of patients with familial adenomatous polyposis, we found no difference in the mean number or size of lower intestinal tract adenomas between patients given curcumin 3,000 mg/day and those given placebo for 12 weeks.
Clinicaltrials.gov ID NCT00641147.
Immune checkpoint inhibitors have been increasingly used to treat various malignant neoplasms. Despite their superior efficacy in treating certain ones, their global immune-activation effect leads to ...systemic side effects, referred to as immune-related adverse events. Immune-related adverse events affect a variety of organs, including the skin, gastrointestinal, hepatobiliary, and endocrine organs. Gastrointestinal tract immune-related adverse events present with a wide range of symptoms with variable severity, which may lead to treatment interruption and administration of immunosuppression therapy in many cases. Histopathologic changes are diverse, overlapping with many other conditions. Therefore, recognizing these changes is crucial in diagnosing immune-related adverse events. This review discusses the pathologic manifestations of gastrointestinal immune-related adverse events and discusses the primary differential diagnoses.
Patients with juvenile polyposis syndrome (JPS), a hereditary autosomal dominant hamartomatous polyposis syndrome, are at increased risk for colorectal adenocarcinoma. The upper gastrointestinal ...tract is less often involved by JPS than the colorectum, and, consequently, upper tract juvenile polyps (JPs) are not well studied. We reviewed upper endoscopies and corresponding biopsies in JPS patients documented in our Polyposis Registry. A total of 199 upper gastrointestinal biopsies from 69 endoscopies were available in 22 of 41 (54%) JPS patients. Thirteen of the 22 patients (59%) had ≥1 gastric JP; 5 also had 6 small bowel JPs. Gastric JP was identified as early as age 7 in a patient with an SMAD4 gene mutation. Two patients (9%) had high-grade dysplasia in gastric JP. Invasive adenocarcinoma was diagnosed in the gastrectomy specimen of 1 patient. Five patients had a huge gastric polyp burden; 3 underwent total gastrectomy. Three patients died of complications associated with extensive upper JP. Histologically, 8 of the 56 (14%) gastric JPs identified had dysplasia. All of the 8 polyps demonstrated intestinalized and pyloric gland differentiation intermixed with foveolar epithelium. Dysplasia was seen arising in all 3 types of epithelium. The flat gastric mucosa in 11 patients was unremarkable without inflammation or intestinal metaplasia. The 6 small bowel JPs had no dysplasia. Our findings suggest that JPS patients are at increased risk for gastric adenocarcinoma. Detection of malignancy in syndromic gastric JP indicates that the current screening procedures are insufficient in removal of precursor lesions to prevent progression to carcinoma.
Diagnostic histochemistry of soft tissue lesions Montgomery, Elizabeth A.
Seminars in diagnostic pathology,
November 2018, 2018-Nov, 2018-11-00, 20181101, Letnik:
35, Številka:
6
Journal Article
Recenzirano
Histochemical methods (HM) were, at one time, extensively used in all facets of anatomic pathology, including analysis of soft tissue lesions. That situation has changed with the advent of other ...adjunctive procedures, but HM still do contribute meaningfully to the evaluation of several tumefactive conditions in the soft tissue. This brief review considers selected neoplastic, quasineoplastic, and pseudoneoplastic lesions in that category, with emphasis on their histochemical properties.
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