Trends in pathology diagnoses during 10 years of a colorectal cancer screening programme.

AIMS: We report pathology findings from the first 10 years of the faecal-occult blood-based Northern Ireland Bowel Cancer Screening Programme, presenting summary data and trends in pathology diagnoses and clinicopathological features of screen-detected cancers. METHODS AND RESULTS: Data were analysed from a comprehensive polyp-level pathology database representing all endoscopy specimens from programme inception in 2010 until 2021. A total of 9800 individuals underwent 13 472 endoscopy procedures, yielding 25 967 pathology specimens and 32 119 diagnoses. Index specimen diagnoses (4.1%) and index colonoscopies (10.4%) yielded a diagnosis of colorectal cancer, representing 1045 cancers from 1020 individuals (25 with synchronous cancers). A further 13 index cancers were identified via computed tomography colonography; 65.3% of cancer diagnoses were in males; 41.7% were stage I, 23.1% stage II, 25.8% stage III and 1.8% stage IV (7.6% unstaged). Of 233 pT1 cancers diagnosed within local excision specimens, 79 (33.9%) had completion surgery. Ten-year trends showed a steady decline in the proportion of index colonoscopies that yielded a diagnosis of cancer (14.7% in year 1; 4.8% in year 11) or advanced colorectal polyp. There was a strong upward trend in diagnoses of sessile serrated lesions, which overtook hyperplastic polyps in proportions of total index diagnoses by the end of the study time-frame (8.7% compared to 8.5%). CONCLUSIONS: Over the first 10 years of a population colorectal cancer screening programme, 'real world' pathology data demonstrate success in the form of reduced diagnoses of cancer and advanced colorectal polyp with passage of successive screening rounds. Interesting trends with respect to serrated polyp diagnoses are also evident, probably related to pathologist and endoscopist behaviour.

An AI-Driven Hybrid Framework for Intrusion Detection in IoT-Enabled E-Health.

E-health has grown into a billion-dollar industry in the last decade. Its device's high throughput makes it an obvious target for cyberattacks, and these environments desperately need protection. In this scientific study, we presented an artificial intelligence (AI)-driven software-defined networking (SDN)-enabled intrusion detection system (IDS) to address increasing cyber threats in the E-health and internet of medical things (IoMT) environments. AI's success in various fields, including big data and intrusion detection systems, has prompted us to develop a flexible and cost-effective approach to protect such critical environments from cyberattacks. We present a hybrid model consisting of long short-term memory (LSTM) and gated recurrent unit (GRU). The proposed model was thoroughly evaluated using the publicly available CICDDoS2019 dataset and conventional evaluation measures. Furthermore, for proper validation, the proposed framework is compared with relevant classifiers, such as cu-GRU+ DNN and cu-BLSTM. We have further compared the proposed model with existing literature to prove its efficacy. Lastly, 10-fold cross-validation is also used to verify that our results are unbiased. The proposed approach has bypassed the current literature with extraordinary performance ramifications such as 99.01% accuracy, 99.04% precision, 98.80 percent recall, and 99.12% F1-score.

Metastasis of Renal Cell Carcinoma to the Stomach Twenty One Years from Initial Diagnosis.

A female in her 80's presented to our Emergency Department following a fall. She reported general malaise, weight loss and raised inflammatory markers. Background included renal cell carcinoma 21 years previous, managed with radical nephrectomy. During her inpatient stay she had an episode of haematemesis. Upper GI endoscopy revealed a 3cm polypoidal lesion on the greater curve of the upper stomach. This had an irregular pit pattern endoscopically and was friable. Multiple biopsies revealed metastatic clear cell carcinoma of renal origin; the same sub-type as her previous renal tumour. This is a rare manifestation of metastatic renal cell carcinoma and from literature review, is only the 2nd case we can find with a lag time of >20 years from the initial diagnosis to presenting with metastatic gastric disease.

Statewide Longitudinal Trends in Transmitted HIV-1 Drug Resistance in Rhode Island, USA.

BACKGROUND: HIV-1 transmitted drug resistance (TDR) remains a global challenge that can impact care, yet its comprehensive assessment is limited and heterogenous. We longitudinally characterized statewide TDR in Rhode Island. METHODS: Demographic and clinical data from treatment-naïve individuals were linked to protease, reverse transcriptase, and integrase sequences routinely obtained over 2004-2020. TDR extent, trends, impact on first-line regimens, and association with transmission networks were assessed using the Stanford Database, Mann-Kendall statistic, and phylogenetic tools. RESULTS: In 1123 individuals, TDR to any antiretroviral increased from 8% (2004) to 26% (2020), driven by non-nucleotide reverse transcriptase inhibitor (NNRTI; 5%-18%) and, to a lesser extent, nucleotide reverse transcriptase inhibitor (NRTI; 2%-8%) TDR. Dual- and triple-class TDR rates were low, and major integrase strand transfer inhibitor resistance was absent. Predicted intermediate to high resistance was in 77% of those with TDR, with differential suppression patterns. Among all individuals, 34% were in molecular clusters, some only with members with TDR who shared mutations. Among clustered individuals, people with TDR were more likely in small clusters. CONCLUSIONS: In a unique (statewide) assessment over 2004-2020, TDR increased; this was primarily, but not solely, driven by NNRTIs, impacting antiretroviral regimens. Limited TDR to multiclass regimens and pre-exposure prophylaxis are encouraging; however, surveillance and its integration with molecular epidemiology should continue in order to potentially improve care and prevention interventions.

Bronchus-like Structures in Ovarian Teratomas: Report of a Series of a Previously Unreported Phenomenon With Potential For Misdiagnosis.

We report 10 cases of a previously undescribed lesion within ovarian teratomas which we designate bronchus-like structures. The lesions occurred in patients aged 16 to 56 yr (mean: 36) and involved the left ovary (n=5) or right ovary (n=5). Nine cases were mature teratomas (dermoid cysts/mature cystic teratomas or mature solid teratomas), 1 with somatic malignant transformation, and 1 was an immature teratoma. The bronchus-like structures ranged in size from 2.5 to 10 mm and were unifocal (7 cases) or multifocal (3 cases). The morphology was relatively constant in all cases and characterised by a well-formed bronchus surrounded by glandular structures, some of which were dilated, separated by stroma containing a variable amount of smooth muscle. In all but 1 case, a proportion of the glands contained abundant foamy cytoplasm. There was little or no nuclear atypia or mitotic activity. At low-power, the glands often had a somewhat "infiltrative" appearance and one case was originally diagnosed as a "pulmonary-type" adenocarcinoma arising in a dermoid cyst. In all cases, there was diffuse staining of the bronchus and glands with TTF1 and Napsin A, confirming the cell lineage. Follow-up in 4 cases (18-130 mo; median: 64 mo) showed no evidence of recurrence; 1 patient died from an unrelated malignancy. In reporting this apparently rare but possibly underrecognized benign lesion arising within ovarian teratomas, we discuss the differential diagnosis and stress that pathologists should be aware of this phenomenon in order to avoid an erroneous diagnosis of malignancy.

Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations.

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes. Most tumors (16/21) showed predominantly classic morphology, comprised of alternating hyper- and hypocellular areas of primitive small cells and differentiating rhabdomyoblasts in a loose myxoid/edematous stroma. A cambium layer was noted in all; seven had heterologous elements (six with fetal-type cartilage) and eight displayed focal anaplasia. The remaining five neoplasms showed only a minor component (≤20%) of classic morphology, with anaplasia noted in four and tumor cell necrosis in three. The most frequent mutations detected were in DICER1 (14/21), TP53 (7/20), PI3K/AKT/mTOR pathway (7/20), and KRAS/NRAS (5/20). Copy-number alterations were present in 10/19 tumors. Overall, 8/14 DICER1-associated ucERMS showed concurrent loss of function and hotspot mutations in DICER1, which is a feature more likely to be seen in tumors associated with DICER1 syndrome. Germline data were available for two patients, both DICER1 wild type (one with concurrent loss of function and hotspot alterations). DICER1-associated ucERMS were more likely to show a classic histological appearance including heterologous elements than DICER1-independent tumors. No differences in survival were noted between the two groups, but both patients with extrauterine disease at diagnosis and two with recurrences died from disease. As no patients had a known personal or family history of DICER1 syndrome, we favor most DICER1-associated ucERMS to be sporadic.

Elbasvir/grazoprevir administered for 12 weeks via percutaneous endoscopic gastrostomy tube achieves sustained virologic response: A case report and a review of the literature.

Enteral tubes are necessary for certain patients; however, medication absorption can be affected by this route of administration potentially resulting in decreased efficacy. All first-line treatments for Hepatitis C Virus (HCV) infection are only available as tablets and may have decreased absorption if administered via an enteral tube. This report describes the first case of a pegylated interferon and ribavirin treatment-experienced patient who successfully achieved HCV cure after 12 weeks of elbasvir/grazoprevir administered via percutaneous gastrostomy tube. We further review the available pharmacokinetic and clinical literature regarding administration via enteral feeding tubes for all first-line direct-acting antivirals (DAAs). The literature suggests that crushed administration can be considered for DAAs in patients with gastric access. However, caution should be exercised in patients with extragastric enteral tubes and in those with altered gastrointestinal tract anatomy.

Late Development of Metastatic Ovarian Mucinous Adenocarcinoma From Primary Gallblader Adenocarcinoma and High-grade Dysplasia.

The ovary is a common site of metastatic mucinous adenocarcinoma. In most, but not all, cases the presence of a primary neoplasm elsewhere is already known and the metastasis is picked up at diagnosis or is discovered a relatively short time following the diagnosis of the primary neoplasm. We report 2 cases of metastatic gallbladder adenocarcinoma involving the ovaries of women aged 65 and 59 after long time periods of 8 and 5 yr following diagnosis of high-grade dysplasia or early adenocarcinoma of the gallbladder, respectively. In both cases, a review of the original operative notes suggested the possibility of intraoperative gallbladder rupture or bile leakage suggesting that the metastatic disease may have developed secondary to "seeding." In both cases, p53 immunohistochemistry revealed identical null mutation-type immunoreactivity within the gallbladder and ovarian neoplasms, assisting in confirming the ovarian disease as a metastasis from the gallbladder. The possibility of late ovarian metastasis of gallbladder dysplasia or adenocarcinoma secondary to rupture/bile leakage should be borne in mind.

Recent Updates to the Advisory Committee On Immunization Practices Recommendations for Pneumococcal and Herpes Zoster Vaccination.

Pneumococcal and herpes zoster - shingles - vaccination prevent a great deal of morbidity, particularly in elderly and immunocompromised hosts. Vaccination of children with conjugate pneumococcal vaccine in recent years has greatly reduced illness in older individuals as well. This article will review the historical and current recommendations for pneumococcal and herpes zoster vaccination and the rationale for changes at the level of the CDC's Advisory Committee on Immunization Practices.

Hydroxychloroquine use in hospitalised patients with COVID-19: An observational matched cohort study.

AIM: To assess the efficacy and safety of hydroxychloroquine with or without azithromycin) in hospitalized adult patients with COVID-19. METHODS: We utilized a hospital based prospective data registry. The primary end point was to assess the impact of hydroxychloroquine with or without azithromycin, on outcome, length of hospitalization, and time to clinical improvement. We utilized treatment effects with inverse-probability-weighting and Cox proportional hazards models. All analyses accounted for age, gender, race, severity on admission, days from symptoms onset and chronic comorbidities. RESULTS: 36 patients received hydroxychloroquine and were age- and sex-matched to 72 patients with COVID-19 who received supportive care. Compared to supportive care, the use of HCQ did not shorten the time to clinical improvement (+0.23 days; 95% CI: -1.8-2.3 days) nor did it shorten the duration of hospital stay (+0.91 days; 95% CI: -1.1-2.9 days). Additionally, HCQ did not decrease the risk of COVID-19 in-hospital death (aHR 1.67; 95% CI: 0.29-9.36). Finally, we observed a slight QTc prolongation from a baseline of 444 ± 26 ms to 464 ± 32 ms (mean±SD) among patients receiving hydroxychloroquine with or without azithromycin. CONCLUSION: This study did not yield benefits from hydroxychloroquine use in patients with COVID-19 and monitoring for adverse events is warranted. Nevertheless, the treatment was safely studied under the guidance of an antimicrobial stewardship program.

Patient autonomy and doctor's concern - a case of intravenous drug abuser.

Intravenous substance abuse is often associated with physical and psychological harm, and often requires urgent medical attention. We report a case of a young male who presented with life-threatening complications of intravenous drug abuse, but refused to give details or agree to the proposed treatment, raising concerns for the team of doctors. A compos mentis patient has a right to decide what should be done to his body. Medical management or surgical interventions cannot be initiated without the patient's consent even if these are lifesaving procedures, or a procedure meant to benefit the patient. Medical practitioner can be liable for assault (criminal law), medical negligence (law of tort), damages (civil action) and even human rights issues may be raised if a patient's autonomy is not respected.

Unclassifiable Malignant Extraovarian Sex Cord-Stromal Tumors: Report of 3 Cases and Review of Extraovarian Sex Cord-Stromal Tumors.

We report 3 cases of primary extraovarian unclassifiable malignant sex cord-stromal tumors. In all cases, the tumors involved the pelvis, peritoneum, and/or omentum and the morphologic features were essentially those of a poorly differentiated malignant neoplasm. A diagnosis of sex cord-stromal tumor was made on the basis of expression of several markers of ovarian sex cord-stromal tumors and exclusion of other neoplasms. In 1 case, an elevated serum testosterone was present at tumor progression. In reporting these cases, we draw attention to the problems in establishing a diagnosis that can be attributed to the extreme rarity of sex cord-stromal tumors in an extraovarian location and the rarity of unclassifiable malignant sex cord-stromal tumors in general, resulting in pathologists not considering this diagnosis. We review sex cord-stromal tumors occurring in an extraovarian location.

A comparison of endoscopy versus pathology sizing of colorectal adenomas and potential implications for surveillance colonoscopy.

BACKGROUND AND AIMS: The aim of this study was to compare endoscopy and pathology sizing in a large population-based series of colorectal adenomas and to evaluate the implications for patient stratification into surveillance colonoscopy. METHODS: Endoscopy and pathology sizes available from intact adenomas removed at colonoscopies performed as part of the Northern Ireland Bowel Cancer Screening Programme, from 2010 to 2015, were included in this study. Chi-squared tests were applied to compare size categories in relation to clinicopathologic parameters and colonoscopy surveillance strata according to current American Gastroenterology Association and British Society of Gastroenterology guidelines. RESULTS: A total of 2521 adenomas from 1467 individuals were included. There was a trend toward larger endoscopy than pathology sizing in 4 of the 5 study centers, but overall sizing concordance was good. Significantly greater clustering with sizing to the nearest 5 mm was evident in endoscopy versus pathology sizing (30% vs 19%, P < .001), which may result in lower accuracy. Applying a 10-mm cut-off relevant to guidelines on risk stratification, 7.3% of all adenomas and 28.3% of those 8 to 12 mm in size had discordant endoscopy and pathology size categorization. Depending on which guidelines are applied, 4.8% to 9.1% of individuals had differing risk stratification for surveillance recommendations, with the use of pathology sizing resulting in marginally fewer recommended surveillance colonoscopies. CONCLUSIONS: Choice of pathology or endoscopy approaches to determine adenoma size will potentially influence surveillance colonoscopy follow-up in 4.8% to 9.1% of individuals. Pathology sizing appears more accurate than endoscopy sizing, and preferential use of pathology size would result in a small, but clinically important, decreased burden on surveillance colonoscopy demand. Careful endoscopy sizing is required for adenomas removed piecemeal.

Prognostic value of added stratification of circumferential resection margin status in oesophageal carcinoma.

AIMS: Involved circumferential resection margin (CRM) (R1) in oesophageal carcinoma (OC) has conflicting definitions. This study aimed to compare two such definitions applied to a cohort of OC resection specimens and also evaluated a novel three-tier CRM stratification. METHODS AND RESULTS: OC patients with pT3 disease were classified as R0 or R1 on the basis of Royal College of Pathologists (UK) (RCPath) and College of American Pathologists (CAP) criteria and group survivals were compared. Patients were then stratified into three groups on the basis of tumour distance from the CRM (>1 mm, 0.1-1 mm, 0 mm). A total of 195 patients were included. According to RCPath criteria, 50 resections were R0 and 145 R1; median survival was 72.0 and 18.1 months. Using CAP criteria, 137 resections were R0 and 58 R1; median survival was 30.1 and 12.6 months. Using three-tier stratification, tumour was clear by >1 mm (R0) in 50 cases, 0.1-1 mm from CRM (RCPath R1; CAP R0) in 87 cases and 0 mm (R1) in 58 cases; median survival was 72.0, 24.6 and 12.6 months, respectively. Survival difference was statistically significant using each binary system and also the three-tier system. CONCLUSIONS: Both RCPath and CAP criteria to define CRM have similar prognostic value. A novel three-tier classification of CRM status provides more detailed prognostication.

Ovarian serous cystadenofibroma with signet ring-stromal cells: report of 2 cases.

We report 2 ovarian serous cystadenofibromas with signet ring cells within the stromal component. The signet ring-stromal cells were widespread in 1 case and focal in the other. Immunohistochemically, they were negative with cytokeratin and other epithelial markers and positive with mesenchymal markers. The occurrence of signet ring-stromal cells in ovarian serous cystadenofibromas is an unusual pseudoneoplastic phenomenon, which has not been reported previously, although signet ring cells may occur within a variety of ovarian stromal neoplasms, including fibromas, sclerosing stromal tumors, and signet ring-stromal tumors. In reporting these cases, we review ovarian stromal neoplasms and other lesions with signet ring cells.

Symplastic atypia in neoplastic and non-neoplastic endometrial stroma: report of 3 cases with a review of atypical symplastic cells within the female genital tract.

SUMMARY: We report 3 cases in which endometrial stromal cells exhibited marked nuclear atypia with a symplastic appearance. Two cases involved non-neoplastic endometrial stroma, one within an ovarian endometriotic cyst and the other within normal eutopic endometrium. In the third case, the symplastic change involved the neoplastic cells of an endometrial stromal sarcoma. Symplastic endometrial stromal cells have rarely been described in normal endometrium and in endometrial stromal sarcoma but, as far as we are aware, this phenomenon has not been reported previously in endometriosis. In the 3 cases, the atypical cells were a focal finding. The abnormal nuclei were markedly enlarged, atypical, and hyperchromatic with multilobated forms but without mitotic activity. This unusual phenomenon is a benign change when involving non-neoplastic endometrial stroma and is of no clinical significance. It is analogous to the presence of atypical symplastic nuclei in normal tissues and in other pathologic lesions in the female genital tract. In reporting these cases, we review normal tissues and pathologic lesions in the female genital tract with atypical symplastic nuclei.

Pathology of pulmonary aspergillomas.

Aspergilloma refers to a fungal ball formed by saprophytic overgrowth of Aspergillus species and is seen secondary to cavitatory/cystic respiratory diseases. Paucity of clinical and pathological data of aspergilloma in India prompted us to analyze cases of aspergilloma over 15 years. The clinical features were recorded in all and correlated with detailed pathological examination. Aspergillomas were identified in 41 surgical excisions or at autopsy. There was male predominance; half the patients were in their fourth decade. Episodic hemoptysis was the commonest mode of presentation (85.4%). Forty aspergillomas were complex, occurring in cavitatory lesions (82.9%) or in bronchiectasis (14.6%). Simple aspergilloma was seen as an incidental finding in only one. Tuberculosis was the etiological factor in 31 patients, producing cavitatory or bronchiectatic lesions; other causes were chronic lung abscess and bronchiectasis (unrelated to tuberculosis). Surgical resections are endorsed in view of high risk of unpredictable, life-threatening hemoptysis.

Small cell carcinoma of the appendix.

BACKGROUND: An extrapulmonary small cell carcinoma is a rare condition. It has similar histological features to pulmonary small cell carcinoma and is equally aggressive. CASE PRESENTATION: We present the case of a 60-year-old woman who presented with right upper quadrant pain. Computerised tomography revealed an appendiceal lesion and multiple liver metastases. Exploratory laparotomy and right hemicolectomy was performed with histopathological analysis confirming a primary small cell carcinoma of her appendix. CONCLUSION: This is the first reported case of a pure extrapulmonary carcinoma arising from the appendix.

Bilateral retinal detachment in a patient with Vogt-Koyanagi-Harada syndrome.

We present a 38-year-old woman with bilateral serous retinal detachments and bilateral panuveitis on fundoscopic exam. CT of the orbits and MRI scans revealed bilateral ocular choroidal thickening and bilateral retinal detachments; however, no other CNS or meningeal lesion was detected. This patient met the clinical criteria for Vogt-Koyanagi-Harada (VKH) Syndrome. Review of VKH syndrome as well as the radiographic findings will be discussed.

Role of delayed Tc-99m HMPAO labeled leukocyte scintigraphy in the diagnosis of coronary mycotic aneurysm.

Coronary mycotic aneurysms are rare with a poor prognosis. Atherosclerosis often predisposes to aneurysmal dilatation. In children, Kawasaki disease and in adults trauma, vasculitis, syphilis, dissection, and postcoronary angioplasty contribute to coronary mycotic aneurysms. Radiolabeled leukocytes have been used in the diagnosis of prosthetic valve endocarditis and vascular graft infections. Abnormal accumulation of radiolabeled leukocytes have also been reported in infra renal aortic aneurysms. We present a case of a coronary mycotic aneurysm where delayed Tc-99m HMPAO labeled leukocyte imaging played an important role leading to the diagnosis.