Retrospective analysis of discordant results between histology and other clinical diagnostic tests on helicobacter pylori infection.

BACKGROUND: A reliable test is essential for diagnosing Helicobacter pylori (H. pylori) infection, and crucial for managing H. pylori-related diseases. Serving as an excellent method for detecting H. pylori infection, histologic examination is a test that clinicians heavily rely on, especially when complemented with immunohistochemistry (IHC). Additionally, other diagnostic tests for H. pylori, such as the rapid urease test (CLO test) and stool antigen test (SA), are also highly sensitive and specific. Typically, the results of histology and other tests align with each other. However, on rare occasions, discrepancy between histopathology and other H. pylori diagnostic tests occurs. AIM: To investigate the discordance between histology and other H. pylori tests, the underlying causes, and the impact on clinical management. METHODS: Pathology reports of gastric biopsies were retrieved spanning August 2013 and July 2018. Reports were included in the study only if there were other H. pylori tests within seven days of the biopsy. These additional tests include CLO test, SA, and H. pylori culture. Concordance between histopathology and other tests was determined based on the consistency of results. In instances where histology results were negative while other tests were positive, the slides were retrieved for re-assessment, and the clinical chart was reviewed. RESULTS: Of 1396 pathology reports were identified, each accompanied by one additional H. pylori test. The concordance rates in detecting H. pylori infection between biopsy and other tests did not exhibit significant differences based on the number of biopsy fragments. 117 discrepant cases were identified. Only 20 cases (9 with CLO test and 11 with SA) had negative biopsy but positive results in other tests. Four cases initially stained with Warthin-Starry turned out to be positive for H. pylori with subsequent IHC staining. Among the remaining 16 true discrepant cases, 10 patients were on proton pump inhibitors before the biopsy and/or other tests. Most patients underwent treatment, except for two who were untreated, and two patients who were lost to follow-up. CONCLUSION: There are rare discrepant cases with negative biopsy but positive in SA or CLO test. Various factors may contribute to this inconsistency. Most patients in such cases had undergone treatment.

Cardiothoracic operating room blood gas workflow performance improvement initiative.

OBJECTIVES: To evaluate the current workflow of blood gas ordering and testing in a cardiothoracic operating room to identify opportunities to streamline the process, using performance improvement methodologies. METHODS: Issues with specimen relabeling were identified that lead to delayed results and potential patient safety concerns. Blood gas specimen relabeling was evaluated for operating room cases from August 2018 to December 2022. An OpTime Epic Sidebar button for arterial blood gas and venous blood gas orders was created in January 2019 to streamline the ordering process so that laboratory barcode labels were then printed in the operating room and attached to the specimen, eliminating the need for relabeling by the technologists. RESULTS: This Epic Sidebar intervention led to a drastic improvement of appropriate labeling, which has been sustained. From March 2019 to January 2023, with our new workflow, over 95% of blood gas specimens arrived barcode labeled compared to less than 1% in the preintervention era. CONCLUSIONS: A multidisciplinary team with key stakeholders is important to address complex care issues. Performance improvement methodology is critical to develop interventions that hardwire the process. This intervention led to a sustained reduction in secondary relabeling of patient samples and improved timeliness of reporting of blood gas results.

Comparing inpatient management of chronic pelvic pain flares before and after the COVID-19 pandemic.

Abstract: Patients with chronic pelvic pain (CPP) may experience pain exacerbations requiring hospital admissions. Due to the effects of backlogged elective surgeries and outpatient gynaecology appointments resulting from the COVID-19 pandemic, we hypothesised that there would be an increased number of women admitted with CPP flares. We conducted a retrospective review of all acute gynaecology admissions at the Royal Infirmary of Edinburgh from July to December 2018 (pre-COVID) and 2021 (post-COVID lockdown). We collected information on the proportion of emergency admissions due to CPP, inpatient investigations and subsequent management. Average total indicative hospital inpatient costs for women with CPP were calculated using NHS National Cost Collection data guidance. There was no significant difference in the number of emergency admissions due to pelvic pain before (153/507) and after (160/461) the COVID-19 pandemic. As high as 33 and 31% had a background history of CPP, respectively. Across both timepoints, investigations in women with CPP had low diagnostic yield: <25% had abnormal imaging findings and 0% had positive vaginal swab cultures. Women with CPP received significantly more inpatient morphine, pain team reviews and were more likely to be discharged with strong opioids. Total yearly inpatient costs were £170,104 and £179,156 in 2018 and 2021, respectively. Overall, emergency admission rates for managing CPP flares was similar before and after the COVID-19 pandemic. Inpatient resource use for women with CPP remains high, investigations have low diagnostic yield and frequent instigation of opiates on discharge may risk dependence. Improved community care of CPP is needed to reduce emergency gynaecology resource utilisation. Lay summary: Existing treatments for chronic pelvic pain (CPP) and endometriosis focus on surgery or hormone medication, but these are often ineffective or associated with unacceptable side-effects. As a result, women continue to experience chronic pain and often have 'flares' of worsening pain that may lead to hospital admission. The COVID-19 pandemic resulted in backlogged gynaecology clinics and surgeries. The aim of this study was to compare the management of emergency pelvic pain admissions for women with CPP before and after COVID-19. We also aimed to better understand their in-hospital management and estimate their hospital length of stay costs. We did not find an increase in CPP patients admitted for pelvic pain flares after the COVID-19 lockdown. Women with CPP often undergo multiple hospital tests and are often prescribed with strong pain medications which can cause long-term problems. Efforts are needed to improve long-term pain management for women with CPP.

Female Reproductive Systems: Hormone Dependence and Receptor Expression.

The female reproductive system which consists of the ovaries, uterus (myometrium, endometrium), Fallopian tubes, cervix and vagina is exquisitely sensitive to the actions of steroid hormones. The ovaries play a key role in the synthesis of bioactive steroids (oestrogens, androgens, progestins) that act both within the tissue (intracrine/paracrine) as well as on other reproductive organs following release into the blood stream (endocrine action). Sex steroid receptors encoded by the oestrogen (ESR1, ESR2), progesterone (PR) and androgen (AR) receptor genes, which are members of the superfamily of ligand activated transcription factors are widely expressed within these tissues. These receptors play critical role(s) in regulation of cell proliferation, ovulation, endometrial receptivity, myometrial cell function and inflammatory cell infiltration. Our understanding of their importance has been informed by studies on human tissues and cells, which have employed immunohistochemistry as well as a wide range of molecular and genetic methods to identify which processes are dependent steroid ligand activation. The development of mice with targeted deletions of each of these receptors has provided complementary data that has extended our appreciation of cell-cell interactions in the fine tuning of reproductive tissue function. This large body of work has formed the basis of new and improved therapeutics to treat conditions such as infertility.

Ureteral metastasis in colorectal cancer: A case report and review of literature.

Colorectal cancer (CRC) is a common clinical entity. A significant proportion of patients experience metastatic disease, typically in the form of lung and liver spread. We present the case of a CRC cancer patient with distant metastasis to the ureter, causing hydronephrosis. Ureteroscopy and biopsy confirmed the diagnosis and the patient was subsequently treated with percutaneous nephrostomy tube placement. Distant spread of CRC to the ureter represents an exceedingly rare phenomenon. This case highlights the importance of heightened index of suspicion for ureteral involvement in CRC when hydronephrosis is identified on staging or surveillance cross sectional imaging.

B7-H3 and PD-L1 Expression Are Prognostic Biomarkers in a Multi-racial Cohort of Patients with Colorectal Cancer.

BACKGROUND: Immunotherapy has emerged as an effective and durable treatment modality for solid cancers. However, its use in colorectal cancer (CRC) is limited to deficient mismatch repair (dMMR) tumors. As such, assessing immune regulatory proteins from the B7-CD28 family, other than PD-1, PD-L1, and CTLA-4, is critical. This study aimed to evaluate the expression of novel protein regulators in a racially diverse population of patients with CRC. METHODS: A tumor microarray was created for 214 samples from a multiracial patient population with metastatic CRC, and expression of HHLA2, B7-H3, PD-L1, CK7, CK20, and CDX2 was determined. The expression pattern was scored as 0 to 12, based on tumor tissue prevalence and the intensity. Clinical information was obtained by chart review and vital statistics from the National Death Index. Associations between low and high expression groups for each protein by race/ethnic groups were assessed, and Kaplan-Meier curves were plotted to evaluate association with survival. RESULTS: The median age at diagnosis was 61 years, with a female predominance. The majority of the patients were diagnosed with de novo metastatic disease with left-sided, moderately differentiated tumors. There were no racial disparities in the expression of any protein. Overall, a high frequency of tumors had no expression of B7-H3 (62.5%) or PD-L1 (43.5%). Low expression of both PD-L1 and B7-H3 was a significant prognostic biomarker associated with better survival (median overall survival, 43.3 months vs. 24.6 months; P < .01). CONCLUSION: In this multiracial tumor microarray of CRC samples, low PD-L1 and B7-H3 expression was associated with an improved prognosis. There was no significant variation among races with respect to the relevant CRC protein markers.

The predictive value of positive and suspicious urine cytology: Are they different?

BACKGROUND: Urine cytology evaluation is an effective test in the detection of high-grade urothelial carcinoma (HGUC). While the guideline distinguishes the 2 categories: "positive for HGUC" (PHGUC) and "suspicious for HGUC" (SHGUC), the association between these categories with their subsequent follow-up biopsies remains unclear. This study aims to determine and compare the positive predictive value (PPV) of the specimens in PHGUC and SHGUC categories with their respective histologic diagnoses. METHODS: During the period of 03/01/2008 to 07/31/2018, urine cytology cases diagnosed as PHGUC and SHGUC with subsequent bladder biopsy within 12 months were retrieved. All cases were correlated with first biopsy obtained during 12 months of cytology specimen. Biopsy result with HGUC, carcinoma in situ, or non-urothelial carcinoma diagnoses were considered as concordance. RESULTS: 378 cases (229 SHGUC and 149 PHGUC) were identified from 263 patients. For the 229 SHGUC cases, the PPV was 72% (n = 166) and for the 149 PHGUC cases, the PPV was 85% (n = 127). While both categories have high PPV, they are statistically significant (p < 0.0001). Additionally, 33 cases were found to have low-grade urothelial carcinoma (LGUC), constituting a portion of discordant results. CONCLUSION: PHGUC and SHGUC categories are both associated with a high risk of malignancy, however, there is a statistically significant difference between them in our study, supporting the PSRUC guidelines of two separate categories. In instances when urine cytology is discordant with biopsy results, further investigation and clinical follow up is warranted. LGUC appears to remain a common pitfall especially in the suspicious category.

Peptide Receptor Radionuclide Therapy with 67Cu-CuSarTATE Is Highly Efficacious Against a Somatostatin-Positive Neuroendocrine Tumor Model.

Peptide receptor radionuclide therapy (PRRT) using radiolabeled octreotate is an effective treatment for somatostatin receptor 2-expressing neuroendocrine tumors. The diagnostic and therapeutic potential of 64Cu and 67Cu, respectively, offers the possibility of using a single somatostatin receptor-targeted peptide conjugate as a theranostic agent. A sarcophagine cage amine ligand, MeCOSar (5-(8-methyl-3,6,10,13,16,19-hexaaza-bicyclo[6.6.6]icosan-1-ylamino)-5-oxopentanoic acid), conjugated to (Tyr3)-octreotate, called 64Cu-CuSarTATE, was demonstrated to be an imaging agent and potential prospective dosimetry tool in 10 patients with neuroendocrine tumors. This study aimed to explore the antitumor efficacy of 67Cu-CuSarTATE in a preclinical model of neuroendocrine tumors and compare it with the standard PRRT agent, 177Lu-LuDOTA-Tyr3-octreotate (177Lu-LuTATE). Methods: The antitumor efficacy of various doses of 67Cu-CuSarTATE in AR42J (rat pancreatic exocrine) tumor-bearing mice was compared with 177Lu-LuTATE. Results: Seven days after a single administration of 67Cu-CuSarTATE (5 MBq), tumor growth was inhibited by 75% compared with vehicle control. Administration of 177Lu-LuTATE (5 MBq) inhibited tumor growth by 89%. Survival was extended from 12 d in the control group to 21 d after treatment with both 67Cu-CuSarTATE and 177Lu-LuTATE. In a second study, the efficacy of fractionated delivery of PRRT was assessed, comparing the efficacy of 30 MBq of 67Cu-CuSarTATE or 177Lu-LuTATE, either as a single intravenous injection or as two 15-MBq fractions 2 wk apart. Treatment of tumors with 2 fractions significantly improved survival over delivery as a single fraction (67Cu-CuSarTATE: 47 vs. 36 d [P = 0.036]; 177Lu-LuTATE: 46 vs. 29 d [P = 0.040]). Conclusion: This study demonstrates that 67Cu-CuSarTATE is well tolerated in BALB/c nude mice and highly efficacious against AR42J tumors in vivo. Administration of 67Cu-CuSarTATE and 177Lu-LuTATE divided into 2 fractions over 2 wk was more efficacious than administration of a single fraction. The antitumor activity of 67Cu-CuSarTATE in the AR42J tumor model demonstrated the suitability of this novel agent for clinical assessment in the treatment of somatostatin receptor 2-expressing neuroendocrine tumors.