Is annual screening by fecal immunochemical test necessary after a recent colonoscopy?

Objective: The population-based colorectal cancer screening guidelines in Japan recommend an annual fecal immunochemical test (FIT). However, there is no consensus on the need for annual FIT screening for patients who recently performed a total colonoscopy (TCS). Therefore, we evaluated the repeated TCS results for patients with positive FIT after a recent TCS to assess the necessity of an annual FIT. Methods: We reviewed patients with positive FIT in opportunistic screening from April 2017 to March 2022. The patients were divided into two groups: those who had undergone TCS within the previous 5 years (previous TCS group) and those who had not (non-previous TCS group). We compared the detection rates of advanced neoplasia and colorectal cancer between the two groups. Results: Of 671 patients, 151 had received TCS within 5 years and 520 had not. The detection rates of advanced neoplasia in the previous TCS and non-previous TCS groups were 4.6% and 12.1%, respectively (p < 0.01), and the colorectal cancer detection rates were 0.7% and 1.5%, respectively (no significant difference). The adenoma detection rates were 33.8% in the previous TCS group and 40.0% in the non-previous TCS group (no significant difference). Conclusions: Only a few patients were diagnosed with advanced neoplasia among the patients with FIT positive after a recent TCS. For patients with adenomatous lesions on previous TCS, repeated TCS should be performed according to the surveillance program without an annual FIT. The need for an annual FIT for patients without adenomatous lesions on previous TCS should be prospectively assessed in the future.

Steroid lifting method during endoscopic submucosal dissection: A novel strategy for stricture prevention.

A 73-year-old male patient was referred to us with a long Barrett's esophagus (BE). He had a history of pulmonary embolism under anticoagulant therapy. Esophagogastroduodenoscopy showed a C8M9 BE with no macroscopic lesions. Random biopsies from the BE revealed multifocal high-grade dysplasia. The case was discussed in a multidisciplinary team conference and the decision for full resection of BE with endoscopic submucosal dissection (ESD) was made. Considering the large ESD resection and the high risk of stricture, we developed a novel preventive technique: the "steroid lifting method" for submucosal injection during ESD. Complete circumferential ESD with en bloc resection was performed using the "steroid lifting method", without adverse events. Oral liquids were initiated on day 1 and the patient was discharged on day 4. Oral prednisolone (30 mg per day) was started and tapered for a total of 6 weeks. The pathological examination confirmed multifocal high-grade dysplasia, with radical and curative resection. The patient had neither stricture, dysphagia nor recurrence of Barrett's mucosa at the 2, 6, 12, and 24-month follow-up. International guidelines recommend oral prednisolone and triamcinolone injection to prevent stricture formation in large ESD of esophageal squamous cell carcinoma. However, there is no solid data on BE ESD. The risk factors for stricture formation and the optimal preventive management after large BE ESD is not known. The "steroid lifting method" might be an option in this context. Large prospective studies addressing stricture formation and preventive measures on BE ESD are necessary.

Case report: Novel germline c.587delA pathogenic variant in familial multiple endocrine neoplasia type 1.

Multiple Endocrine Neoplasia type 1 (MEN1) is a rare genetic disease, characterized by co-occurrence of several lesions of the endocrine system. In MEN1, the pathogenic MEN1 gene mutations lead to the Abnormal expression of menin, a critical tumor suppressor protein. We here reported a case of a 14-year-old male with insulinoma and primary hyperparathyroidism. Genetic testing demonstrated a novel heterozygote variant c.587delA of MEN1, resulting in the substitution of the 196th amino acid, changing from glutamic acid to glycine, followed by a frameshift translation of 33 amino acids. An identical variant was identified in the proband's father, who was further diagnosed with hyperparathyroidism. To the best of our knowledge, this is the first report of MEN1 syndrome caused by the c.587delA MEN1 variant. Observations indicated that, despite sharing the same MEN1 gene change, family members exhibited diverse clinical phenotypes. This underscored the presence of genetic anticipation within the familial context.

Performance of Faecal Immunochemical Testing for Colorectal Cancer Screening at Varying Positivity Thresholds.

BACKGROUND: The positivity thresholds of faecal immunochemical testing (FIT) in colorectal cancer (CRC) screening vary between countries. AIMS: To explore the trade-off between colonoscopies performed, adverse events and lesions detected at different FIT thresholds in a Norwegian CRC screening trial. METHODS: We included first participation in biennial FIT screening for 47,265 individuals aged 50-74 years. Individuals with FIT > 15 µg Hb/g faeces were referred for colonoscopy. We estimated the number of colonoscopies, adverse events, screen-detected CRCs, advanced adenomas and serrated lesions expected at FIT thresholds currently or recently used in other European countries ranging between 20 and 150 µg/g. RESULTS: At the 15 µg/g threshold (Norway), 3705 participants underwent colonoscopy, of whom 203 had CRC, 1119 advanced adenomas and 256 advanced serrated lesions. Using a 47 µg/g threshold, 1826 (49.3%) individuals would have undergone colonoscopy, and 154 (75.9%) would have been diagnosed with CRC, 702 (62.7%) with advanced adenoma and 128 (50.0%) with advanced serrated lesion compared to the 15 µg/g threshold. At 150 µg/g, the corresponding figures would have been 838 (22.6%) undergoing colonoscopy, 114 (56.2%) with CRC, 345 (30.8%) advanced adenoma and 54 (21.1%) advanced serrated lesions. The detection rate of stage I CRC was 0.22% at 15 µg/g and 0.11% at 150 µg/g. Post-colonoscopy bleeding rates were 0.8% and 1.7%, respectively. CONCLUSIONS: Increasing the FIT threshold reduces colonoscopy demand, but substantially decreases lesion detection and unfavourably changes CRC stage distribution. The risk of adverse events at colonoscopy increased with FIT threshold, requiring country-specific information on adverse events. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01538550.

Long-term effectiveness of the nine-valent human papillomavirus vaccine: Interim results after 12 years of follow-up in Scandinavian women.

A pivotal study in women aged 16-26 years demonstrated that the nine-valent human papillomavirus (9vHPV) vaccine was efficacious against high-grade cervical dysplasia related to the HPV types covered by the vaccine. To evaluate whether effectiveness remains above 90% for up to 14 years post-vaccination, a long-term follow-up (LTFU) extension of the study was conducted in Denmark, Norway, and Sweden (N = 2,029). Interim findings at 12 years post-vaccination are reported. Effectiveness of the vaccine was measured by comparing the percentage reduction in incidence of HPV16/18/31/33/45/52/58-related high-grade cervical dysplasia in the LTFU cohort with the expected incidence in an unvaccinated cohort. Cervical pre-cancer/cancer diagnoses were identified using national health registries. Tissue samples were obtained from national and regional biobanks for polymerase chain reaction HPV testing, and pathology diagnosis adjudication. Potential waning of vaccine effectiveness and statistical significance were assessed using a control chart method. During LTFU, there were no cases of HPV16/18/31/33/45/52/58-related high-grade cervical dysplasia over 10,396.2 person-years' follow-up in the per-protocol effectiveness population (n = 1,628). No signals indicated vaccine effectiveness decreasing below 90%. Statistically significant protection was provided by the 9vHPV vaccine through at least 10 years, with complete, although not statistically significant, effectiveness through 12 years.

Diagnosis and management of pituitary adenomas in children and adolescents.

BACKGROUND: Pituitary adenomas (PA) - also now called pituitary neuroendocrine tumours or Pit-NETS - are rare in children and adolescents, and exceptional below the age of 10. Most evidence-based high-quality data are derived from larger studies in adult patients. AIMS: We will review recent knowledge on the epidemiology, clinical features, diagnosis and treatment modalities of the different types of pituitary adenomas diagnosed in children and adolescents, emphasizing the many reasons why these cases should be discussed within pituitary-specific multidisciplinary teams with experts from both paediatric and adult practice. CONCLUSIONS: Paediatric PA present multiple peculiarities that may challenge their adequate management. They are overall proportionally larger and more aggressive than in adults, with potential mass effects including hypopituitarism. Hormonal hypersecretion is frequent, resulting in clinical syndromes affecting normal growth and pubertal development. Prolactinomas represent the most frequent subtype of PA found during childhood, followed by adrenocorticotropin (ACTH) and growth hormone (GH)-secreting adenomas, while clinically non-functioning adenomas are exceptionally diagnosed before the age of 16. The occurrence of a pituitary tumour in a young individual should also prompt genetic testing in each case, searching for either germline mutations in one of the known genes that may drive inherited/familial PA (such as the multiple endocrine neoplasia type 1 or MEN1 gene, or the aryl hydrocarbon receptor Interacting protein or AIP gene), or for a mosaic activating mutation of GNAS as found in the McCune-Albright syndrome.

Excision combined with ocular surface reconstruction followed by topical chemotherapy for ocular surface squamous neoplasia.

PURPOSE: To investigate the visual prognosis of ocular surface squamous neoplasia (OSSN) after tumor resection and ocular surface reconstruction, and clarify factors that influence recurrence. STUDY DESIGN: Retrospective cohort study. METHODS: Medical records of all patients who underwent surgical treatment for OSSN at our hospital between January 1996 and December 2019 were reviewed. Tumor size/location, histological classification, surgical procedure, intraoperative mitomycin-C use, and postoperative topical 5-fluorouracil (5-FU) administration were examined, and pre and postoperative visual acuity (VA) were compared to elucidate factors that influence disease recurrence. RESULTS: Tumor excision was performed in 70 eyes of 70 cases (43 men, 27 women; average age: 71.6 ± 12.6 years) with dysplasia (8 eyes), carcinoma in situ (26 eyes), and invasive squamous cell carcinoma (36 eyes). Tumors were found in the limbus (N = 59 eyes), palpebral conjunctiva (N = 8 eyes), and from the bulbar to palpebral conjunctiva (N = 3 eyes). Surgical procedures performed were limbal transplantation/keratoepithelioplasty (N = 29 eyes), cultivated oral mucosal epithelial transplantation (N = 3 eyes), and auto-conjunctival epithelium transplantation (N = 2 eyes). Ocular surface was reconstructed using amniotic membrane, donor cornea, or cultivated epithelial sheet. The mean follow-up was 38.6 ± 38.6 months (range, 2 months to 13.8 years). VA postoperatively improved in 25 (61.0%) cases. Recurrence occurred in 19 (27.1%) cases at from 2 to 50 months (median: 12.5 months) postoperative. Uni- and multivariate analyses revealed that presurgical tumor size and postoperative administration of 5-FU were significantly related to recurrence. CONCLUSION: Combined surgical excision and postoperative topical 5-FU administration effectively prevented OSSN recurrence, and ocular surface reconstruction contributed to improvement of VA.

Computed tomographic features of pulmonary and extrapulmonary lesions can be useful in prioritizing the diagnosis of hemangiosarcoma metastases in dogs.

OBJECTIVE: The aim of this study was to evaluate the CT features of pulmonary metastases in dogs with hemangiosarcoma (HSA) at various sites. Additionally, the CT characteristics of extrapulmonary metastases in the same population were assessed. METHODS: Retrospective, observational, and descriptive study conducted from April 2013 to January 2024. Dogs with histologically confirmed HSA and suspected or cytologically/histologically confirmed lung metastases were included. Dogs were excluded if they had a second primary tumor or only 1 unsampled pulmonary nodule. RESULTS: 33 dogs were included, with 26/33 [78.8%] having more than 10 metastatic pulmonary nodules. Most nodules were generalized (24/33 [72.7%]), miliary (29/33 [87.9%]) to subcentimetric (32/33 [97%]) in size, well-defined margins (29/33 [87.9%]), or a perilesional halo sign (24/33 [72.7%]). When more than 10 nodules were present, a generalized distribution was prevalent, while a peripheral location was more common when 2 to 10 nodules were present (P < .0001). In 32/33 (97%) cases, a pulmonary vessel was directly connected to the nodule (feeding vessel). After contrast administration, most lung metastases appeared homogenous (26/33 [78.8%]), although some showed areas of intense enhancement (5/33 [15.1%]) a feature also observed in extrapulmonary metastases with varying frequency (0% to 85.7%). CONCLUSIONS: Pulmonary HSA metastases were characterized by generalized, small (miliary/subcentimetric), well-defined nodules, commonly associated with a halo sign and feeding vessel. Intralesional areas of spotty postcontrast linear or amorphous strong hyperdensity were frequently observed especially in extrapulmonary metastases. CLINICAL RELEVANCE: These features may help radiologists and clinicians orient their diagnosis toward metastatic HSA.

Progression of Intraductal Papillary Mucinous Neoplasms of the Pancreas After Liver Transplantation.

BACKGROUND: Intraductal papillary mucinous neoplasms (IPMNs) are the most commonly identified pancreatic cystic neoplasms. Incidentally detected IPMNs are common among liver transplant recipients. The risk of IPMN progression to pancreatic cancer in transplant recipients and the impact of immunosuppression on the risk of malignant transformation of IPMN are unclear. METHODS: In this retrospective study of consecutive liver transplant recipients across Mayo Clinic over a 13-year period, patients were assessed for possible IPMN by automated chart review. Pancreatic cystic lesions were characterized as suspected IPMNs based on imaging criteria. Cox proportional hazards models were used to determine the association between IPMN progression (the development of cancer or worrisome features) and clinical and immunosuppression regimen characteristics. RESULTS: Of 146 patients with suspected IPMNs, progression occurred in 7 patients (2 cases of IPMN-associated cancer and 5 cases of worrisome features) over an average follow-up of 66.6 months. Immunosuppression type, medication number, and tacrolimus trough levels were not associated with IPMN progression (p > 0.05). Combined kidney and liver transplantation (p = 0.005) and pretransplant cholangiocarcinoma (p = 0.012) were associated with IPMN progression. CONCLUSION: IPMN progression is rare after liver transplantation even over an extended follow-up period. The findings were notable for the absence of an association between IPMN progression and immunosuppression regimen. Larger studies are needed given the low incidence.

Special AT-rich sequence-binding protein 2 immunohistochemistry in the diagnosis of osteosarcoma in dogs.

Malignant osteoblasts can have markedly pleomorphic phenotypes and variable amounts of tumour-associated matrix, complicating the ability of pathologists to accurately differentiate osteosarcoma (OSA) from other types of neoplasms using only histopathology. Current immunohistochemical markers for animals have limited sensitivity and specificity in identifying OSA or produce inconsistent results. Immunohistochemistry (IHC) for special AT-rich sequence-binding protein 2 (SATB2) has been used in human medicine to aid in identification of normal and neoplastic osteoblasts, and the objective of this study was to determine whether this marker could also be useful for the diagnosis of canine OSA. Initially, SATB2 IHC was performed on eight samples from cases of well-differentiated canine OSA and on other tumour types for which OSA is a differential diagnosis, as well as on normal tissues, to assess sensitivity and cross-reactivity. Following confirmation that SATB2 is immunoreactive for normal and neoplastic canine osteoblasts and negative in other non-osseous mesenchymal cell types and organs, SATB2 IHC was tested on 123 cases of poorly differentiated malignant neoplasms as part of a panel with other immunohistochemical markers, as appropriate, based on histomorphology and differential diagnoses. The conclusion is that SATB2 IHC is a sensitive and specific marker for identifying canine OSA when used in a panel with other immunohistochemical markers and in conjunction with supportive clinical history.

Small cyst size and lack of growth as negative predictors of malignant transformation in low-risk intraductal papillary mucinous neoplasms of the pancreas: A systematic review and meta-analysis.

BACKGROUND AND AIM: For branch-duct intraductal papillary mucinous neoplasms (BD-IPMNs) without worrisome features (WFs) or high-risk stigmata (HRS), current guidelines recommend surveillance. However, these intraductal papillary mucinous neoplasm (IPMNs), especially the small and stable-sized ones, carry a low risk of malignant transformation. Our aim was to assess whether small cyst size and absence of rapid growth provide reassurance against the development of WFs/HRS and malignancy (high-grade dysplasia (HGD) or pancreatic cancer (PC)). METHODS: PubMed/Medline, Embase, the Cochrane Library and the Web of Science Core Collection were systematically searched from inception to May 2023 to identify studies investigating surveillance outcomes of low-risk BD-IPMNs. Studies assessing baseline cyst size and/or growth in relation to WFs/HRS and/or HGD/PC were included. The Newcastle-Ottawa scale tool was used to assess study quality. RESULTS: Of the 1937 identified manuscripts, 21 studies were eligible for inclusion. The quality of these studies was considered reasonable. A negative association between cyst size and WFs/HRS development was found in 11 out of 13 relevant studies, but only one out of nine studies reported a negative association between size and malignancy. Regarding cyst growth, four out of six studies described a negative association with the development of WFs/HRS, and all six reported a negative association with malignancy. The pooled relative risk (RR) of developing WFs/HRS or malignancy for cysts ≤15 mm was 0.37 (95% CI 0.25-0.57) and the RR of developing malignancy for cyst growth <2-2.5 mm/year was 0.04 (95% CI 0.02-0.09)). CONCLUSION: This systematic review and meta-analysis shows that small and stable-sized low-risk BD-IPMNs are associated with a markedly low progression rate, with stable cyst size being the most reassuring feature. Because of substantial heterogeneity in definitions and reported outcome measures, prospective studies are needed to confirm that surveillance of small and stable sized cyst can be de-intensified or even discontinued.

Efficacy of Racecadotril in a Patient Affected by a Therapy-Refractory VIPoma and Carcinoid Syndrome.

Neuroendocrine neoplasms (NENs) encompass a heterogeneous spectrum of tumors originating from the diffuse neuroendocrine cell system. Approximately 30% of NEN exhibit functional activity with clinical syndromes through hormone-mediated effects. Synchronous and metachronous functioning syndromes, resulting from the simultaneous release of distinct hormones, are exceptionally rare. Of note, hormonal excess syndromes can have a greater effect on patients' morbidity and mortality than the tumor mass itself. We present the case of a 49-year-old male patient affected by an oligo-metastatic ileal NEN, concurrently demonstrating vasointestinal peptide (VIP) and serotonin excretion, complicated by pulmonary tuberculosis. After the first cycle of Lutetium-177-DOTATATE peptide-radio-receptor therapy, the patient developed a severe watery diarrhea, hypokalemia, and achlorhydria (WDHA) syndrome, despite receiving high-dose somatostatin analogues, everolimus, and telotristat ethyl, without any surgical options. The WDHA syndrome necessitated intensive-care-unit (ICU) admission with continual intravenous administration of electrolytes and fluids. With limited alternatives, an off-label intervention using the enkephalinase inhibitor racecadotril was initiated. After 5 days of treatment, the WDHA syndrome exhibited sufficient control, facilitating the patient's discharge from the ICU. This case report underscores racecadotril as an individualized, off-label treatment strategy for patients with severe VIPoma and serotonin-driven WDHA syndrome, where conventional therapeutic avenues have been exhausted.

Barriers and facilitators for adherence to follow-up by HR-HPV-positive women with premalignant cervical lesions: a mixed-design study in Mexico.

BACKGROUND: Mexico reports low follow-up completion rates among women with abnormal cervical cancer screenings. This study aimed to identify barriers and facilitators to follow-up adherence among women with human papillomavirus (HPV) infection and premalignant cervical lesions in Mexico. METHODS: A mixed-methods study was conducted from February to April 2019. Participants included women undergoing follow-up care for high-risk human papillomavirus (HR-HPV) and premalignant lesions, along with health personnel from the Women's Healthcare Center (CAPASAM) in Mexico. Quantitative data were obtained from the Women's Cancer Information System and through a questionnaire about factors affecting follow-up adherence. Additionally, the health personnel involved completed a compliance checklist regarding care regulations. Descriptive statistics were used for analysis. Qualitative data were collected via semi-structured interviews with both groups, followed by a content analysis based on identified categories. The Hazard Analysis and Critical Control Point System confirmed care process risks. Proposals to enhance the Early Detection Program for Prevention and Control of Cervical Cancer were collected from a CAPASAM health personnel nominal group. RESULTS: Identified barriers to follow-up included low income among CAPASAM users, family provider roles limiting time for appointments, long waits for testing and results delivery, distant facilities, insufficient service hour communication, inadequate health personnel training, and a lack of systematic counseling. Hesitation toward follow-up was also linked to shame, apprehension, uncertainty, test aversion, fear of positive results, and limited cervical cancer and screening knowledge. Patriarchal attitudes of partners and limited access to the now-discontinued PROSPERA government program further discouraged follow-up. Facilitators comprised respectful treatment by CAPASAM staff, no-cost services, health campaigns, and positive user attitudes. CONCLUSIONS: The study found more barriers than facilitators to follow-up adherence, highlighting the need for strategies to bolster the Early Detection Program. Future strategies must address the comprehensive array of factors and incorporate stakeholder perspectives.

FcγR3A polymorphism influences natural killer cell activation and response to anti-PD-L1 (avelumab) in gestational trophoblastic neoplasia.

BACKGROUND: Low-risk gestational trophoblastic neoplasia (GTN) are currently receiving monochemotherapy as first-line therapy. In the case of a resistance, a second-line mono- or polychemotherapy is proposed. As an alternative to these toxic and historic chemotherapy agents, the efficacy of the anti-PD-L1 monoclonal antibody (avelumab) was assessed in the TROPHIMMUN phase II trial Cohort A. Avelumab yielded a 53% cure rate with an acceptable tolerance profile, including normal further pregnancy and delivery. Beyond the blockade of PD-1/PD-L1 interactions, avelumab effect could rely on the induction of antibody-dependent cell-mediated cytotoxicity (ADCC) mediated by FcγR3A-expressing natural killer (NK) cells. OBJECTIVE: This translational study aimed at testing whether ADCC is involved in avelumab efficacy on GTN and if FcγR3A affinity polymorphism could help predicting the response to avelumab in GTN. STUDY DESIGN: The expression of PD-L1 by the tumor and the phenotype of NK cells infiltrating GTN were verified by performing transcriptomic and proteomic analyses. Then, JEG-3 choriocarcinoma cells were cocultured with human NK cells in presence and absence of avelumab. The impact of FcγR3A functional polymorphism was assessed on the activation status of NK cells and the viability of JEG-3 choriocarcinoma cells. Finally, the data from TROPHIMMUN trial were reanalyzed to determine the impact of the FcγR3A polymorphism of patients on their response to avelumab. RESULTS: We confirmed that FcγR3A+ NK cells infiltrated PD-L1-expressing GTN. In vitro, avelumab-coated JEG-3 choriocarcinoma cells induced NK cell activation, which promoted the destruction of JEG-3 cells. NK cell activation was abolished when the Fc portion of avelumab was removed, demonstrating the importance of Fcγ receptor in this process. Using this model of ADCC, we demonstrated that high-affinity FcγR3A polymorphism on NK cells was associated with better in vitro response to avelumab. In line with this result, patients from the TROPHIMMUN trial homozygous for the high affinity FcγR3A polymorphism had better clinical response to avelumab. CONCLUSIONS: Our work demonstrates that ADCC contributes to the therapeutic effect of avelumab in GTN and that the individual patient response is impacted by the FcγR3A polymorphism. The FcγR3A polymorphism could be used as a biomarker to identify patients diagnosed with monochemoresistant GTN who are most likely to respond to avelumab.

Treatment of ocular surface squamous neoplasia in an Indian rural facility: a study of 38 eyes.

PURPOSE: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. METHODS: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. RESULTS: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. CONCLUSION: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Incidence, duration, and severity of neutropenia in adults with B-cell acute lymphoblastic leukemia receiving blinatumomab consolidation.

Blinatumomab is a CD3 × CD19 antibody approved for adults with B-cell acute lymphoblastic leukemia (B-ALL). Blinatumomab is not considered myelosuppressive, but significant neutropenia has been seen in practice. We reviewed 95 patients with B-ALL who received blinatumomab at Dana-Farber Cancer Institute between 2015 and 2024. Of these, 71 patients were treated in morphologic remission with absolute neutrophil count (ANC) ≥1 × 109/L, for which 41% experienced grade ≥3 neutropenia and 13% developed ANC <0.1 × 109/L during blinatumomab. Neutropenia occurred more frequently during cycle 2 than cycle 1, and neutropenia did not necessarily portend worse neutropenia in later cycles. Multivariable analysis did not identify concurrent tyrosine kinase inhibitor use as a significant covariate for neutropenia. The nine patients who experienced ANC <0.1 × 109/L did not develop serious infections and received supportive care. Neutropenia occurs frequently and may be severe in patients with B-ALL who receive blinatumomab during remission, but complications appear manageable.

RAP1-GTPase immunostaining is altered in human precancerous and cancerous cervical lesions.

Aim: This study investigated RAP1 immunostaining variation in different cell types during CC progression.Methods: Paraffin-embedded cervical tissues from 101 patients were categorized into control, pre-neoplastic and neoplastic groups. RAP1 immunolocalization, HPV detection and genotyping were performed. A semiquantitative immunoreactive score was employed to compare labeling intensity, cellular localization, nuclear labeling, percentage and distribution of reactive cells.Results: 73% (72/99) of cervical specimens were HPV+. RAP1 was localized in the nucleus and cytoplasm of all samples. Cytoplasmic RAP1 immunoscore was higher than nuclear score in all CC groups. RAP1 intensity increased with lesion severity. SCC samples exhibited predominantly intense RAP1 immunostaining.Conclusion: RAP1 is an efficient biomarker for detecting invasive CC lesions but has limited utility in distinguishing SCC grades.

[Box: see text].

Clinical validation of the Roche cobas HPV test on the Roche cobas 5800 system for the purpose of cervical screening.

This study assessed the relative clinical sensitivity and specificity, as well as reproducibility, for high-risk HPV types of the Roche cobas HPV test when processed using the Roche cobas 5800 system. The results from this study demonstrate that the cobas HPV test using the cobas 5800 system fulfils the Meijer criteria for use in population-based cervical screening. This clinical validation study also examines the clinical sensitivity and specificity based on partial genotyping, with separate detection of HPV16 and HPV18, compared with the Roche cobas 4800 HPV test, a second-generation standard comparator assay. The cobas HPV test has a relative clinical sensitivity of 1.000, when compared with the cobas 4800 HPV test to detect histologically confirmed CIN2+ lesions in woman aged 30 years or older, with a relative clinical specificity of 0.995. The general intra- and inter-laboratory agreement for the cobas HPV test on the cobas 5800 system for finding a HPV positive result were 99.1% and 99.6%, respectively.IMPORTANCEThis study demonstrates, for the first time, the clinical performance of the Roche cobas HPV test when processed using the new cobas 5800 system [cobas (5800)]. This study shows that the cobas (5800) demonstrates relative clinical sensitivity and specificity, when compared with a standard comparator HPV test, which meets the international HPV test validation requirements. Intra- and inter-laboratory reproducibility also fulfills these criteria. The current study demonstrates that the cobas (5800) can be used for primary HPV-based cervical screening on cervical specimens.