Introduction Urinary bladder lesions encompass a wide spectrum, from benign inflammatory conditions to malignant neoplasms, presenting diagnostic and therapeutic challenges. Urothelial carcinoma predominates among bladder malignancies, exhibiting diverse clinical presentations and prognoses. Objective This study aimed to delineate the histopathological spectrum of urinary bladder lesions and correlate demographic profiles, clinical features, and cystoscopic findings with various bladder lesions. Methods This prospective descriptive observational study spanned 24 months at a tertiary care center, involving 65 cases of urinary bladder biopsies, including transurethral resection of bladder tumors, cystoscopic biopsies, and cystectomy specimens. The histopathological examination followed the WHO 2022 classification of urinary bladder tumors and the American Joint Committee on Cancer eighth edition staging. Clinical data, including age, gender, cystoscopic findings, and presenting symptoms, were correlated with histopathological diagnoses to explore the spectrum of bladder lesions. Results Neoplastic lesions predominated, constituting 92.3% of cases, with urothelial carcinoma comprising 83.33% of these cases. Among neoplastic lesions, invasive high-grade urothelial carcinoma (36.7%) and non-invasive low-grade papillary urothelial neoplasm (20.0%) were the most frequently observed subtypes. Non-neoplastic lesions accounted for 7.7%, including various forms of cystitis. Hematuria was the predominant presenting symptom (81.5%), while cystoscopic examinations revealed that most lesions were situated in the lateral bladder wall. High-grade urothelial carcinomas were mostly associated with muscularis propria invasion. Conclusion This study underscores the critical role of histopathological examination in diagnosing and managing urinary bladder diseases and distinguishing between non-neoplastic and neoplastic lesions. Urothelial carcinoma, prevalent among older age groups, often demonstrated muscle invasion indicative of high-grade tumors. Including the muscle layer in cystoscopic biopsies is crucial for an accurate diagnosis. Conversely, though less common, non-neoplastic conditions encompass various forms of cystitis. These findings highlight the importance of precise diagnostic tools such as cystoscopy and histopathological examination for the early detection and management of bladder neoplasms. Histopathological assessment offers essential prognostic guidance, aids in precise staging and grading, and directs tailored treatment strategies.

The aim of this study is to investigate the correlation between the incidence of spontaneous tumours of various origins and the localisation in dogs with sex, breed, and age factors. A total of 360 tumours with various localisation were studied pathomorphologically. Histopathologic data sets from 360 dog tissue samples were processed and statistically examined. A chi-square test of independence was conducted to examine the relationships among the various levels of the specified variables. Logistic regression models were employed for dichotomous outcomes to ascertain the influence of certain explanatory variables on the tumour types. Characteristic pathomorphological changes observed during examination of dogs with oncologic diseases were determined. The most common neoplasms were mammary tumours, accounting for 43% of the cases. The mammary gland tumours were most common in mongrel dogs (25%), with German Shepherds (17.3%), Poodles, Dachshunds, Central Asian Shepherds (6.7% each), and Rottweilers (5.7%) following. The highest frequency of these tumours appeared at 8 years of age, predominantly originating from the ductal epithelium, which represented 46.4% of all the malignant cases.

Data about the oncological outcomes in women with borderline ovarian tumor (BOT) undergoing uterine-sparing surgery without ovarian preservation are poor. We aimed to assess the oncological outcomes in women with BOT undergoing uterine-sparing surgery without ovarian preservation. A multi-center observational retrospective cohort study was performed including all consecutive postmenopausal patients who underwent surgical treatment for BOT at three tertiary level referral centers for gynecologic oncology from January 2005 to December 2016. Patients were divided into two groups for comparisons: patients undergoing hysterectomy (hysterectomy group) and patients undergoing uterine-sparing surgery (no hysterectomy group). Study outcomes were disease-free survival (DFS), overall survival (OS), disease-specific survival (DSS) and surgical complications rate. Ninety-eight patients were included: 44 in the hysterectomy group and 54 in the no hysterectomy group. The 5- and 10-year DFS rates were 97.7% (95% CI: 84.9-99.7) and 92.3% (95% CI: 69.7-98.2), in the hysterectomy group, and 86.8% (95% CI: 74.3-93.5) and 86.8% (95% CI: 74.3-93.5), in the no hysterectomy group, respectively, without significant differences (p=0.16). Hazard ratio for DFS was 0.26 (95% CI: 0.06-1.68) for the hysterectomy group. The 5- and 10-year OS rates were 100.0% (95% CI: -) and 100.0% (95% CI: -), in the hysterectomy group, and 98.2% (95% CI: 87.6-99.7) and 94.4% (95% CI: 77.7-98.7), in the no hysterectomy group, respectively, without significant differences (p=0.23). No significant difference in complication rate was reported among the groups (p=0.48). As hysterectomy appears to not impact survival outcomes of women with BOT, it might be avoided in the surgical staging.

BACKGROUND: When children and young people (CYP) are diagnosed with a brain tumour, Magnetic Resonance Imaging (MRI) is key to the clinical management of this condition. This can produce hundreds, and often thousands, of Magnetic Resonance Images (MRIs).
METHODS: Semi-structured interviews were undertaken with 14 families (15 parents and 8 patients), and analysed using Grounded Theory. Analysis was supported by the Framework Method.
RESULTS: Although the focus of the research was whether paediatric patients and their families find viewing MRIs beneficial, all patients and parents discussed difficult times during the illness and using various strategies to cope. This article explores the identified coping strategies that involved MRIs, and the role that MRIs can play in coping. Coping strategies were classified under the aim of the strategy when used: \'Normalising\'; \'Maintaining hope and a sense of the future\'; \'Dealing with an uncertain future\'; and \'Seeking Support\'.
CONCLUSIONS: Coping and finding ways to cope are clearly used by patients and their families and are something that they wish to discuss, as they were raised in conversations that were not necessarily about coping. This suggests clinicians should always allow time and space (in appointments, consultations, or impromptu conversations on the ward) for patient families to discuss ways of coping. MRIs were found to be used in various ways: to maintain or adapt normal; maintain hope and a sense of the future; deal with an uncertain future; and seek support from others. Clinicians should recognise the potential for MRIs to aid coping and if appropriate, suggest that families take copies of scans (MRIs) home. Professional coaches or counsellors may also find MRIs beneficial as a way to remind families that the child is in a more stable or \'better\' place than they have been previously.

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CPC634 is docetaxel entrapped in core-cross linked polymeric micelles. In preclinical studies, CPC634 demonstrated enhanced pharmacokinetics and improved therapeutic index. This phase I dose escalation study is the first-in-human study with CPC634.
adult patients with advanced solid tumours received CPC634 intravenously either 3-weekly (Q3W) (part 1, dose range 15-100 mg/m2), 2-weekly (Q2W) (part 2, 45 mg/m2) or Q3W with dexamethasone premedication (part 3, 60 mg/m2).
thirty-three patients were enrolled. Skin toxicity was dose limiting (DLT) at ≥60 mg/m2 in part 1 and at 45 mg/m2 in part 2 and was the most common CPC634 related grade ≥ 3 adverse event (24%). With dexamethasone premedication no DLTs were observed at 60 mg/m2 Q3W. CPC634 exhibited a dose-proportional pharmacokinetic profile. At 60 mg/m2, the plasma area under the curve was 4067.5 ± 2974.0 ng/h/mL and the peak plasma level 217.3 ± 91.9 ng/mL with a half-life of 39.7 ± 9.4 h for released docetaxel.
CPC634 could be administered safely upon pretreatment with dexamethasone. Cumulative skin toxicity was the main DLT. The recommended phase 2 dose was determined at 60 mg/m2 Q3W with dexamethasone premedication.

Tislelizumab is an investigational, humanized, IgG4 monoclonal antibody with high affinity and binding specificity for programmed cell death-1 (PD-1) that was engineered to minimize binding to FcγR on macrophages in order to abrogate antibody-dependent phagocytosis, a mechanism of T-cell clearance and potential resistance to anti-PD-1 therapy.
The purpose of this phase 1/2, open-label, non-comparative study was to examine the safety, tolerability, and antitumor activity of tislelizumab in adult (≥18 years) Chinese patients with histologically or cytologically confirmed advanced solid tumors with measurable disease. The phase 1 portion of the study consisted of a dose-verification study and a pharmacokinetic (PK) substudy; phase 2 was an indication-expansion study including 11 solid tumor cohorts. Patients previously treated with therapies targeting PD-1 or its ligand, programmed cell death ligand-1 were excluded. During dose-verification, dose-limiting toxicities (DLTs) were monitored; safety and tolerability were examined and the previously determined recommended phase 2 dose (RP2D) was verified. The primary endpoint of phase 2 was investigator-assessed objective response rate per Response Evaluation Criteria in Solid Tumors V.1.1.
As of December 1, 2018, 300 patients were treated with tislelizumab 200 mg intravenously once every 3 weeks (Q3W). Median duration of follow-up was 8.1 months (range 0.2-21.9). No DLTs were reported during the phase 1 dose-verification study and the RP2D was confirmed to be 200 mg intravenously Q3W. Most treatment-related adverse events (62%) were grade 1 or 2, with the most common being anemia (n=70; 23%) and increased aspartate aminotransferase (n=67; 22%). Of the 251 efficacy evaluable patients, 45 (18%) achieved a confirmed clinical response, including one patient from the PK substudy who achieved a complete response. Median duration of response was not reached for all except the nasopharyngeal carcinoma cohort (8.3 months). Antitumor responses were observed in multiple tumor types.
Tislelizumab was generally well tolerated among Chinese patients. Antitumor activity was observed in patients with multiple solid tumors.
CTR20160872.

To compare the clinical efficacy of New York Esophageal squamous cell carcinoma-1 (NY-ESO-1) vaccine with ISCOMATRIX adjuvant versus ISCOMATRIX alone in a randomized, double-blind phase II study in participants with fully resected melanoma at high risk of recurrence.
Participants with resected stage IIc, IIIb, IIIc and IV melanoma expressing NY-ESO-1 were randomized to treatment with three doses of NY-ESO-1/ISCOMATRIX or ISCOMATRIX adjuvant administered intramuscularly at 4-week intervals, followed by a further dose at 6 months. Primary endpoint was the proportion free of relapse at 18 months in the intention-to-treat (ITT) population and two per-protocol populations. Secondary endpoints included relapse-free survival (RFS) and overall survival (OS), safety and NY-ESO-1 immunity.
The ITT population comprised 110 participants, with 56 randomized to NY-ESO-1/ISCOMATRIX and 54 to ISCOMATRIX alone. No significant toxicities were observed. There were no differences between the study arms in relapses at 18 months or for median time to relapse; 139 vs 176 days (p=0.296), or relapse rate, 27 (48.2%) vs 26 (48.1%) (HR 0.913; 95% CI 0.402 to 2.231), respectively. RFS and OS were similar between the study arms. Vaccine recipients developed strong positive antibody responses to NY-ESO-1 (p≤0.0001) and NY-ESO-1-specific CD4+ and CD8+ responses. Biopsies following relapse did not demonstrate differences in NY-ESO-1 expression between the study populations although an exploratory study demonstrated reduced (NY-ESO-1)+/Human Leukocyte Antigen (HLA) class I+ double-positive cells in biopsies from vaccine recipients performed on relapse in 19 participants.
The vaccine was well tolerated, however, despite inducing antigen-specific immunity, it did not affect survival endpoints. Immune escape through the downregulation of NY-ESO-1 and/or HLA class I molecules on tumor may have contributed to relapse.

Adoptive cell therapy (ACT) with tumor-reactive T cells has shown consistent clinical efficacy. We evaluated the response to ACT in combination with interferon alpha (IFNa) preconditioning in patients with stage IV metastatic melanoma, most of which were progressive on cytotoxic T-lymphocyte-associated protein 4 and/or programmed cell death protein 1 checkpoint blockade therapy.
Thirty-four patients were treated with ex vivo expanded tumor reactive T cells, derived from mixed lymphocyte autologous tumor cultures, or with autologous tumor-infiltrating lymphocytes and evaluated for clinical response. Clinical and immunological parameters associated with response were also evaluated.
Best overall response defined as clinical benefit, comprising either complete response, partial response or stable disease >6 months, was observed in 29% of the patients. Forty-three per cent of the 14 immunotherapy-naïve patients and 20% of the 20 patients progressive on prior immunotherapy benefited from ACT. The overall survival (OS) was 90% versus 28.6% at 1 year and 46.7% versus 0% at 3 years follow-up, of responder and non-responder patients, respectively. Median OS was 36 versus 7 months, respectively. IFNa pretreatment resulted in leukopenia, neutropenia and lymphopenia, which was sustained during the treatment in clinical responders and associated with response. Differences in antigen specificity, but not in phenotype, cytokine profile or CD8+ T cell number of the ACT products correlated with clinical response. Cross-reactivity of the ACT products to one or more allogeneic human leukocyte antigen-matched melanoma cell lines was associated with short OS after treatment while the ACT products of very long-term survivors showed no cross-reactivity but recognized patient-specific neoantigens.
This study demonstrates that ACT in combination with a mild IFNa preconditioning regimen can induce clinical benefit even in immunotherapy pretreated patients, although with lower success than in immunotherapy-naïve patients. ACT products comprising neoantigen reactivity may be more effective.

Patients with advanced rare cancers have poor prognosis and few treatment options. As immunotherapy is effective across multiple cancer types, we aimed to assess pembrolizumab (programmed cell death 1 (PD-1) inhibitor) in patients with advanced rare cancers.
In this open-label, phase 2 trial, patients with advanced rare cancers whose tumors had progressed on standard therapies, if available, within the previous 6 months were enrolled in nine tumor-specific cohorts and a 10th cohort for other rare histologies. Pembrolizumab 200 mg was administered intravenously every 21 days. The primary endpoint was non-progression rate (NPR) at 27 weeks; secondary endpoints were safety and tolerability, objective response rate (ORR), and clinical benefit rate (CBR).
A total of 127 patients treated between August 15, 2016 and July 27, 2018 were included in this analysis. At the time of data cut-off, the NPR at 27 weeks was 28% (95% CI, 19% to 37%). A confirmed objective response (OR) was seen in 15 of 110 (14%) evaluable patients (complete response in one and partial response in 14). CBR, defined as the percentage of patients with an OR or stable disease ≥4 months, was 38% (n=42). Treatment was ongoing in 11 of 15 patients with OR at last follow-up. In the cohort with squamous cell carcinoma (SCC) of the skin, the NPR at 27 weeks was 36%, ORR 31%, and CBR 38%. In patients with adrenocortical carcinoma (ACC), NPR at 27 weeks was 31%, ORR 15%, and CBR 54%. In the patients with carcinoma of unknown primary (CUP), NPR at 27 weeks was 33%, ORR 23%, and CBR 54%. In the paraganglioma-pheochromocytoma cohort, NPR at 27 weeks was 43%, ORR 0%, and CBR 75%. Treatment-related adverse events (TRAEs) occurred in 66 of 127 (52%) patients, and 12 (9%) had grade ≥3 TRAEs. The most common TRAEs were fatigue (n=25) and rash (n=17). There were six deaths, all of which were unrelated to the study drug.
The favorable toxicity profile and antitumor activity seen in patients with SCC of skin, ACC, CUP, and paraganglioma-pheochromocytoma supports further evaluation of pembrolizumab in this patient population.
NCT02721732.