Pilot study on differential gene expression in relation to vincristine response in canine transmissible venereal tumor.

Percutaneous cryoablation (PC) has been incorporated among first-line treatment options for desmoid-type fibromatosis (DF). Loco-regional therapies, including PC, induce tissue changes that may precede measurable tumor shrinkage, thereby limiting the reliability of purely dimensional response criteria. To address this limitation, we compared response evaluation criteria in solid tumors (RECIST) 1.1 and magnetic resonance imaging (MRI)-adapted (M-)RECIST in patients with DF treated with PC. We retrospectively identified all consecutive patients with progressing extra-abdominal DF treated with PC. Responses were assessed with RECIST 1.1 and M-RECIST, the latter relying on T2- and diffusion-weighted imaging, as well as unenhanced and contrast-enhanced T1-weighted imaging, to define residual viable tumor. Non-progression (NPR) and overall response rates (ORR) were defined as the percentage of patients without radiological progression and partial/complete responses, respectively. Thirty-four patients (females/males, 26/8) and 37 procedures were identified. RECIST 1.1 and M-RECIST were applicable in 35 and 34 procedures, respectively. At a median follow-up of 15.7 months (interquartile range [IQR] 19.5), RECIST 1.1. Responses were: 10/35 (28.6%) partial response (PR), 22/35 (62.9%) stable disease (SD), and 3/35 (8.6%) progressive disease (PD), with ORR 28.6% and NPR 91.4%. At a median follow-up of 16.0 months (IQR 20.5), M-RECIST responses were: 15/34 (44.1%) complete response (CR), 12/34 (35.3%) PR, 4/34 (11.8%) SD, and 3/34 (8.8%) PD, with ORR 79.4% and NPR 91.2%. Overall concordance was negligible. M-RECIST yielded higher NPR/ORR than RECIST 1.1. These findings pave the way for studies addressing whether this shift in response categorization associates with improved outcomes prediction. This work provides supporting evidence for the implementation of residual viable disease assessment in evaluating DF responses to PC. In patients with DF, responses to cryoablation can be characterized using purely dimensional and viability-based criteria. RECIST 1.1 and M-RECIST yielded complete agreement for PD. M-RECIST may refine response categorization below the progression threshold.

Patients with relapsed/refractory multiple myeloma (RRMM) who are penta-drug refractory, defined as resistant to two proteasome inhibitors, two immunomodulatory agents, and an anti-CD38 monoclonal antibody, face a dismal prognosis, particularly after exposure to T-cell-redirecting therapies. Selinexor, an oral exportin-1 inhibitor, offers a distinct mechanism of action and may retain efficacy in this difficult setting. We conducted a retrospective analysis at six German tertiary centers (2023-2025) to evaluate the efficacy and safety of selinexor plus bortezomib and dexamethasone (SVd) in penta-refractory MM after both BCMA- and GPRC5D-targeted therapies. Eighteen patients were identified, with a median of seven prior lines of therapy. High-risk cytogenetic abnormalities were present in seven cases, including del17p in six. The overall response rate (ORR) was 61%, including one complete, five very good partial, and five partial responses, and median progression-free survival (PFS) was 4.3 months. Among nine patients (50%) with extramedullary disease (EMD), three achieved complete and one near-complete EMD resolution. Two patients who had relapsed after CAR T-cell treatment with idecabtagene vicleucel achieved partial and very good partial responses and were successfully transitioned to a second CAR T-cell therapy with ciltacabtagene autoleucel. Hematologic toxicities under SVd were manageable, and no treatment-related deaths occurred. SVd demonstrates meaningful activity in patients with penta-refractory MM and prior failure of BCMA/GPRC5D-targeted immunotherapies. The ORR of 61%, disease control in 78% of patients, and median PFS of 4.3 months support further evaluation of SVd in this highly refractory setting after failure of BCMA- and GPRC5D-directed approaches.

This study aimed to verify the efficacy and safety of balloon-occluded alternative infusion of cisplatin solution and gelatin particles of transarterial chemoembolization (BOAI-TACE) for hepatocellular carcinoma (HCC) refractory or intolerant to atezolizumab plus bevacizumab combination therapy. This prospective, single-arm study was performed at five hospitals from May 2021 to December 2024. The primary endpoint was objective response ratio (ORR) for BOAI-TACE at eight weeks after treatment. To evaluate safety, adverse events and changes in liver function were monitored. A total of ten patients were enrolled in this study with one exclusion for medical reasons. The results were complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) for 5, 1, 1 and 2 patients, respectively. ORR (CR+PR) was 60% (95% confidence interval=26.2%-87.8%), meeting the primary endpoint. One patient suffered acute cholecystitis requiring surgery but recovered and was discharged after surgery. Another patient suffered right diaphragm paralysis after treatment but only mild shortness of breath on exertion remained. There were no statistically significant changes in liver function before and after BOAI-TACE. All nine patients were alive six months after treatment. BOAI-TACE is safe and effective in patients with HCC, even those with refractory or intolerant to immune checkpoint inhibitor therapy.

The Kirsten rat sarcoma viral oncogene homolog (KRAS) is one of the most frequently mutated oncogenes and is associated with poor prognosis. Long considered an undruggable target, KRAS has recently become actionable with the development of direct inhibitors, particularly against the G12C mutation. Our group previously reported promising efficacy and safety results for glecirasib (JAB-21822), a novel KRASG12C inhibitor, in phase I/II trials involving solid tumors harboring KRASG12C mutations (ClinicalTrials.gov NCT05009329, NCT05194995). Nevertheless, primary (5.61%) and acquired (9.64%) resistance were observed. This study analyzed 18 patients with advanced solid tumors harboring the KRASG12C mutation from the JAB-21822 cohort. Longitudinal blood samples (N = 45) were collected at baseline, during partial response or stable disease, and at disease progression. Circulating tumor cells (CTCs) were isolated via a microfluidics platform (CTC100, Cellomics) and categorized into epithelial (E-CTCs), mesenchymal (M-CTCs), and epithelial/mesenchymal mixed (E/M-CTCs) subtypes. At progression, the proportion of E-CTCs showed a decreased trend, while that of E/M-CTCs increased significantly (p = 0.03). In long-term responders, the inflection points of declining M-CTC levels correlated with clinical progression and were consistent with radiographic outcomes. Baseline CTC counts > 1 were associated with shorter progression-free survival (PFS; p = 0.046). E-CTC ≤ 1 correlated with longer PFS (p = 0.025), and M-CTC ≤ 1 with longer overall survival (OS; p = 0.033). E/M-CTC ≤ 1 showed a trend toward improved OS (p = 0.086). In addition, patients with > 1 CTC who received local radiotherapy for progressive lesions after glecirasib targeted therapy had significantly prolonged PFS and OS compared to those who did not (p < 0.05).

Chronic graft-versus-host disease (cGVHD) is the primary contributor to morbidity and mortality following allogeneic stem cell transplantation (ASCT). Belumosudil, a ROCK2 inhibitor, was approved for the cGVHD treatment after at least two prior lines of systemic therapy, based on prospective data. The current study evaluated the real-world efficacy and safety of belumosudil across all major adult and pediatric SCT centers in Israel. This retrospective study included all consecutive patients with cGVHD treated with belumosudil via compassionate use programs at nine centers. Key baseline characteristics, ASCT details, and cGVHD features were collected from patients' electronic medical records. The analyzed outcomes encompassed overall response rate (ORR), glucocorticoid dose reduction, failure-free survival (FFS), and overall survival (OS). Data on the safety and tolerability of this therapy were also assessed. The cohort included 45 heavily pretreated (median of 4 prior systemic therapies) patients at a median age of 46 (range, 4-75) years. Severe cGVHD with multi-organ involvement was documented in 84.4% of patients. The ORR was 55.6% (n=25), with 6.7% achieving complete response and 48.9%-partial response. The median time to the best response was 100days. A significant reduction in the glucocorticoid dosage was observed, with the median dose decreasing from 0.29mg/kg/day at baseline to 0.02mg/kg/day at the last follow-up. The 6-month and estimated 12-month OS rates were 95% and 75%, respectively. The most common adverse event was pulmonary infections (17.8%); only one patient discontinued treatment due to an adverse event. Female sex was associated with a borderline statistically significant improvement in FFS. Results of this study demonstrate that belumosudil is effective and well-tolerated even in a heavily pretreated real-world patient population with severe and refractory cGVHD. The observed response rates, glucocorticoid dose reductions, and encouraging survival outcomes point to belumosudil as a crucial therapeutic option for this challenging condition.

Circulating M-MDSC Expansion During Therapy Associates With Treatment Response in Multiple Myeloma: A Longitudinal Observational Study.

Targeting intratumoral heterogeneity in pancreatic cancer with sequential TIL infusions.

Hailey–Hailey disease (HHD), or benign familial chronic pemphigus, is a rare autosomal-dominant genodermatosis caused by mutations in the ATP2C1 gene, which encodes the calcium/manganese (Ca2+/Mn2+) ATPase hSPCA1 that regulates Ca2+ homeostasis in the Golgi apparatus. Mutations in this gene disrupt desmosome formation and keratinocyte adhesion, leading to epidermal acantholysis and recurrent vesicopustular and erosive lesions in intertriginous areas. HHD follows a chronic relapsing course, with flares triggered by heat, friction, or infections, markedly impairing quality of life. Therapeutic management is challenging, and standardized treatment guidelines are lacking [1]. Emerging evidence suggests a potential role for oral magnesium chloride (MgCl2) in disease control [2]. In this context, we report the case of a 60-year-old man with a 20-year history of recurrent erythematous eruptions on the presternal region and inguinal folds, exacerbated by sweating (Figure 1A). He reported partial and transient responses to topical corticosteroids, antibiotics, and antifungals. He was initially treated as having severe seborrheic dermatitis with systemic antifungal and topical antimicrobial agents, but he developed new fissuring and yellowish serous exudation in the inguinal folds despite reduced erythema. The family history—his son had similar lesions—together with the chronic course and clinical features prompted suspicion of HHD. Punch biopsy showed suprabasal acantholysis with widespread intraepidermal clefting and the characteristic “dilapidated brick wall” pattern. Direct immunofluorescence was negative for IgG, IgA, IgM, and C3, confirming HHD and excluding autoimmune blistering disorders. Because the patient was reluctant to pursue systemic therapy, oral MgCl2 300 mg/day was started. By 4 weeks, the lesions had cleared (Figure 1B), and after 12 months of continuous therapy, he reported only occasional, mild flares controlled with topical steroids. No other systemic treatments were given; serum Mg2+ was not measured, and renal function was normal. To date, four publications with follow-up data report five histologically confirmed HHD patients (three women, two men; mean age 52.6 years) treated with oral MgCl2. In three patients, magnesium chloride hexahydrate (MgCl2·6H2O, 33 g/L solution, 70 mL/day ≈276 mg elemental Mg2+) produced clinical improvement within 1–2 weeks and near-complete remission by 4 weeks; two of these also received topical corticosteroids or clotrimazole–fusidic acid [2, 3]. In two additional cases, adding oral MgCl2 (≈286–300 mg/day) to ongoing naltrexone yielded benefits not achieved with naltrexone alone, including faster response and sustained clearance [4, 5]. In all reported cases, no significant adverse effects were noted aside from the unpleasant taste of the magnesium solution. Numerous topical, systemic, and procedural therapies for HHD have been explored—including corticosteroids, calcineurin inhibitors, antimicrobials, immunosuppressants, retinoids, biologics, Janus kinase (JAK) inhibitors, laser, dermabrasion, botulinum toxin, and phototherapy—but none are curative, and relapses are frequent [1]. HHD arises from ATP2C1 mutations encoding hSPCA1, a Golgi Ca2+/Mn2+-ATPase; its dysfunction lowers Golgi Ca2+ uptake, disrupts junctional protein synthesis and desmosome assembly, and causes keratinocyte detachment and acantholysis. Rather than correcting the genetic defect, MgCl2 may exert beneficial effects by modulating intracellular Ca2+ availability in HHD: in vitro data indicate that MgCl2 reduces cellular Ca2+ efflux without affecting Golgi filling, a finding consistent with inhibition of plasma-membrane Ca2+-ATPases by elevated intracellular Mg2+, thereby increasing intracellular Ca2+ availability to support desmosome formation [2]. Case reports document rapid clinical responses (often within 1–4 weeks), good tolerability aside from the taste, and low cost. MgCl2 appears safe and potentially effective for prolonged use, either as monotherapy or adjunctive therapy, but it is not a proven disease-modifying treatment for HHD, and evidence remains limited to case reports. Caution is advised in patients with renal impairment. Larger studies with defined dosing, therapy duration, and patient selection are needed. MgCl2 may also merit investigation in other acantholytic dermatoses, such as Darier and Grover diseases [4]. The authors have nothing to report. The research conforms to the ethical standards described by the Declaration of Helsinki. Informed consent has been obtained to publish patients' photographs and data. The authors declare no conflicts of interest. The data that support the findings of this study are available upon request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Precision therapy for BRAF V600E-mutated ameloblastoma: Systematic review insights.

Adjuvant therapy with anti-PD-1 monotherapy in melanoma is well established. However, a perioperative approach starting immunotherapy before surgery appears mechanistically more reasonable and emerging research results suggest a clinical benefit. This study aims to provide a comprehensive overview of the current use of perioperative anti-PD-1 monotherapy in Germany. Patients with stageIII melanoma who received perioperative anti-PD-1 monotherapy from April 2019 to March 2025 were included. Data from eight German skin cancer centers were retrospective collected including histological and radiological assessments. We identified 75 melanoma patients with perioperative anti-PD-1 monotherapy. Surgery was conducted in 75% of patients after a median of 11weeks after therapy initiation. Pathological assessment revealed a major pathological response (MPR) in 46.5% of cases, a partial pathological response in 23.2%, and no pathological response in 30.4%. A moderate to strong correlation between radiological and pathological responses was identified. During a median follow up period of 11.6months, melanoma recurrence was observed in 16 patients (21%). The longest recurrence-free survival was seen in the MPR group. Perioperative anti-PD-1 monotherapy has been implemented in routine clinical practice in German skin cancer centers. The observed outcomes are comparable to data reported from prospective studies.

Trastuzumab deruxtecan (T-DXd) has recently reshaped the management of HER2-low metastatic breast cancer. While pivotal trials relied on CT-based RECIST 1.1, [18F]FDG PET/CT provides high diagnostic sensitivity and valuable semi-quantitative metrics, though its role in monitoring antibody-drug conjugates remains insufficiently defined. This study assessed the prognostic value of PET-derived parameters and PERCIST criteria in patients treated with T-DXd. This retrospective study included all HER2-low metastatic breast cancer patients treated with T-DXd between 2022 and 2025 at the Strasbourg Europe Cancer Institute (ICANS) who underwent [18F]FDG PET/CT. Semi-quantitative parameters (SUVmax, SULpeak) and metabolic response according to PERCIST 1.0 were collected. Their association with overall survival (OS), metabolic progression-free survival (mPFS) and time-to-treatment change (TTT) was analyzed using Cox models and Kaplan-Meier curves. Forty-three patients were included. Baseline SULpeak of the most hypermetabolic lesion was an independent prognostic factor for OS, mPFS and TTT (p < 0.05). A ROC-derived cutoff of 6 identified two prognostic groups, with SULpeak < 6 associated with significantly improved outcomes. Early metabolic response was also linked to longer OS and PFS (p< 0.05), with median PFS of 9.2 vs. 4.2 months (HR 2.67; 95% CI 1.30-5.47). Combining baseline SULpeak and metabolic response (complete or partial metabolic response) defined three risk groups with significantly different OS and PFS. [18F]FDG PET/CT provides significant prognostic information in HER2-low metastatic breast cancer treated with T-DXd. Baseline SULpeak and early PERCIST response enable meaningful risk stratification. The proposed prognostic model requires prospective validation before clinical implementation.

Complete urinary tract exenteration (CUTE) is an extremely radical procedure for multifocal urothelial carcinoma (UC) involving the bilateral upper urinary tract and the bladder, inevitably requiring postoperative hemodialysis. However, reports on robot-assisted CUTE are limited, and its perioperative safety has not been sufficiently established. The role of perioperative management in this highly invasive procedure remains unclear. This study aimed to report two patients with multifocal UC who underwent robot-assisted CUTE without preexisting dialysis, with perioperative management including hemodialysis initiation. Two non-dialysis patients with multifocal UC underwent robot-assisted CUTE following neoadjuvant chemotherapy, as postoperative renal failure was inevitable. Patient 1 received gemcitabine plus cisplatin, whereas Patient 2 initially received gemcitabine plus cisplatin, but was subsequently switched to gemcitabine plus carboplatin due to renal dysfunction developing. Both patients achieved a partial response. Given concerns regarding perioperative hemodynamic instability associated with this highly invasive procedure, an arteriovenous shunt was not created preoperatively; instead, jugular catheter-based dialysis access was used, with a planned arteriovenous shunt to be created at a later stage. Surgery was performed using the da Vinci Xi system with two re-docking procedures. The operative times were 461 and 456 min, and estimated blood losses were 90 and 22 ml. Both patients required postoperative blood transfusion. Hemodialysis was initiated on postoperative day 1. No major perioperative complications occurred, and the patients were discharged on postoperative days 21 and 18. Robot-assisted CUTE may be a feasible surgical option for selected non-dialysis patients with multifocal UC. This approach may enable a safe transition to postoperative dialysis and favorable recovery, while allowing for complete surgical resection with acceptable perioperative outcomes. Further studies are necessary to define its clinical role.

This exploratory phase Ib study aimed to evaluate the efficacy and safety of AL2846, a multi-kinase inhibitor, in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) following disease progression on prior VEGFR-targeted therapy. This multi-center, open-label, phase Ib study enrolled patients with RR-DTC treated with prior tyrosine kinase inhibitor (TKI) therapy. Eligible patients received oral 90 mg or 120 mg of AL2846 capsules, once daily. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), and safety. From February 16, 2023 to March 13, 2025, 33 patients (90 mg, n = 21; 120 mg, n = 12) were enrolled in this study. All patients had disease progressed following one or two prior VEGFR-targeted therapy. The median age was 59 years (47, 63), and 17 (51.5%) patients were female. The ORR was 12.12%, with two partial responses observed in each dose group. The DCR was 100% in the 90 mg group and 91.67% in the 120 mg group, respectively. The median PFS in 90 mg was 18.33 months [95% confidence interval (CI), 10.97-not estimable], with a 6-month PFS rate of 94.4% and a 12-month PFS rate of 70.8%. The most common treatment-related adverse events (TRAE) included aspartate aminotransferase/alanine aminotransferase increased, hypertension, proteinuria, hypocalcemia, and hand-foot syndrome. Grade ≥3 TRAEs occurred in 47.62% of patients in the 90 mg group and 41.67% in the 120 mg group. AL2846 showed an acceptable safety profile and a promising antitumor activity in previously TKI-treated patients with RR-DTC, with 90 mg having a more favorable effect.

Enfortumab vedotin is a Nectin-4-directed antibody-drug conjugate approved for metastatic urothelial carcinoma. Cardiac adverse events such as pericardial effusion or tamponade associated with enfortumab vedotin are extremely rare. A 50-year-old man with metastatic UC developed chest pain and dyspnea 3 days after the first EV infusion, followed by rapid progression to cardiac tamponade on Day 9. Emergency pericardiocentesis and thoracoscopic pericardial fenestration drained 2400 mL of pericardial and pleural fluid. Pericardial cytology revealed inflammatory cells without malignancy, while pleural nodules confirmed urothelial carcinoma. Infectious causes were excluded, and an acute EV-related inflammatory reaction was suspected. EV was safely resumed on postoperative Day 20, achieving a sustained partial response for 8 months without recurrence of pericardial effusion. This rare case highlights the potential for acute, enfortumab vedotin-related inflammatory pericardial effusion and emphasizes the importance of early recognition and prompt surgical intervention.

Development and validation of artificial intelligence-assisted volumetric response criteria in pleural mesothelioma (ARTIMES): a retrospective, multicohort, multicentre study.

Metastatic Meningioma with Systemic Involvement: Discussion of Molecular, Genomic, and Radiological Features.

Cholangiocarcinoma (CCA) is a heterogeneous malignancy with a broad morphologic spectrum, from overtly malignant tumours to deceptively bland lesions closely mimicking benign biliary proliferations. This may result in diagnostic difficulty, particularly on biopsies. CCAs harbour a wide spectrum of genetic alterations, including mutations (IDH1/2), amplifications (ERBB2) and fusions (FGFR2), several of which are actionable, making molecular profiling a key component of clinical management. We report a case illustrating this pitfall and highlighting the decisive role of molecular analysis. A 41-year-old man was incidentally found to have a 15-mm hepatic nodule. Magnetic resonance imaging confirmed a solitary lesion in a steatotic liver. Liver function tests were normal, and positron emission tomography showed no abnormal FDG uptake. Because imaging findings were inconclusive, a biopsy was performed. Histologically, the biopsy showed background steatohepatitis with stage F2 fibrosis. The lesion consisted of a well-circumscribed tubular proliferation embedded in abundant collagenous stroma and surrounded by a prominent lymphoid infiltrate. The cells displayed absent to mild cytologic atypia, rare hyperchromatic nuclei and prominent mucin secretion (Figure 1). Immunohistochemistry supported a biliary phenotype (CK7 and CK19 positive) and excluded metastatic carcinoma. p53 staining was wild-type, BAP1 expression was retained, and the Ki-67 proliferation index was low (~10%). Overall, the lesion was considered indeterminate, with concern for very well-differentiated intrahepatic CCA (iCCA). Staging revealed no extrahepatic disease, and an atypical liver resection was performed. Gross examination revealed a well-defined, white nodule measuring 14 mm. Microscopically, the lesion was sharply demarcated and associated with a prominent peripheral lymphoid infiltrate. It was composed of small, regular mucin-producing tubules embedded in fibro-hyaline stroma, without cytologic atypia, mitoses, vascular or perineural invasion (Figure 1). These features closely resembled a bile duct adenoma (BDA), and no unequivocal features of malignancy were identified. Surgical margins were negative, and no adjuvant therapy was initially planned. Given the unusual presentation in a young patient and the diagnostic uncertainty, comprehensive molecular profiling was performed. DNA sequencing revealed no pathogenic alterations. However, RNA fusion analysis identified a novel HIP1R-ALK fusion. The in-frame fusion involved canonical ALK exon 20 and preserved the tyrosine kinase domain while truncating regulatory regions, consistent with constitutive oncogenic activation. Diffuse and strong ALK protein overexpression (3+) was confirmed by immunohistochemistry (Figure 2). Based on these findings, the diagnosis was revised to well-differentiated ALK-rearranged iCCA, a rare molecular subtype. The patient remains alive and disease-free 1 year after surgery. This case illustrates a challenging scenario in liver pathology: the distinction between benign biliary proliferations and well-differentiated iCCA. Entities such as BDA, ductular reaction, von Meyenburg complexes and biliary adenofibroma may closely mimic carcinoma,1 particularly when cytologic atypia, infiltrative growth and vascular or perineural invasion are absent. In addition, cholangiolocarcinoma, a subtype of small duct iCCA, represents an important differential diagnosis, as it is characterized by bland, ductular or cord-like proliferations resembling reactive bile ductules and frequently arises in the setting of chronic liver disease. However, cholangiolocarcinoma typically exhibits an infiltrative growth pattern rather than a sharply demarcated, adenoma-like architecture. Conversely, well-differentiated iCCA may show bland morphology and low proliferative activity, rendering morphology and immunohistochemistry alone insufficient and highlighting the value of molecular analysis. ICCAs sometimes harbour actionable genetic alterations, including FGFR2 fusions and IDH1 mutations. In contrast, ALK rearrangements are exceedingly rare, with only six cases reported to date. These cases span a wide age range (26–76 years), predominantly involve intrahepatic tumours (4/6), and show variable differentiation and fusion partners (EML4, STRN and AMBRA1). Importantly, three patients achieved partial responses to ALK inhibitors, underscoring the therapeutic relevance of detecting such alterations.2-5 In the present case, identification of a novel HIP1R-ALK fusion in a biliary lesion with adenoma-like morphology provides strong evidence of a true neoplastic process driven by an oncogenic event. Together with prior reports of BRAF-mutated BDAs6 and progression to invasive carcinoma, this finding supports the concept that BDAs may represent early forms of iCCA. While routine molecular testing of all BDAs is not justified, our case suggests that molecular analysis should be considered in adenoma-like biliary lesions showing diagnostic uncertainty or occurring in unusual clinical settings. In this context, ALK immunohistochemistry and possibly BRAFV600E immunohistochemistry should be evaluated as readily accessible ancillary tools in routine clinical practice. In conclusion, this case is notable for its deceptively benign morphology and unexpected HIP1R-ALK fusion. It emphasizes the importance of integrating morphology with molecular profiling in diagnostically challenging biliary lesions and expands the molecular spectrum of ALK-rearranged iCCA, with potential therapeutic implications. ACB, MD, RG and JS performed the histopathological analyses. ACB, HR and JS interpreted molecular analyses. FM was responsible for the clinical care of the patient and performed surgery. ACB and JS wrote the paper. None declared. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.

Rituximab is recommended as the first-line treatment for moderate- to high-risk primary membranous nephropathy (PMN). Obinutuzumab, a highly humanized anti-CD20 monoclonal antibody, has been shown to exhibit enhanced efficacy in laboratory studies. This study aimed to investigate the efficacy, side effects, and potential remission predictors of obinutuzumab in PMN treatment. This retrospective cohort study included PMN patients who presented with nephrotic syndrome and who were treated with obinutuzumab (1g on day 1 and day 28 in the majority of patients) between March 2022 and December 2023. Logistic regression, Kaplan-Meier curve analysis, and the log-rank test were used to assess treatment effectiveness and predictors of remission. Safety profiles were also recorded and analyzed. A total of 66 PMN patients, with a mean age of 50 ± 13 years, were enrolled, and 48 (72.7%) were male. The average follow-up duration was 18.1 ± 8.0 months. During the follow-up period, 60 patients (90.9%) achieved clinical remission, including 31 (47.0%) who achieved complete remission. The median time to the first recorded partial response (PR) was 4 (IQR 2 ~ 8) months. The anti-phospholipase A2 receptor antibody (aPLA2Rab) decrease rate during the first month of treatment was 88.3% (IQR 68.0%~95.7%). In total, 47/52 (90.4%) patients in the low aPLA2Rab group (aPLA2Rab < 150 RU/ml) and 13/14 (92.9%) in the high aPLA2Rab group (aPLA2Rab ≥ 150 RU/ml) achieved clinical remission. The remission rate of the low aPLA2Rab group did not significantly differ from that of the high aPLA2Rab group (HR = 1.656, 95% CI 0.895 ~ 3.065; P = 0.108). Decrease in aPLA2Rab at month-1 was associated with complete remission (OR = 1.033, 95% CI 1.003 ~ 1.063; P = 0.033) and had a predictive value for complete remission (AUC = 0.734, 95% CI 0.606 ~ 0.862; P = 0.002), and patients were more likely to achieve complete remission when the decrease rate exceeded 90.8%, with a sensitivity of 65.5% and a specificity of 75.8%. No serious adverse events were observed; the most common were mild infusion-related reactions (48.5%). Obinutuzumab rapidly and persistently reduces serum aPLA2Rab levels in PMN patients, leading to a favorable clinical remission rate. Decrease in aPLA2Rab at month-1 after treatment can predict clinical remission of PMN.

Low-grade serous carcinoma of the ovary (LGSOC) is relatively resistant to chemotherapy. Given its biological parallels to hormone receptor-positive breast cancer, including responsiveness to anti-estrogen therapies, we conducted a pilot phase II study to assess clinical benefit of neoadjuvant fulvestrant and abemaciclib in women with advanced, unresectable LGSOC (NCT03531645). Imaging assessments were performed every 8 weeks until resectable. The primary endpoint was clinical benefit rate (CBR). Exploratory objectives included evaluation of safety profile, accessing biomarkers related to clinical benefit, and description of tumor phenotypic changes. Fifteen patients were enrolled and evaluable for efficacy. CBR was 100%, with 1/15 patients (7%) achieving complete response (CR), 8/15 patients (53%) achieving partial response (PR), and 6/15 (40%) exhibiting stable disease (SD). Interval cytoreductive surgery (ICS) was performed in 9 patients (60%), with 7 (78%) achieving complete or optimal resection. Fourteen tumor samples underwent transcriptomic and proteomic profiling. Tumors from long-term survivors showed significantly higher baseline expression of cell-cycle-related programs and estrogen signaling-related genes, both suppressed upon treatment. Neoadjuvant fulvestrant and abemaciclib was well tolerated, achieved high response rates, and enabled optimal surgical resection in most patients. Tumor proliferative activity and estrogen signaling dependency may predict therapy response.