Experienced Relapse Research Articles

Orbital and eyelid inflammatory myofibroblastic tumors: a clinicopathological analysis of 13 cases

Objective: To investigate the clinicopathological features of orbital and eyelid inflammatory myofibroblastic tumors (IMTs). Methods: A retrospective analysis was conducted among 13 patients with IMTs treated at Tianjin Eye Hospital between January 2000 and October 2023. The clinicopathological data, immunohistochemical staining characteristics, molecular phenotypes, and follow-up outcomes were collected and analyzed. Results: The study cohort comprised 7 males and 6 females. The median age was 44 (22, 68) years. The tumor was observed in the left eye in 6 cases and the right eye in 7 cases. The age at onset ranged from 5 to 76 years, with a disease course of 1 month to 2 years before tumor excision. The tumor was located within the orbit in 10 cases (including one case of a systemic multifocal lesion) and in the eyelid in 3 cases. Pathological characteristics of the tumors were mainly proliferation of spindle or ovoid fibroblasts and myofibroblasts, with varying degrees of mucoid degeneration or collagenization of the mesenchyme, and varying amounts of lymphocytes and plasma cells infiltrated in the background. Immunohistochemical analysis revealed that Vimentin and α-SMA were positive in all cases (13/13, 13/13), ALK1 was positive in 5 cases (5/11), CK was positive in 1 case (1/1), and Desmin was positive in 1 case (1/6). ALK fluorescence in situ hybridization was positive in 2 out of 3 cases, and EBER in situ hybridization was negative in 6 cases. Nine patients were available for the follow-up of 7 to 139 months. Seven patients remained tumor-free, 2 experienced relapses, and no deaths or metastases were reported. Conclusions: Orbital and eyelid IMTs predominantly occurred in adults, with localized lesions in most cases and favorable prognoses. The disease was histopathologically characterized by proliferation of fibroblasts and myofibroblasts. The accurate diagnosis depended on a comprehensive assessment of the morphological features of the tumor histopathology as well as immunohistochemical markers such as ALK and α-SMA, and molecular detection.

Tumor-Associated Edema in Children with Kaposi Sarcoma: 14 Years’ Experience at Kamuzu Central Hospital, Lilongwe, Malawi

Background/Objectives: Kaposi sarcoma (KS) is a common lymphatic endothelial cancer among children with and without HIV in central and eastern Africa. Despite its clinical heterogeneity, its various clinical phenotypes are often grouped together in staging and treatment algorithms. Patients with KS tumor-associated edema, referring to hard, non-pitting lesions which often lead to chronic disability, represent a unique, understudied subgroup of children with KS. To continue our work defining the distinct phenotypes of pediatric KS, this study aimed to assess the clinical progression and outcomes of KS edema in children. Methods: A retrospective cohort study was conducted at Kamuzu Central Hospital in Lilongwe, Malawi, focusing on children diagnosed with KS edema between 2010 and 2023. Results: We identified 52 children with KS edema, representing 27% of all patients with KS. Initial chemotherapy resulted in a clinical response in 92% of patients, but 46% experienced relapse or disease progression with a median time to first relapse of 12 months. Multiple progressions were common, with 31% of patients experiencing two or more events. Event-free survival at two years was 32%, dropping to 24% at five years, while overall survival was 73% at two years and 57% at five years. Relapse was more common among patients with KS edema versus those without it (relative risk = 2.1; 95%CI, 1.4–3.2; p < 0.001). Eight patients (15%) relapsed with visceral disease, five of whom originally presented with KS edema alone. Conclusions: Patients with KS edema have a unique, relapsing-remitting pattern of disease with a high risk of relapse relative to other forms of KS with subsequent long-term mortality, even after initial positive treatment responses. Late relapse and mortality with visceral disease are possible even among children presenting initially with KS edema alone. Children with KS edema require long-term follow-up, and novel treatment approaches tailored towards preventing frequent relapse are needed.

Primary orbital mesenchymal chondrosarcoma: clinicopathological characteristics and prognostic prediction

PurposeThis study aimed to analyze the clinicopathological characteristics of a rare malignant tumour, primary orbital mesenchymal chondrosarcoma (MCS), and identify the risk factors influencing its prognosis. MethodsA total of 15 patients with histologically confirmed primary orbital MCS were enrolled between April 2013 and October 2022. The relationships between clinicopathological features and outcomes, including recurrence and survival were analyzed. ResultsDuring the follow-up period, 9 patients (60%) experienced disease relapse, and 7 patients (46.7%) succumbed to the disease. Immunohistochemical analysis showed positive rates for SMA, CD-99, S-100, vimentin, and Bcl-2 at 60%, 60%, 53.3%, 100%, and 93.3%, respectively. The Ki67 index was positively associated with the recurrence and mortality rates. ConclusionOur study suggested that the Ki67 index could be a vital prognostic factor for MCS. Further follow-up studies are required to assess the efficacy of chemotherapy and radiotherapy in improving patient outcomes.

Longitudinal analysis of the gut microbiota during anti-PD-1 therapy reveals stable microbial features of response in melanoma patients

Immune checkpoint inhibitors (ICIs) improve outcomes in advanced melanoma, but many patients are refractory or experience relapse. The gut microbiota modulates antitumor responses. However, inconsistent baseline predictors point to heterogeneity in responses and inadequacy of cross-sectional data. We followed patients with unresectable melanoma from baseline and during anti-PD-1 therapy, collecting fecal and blood samples that were surveyed for changes in the gut microbiota and immune markers. Varying patient responses were linked to different gut microbiota dynamics during ICI treatment. We select complete responders by their stable microbiota functions and validate them using multiple external cohorts and experimentally. We identify major histocompatibility complex class I (MHC class I)-restricted peptides derived from flagellin-related genes of Lachnospiraceae (FLach) as structural homologs of tumor-associated antigens, detect FLach-reactive CD8+ Tcells in complete responders before ICI therapy, and demonstrate that FLach peptides improve antitumor immunity. These findings highlight the prognostic value of microbial functions and therapeutic potential of tumor-mimicking microbial peptides.

Research progresses of imaging studies on preoperative prediction of microvascular invasion of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the predominant form of primary liver cancer, accounting for approximately 90% of liver cancer cases. It currently ranks as the fifth most prevalent cancer worldwide and represents the third leading cause of cancer-related mortality. As a malignant disease with surgical resection and ablative therapy being the sole curative options available, it is disheartening that most HCC patients who undergo liver resection experience relapse within five years. Microvascular invasion (MVI), defined as the presence of micrometastatic HCC emboli within liver vessels, serves as an important histopathological feature and indicative factor for both disease-free survival and overall survival in HCC patients. Therefore, achieving accurate preoperative noninvasive prediction of MVI holds vital significance in selecting appropriate clinical treatments and improving patient prognosis. Currently, there are no universally recognized criteria for preoperative diagnosis of MVI in clinical practice. Consequently, extensive research efforts have been directed towards preoperative imaging prediction of MVI to address this problem and the relative research progresses were reviewed in this article to summarize its current limitations and future research prospects.

Immunohistochemical Expression of Cyclin D1 in Invasive Breast Carcinoma

Objective: This study was conducted to determine the immunohistochemical expression of cyclin D1 in invasive breast carcinoma and its association with already established prognostic parameters like estrogen receptor (ER), progesterone receptor (PR), HER2/Neu, and Ki67 status. Study Design & Setting: Cross sectional Observational. Department of Pathology, Armed Forces Institute of Pathology, Rawalpindi Methodology: The study included 350 cases of invasive breast cancer diagnosed between January 2023 and December 2023. Data collected included patient age, histological subtype, molecular subtypes, tumor size, and the presence of estrogen (ER) and progesterone (PR) receptors, as well as HER2/Neu and Ki67 status. Patients who had undergone chemotherapy, received radiation to the breasts, or experienced relapse were excluded from the study. Immunohistochemistry was conducted using a Cyclin D1 antibody to assess Cyclin D1 expression in tissue samples. The expression levels were categorized as negative, weak, moderate, strong staining in tumor cells. Data analysis was performed using SPSS 29.0, and statistical comparisons were made between Cyclin D1 staining and ER, PR, HER2/Neu, and Ki67 status. Results: Cyclin D1 moderate to strong staining was seen in 173/352 (49.14%) cases of invasive BC. Cyclin D1 expression was slightly statistically significantly associated with ER (x2 = 7.78, P value <0.051) and Ki67 positivity (÷2 = 7.27, P value <0.064). Conclusion: Cyclin D1 has the potential to serve as a prognostic marker. Incorporating it into the routine IHC workup for breast cancer could enhance patient management, especially with the development of new targeted therapies that inhibit the Cyclin D-CDK4/6 axis.

Evaluation of prognostic factors for late recurrence in clear cell renal carcinoma: an institutional study.

Following nephrectomy with curative intent, a subset of patients diagnosed with non-metastatic renal cell carcinoma (nmRCC) will present late recurrences, with metastatic relapses after 5 years from the surgical intervention. The aim of this study is to evaluate the prevalence of late recurrences in Romanian patients with nmRCC that have undergone surgery and to assess the clinicopathological characteristics prognostic for late-relapse RCC. This is a single-center, retrospective and observational study that analyzed patients with nmRCC with clear cell histology who underwent surgical resection of the primary tumor with curative intent. The patients included in the study were treated and further surveilled according to a personalized follow-up plan between January 2011 and December 2012 in The Oncology Institute "Prof. Dr. Ion Chiricuţă", Cluj-Napoca, Romania. Study endpoints included median disease-free survival (DFS), median overall survival (OS), as well as evaluation of possible prognostic factors indicative of late relapse. In the study cohort (n=51), the median DFS was 46 months and median OS was 130 months. DFS was significantly correlated with the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score (p=0.04, HR=2.48; 95% CI [1.02, 6.01]), neutrophil to lymphocyte ratio (NLR) (a higher NLR value was associated with a poorer DFS, p=0.035), tumor size (T4 tumors vs. T1 p<0.05, HR=9,81; 95% CI [2.65, 36.27]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=4,16; 95% CI = [1.13,15.22]). Fifty one percent of the patients included experienced disease relapse. From this subgroup, a significant percentage of 42% patients presented disease recurrence after 60 months from nephrectomy. OS was correlated to IMDC score (p=0.049, HR=2.36; 95% CI [1, 5.58]) and Fuhrman nuclear grade (Fuhrman grade 1 vs. Fuhrman grade 3 p<0.05, HR=3,97; 95% CI [1.08, 14.54]). The results of this study support the previously presented biological behavior of RCC, demonstrating that late recurrences in RCC are not uncommon occurrences and patients with localized RCC should be followed up for a longer interval after the surgery for the primary tumor. In addition, the study strengthens the data supporting certain biomarkers as valuable prognostic factors determining survival outcomes of patients with RCC.

Real-world healthcare resource utilization, costs, and predictors of relapse among US patients with incident schizophrenia or schizoaffective disorder

Schizophrenia and schizoaffective disorder present burdens to patients and health systems through elevated healthcare resource utilization (HCRU) and costs. However, there is a paucity of evidence describing these burdens across payor types. To identify unmet needs, this study characterized patients with schizophrenia or schizoaffective disorder by payor type. We identified patients aged 12–94 years with newly diagnosed schizophrenia or schizoaffective disorder (index date) between 01/01/2014 and 08/31/2020 with continuous enrollment for 12 months before and after index date from the Healthcare Integrated Research Database. After stratifying by post-index relapse frequency (0, 1, or ≥2) and payor type (commercial, Medicare Advantage/Supplemental (Medigap)/Part D, or managed Medicaid), we examined patient characteristics, treatment patterns, HCRU, costs, and relapse patterns and predictors. During follow-up, 25% of commercial patients, 29% of Medicare patients, and 37% of Medicaid patients experienced relapse. Atypical antipsychotic discontinuation was most common among Medicaid patients, with 65% of these patients discontinuing during follow-up. Compared to commercial patients, Medicare and Medicaid patients had approximately half as many psychotherapy visits during follow-up (12 vs. 5 vs. 7 visits, respectively). Relative to baseline, average unadjusted all-cause costs during follow-up increased by 105% for commercial patients, 66% for Medicare patients, and 77% for Medicaid patients. Patients with schizophrenia or schizoaffective disorder had high HCRU and costs but consistently low psychotherapy utilization, and they often discontinued pharmacologic therapy and experienced relapse. These findings illustrate the high burden and unmet need for managing these conditions and opportunities to improve care for underserved patients.

Amikacin Liposomal Inhalation Suspension for Non-Tuberculous Mycobacteria Lung Infection: A Greek Observational Study.

Background and Objectives: Intravenous amikacin, recommended for severe or recurrent M. avium complex (MAC) infections and as initial treatment for M. abscessus lung disease, is often limited by serious adverse effects such as renal and auditory toxicities. Inhaled Amikacin Liposome Inhalation Suspension (ALIS) enhances pulmonary drug deposition while minimizing systemic adverse effects, and it has recently been introduced as an add-on therapy for refractory MAC infections or when other standard treatments are inadequate. This study aims to retrospectively describe the outcomes of Greek patients with difficult-to-treat non-tuberculous mycobacterial (NTM) lung disease following the addition of ALIS to guideline-based therapy. Materials and Methods: Seventeen consecutive patients (median age: 66 years) treated with ALIS as an add-on therapy to a standard regimen at "Sotiria" General Hospital of Chest Diseases (Athens, Greece) from 2020 to 2023 were enrolled in this study. These patients had recurrent or refractory NTM lung disease and/or limited treatment options due to prior treatment-related adverse effects. Clinical, radiological, and microbiological data on treatment response and overall outcomes after ALIS initiation were recorded for each patient. Results: By the end of 2023, 14 out of 17 patients had either successfully completed or were continuing their ALIS therapy. At 6 months, 85.7% (12/14) showed clinical, microbiological, and radiological improvement. However, 25% (3/12) of treated patients, primarily those with monomicrobial or combined M. abscessus lung disease, experienced disease relapse after therapy completion. The most frequent adverse effects related to ALIS were mild and localized to the respiratory tract, with only one patient discontinuing therapy due to hypersensitivity pneumonitis. Conclusions: Adding ALIS to standard regimens was effective and safe in a small group of Greek patients with refractory or recurrent NTM lung disease, particularly those who had discontinued intravenous aminoglycosides due to significant adverse effects, with notable responses observed in MAC lung disease. Further research is needed to validate these findings in clinical practice and to investigate ALIS's role in NTM lung disease caused by other species.

INTEREST OF REGULAR ASSAYS OF AQUEOUS HUMOR INTERLEUKIN-10 LEVELS IN MONITORING OF VITREORETINAL LYMPHOMA.

To investigate the variation of interleukin-10 (IL-10) levels in the aqueous humor (AH) of patients with vitreoretinal lymphoma (VRL) throughout therapy and follow-up and analyze the relation of these variations with VRL clinical course and relapse. This study retrospectively included consecutive patients diagnosed with VRL in a single center. AH IL-10 samples and patient clinical course were evaluated. The response to treatment was evaluated according to the criteria set by the International Primary Central Nervous System Lymphoma Collaborative Group. A total of 59 eyes of 34 patients were included. Interleukin-10 levels decreased significantly at first AH sample after therapy induction (median [IQR] 3.0 [2.8-3.6] months) among patients in complete clinical remission (P < 0.001). Among patients in complete clinical remission with residual detectable IL-10 in AH after therapy induction (85.3% systemic chemotherapy, 11.8% intravitreal methotrexate, 2.9% palliative care), 87.5% experienced ocular relapse within 5 years. The detection of IL-10 in AH at the first visit after induction for complete clinical remission obtained a sensitivity of 77.8% (95% CI 0.45-0.96) and a specificity of 96.4% (95% CI 0.82-0.99) to predict ocular relapse. For relapsing eyes (N = 26), IL-10 significantly increased between the last IL-10 measurement and the time of the first ocular relapse (P < 0.001). In 76.0% of cases, an increase in IL-10 was detected earlier than clinical relapse with a mean (SD) of 4.0 (2.4) months. The present study suggested the usefulness of IL-10 in the prognosis of VRL. This study showed a relation between IL-10 in AH and tumoral activity, and for the first time with disease relapse.

Clinical course and radiographic resolution of pneumonia in dogs treated with a shorter versus longer course of antimicrobials: a randomized, double-masked, placebo-controlled study.

To describe clinical and radiographic outcomes in dogs with uncomplicated pneumonia receiving a shorter (2-week) versus longer (4-week) duration of antimicrobial therapy. 30 client-owned dogs with radiographic evidence of pneumonia. Dogs were randomly assigned to either a 2-week course of antimicrobials followed by a 2-week course of placebo medication (2-week group) or a 4-week course of antimicrobials (4-week group). All study investigators and owners were masked to the treatment group. Dogs were reevaluated at 12 ± 2 days and again at 28 ± 2 days for a physical examination and thoracic radiography. Standard documentation at visits included owner-reported clinical signs, nurse-acquired history, the clinician's physical examination, the number of affected lung lobe segments, and the global radiographic severity scores assigned. Outcomes investigated included the persistence of clinical and radiographic signs of pneumonia. 28 dogs (93.3%) experienced complete resolution of clinical signs by the first visit, and no dogs in either group experienced relapse of clinical signs during the study period. Eighteen of 30 dogs (60%) and 25 of 30 dogs (83%) experienced complete resolution of radiographic lesions at the first and second study visits, respectively. The remaining 5 dogs (17%) had either stable (4 dogs) or continued (1 dog) improvement in radiographic lesions. Resolution of clinical and radiographic signs followed similar courses in dogs with uncomplicated pneumonia receiving a 2-week course of antimicrobials compared to a 4-week course. Clinical signs may be more useful for guiding discontinuation of antimicrobial therapy for pneumonia than radiographic signs.

TNFRSF10D expression as a potential biomarker for cisplatin-induced damage and ovarian tumor relapse prediction

Among gynecological malignancies, ovarian cancer (OC) presents the most challenging diagnostic scenario. Despite exhaustive efforts, up to 90 % of patients treated with taxane/platinum-based chemotherapy experience relapse, leading to poor survival rates. Identifying new molecular markers that can characterize disease aggressiveness, chemoresistance, recurrence risk, and metastasis is crucial. This study aimed to assess the susceptibility of three ovarian tumor cell lines (TOV-21G, SKOV-3, and OV-90) to cisplatin and paclitaxel, and to investigate the influence of these treatments on the mRNA expression of TANK, RIPK1, NFKB1, TNFRSF10D, and TRAF2. Among the cell lines, SKOV-3 ovarian adenocarcinoma cells demonstrated the highest resistance to cisplatin treatment (0.125 mg/mL), followed by TOV-21G (0.076 mg/mL) and OV-90 cells (0.028 mg/mL). Regarding paclitaxel treatment, the SKOV-3 cell line exhibited the highest resistance (1.4 µg/mL), followed by OV-90 (1.3 µg/mL) and TOV-21G cells (0.9 µg/mL). Gene expression analysis after paclitaxel treatment remained unchanged; however, after cisplatin treatment, TNFRSF10D was observed to be upregulated nearly 100-fold in SKOV-3 compared to all other cell lines studied. SKOV-3 is described as cisplatin and tumor necrosis factor-resistant. Despite the defective signaling of the TNFRSF10D receptor for apoptosis, it can activate the NFKB transcription factor through non-canonical TRAIL signaling, contributing to a pro-inflammatory immune response. In light of this, damage associated with cisplatin increases TNFRSF10D expression and may promote cell survival through non-canonical NFKB pathway activation. This suggests that resistance to TRAIL-induced apoptosis in these cells could serve as a promising chemoresistance biomarker in OC.

Robotic Recto-Sigmoid Resection with Total Intracorporeal Colorectal Anastomosis (TICA) in Recurrent Ovarian Cancer

BackgroundAbout 70% of women affected by ovarian cancer experience relapse within 2 years of diagnosis. Traditionally, the standard treatment for recurrent ovarian cancer (ROC) has been represented by systemic chemotherapy.1 Recently, several retrospective studies have suggested that secondary cytoreductive surgery could provide better clinical outcomes than chemotherapy alone, in the case of complete tumor cytoreduction.2,3 About 50% of patients with ROC have a pelvic component of the disease and 22% of patients present isolated pelvic recurrence, often involving the rectum.4,5 Minimally invasive secondary cytoreductive surgery is a feasible option and is associated with favorable perioperative outcomes.6–8 It is crucial to fully explore the peritoneal cavity before starting cytoreductive procedures in order to confirm the absence of carcinomatosis.9 The robotic system facilitates the identification of anatomical structures and makes it easier to perform complex surgical steps in narrow spaces. It also allows the integrated use of surgical tools such as intraoperative ultrasound and indocyanine green application.MethodsIn this video, we present the case of a 64-year-old woman who experienced a rectal recurrence of ovarian cancer after a platinum-free interval of 12 months. We describe, in a step-by-step manner, the surgical procedure of a robotic rectosigmoid resection with totally intracorporeal colorectal anastomosis (TICA).10–12ResultsRobotic secondary cytoreduction with complete gross resection was achieved. The patient did not report any intraoperative or postoperative complications. Final histology confirmed ROC.ConclusionTotally robotic rectosigmoid resection is a feasible option in isolated bowel recurrences. Thanks to continuous technical evolution, robot-assisted surgery has the potential to have a central role in the fight against solid tumors. Integration of multiple pre- and intraoperative technologies allows personalized surgery to be performed for each different patient.13,14

Long-term Clinical Outcomes of Patients With Negative Pathology (pN0) at Primary Retroperitoneal Lymph Node Dissection

BackgroundPatients who undergo primary retroperitoneal lymph node dissection (pRPLND) for early-stage testicular cancer and have no cancer (pN0) found in the retroperitoneum are believed to have an excellent prognosis. However, some experience relapse, potentially due to limitations of current staging methods. We aim to describe long-term outcomes and relapse patterns among a contemporary cohort of patients found to be pN0 at pRPLND to identify opportunities for improved diagnostic approaches and optimal patient selection. MethodsWe reviewed our prospectively maintained database for patients who underwent pRPLND for nonseminomatous germ cell tumors at our tertiary cancer center during the period from January 1, 2000, through September 30, 2023 (n = 628). We excluded 282 patients with node-positive pathology for a final analytic cohort of 346 patients. Our primary outcome was recurrence-free survival (RFS). Secondary outcomes included timing and location of recurrence. ResultsOf 346 included patients with pN0 pathology, 23 experienced relapse with a 2-year RFS rate of 93% (95% confidence interval: 90, 96). Most recurrences (70%) occurred in the lungs and within 6 months of pRPLND. Serum tumor markers were positive in 43% of patients at the time of relapse. All patients who relapsed were treated with salvage chemotherapy; 6 patients required additional surgical procedures. There was no testis cancer–related deaths. ConclusionsTwo-year RFS for patients with pN0 pRPLND pathology is excellent. All recurrences were outside of the retroperitoneum, suggesting subclinical distant metastases at time of surgery and the benefits of a bilateral template dissection. Improved diagnostics may help better identify patients with disease within or outside of the retroperitoneum prior to pRPLND, helping guide treatment decisions.

Tofacitinib for the treatment of immune-related adverse events in cancer immunotherapy: a multi-center observational study

BackgroundTreatment strategy against immune-related adverse events (irAEs) induced by immune checkpoint inhibitors (ICIs) frequently requires other immunosuppressive agents. Tofacitinib is a rapidly acting JAK-STAT inhibitor with proven efficacy in multiple autoimmune diseases. We aimed to evaluate the efficacy and safety of tofacitinib in the management of irAEs in cancer patients.MethodsCancer patients who received ICIs and were treated with tofacitinib for the management of irAEs at 6 institutions were retrospectively included in this study. Demographic and clinical characteristics were obtained from electronic medical records. Longitudinal assessment of cardiac troponin T (cTnT) with clinical assessment was utilized to evaluate the benefit of tofacitinib treatment in patients with ICI myocarditis. Overall survival (OS) was also assessed.ResultsFifty-three patients were included in this study. The median time from irAE onset to tofacitinib therapy was 17 (range, 2–186) days and the median duration of tofacitinib treatment was 52.5 (range, 3–277) days. Enrolled patients were subdivided into 3 groups based on clinical severity and steroid responsiveness including 11 life-threatening cases, 30 steroid-resistant cases, and 12 cases with steroid taper failure. Clinical remission rate in each group was 54.5%, 96.7%, and 100%, respectively (P < 0.01). Tofacitinib was well-tolerated with 4 patients (7.5%) developing infectious events. From the ICI initiation, the overall median OS was 16.1 (95% CI 7.8–26.9) months.ConclusionTofacitinib showed promising clinical efficacy in patients experiencing irAEs, particularly in patients who failed to respond to steroids or experienced relapse during steroid tapering. Moreover, and most importantly, tofacitinib exhibited a favorable safety profile in cancer patients developing irAEs in terms of both toxicity and anti-tumor activity. Future prospective studies are warranted.

Assessment of the Circulating PD-1 and PD-L1 Levels and P53 Expression as a Predictor of Relapse in Pediatric Patients with Wilms Tumor and Hypernephroma.

Background/Objectives: Wilms tumor (WT) is the most common form of pediatric renal tumor, accounting for over 90% of cases followed by hypernephroma. Some pediatric patients with WT (10%) experience relapse or metastasis and have poor survival rates. PD-L1 assists cancer cells in escaping damage from the immune system. P53 mutations are found in relapsed WT tumor samples. We hypothesized that testing circulating PD-1 and PD-L1 and P53 expression levels could offer a simple method to predict patient relapse and explore novel treatments for pediatric WTs and hypernephroma. Methods: Flow cytometric detection of cPD-1, cPD-L1, and P53 expression in relapsed and in-remission WT and hypernephroma before and after one year of chemotherapy was performed. Results: Our data shows increased levels of cPD-L1 in relapsed pediatric patients with WT or hypernephroma before and after chemotherapy. There were also slight and significant increases in cPD-1 levels in relapsed groups before chemotherapy. Additionally, we observed significant decreases in P53 expression after one year of chemotherapy in relapsed pediatric patients. Conclusions: Our study found that circulating PD-L1 can be used as a predictor marker for WT and hypernephroma relapse. In conclusion, these circulating markers can assist in monitoring relapse in WT and hypernephroma patients without the need for several biopsies.

Glutathione overproduction mediates lymphoma initiating cells survival and has a sex-dependent effect on lymphomagenesis

Lymphoid tumor patients often exhibit resistance to standard therapies or experience relapse post-remission. Relapse is driven by Tumor Initiating Cells (TICs), a subset of tumor cells capable of regrowing the tumor and highly resistant to therapy. Growing cells in 3D gels is a method to discern tumorigenic cells because it strongly correlates with tumorigenicity. The finding that TICs, rather than differentiated tumor cells, grow in 3D gels offers a unique opportunity to unveil TIC-specific signaling pathways and therapeutic targets common to various cancer types. Here, we show that culturing lymphoid cells in 3D gels triggers reactive oxygen species (ROS) production, leading to non-tumor lymphoid cell death while enabling the survival and proliferation of a subset of lymphoma/leukemia cells, TICs or TIC-like cells. Treatment with the antioxidant N-acetylcysteine inhibits this lethality and promotes the growth of primary non-tumor lymphoid cells in 3D gels. A subset of lymphoma cells, characterized by an increased abundance of the antioxidant glutathione, escape ROS-induced lethality, a response not seen in non-tumor cells. Reducing glutathione production in lymphoma cells, either through pharmacological inhibition of glutamate cysteine ligase (GCL), the enzyme catalyzing the rate-limiting step in glutathione biosynthesis, or via knockdown of GCLC, the GCL catalytic subunit, sharply decreased cell growth in 3D gels and xenografts. Tumor cells from B-cell lymphoma/leukemia patients and λ-MYC mice, a B-cell lymphoma mouse model, overproduce glutathione. Importantly, pharmacological GCL inhibition hindered lymphoma growth in female λ-MYC mice, suggesting that this treatment holds promise as a therapeutic strategy for female lymphoma/leukemia patients.

Polyamine Anabolism Promotes Chemotherapy-Induced Breast Cancer Stem Cell Enrichment.

Breast cancer patients may initially benefit from cytotoxic chemotherapy but experience treatment resistance and relapse. Chemoresistant breast cancer stem cells (BCSCs) play a pivotal role in cancer recurrence and metastasis, however, identification and eradication of BCSC population in patients are challenging. Here, an mRNA-based BCSC signature is developed using machine learning strategy to evaluate cancer stemness in primary breast cancer patient samples. Using the BCSC signature, a critical role of polyamine anabolism in the regulation of chemotherapy-induced BCSC enrichment, is elucidated. Mechanistically, two key polyamine anabolic enzymes, ODC1 and SRM, are directly activated by transcription factor HIF-1 in response to chemotherapy. Genetic inhibition of HIF-1-controlled polyamine anabolism blocks chemotherapy-induced BCSC enrichment in vitro and in xenograft mice. A novel specific HIF-1 inhibitor britannin is identified through a natural compound library screening, and demonstrate that coadministration of britannin efficiently inhibits chemotherapy-induced HIF-1 transcriptional activity, ODC1 and SRM expression, polyamine levels, and BCSC enrichment in vitro and in xenograft and autochthonous mouse models. The findings demonstrate the key role of polyamine anabolism in BCSC regulation and provide a new strategy for breast cancer treatment.

Presurgical Mapping With Ultra-high Frequency Ultrasound of Hidradenitis Suppurativa Lesions Treated With Wide Local Excision and Secondary Intention Healing.

Hidradenitis suppurativa (HS) is a challenging chronic inflammatory condition often requiring surgical intervention, such as wide local excision. Preoperative mapping with ultra-high frequency ultrasound (UHFUS) enables detailed assessment of lesion extension, particularly identifying tunnels and fistulas, facilitating surgical planning. This study aimed to analyze recurrence rates of HS lesions previously mapped with UHFUS and treated with wide excision and secondary intention healing. A retrospective single-center study enrolled 40 patients with HS undergoing wide excision surgery after UHFUS mapping. Patients were assessed weekly until complete healing and then every 3 months, evaluating clinical and sonographic signs of relapse and pain using the visual analogue scale. Results showed a population predominantly composed of women (65%) with a mean age of 39 years and a medium HS-Hurley score of 2.5. Over a 22-month follow-up, only 10% experienced clinical relapse, achieving an 90% total remission rate. Pain scores decreased significantly from Week 0 to Week 4. The study highlights the clinical challenge of HS management, particularly regarding surgical planning and lesion margin definition. The remission rate observed in this study suggests the effectiveness of UHFUS-guided surgical approaches. Future studies should extend observation periods to further validate these findings.

Long-term efficacy and safety of tofacitinib in patients with ulcerative colitis: 3-year results from a real-world study.

The efficacy and safety of tofacitinib for the treatment of refractory ulcerative colitis (UC) has been demonstrated in clinical trials. Although, a series of reports with real-world evidence of its short-term efficacy and safety profiles have already been published, reports of long-term real-world data have been limited. We aimed to show our 3-year evidence on the clinical use of tofacitinib for the treatment of UC, focusing on its efficacy and safety profiles. A retrospective observational study was conducted on patients who started tofacitinib for active refractory UC at our hospital. The primary outcome was the retention rate until 156 weeks after initiating tofacitinib. The secondary outcomes were short-term efficacy at 4, 8, and 12 weeks; long-term efficacy at 52, 104, and 156 weeks; prognostic factors related to the cumulative retention rate; loss of response; and safety profile, including adverse events. Forty-six patients who were able to be monitored for up to 156 weeks after tofacitinib initiation, were enrolled in this study. Continuation of tofacitinib was possible until 156 weeks in 54.3%, with > 50% response rates and > 40% remission rates. Among patients in whom response or remission was achieved and tofacitinib was deescalated after 8 weeks of induction treatment, 54.3% experienced relapse but were successfully rescued by and retained on reinduction treatment, except for 1 patient. No serious AEs were observed in the study. Tofacitinib is effective and safe as long-term treatment in a refractory cohort of UC patients in real-world clinical practice.