Recurrent Lesions Research Articles

Efficacy of low-dose rituximab versus immunosuppressants in refractory orbital inflammatory pseudotumors with intracranial extension

ObjectiveThe aim of this study was to compare the efficacy of low-dose rituximab (RTX) and immunosuppressants in treating orbital inflammatory pseudotumor (OIP) with intracranial extension, a refractory and high-relapse disease.MethodsPatients who had been diagnosed with refractory OIP with intracranial extension and who were refractory to systemic corticosteroids were retrospectively recruited at the Neuro-Ophthalmology Department at the Chinese People’s Liberation Army General Hospital between December 2018 and September 2022. After methylprednisolone pulse therapy, we added 2 mg of tacrolimus per day, 1500 mg of mycophenolate mofetil per day, or 200 mg of rituximab at days 1 and 15, and then monitored those with CD19+ B cells of under 1% as adjuvant therapy.ResultsEleven patients (six males and five females) were included, with a mean age of 45.5 ± 11.8 years (age range: 21–64 years). The average follow-up period was 3.8 years (range: 2–5). Eight patients (72.7%) had different levels of decreased vision at onset of the illness and four patients (36.4%) had severely impaired vision (three with no light perception, one with some light perception). Four patients (36.4%) showed clinical course worsening or lack of remission when treated with corticosteroids. Seven patients (63.6%) had a typical relapsing course, and the annual recurrence rate was higher than 7.36 ± 3.73 times. Of these seven, four (57.1%, 4/7) were able to undergo successful management with immunosuppressants. Three (42.9%, 3/7) failed with immunosuppressants but succeeded in controlling relapse with RTX.ConclusionOIP with intracranial extension is uncommon. More than half of patients with OIP with intracranial extension may be satisfactorily treated with corticosteroids combined with immunosuppressants. However, for patients who still experience recurrence or slow reduction of lesions after applying this combined therapy, RTX may be a better option.

Imaging characteristics and treatment of recurrent germinoma.

An MRI protocol for germinoma surveillance after complete remission has not been established. Moreover, the standard treatment for recurrent or refractory germinoma has not been determined. In this study, the authors explored the imaging characteristics of recurrent germinoma and discuss their institution's experience with multidisciplinary treatment of this malignancy. The medical records of 16 patients (14 male, 2 female) with recurrent germinoma and 62 patients (52 male, 10 female) without recurrence who were treated at the authors' institution between 1989 and 2023 were retrospectively examined. Data including diagnostic imaging, tumor markers, treatment at diagnosis and recurrence, and overall survival were collected from patients' medical records and statistically analyzed. No patients with recurrence received craniospinal irradiation (CSI) as an initial therapy, and local irradiation was a significant risk factor of recurrence (p = 0.0072). The period between the start of first-line treatment and confirmation of the first recurrence ranged from 4.2 to 272 months (median 66.8 months). Among the recurrences, 13 tumors occurred outside the radiation field, including 6 cases of spinal cord/canal recurrence. One-third of patients did not exhibit elevated tumor marker levels in the serum. Fourteen patients had contrast-enhanced recurrent lesions. In the 2 patients with non-contrast-enhanced lesions, recurrence was detected by high signal intensity on diffusion-weighted imaging (DWI) and elevated tumor marker levels in CSF. Fifteen patients received chemotherapy for the first recurrence, and 14 received radiation therapy, with 9 receiving CSI. The patients who received CSI survived without further recurrence during the study period. However, the median progression-free survival and overall survival after the first recurrence among patients who did not undergo CSI were 12.2 and 37.4 months, respectively, which were shorter than those for patients treated with CSI (both p < 0.01, log-rank test). Spinal MRI for surveillance in patients with recurrent germinoma, especially for those who do not receive CSI, is recommended. DWI might be useful for detecting recurrent germinoma. Aggressive treatment at the time of recurrence is crucial, and even if remission is achieved with chemotherapy, CSI for consolidation is important to prevent further recurrence.

Outcomes of Endoscopic Submucosal Dissection for High-Risk Colorectal Colitis-Associated Neoplasia in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) patients have an increased risk of developing colorectal cancer. High-risk colorectal colitis-associated neoplasia (HR-CAN) can be difficult to treat using traditional endoscopic resection methods. Aim of the study is to evaluate the outcomes of endoscopic submucosal dissection (ESD) on IBD patients with HR-CANs. In this retrospective multicenter study, we consecutively included IBD patients referred to expert Italian endoscopy centers who underwent ESD or hybrid-ESD (hESD) for HR-CANs. Main outcomes were the rate of en-bloc, R0, curative resections, adverse events (AEs), the rate of local recurrence, metachronous lesions, and post-resection surgery. Kaplan-Meier method was used to analyze survival curves. Risk factors associated to main outcomes were investigated by univariable analysis. Ninety-one colonic IBD patients (83.4% ulcerative colitis, disease duration of 15.3 ± 8.7 years) with 96 HR-CANs (53.1% high-grade dysplasia/adenocarcinoma, size 34.8 mm ± 16.2 mm) were included. ESD and hESD were performed in 82.3% and 17.7% of cases. En-bloc, R0, and curative resections were achieved in 95.9% (95% CI 0.958; 0.896-0.988), 85.4% (95% CI 0.854; 0.767-0.917), and 83.3% (95% CI 0.833; 0.743-0.901) of cases. AEs occurred in 12.5% (95% CI 0.125; 0.066-0.208) of cases, which were all conservatively managed. After a mean follow-up of 23.4 ± 16.1 months, local recurrence and metachronous lesions occurred each in 3.1% (95% CI 0.031; 0.006-0.088) of cases. Post-resection surgery was required in 11.5% (95%CI 0.114; 0.058-0.195) of cases. ESD of HR-CANs shows favorable outcomes on the medium and long-term course in IBD patients.

P0617 Feasibility and safety of endoscopic submucosal dissection in inflammatory bowel disease (ESDEUR-IBD): an interim analysis of European retrospective study

Abstract Background Colectomy is the primary treatment for dysplastic lesions in inflammatory bowel disease (IBD). Since the development of advanced endoscopic techniques, the management of dysplasia is evolving. Endoscopic submucosal resection (ESD) could be used in selected cases at referral centres as an alternative to colectomy. However, the feasibility and safety in IBD remains limited. Main aim: To evaluate en-bloc resection rate and the need of colectomy due to ESD failure in IBD. Secondary aims: to assess the complications of ESD, the local recurrence of dysplastic lesions, the presence of synchronous and metachronous lesions and the risk of IBD relapse following the procedure. Methods Multicentre, retrospective study of IBD patients who underwent ESD for suspected colonic dysplastic lesions at least one month before the inclusion date. Patients with total colectomy before ESD, invisible dysplasia at the time of ESD, or pregnancy were excluded. En-bloc resection rate and colectomy due to ESD failure at the short term were evaluated by logistic regression analysis. The risk of IBD relapse was evaluated by Cox regression analysis. Results Forty-eight patients from 16 centres were included: 36 with ulcerative colitis, 9 with Crohn’s disease and 2 with IBD-unclassified. The mean age at ESD was 63 years (SD 13). The majority of the lesions (n=28, 60%) were located in rectum. Forty lesions (87%) were located in areas previously inflamed. En-bloc and R0 were achieved in 45 (94%) and 37 patients (77%), respectively. Colectomy due to ESD failure was required in 4 patients (8.3%) (Figure 1A). No risk factors were associated with colectomy in multivariable analysis, including inflammatory activity, IBD treatments or characteristics of the lesions. Complications occurred in 16 patients (33%): 6 required pharmacologic therapy, 5 needed endoscopic or radiologic intervention, and 2 underwent surgery (Table 1). No deaths were reported. At least one surveillance colonoscopy after ESD was performed in 35 patients (73%). Local recurrence was observed in 2 patients while other dysplastic lesions were detected in 9 (29%) during the follow-up (median 2.5 years, IQR 0.5-4). All of these lesions were removed endoscopically. Synchronous and metachronous lesions were identified in 4 (25%) and 7 patients (26%), respectively. IBD relapse occurred in 8 patients during the follow-up, with an incidence rate of 7% person-year (CI 95%:3-15) (Figure 1B). Conclusion ESD avoids colectomy in 80% of IBD patients with dysplastic lesions. One-third of the patients experienced complications, all of them resolved with no sequelae. Given the risk of new dysplastic lesions, ongoing monitoring with surveillance colonoscopies is recommended.

Postoperative outcomes of biopsy versus debulking surgery for immunoglobulin G4-related ophthalmic disease: a retrospective comparative study.

To compare the postoperative outcomes of corticosteroid therapy following biopsy with those following debulking surgery in patients with immunoglobulin G4 (IgG4)-related ophthalmic disease (IgG4-ROD). Retrospective comparative study. Fifteen patients diagnosed with IgG4-ROD (5 unilateral, 10 bilateral) were retrospectively analyzed. IgG4-ROD was diagnosed based on imaging, histopathology, and blood test results. The biopsy group included patients who underwent resection of minimal tissue for diagnosis, whereas the debulking group included patients who underwent resection of a substantial portion of the mass to decrease the tumor size. Postoperative outcomes after steroid administration, recurrence rates, and changes in lacrimal gland function were compared between the groups. The biopsy and debulking groups included seven and eight patients, respectively. All patients in the biopsy group and 25% of patients in the debulking group required steroid treatment postoperatively (p = 0.0070). Relapse occurred in 71.4% and 12.5% (p = 0.041) and maintenance therapy was required in 57.1% and 12.5% (p = 0.12) patients in the biopsy and debulking groups, respectively. Twelve patients had extraorbital lesions, with one patient receiving corticosteroid treatment for sphenoid bone lesion. Schirmer I test values did not differ preoperatively and postoperatively in either group (biopsy: p = 0.47; debulking: p = 0.72). One patient from the biopsy group developed severe dry eyes, necessitating lacrimal canalicular excision. Debulking surgery effectively reduced the requirement for postoperative steroid administration for recurrent lacrimal gland lesion in patients with IgG4-ROD, indicating its potential as an effective alternative to current standard treatment.

A Recurrent Nocardial Corneal Ulcer

Purpose: To present a case of recurrent &lt;i&gt;Nocardia&lt;/i&gt; keratitis following the use of topical steroids.Case summary: A 57-year-old man presented with decreased visual acuity and conjunctival injection in the right eye which began 15 days prior. Slit-lamp examination revealed epithelial defects smaller than the circular infiltrate and empirical topical treatment was initiated. Since the corneal lesion improved with a therapeutic contact lens and topical antibiotics, a steroid eye drop was added. After 7 days, the corneal infiltrate worsened in a wreath-like pattern with a positive result on a KOH (potassium hydroxide) smear, and antifungal eye drops were started. However, &lt;i&gt;Nocardia&lt;/i&gt; species was confirmed on the 9th day of culture. While complete epithelial regeneration was achieved after 10 days using amikacin eye drops, steroid eye drops were reused to reduce the corneal haze. Twenty days later, the corneal infiltrate and epithelial defects reappeared adjacent to the initial opacity, and a culture confirmed &lt;i&gt;Nocardia&lt;/i&gt;. Gradual improvement was achieved with amikacin eye drops and oral Septrin. Ultimately, a combination of moxifloxacin, tobramycin, and bromfenac eye drops was tapered over several months, resulting in healing with mild opacity.Conclusions: &lt;i&gt;Nocardia&lt;/i&gt; keratitis commonly arises from trauma involving soil, progresses slowly, and is often misdiagnosed as a fungal infection. While amikacin eye drops proved effective, prolonged topical treatment is essential. Early steroid use should be considered cautiously, as it may lead to recurrence and worsening of the corneal lesion.

Recurrence Patterns and Management after Pleurectomy Decortication for Pleural Mesothelioma.

We hypothesize that recurrence following pleurectomy decortication (PD) is primarily local. We explored factors associated with tumor recurrence patterns, disease-free interval (DFI), and post-recurrence survival (PRS). Tumor recurrence is a major barrier for long-term survival after pleural mesothelioma (PM) surgery. All patients who underwent PD between 1998 and 2022 were identified. Patients with diffuse PM who achieved macroscopic complete resection and had sufficient information on tumor relapse were included. Postoperative scans were reviewed to determine the timing and sites of the first recurrence. A total of 436 patients had tumor recurrence during follow-up. Local recurrences occurred most frequently (N=370, 85%) and represented the only recurrence site in 29% (N=129) of cases. Patients with sarcomatoid tumors relapsed earlier than other subtypes (P=0.003) with more frequent distant spread compared to other subtypes (P<0.001). Multivariable analysis revealed that age (P=0.015), preoperative tumor volume (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), and TNM stage IV (P=0.003) were associated with DFI. Similarly, age (P=0.042), performance status (P<0.001), epithelioid histology (P<0.001), intraoperative chemotherapy (P<0.001), TNM stages III and IV (P=0.003 and 0.010 respectively), type of surgery (P=0.019), and number of recurrent lesions (P=0.024) were associated with PRS. Recurrence surgery (HR 0.46, 95% CI 0.29-0.74) and chemotherapy (HR 0.69, 95% CI 0.54-0.92) were independently associated with PRS in patients with distant with or without local recurrences. PM is frequently associated with local recurrence. Repeat surgical resection is feasible and can achieve good local control in selected cases.

The impact of cross disciplinary communication methods on the support needs, quality of life, and emotions of patients with advanced lung cancer

Background: The condition of advanced lung cancer patients is already quite severe. At this stage, the tumor has basically spread to other areas or caused multiple recurrent lesions, which not only increases the difficulty of treatment but also leads to a significant decrease in disease control rate. Aim: To analyze the impact of cross disciplinary communication methods on patients with advanced lung cancer. Methods: A comparative study involving 152 advanced lung cancer patients from January 2022 to January 2024 was conducted. Patients were randomly divided into an observation group (73 cases, using interdisciplinary communication) and a control group (79 cases, using routine nursing). An interdisciplinary team, including nurses, physicians, head nurses, and psychology experts, developed communication plans. The study compared emotional states (DASS-21), supportive care needs (SCNS-SF34), disease uncertainty (MUIS), quality of life (FACT-L), and compliance between the two groups. The study's limitation is the relatively single sample selection, potentially affecting result generalizability. Result: After intervention, the DASS-21 score, SCNS-SF34 score, and MUIS score in the observation group were lower than those in the control group, while the FACT-L score was higher than that in the control group (P &lt; 0.05); the good compliance rate of the observation group was 97.26% (71/73), which was higher than that of the control group (86.08% (68/79) (P &lt; 0.05). Conclusion: For patients with advanced lung cancer, adopting cross disciplinary communication for intervention can not only effectively alleviate their negative emotions and reduce their sense of disease uncertainty, but also maximize the satisfaction of their supportive care needs, ensure their quality of life, and to some extent, obtain good cooperation from patients.

Total Pelvic Exenteration with Presacral Fascia and Pelvic Musculature Excision for Pelvic Recurrence of Rectal Cancer.

Local relapse has not been eradicated even in the era of total mesorectum excision.1,2 Although various approaches have been attempted, R0 resection remains the only potentially curative treatment.3,4 PATIENT AND METHODS: A 45-year-old woman with a history of laparoscopic abdominoperineal resection was diagnosed with pelvic recurrence 7 months ago. Then, she received chemoradiotherapy. Magnetic resonance imaging (MRI) and positron emission tomography-computed tomography (PET-CT) showed pelvic recurrences at the surface of the right piriformis and obturator internus, posterior vaginal wall, and presacral fascia. The patient also had bilateral hydronephrosis. No distant metastasis was found. First, the lateral pelvic lymph nodes were removed. Then, the internal iliac arteries and veins were transected. Next, the fibrotic ureters were isolated and cut. Then, presacral fascia at the S4 and S5 levels was excised. Anteriorly, the urethra and vagina were transected. Lastly, the suspected pelvic recurrent lesions were resected en bloc with partial right piriformis, obturator internus, and gluteus maximus through a combined abdominal and perineal approach. Greater omental pedicle flap was transplanted into the pelvic cavity and pelvic floor was reconstructed. The operative time was 600min, and blood loss was 400ml. Postoperative course was uneventful, and the patient was discharged 14days after surgery. Pathology report showed a moderately differentiated rectal adenocarcinoma invading the vagina, presacral fascia, and pelvic musculature. All margins were negative. As demonstrated by this case, image-guided total pelvic exenteration with presacral fascia and sidewall musculature excision provides an opportunity to cure pelvic recurrence of rectal cancer.5.

Identification of a dual JAK3/TEC family kinase inhibitor for atopic dermatitis therapy.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder characterized by recurrent eczematous lesions and severe itching, for which clinical treatments are limited. Selectively inhibiting Janus Kinase 3 (JAK3) and tyrosine kinase expressed in hepatocellular carcinoma (TEC) family kinases is proposed as a promising strategy to treat AD with possible reduced side effects and enhanced efficacy. In this study, we developed a dual JAK3/TEC family kinase inhibitor ZZB, which demonstrated potent inhibitory activity with IC50 values of 0.89nM against JAK3 and 11.56nM against TEC kinase interleukin-2-inducible T-cell kinase (ITK). Docking studies revealed that ZZB forms a covalent bond with the unique cysteine residue at position 909 (Cys909) in JAK3 and Cys442 in ITK. Utilizing human peripheral blood mononuclear cells, we discovered ZZB selectively inhibits JAK3-dependent cytokines signaling and ITK-mediated CD4+ T cell activation. Moreover, in vitro studies indicated ZZB significantly suppresses the proliferation and differentiation of CD4+ T cells, as well as the cytolytic function of CD8+ T cells and NK cells. We then conducted a pharmacokinetic study in mice and observed a favorable pharmacokinetic profile for ZZB. In a mouse model of AD induced by repeated application of 2,4-dinitrochlorobenzene to the shaved dorsal skin, oral administration of ZZB (100mg/kg) markedly improved skin condition and reduced immune cell infiltration, matching the efficacy of the positive drug dexamethasone. We conclude that the JAK3/TEC kinase inhibitor ZZB is a highly promising candidate for the treatment of AD.

Adenomyosis patterns on transvaginal sonography could predict the obstetrical outcomes of fertility-sparing surgeries: A retrospective cohort study.

To explore the associations between adenomyosis patterns on transvaginal sonography (TVS) and surgical outcomes. A retrospective cohort study. Peking Union Medical College Hospital, Beijing, China. The medical records of 322 patients diagnosed with adenomyosis who underwent open or laparoscopic fertility-sparing surgeries from March 1 to December 31, 2018, were reviewed. Patients were divided into localized (221 patients) and diffuse (101 patients) adenomyosis groups on the basis of TVS findings. Detailed epidemiological information, imaging evaluations, surgical reports, and pathological findings were retrospectively collected. The median postsurgical follow-up period was 52.8 months (range 6-88 months), with 24 patients (7.4%) lost to follow-up by July 1, 2019. The localized and diffuse adenomyosis groups had similar symptom relief and recurrent uterine lesions. Among the 104 patients who attempted pregnancy, 75 patients (72.1%) conceived, with 35 miscarriages (46.7%) and 59 live births (78.7%). For the whole cohort and the localized adenomyosis and diffuse adenomyosis groups, the cumulative 5-year conception rates were 75%, 83% and 60%, respectively; the cumulative 5-year live birth rates were 63%, 79% and 37%, respectively. The adenomyosis patterns found during sonography were the only independent risk factors related to clinical pregnancy and live birth in the Cox regression model. Patients with diffuse adenomyosis had significantly lower rates of conception (HR 0.5, 95% CI 0.3-1.0) and live birth (HR 0.4, 95% CI 0.2-0.8). Adenomyosis patterns (localized versus diffuse) in pretreatment TVS could predict obstetrical outcomes, irrespective of surgical type and uterine size. The clinical trial registry name is the Cooperative Adenomyosis Network (CAN); the registration number is NCT03230994 (https://clinicaltrials.gov). This study started on June 30, 2017, and was completed on December 30, 2020.

Comparative Efficacy of Ultrasonic Scalpel Surgery With Photodynamic Therapy Versus Trichloroacetic Acid Application in Treating HPV-Related Condyloma Acuminata: A Randomized Clinical Trial.

Human papillomavirus (HPV) infections rank as the most prevalent sexually transmitted infections globally. The Brazilian Ministry of Health recommends the topical use of 70%-90% trichloroacetic acid (TAA) for treating condyloma acuminata, yet this method suffers from a high recurrence rate of 36% and requires roughly six applications. Topical photodynamic therapy (PDT) has shown effectiveness in targeting subclinical lesions, but it also necessitates multiple sessions for complete lesion clearance. This randomized clinical trial evaluates the efficacy of 80% TAA monotherapy against a combined approach of ultrasonic scalpel excision followed by a single PDT session (US + PDT). The US + PDT group required fewer treatment sessions, exhibited superior cosmetic outcomes, and reported zero lesion recurrence during an 18-month follow-up, in contrast to the TAA group's recurrence rate of 33.3%. Notwithstanding, patient-reported pain during PDT application emerged as a significant barrier, affecting treatment adherence and completion rates. Innovating new PDT protocols could potentially address this challenge, enhancing patient compliance and therapeutic success.

Intralesional Steroid Injection Therapy of the Benign Vocal Fold Lesions

Voice therapy and laryngeal microsurgery are the main treatment options for benign vocal fold lesions. However, if patients are unable to endure lengthy voice therapy, or refuse surgery under general anesthesia, clinicians need to try other methods. Recently local steroid injection directly into the true vocal folds (TVF) benign lesions has been focused on alternative treatment options, and good results have been reported. Local steroid injection into the TVF was first described in 1964 by Dr. Yanagihara. Although this initial technique was inaccurate, however, with the advancement of modern endoscopy, recent emerging articles have proposed for the effectiveness of in-office awake vocal fold steroid injection in the treatment of benign vocal fold lesions. Based on previous studies of vocal fold steroid injection in the treatment of benign vocal fold lesions, I will summarize and suggest as follows. Various corticosteroids (triamcinolone acetonide, methylprednisolone, dexamethasone sodium phosphate) are used for the intralesional injection in the treatment of benign vocal fold lesions. The steroid injection approach can be transoral, transcutaneous or via flexible endoscope with operating channel, and injection route depends mainly on availability and individual experience. Intralesional corticosteroid injection significantly reduces benign vocal fold lesion volume and improves voice quality, at least transiently. There are many unresolved issues remain regarding the problem of vocal fold atrophy after steroid injection. Nevertheless, to minimize the risk of vocal atrophy, it is advisable to pay attention to repeating short interval steroid injection or administrating high dose of steroid. And, in case where repeated steroid injections are necessary for benign vocal fold lesions such as vocal nodule, vocal polyp, Reinke’s edema, I suggest that 12 weeks intervals would be safe to prevent vocal fold atrophy. And, to prevent recurrence of benign vocal fold lesions after steroid injection therapy, it is recommended to add post-procedural voice therapy, including vocal hygiene.

How to Predict Recurrence After Resection of Hepatocellular Carcinoma.

Predictors of recurrence following resection of hepatocellular carcinoma (HCC) are not fully established. This study investigated potential risk factors and prognostic scores for this situation. In 297 patients undergoing resection of HCC between 2000 and 2021, risk scores and potential additional risk factors for intrahepatic and extrahepatic recurrence were assessed. Median overall survival was 48.4 months, median time to recurrence 25.1 months. The Alpha-Fetoprotein (AFP)-score differentiated between low and high-risk groups (21.8 vs. 8.3 months, p=0.001), as did the Risk Estimation of Tumor Recurrence After Transplant (RETREAT)-score (16 vs. 9 months, p=0.004) and the Clinical Risk Score (CRS) (14.9 vs. 3.9 months, p=0.002). Advanced T-stage, multiple lesions, and vessel infiltration were significantly associated with any type of recurrence, advanced T-stage, and multiple lesions with intrahepatic recurrence. Predictors of recurrence following resection of HCC were identified. Prognostic scores traditionally used for patients receiving liver transplantation (AFP-score, RETREAT-score, CRS) were predictive also of recurrence after resection of HCC.

Single-cell dissection of multifocal bladder cancer reveals malignant and immune cells variation between primary and recurrent tumor lesions

Bladder carcinoma (BLCA) is characterized by a high rate of post-surgery recurrence and multifocality. Multifocal tumors have a higher risk of recurrence compared to single tumors, significantly impacting bladder cancer-specific mortality. However, the interregional or intraregional heterogeneity within both primary and recurrent tumors remains poorly understood. Here, we employed single-cell RNA sequencing to analyze tumor lesions from five multifocal bladder cancer patients comprising three primary tumors and two recurrent tumors. Our findings revealed that malignant cells derived from recurrent multifocal bladder cancer exhibited higher interregional transcriptional similarity and consistent cellular communication. Furthermore, our analysis uncovered that malignant cells from recurrent tumors may evade immune destruction by suppressing cytokine responses and natural killer cell activity. Notably, we identified a preference for the expression of the tryptophan metabolic enzyme IL4I1 on SPP1+ macrophages in recurrent tumors. Functional analyses have revealed that IL4I1 may promotes tumor progression in recurrent tumors by activating the aryl hydrocarbon receptor (AHR) and recruiting regulatory T cells to suppress adaptive immunity. Taken together, our study provides a comprehensive understanding of primary and recurrent multifocal bladder tumors, offering valuable resources for analyzing the multifocality and recurrence of bladder cancer.

CfDNA fragmentation patterns correlate with tumor burden measured via PSMA PET/CT volumetric parameters in patients with biochemical recurrence of prostate cancer

BackgroundProstate cancer recurrence following primary treatment poses a significant clinical challenge, particularly when detected through biochemical recurrence at low PSA levels. Conventional imaging modalities often fail to localize the disease at this early stage. PSMA PET has demonstrated superior sensitivity in detecting recurrent lesions, even in patients with low PSA. Concurrently, liquid biopsy, through analysis of cell-free DNA (cfDNA), offers a minimally invasive approach for monitoring disease. There is scarce evidence about the association between liquid biopsy and PSMA PET/CT findings. This study aimed to assess the correlation between liquid biopsy and tumor burden assessed by PSMA PET/CT in early recurring prostate cancer patients.ResultsPSMA PET/CT and liquid biopsies of 32 patients in biochemical recurrence were analyzed. 12 patients (37.5%) had no PSMA PET-measurable disease. Four patients (12.5%) presented local recurrence, seven (21.9%) had recurrence in pelvic lymph nodes, one of whom also had local recurrence. Nine patients (28.1%) presented metastatic recurrence, with or without local or nodal recurrence. PSA levels correlated with molecular imaging data (p < 0.05), including whole body PSMA-TV, whole body PSMA-TL, whole body SUVmean and whole body SUVmax. The mean cfDNA fragment size fraction was inversely correlated with tumour burden measured with whole body PSMA-TV, with a Spearman correlation coefficient of -0.451 and a p-value of 0.009. No correlation was found between cfDNA concentration and PET-PSMA data.ConclusionThis prospective study demonstrated a statistically significant negative correlation between cfDNA fragmentation patterns and PSMA PET/CT volumetric parameters in patients with presumed localized prostate cancer with early biochemical recurrence. These findings underscore the potential of liquid biopsy as a biomarker and a complementary tool to PSMA PET/CT to assess disease progression during the follow-up of these patients.

Minimally invasive neurosurgery: application of burr-hole technique across a spectrum of brain lesions.

The burr-hole technique is a minimally invasive transcranial approach designed to minimize the surgical incision size and reduce disruption to brain tissue. We aimed to share our experience with the burr-hole technique for removing brain lesions and to evaluate its effectiveness in treating appropriately sized intra-axial brain lesions. In this retrospective cohort study, we analyzed the clinical features, radiological characteristics, surgical techniques, and outcomes of patients who underwent burr-hole surgery for intra-axial brain lesions between January 2019 and December 2023. A total of 81 patients were included in the study. Gross total resection was achieved in 74 patients (91.4%), whereas subtotal resection was performed in 7 patients (8.6%). There were no perioperative deaths, cerebrospinal fluid leaks, or wound infections. The median follow-up duration was 40.5 months (range, 4.1-63.7 months). At the end of the follow-up period, 14 patients (17.3%) experienced recurrence, including 6 with glioma and 8 with primary cerebral lymphoma. Among these patients, 10 died due to lesion recurrence. The burr-hole approach using a retractable tubular device is a safe and effective method for the removal of brain lesions. As a novel minimally invasive technique, it significantly facilitates and accelerates the evolution of microsurgical outcomes.

Intranodal thyroid inclusions revisited: a morphological analysis and application of BRAF VE1 immunohistochemistry.

The diagnosis of intranodal thyroid inclusions (ITIs) is controversial. We aim to investigate their clinicopathologic features and utilize immunohistochemistry (IHC) to support the diagnosis. Forty-one cases of incidentally found ITIs between 2019 and 2023 were categorized into three groups, namely, Group A: thyroidectomy due to papillary thyroid carcinoma (PTC) with regional lymph node dissection (n = 33), Group B: thyroidectomy due to benign thyroid disease with incidental perithyroid lymph node sampling (n = 4), and Group C: surgery due to other head and neck cancers with lateral neck lymph node dissection (n = 4). The overall incidence of ITIs was 4.17% (33/792) in Group A and 0.76% (4/524) in Group C. All ITIs sufficient for study were negative for BRAF VE1 IHC. HBME-1 and galectin-3 IHC were also negative in all analysed cases. Although various degrees of nuclear changes were present in ITIs, classical PTCnuclear features, i.e. pseudoinclusions, nuclear grooves, and chromatin alterations, were less commonly seen (0%, 29.3%, and 51.2%, respectively) than in metastatic PTC (90%, 95%, and 95%, respectively) (all P < 0.001). Interestingly, 77.3% (17/22) of cases with lymph node metastasis in Group A had coexistence of ITIs and metastasis in the same lymph node. During follow-up, two cases in Group A had PTC recurrence without accompanying ITIs, while none in Group B or C had recurrent thyroid lesions. We propose key diagnostic features for ITIs incorporating morphology and BRAF VE1, HBME-1, and galectin-3 IHC. The distinction between ITIs and metastatic PTC can be clinically relevant.

Rectal bleeding due to cavernous hemangioma in Klippel–Trenuany syndrome: a rare presentation and review of management

Introduction and importance: Klippel–Trenaunay syndrome (KTS) is a rare congenital disorder with an incidence of about 2–5:100 000. It is characterized by the triad of cutaneous hemangiomas, soft tissue or bone hypertrophy, and venous malformations. Gastrointestinal (GI) involvement in KTS, although uncommon, can lead to severe complications such as profuse GI bleeding. Our case highlights the challenges and management strategies of a patient with KTS. Case presentation: A 5-year-old child presented with rectal bleeding since birth, accompanied by swelling and bluish discoloration on left flank, and multiple varicose veins on left leg. Examination revealed small hemangiomatous lesions scattered along the torso and trunk. Barium enema showed diffuse mucosal irregularity with polypoidal filling defects in the rectum and sigmoid colon. Doppler ultrasound revealed slow-flow vascular lesions in the left flank and leg without arteriovenous communication. Computed tomography (CT) scan showed diffuse cavernous hemangiomas in the descending colon, sigmoid colon, and rectum. Histopathology demonstrated numerous dilated, irregular vascular channels with calcification and hemosiderin-laden macrophages. Clinical discussion: GI tract cavernous hemangiomas can cause chronic bleeding and anemia, necessitating careful evaluation. Imaging modalities like CT and Doppler ultrasound are crucial for assessing vascular lesions. Surgical interventions, including partial proctocolectomy and colorectal anastomosis, effectively control bleeding and improve outcomes. A multidisciplinary approach is essential for managing such cases. Conclusion: This case underscores the importance of multidisciplinary management in KTS with GI bleeding. Effective diagnostic imaging and surgical treatment are key to managing severe complications and achieving successful outcomes. Long-term follow-up is crucial to monitor for recurrence and residual lesions.

Long-term follow-up of a randomized, double-blind, phase III, multi-centre study to evaluate the safety and efficacy of field-directed photodynamic therapy (PDT) of mild to moderate actinic keratosis using BF-200 ALA versus placebo and the BF-RhodoLED® lamp.

In actinic keratosis (AK), field cancerization describes areas of skin where multiple visible AK lesions are surrounded by healthy looking skin containing non-visible (subclinical) lesions. As all AK lesions have a risk of progression to cutaneous squamous cell carcinoma, experts advise field-directed treatment. Photodynamic therapy (PDT) is an effective field-directed treatment option for AK; however, long-term efficacy data are still scarce. This publication presents follow-up data of a phase III study evaluating the efficacy and safety of field-directed PDT. The study was conducted in seven centres in Germany. For PDT, participants with AKs on the face and scalp (treatment area of 20 cm2) had received up to two field-directed PDTs using BF-200 ALA or placebo, and illumination with narrow-spectrum red light. Only participants or lesions with complete response 12 weeks after the last PDT were assessed for recurrences. The treatment area was evaluated 6 and 12 months after the last PDT for recurrence, cosmetic outcome and new lesions. Fifty-four participants in the BF-200 ALA and 30 in the placebo group entered the follow-up. The probability of a participant to be initially completely cleared and to remain cleared for 12 months was 57.4% for BF-200 ALA versus 20.0% for placebo. The probability of a lesion to be initially cleared and remain cleared for 12 months was 85.4% for BF-200 ALA versus 31.5% for placebo. 83.3% of participants with cosmetic impairment at baseline rated the cosmetic outcome 12 months after PDT with BF-200 ALA as very good or good. All parameters of skin quality further improved during follow-up. We showed that effectiveness of field-directed PDT with BF-200 ALA and narrow-spectrum red light was maintained during follow-up. Based on our results, field-directed PDT is a beneficial long-lasting treatment for AK patients. 2013-002510-12 (EudraCT); NCT01966120 (Clinicaltrials.gov).