Evaluation of micro-remnant niduses of arteriovenous malformations post-gamma knife radiosurgery by 3D-rotational angiography.

PURPOSE: Recent innovations in radiological imaging have enabled the detection of micro-remnant niduses of arteriovenous malformations (AVMs) after gamma knife radiosurgery (GKS), which have not been previously perceptible. Herein, we focus on the difficulty of evaluating micro-remnant AVMs after GKS that are hardly perceptible on conventional examinations and propose integrating follow-up three-dimensional rotational angiography (3D-RA) in the previous gamma plan as a solution. METHODS: We retrospectively searched NTT Medical Center Tokyo hospital database for patients with AVMs who underwent both two-dimensional digital subtraction angiography (2D-DSA) and 3D-RA as follow-up for GKS from February 2021 to January 2024. Patients with suspected nidus occlusion on the latest non-contrast-enhanced magnetic resonance angiography (NC-MRA) were included, and contrast-enhanced magnetic resonance angiography (CE-MRA), 2D-DSA, and 3D-RA were evaluated. RESULTS: Twelve patients with 13 AVM sites were defined as having complete nidus occlusion on upfront NC-MRA. On 2D-DSA, seven AVM sites showed the presence of slight remaining AVMs based on the detection of remnant drainage veins, however the nidus was not detected in three cases. Nevertheless, 3D-RA detected micro-remnant niduses in all seven AVM sites, and four patients underwent re-GKS. Nine patients with ten AVM sites also underwent CE-MRA, and six AVM sites were diagnosed with radiation-induced parenchymal injury. CONCLUSION: Importing the 3D-RA image into the treatment planning has the potential to be more helpful than NC-MRA or CE-MRA to detect micro-remnant AVMs and evaluate the true remnant volume, and may contribute to a more detailed treatment planning, thereby improving the results of GKS retreatment.

Evaluation of different scoring systems for repeating Transarterial Chemoembolization in Egyptian patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) patients undergoing transarterial chemoembolization (TACE) have a diverse range of outcomes due to their high degree of heterogeneity. Therefore, different predictive scoring systems have been created to assist in decision-making regarding retreatment with TACE. We compared the predictive capabilities of different scoring systems, such as ART, ABCR, and SNACOR, for prediction of the outcome of subsequent TACE in HCC patients. METHOD: In this retrospective study, the three scoring systems were compared for their capability of predicting the outcome of repeating TACE in 149 HCC patients treated at the National Liver Institute, Egypt, between January 2017 and December 2019. We used the likelihood ratio to select the model with the highest predictive capability for overall survival (OS). RESULTS: According to our data, the amount of tumor, the change in Barcelona Clinic Liver Cancer (BCLC) stage following TACE, and the SNACOR score (with a 95% confidence range for HR 1.0305-1.256 and p-value = 0.0106) were the most predictive variables. It was also shown that the ABCR score was a good predictor of survival (90 patients had an ABCR score ≤ 0 with a P- value <0.0001, 56 patients had 0 < ABCR < 4 with a P-value <0.0001, and the ART score was not useful in predicting OS (P-value = 0.18). CONCLUSION: The SNACOR score is the most predictive score for OS and would be the most helpful scoring system in decision-making regarding retreatment with TACE.

Successful rechallenge with azacytidine and venetoclax after sustained treatment-free remission in a relapsed acute myeloid leukemia patient: a case report.

Combined therapy with venetoclax and hypomethylating agents has significantly improved the outcome of unfit patients ineligible for intensive chemotherapy. A recently published exploratory analysis of the VIALE-A trial reported that up to 51% of patients achieving remission survived more than 2 years. These data along with those from reallife settings, lead to questioning how long it is appropriate to continue treatment in long-term survivors. Accordingly, recent retrospective studies suggested the feasibility of suspending therapy in selected patients while maintaining prolonged responses. Also, these studies showed that retreatment may induce a second remission in almost a third of patients. We report the case of a patient who received salvage therapy with venetoclax and azacytidine, that was discontinued few cycles after blasts clearance because of severe hematological toxicity. Despite suspension, he maintained a sustained response lasting almost one year and was successfully retreated with the same combination when a second relapse occurred.

Extrusion of debris during retreatment using various nickel-titanium files in teeth with simulated lateral root perforation.

PURPOSE: To investigate the influence of various nickel-titanium (Ni-Ti) files on debris extrusion during the retreatment of teeth with simulated lateral root perforation, focusing on root resorption. METHODS: Sixty human mandibular premolar teeth were divided into groups with and without perforation and further subdivided based on the retreatment technique. Lateral root perforations were created in one group (Group 1), while the other group had no perforations (Group 2). Two retreatment techniques were compared: Remover (RE)+One RECI (OR) and ProTaper Universal Retreatment (PTUR)+WaveOne Gold (WOG). The weight of the extruded debris was determined. The time of both retreatment procedures was measured. Statistical analyses were performed using a two-way analysis of variance (ANOVA) test (P < 0.05). RESULTS: Teeth with simulated lateral root perforation exhibited higher extrusion of debris during retreatment. In both groups, RE+OR files led to more extruded debris than PTUR+WOG files. However, this difference was statistically significant in Group 2 (P < 0.001). Compared to PTUR+WOG files, RE+OR files showed a statistically significant longer time to remove obturation material (P < 0.001). CONCLUSION: Perforated teeth exhibited significantly higher debris extrusion. While both file systems demonstrated similar debris extrusion in perforated teeth, the RE+OR files significantly increased debris extrusion in non-perforated teeth compared to the PTUR+WOG files.

Lung squamous cell carcinoma responding to nivolumab retreatment six years after initial treatment: A case report.

A 61-year-old man presented to our hospital with a chief complaint of chronic cough. He was diagnosed with lung squamous cell carcinoma at clinical stage cT2aN3M1a. He received chemotherapy up to the fourth line, but both the primary tumor and lymph node metastases increased in size. Nivolumab, administered as the fifth line, resulted in a complete response (CR) that continued for 2 years and 8 months. Treatment was stopped due to the appearance of common terminology criteria for adverse events grade 1 pneumonitis. He was followed up without treatment for 3 years and 8 months, but a left supraclavicular fossa lymph node metastasis appeared. Retreatment with nivolumab was initiated, and the patient achieved CR again. One year and 6 months after retreatment, CR was maintained with nivolumab. This case represents a rare instance in which nivolumab yielded a significant response after a prolonged immune checkpoint inhibitor (ICI)-free interval. Our experience has shown that the long-term response to ICIs may deteriorate in the future. Therefore, retreatment with ICIs may be effective when the initial therapy is successful.

Hypofractionated partial breast re-irradiation in the conservative retreatment of breast cancer local recurrence.

AIM: to evaluate the outcome of partial breast re-irradiation (re-PBI) with intensity modulated RT (IMRT), using a hypofractionated scheme for breast cancer (BC) local recurrence (LR) operated on with repeat breast-conserving surgery (re-BCS). METHODS: IMRT-based re-PBI was performed using either helical or step-and-shoot modality to deliver 37.05 Gy in 13 fractions in 2.5 weeks. Cumulative incidence (CumI) of 2ndLR, toxicity, disease-free (DFS), BC specific (BCSS), and overall (OS) survival were evaluated. RESULTS: Between 5/2012 and 5/2021, 70 patients had re-PBI. Median follow-up (FU) was 6.3 years (Q1-Q3, 4.0-8.1.). Median age at 1stLR was 62. The median primary BC-1stLR interval was 12.4 years (range: 1.6-26.7). Luminal A-like 1stLR accounted for 41% of the cases and median size was 0.8 cm. During FU, 18 (26%) patients showed a subsequent event: three 2snLRs (corresponding to 8-y Cumulative rate of 4%), 3 regional nodal recurrences, 7 distant metastases, and 5 other primary tumors. At 8 years, DFS, BCSS and OS were 76%, 90%, and 90%, respectively. At multivariate analysis, Grade 3 and extensive intraductal component were independent predictors for DFS. For 51 and 46 patients, chronic toxicity and cosmesis were evaluated, respectively: 4% had grade 3 fibrosis and cosmesis was deemed good/excellent in just over 60% of the cases. CONCLUSION: Re-PBI after re-BCS represents a feasible alternative to mastectomy with regard to local control, showing an acceptable toxicity profile. A long-term FU is crucial to better understand the pattern of relapse and consolidate the position of re-PBI in clinical practice.

Characteristics of retinal vascularization in reactivated retinopathy of prematurity requiring treatment and clinical outcome after reinjection of ranibizumab.

This study aimed to determine whether the state of retinal vascularization after anti-vascular endothelial growth factor (anti-VEGF) injection can help predict the risk of reactivated retinopathy of prematurity (ROP) requiring treatment and whether repeated ranibizumab injection will be effective in such cases. We retrospectively reviewed 24 infants (43 eyes) who received ranibizumab monotherapy between January 2021 and December 2022. All eyes were classified as having non-retreated ROP or retreated ROP. The state of ROP at the time of treatment, the time required for resolution of plus disease, and the extent of vascularization at 4 and 8 weeks after treatment were analyzed. Extent of temporal retinal vascularization was measured with serial fundus images using disc-fovea distance (DF) unit and disc diameter (DD). Reactivated ROP requiring treatment occurred in six infants (25.0%) and ten eyes (23.3%) after ranibizumab treatment. The mean retreatment interval was 9.0 ± 3.3 weeks (range 4-16). In the retreated ROP group, the time required for the resolution of plus disease after primary injection was longer compared to the control group (13.3 days vs 5.2 days), with a mean ROP regression time of 3.4 weeks. All eyes in the retreated ROP showed retinal vascularization < 0.5 DF from the original site at 4 weeks after injection. In 90% of cases with retreated ROP, the extent of vascularization at 8 weeks after injection was within 1 DF from the original ROP site, and all cases showed reactivation in the posterior Zone II area. The extent of retinal neovascularization in the retreated group was an average of 0.7 DD (vs 1.7 DD) and 1.3 DD (vs 3.3 DD) at 4 and 8 weeks after injection, respectively. After ranibizumab retreatment, only one reactivated case with vitreous traction progressed to focal retinal detachment, while all other cases regressed with peripheral vascular development. The continuation of delayed retinal blood vessel development after ≥ 8 weeks may indicate a high likelihood of reactivated ROP requiring treatment. In the absence of vitreous traction, ranibizumab reinjection is likely to be effective in treating reactivated ROP requiring treatment.

The ARH score, a practical guide to decision-making for retreatment with hepatic arterial infusion chemotherapy in hepatocellular carcinoma patients.

BACKGROUND: Hepatic arterial infusionchemotherapy (HAIC) is a promising option for large unresectable hepatocellular carcinoma (HCC). Identifying patients who could benefit from continuous HAIC remains a challenge. We aimed to establish an objective model to guide the decision for retreatment with HAIC. METHODS: Between 2015 and 2020, the data of patients with large unresectable HCC without macrovascular invasion or extrahepatic spread undergoing multiple HAIC cycles from 3 different centers were retrieved. We investigated the basic tumor parameters and the effect of HAIC on liver function and tumor response, and their impact on overall survival (OS). A point score (ARH, Assessment for Retreatment with HAIC) was built by using a stepwise Cox regression model in the training cohort (n = 112) and was validated in an independent validation cohort (n = 71). RESULTS: The high α-fetoprotein before the second cycle of HAIC, an increase in Child-Pugh score, and undesirable radiologic tumor responses remained independent negative prognostic factors and were used to create the ARH score. The prognosis of HCC patients deteriorated significantly with the increase in ARH score. The median OS of patients with ARH score 0-2 points and ≥ 2.5 points were 19.37 months and 11.60 months (P < 0.001). All of these results had been confirmed in the external validation cohort and demonstrated significance across multiple subgroups. CONCLUSIONS: The ARH score makes an excellent prediction of the prognosis of HCC patients who received retreatment of HAIC. Patients with an ARH score ≥ 2.5 prior to the second cycle of HAIC may not profit from further sessions.

EGFR-Tyrosine Kinase Inhibitor Retreatment in Non-Small-Cell Lung Cancer Patients Previously Exposed to EGFR-TKI: A Systematic Review and Meta-Analysis.

We performed a systematic review and meta-analysis to assess the efficacy of EGFR-tyrosine kinase inhibitors (TKI) retreatment in advanced/metastatic non-small-cell lung cancer (NSCLC) patients. We systematically searched PubMed, Embase, Cochrane databases, ASCO, and ESMO websites for studies evaluating EGFR-TKI retreatment in advanced/metastatic NSCLC patients. All analyses were performed using R software (v.4.2.2). We included 19 studies (9 CTs and 10 retrospective cohorts) with a total of 886 patients. In a pooled analysis of all patients during retreatment with TKI, median OS was 11.7 months (95% confidence interval [CI] 10.2-13.4 months) and PFS was 3.2 months (95% CI 2.5-3.9 months). ORR was 15% (95% CI 10-21%) and DCR was 61% (95% CI 53-67%). The subanalysis by generation of TKI in the rechallenge period revealed a slightly better ORR for patients on 3rd generation TKI (p = 0.05). Some limitations include the high heterogeneity of some of the analyses and inability to perform certain subanalyses. Our results unequivocally support the benefit of EGFR-TKI rechallenge in EGFR-mutated NSCLC patients progressing on TKI treatment after a TKI-free interval. These findings may be especially valuable in areas where access to novel therapeutic drugs and clinical trials is limited.

Association of Polyp Regression after Loading Phase with 12-Month Outcomes of Eyes with Polypoidal Choroidal Vasculopathy.

PURPOSE: We compared 12-month outcomes of eyes with polypoidal choroidal vasculopathy (PCV) with or without complete regression of polyps observed one month after three monthly intravitreal administrations (loading phase) of aflibercept (2.0 mg/0.05 mL) or brolucizumab (6.0 mg/0.05 mL). METHODS: All patients underwent indocyanine green angiography at both baseline and 3 months after initial injection and were followed up monthly with an as-needed regimen for up to 12 months. A total of 62 patients with PCV were included: 30 eyes were treated with brolucizumab, and 32 were treated with aflibercept. Eyes with complete regression of polyps (regression group) had significantly smaller maximum polyp diameter and were more frequently treated with brolucizumab than those without complete regression (non-regression) group. RESULTS: Best corrected visual acuity was comparable between the two groups at 12 months. Although the 12-month retreatment-free proportion was comparable between the two groups (33.0% versus 27.0%, p = 0.59), a retreatment-free period was significantly longer in the regression group than in the non-regression group (8.3 ± 3.3 versus 6.5 ± 3.6 months, p = 0.022), and the number of additional injections was significantly fewer in the regression group than in the non-regression group (1.2 ± 1.2 versus 3.0 ± 2.6, p = 0.007). CONCLUSIONS: Complete regression of polyps observed after the initial phase possibly prolongs the retreatment-free period and reduces the number of additional injections irrespective of aflibercept or brolucizumab.

Fertility-sparing re-treatment for endometrial cancer and atypical endometrial hyperplasia patients with progestin-resistance: a retrospective analysis of 61 cases.

OBJECTIVE: This study aimed to evaluate the oncological and reproductive outcomes of fertility-preserving re-treatment in progestin-resistant endometrial carcinoma (EC) and atypical endometrial hyperplasia (AEH) women who desire to maintain their fertility. METHODS: Our study included 61 progestin-resistant EC/AEH patients. These patients underwent treatment with gonadotropin-releasing hormone agonist (GnRHa) solely or a combination of GnRHa with levonorgestrel-releasing intrauterine system (LNG-IUD) or aromatase inhibitor (AI). Histological evaluations were performed every 3-4 months. Upon achieving complete remission (CR), we recommended maintenance treatments including LNG-IUD, cyclical oral contraceptives, or low-dose cyclic progestin until they began attempting conception. Regular follow-up was conducted for all patients. The chi-square method was utilized to compare oncological and fertility outcomes, while the Cox proportional hazards regression analysis helped identify risk factors for CR, recurrence, and pregnancy. RESULTS: Overall, 55 (90.2%) patients achieved CR, including 90.9% of AEH patients and 89.7% of EC patients. The median re-treatment time was 6 months (ranging from 3 to 12 months). The CR rate for GnRHa alone, GnRHa + LNG-IUD and GnRHa + AI were 80.0%, 91.7% and 93.3%, respectively. After a median follow-up period of 36 months (ranging from 3 to 96 months), 19 women (34.5%) experienced recurrence, 40.0% in AEH and 31.4% in EC patients, with the median recurrence time of 23 months (ranging from 6 to 77 months). Among the patients who achieved CR, 39 expressed a desire to conceive, 20 (51.3%) became pregnant, 11 (28.2%) had successfully deliveries, 1 (5.1%) was still pregnant, while 8 (20.5%) suffered miscarriages. CONCLUSION: GnRHa-based fertility-sparing treatment exhibited promising oncological and reproductive outcomes for progestin-resistant patients. Future larger multi-institutional studies are necessary to confirm these findings.

The Safety of Removing Fractured Nickel-Titanium Files in Root Canals Using a Nd: YAP Laser.

The fracture of nickel-titanium (Ni-Ti) instruments during root canal instrumentation leads to compromised outcomes in endodontic treatments. Despite the significant impact of instrument facture during a root canal treatment, there is still no universally accepted method to address this complication. Several previous studies have shown the ability of a Neodymium: Yttrium-Aluminum-Perovskite (Nd: YAP) laser to cut endodontic files. This study aims to determine safe irradiation conditions for a clinical procedure involving the use of a Neodymium: Yttrium-Aluminum-Perovskite (Nd: YAP) laser for removing fractured nickel-titanium files in root canals. A total of 54 extracted permanent human teeth (n = 54) were used. This study involved nine distinct groups, each employing different irradiation conditions. Groups 1 s, 3 s, 5 s, 10 s, and 15 s simply consist of irradiation for 1, 3, 5, 10, and 15 s, respectively. After identifying the longest and safest duration time, four additional groups were proposed (labeled A, B, C, and D). Group A was composed of three series of irradiations of 5 s each separated by a rest time of 30 s (L5s + 30 s RT). Group B consisted of three series of irradiations of 5 s each separated by a rest time of 60 s (L5s + 60 s RT). Group C consisted of two series of irradiations of 5 s each separated by a rest time of 30 s (L5s + 30 s RT), and group D consisted of two series of irradiations of 5 s each separated by a rest time of 5 s (L5s + 5 s RT). In all groups, during the rest time, continuous irrigation with 2.5 mL of sodium hypochlorite (3% NaOCl) was carried out. The variation in temperature during irradiation was registered with a thermocouple during irradiation with different protocols. The mean and standard deviation of the temperature increase was noted. The calculation of the temperature was made as the Δ of the highest recorded temperature at the root surface minus (-) that recorded at baseline (37°). Additionally, scanning electron microscopy (SEM) was used after irradiation in all groups in order to assess the morphological changes in the root dentinal walls. The Nd: YAP laser irradiation parameters were a power of 3W, an energy of 300 mJ per pulse, a fiber diameter of 200 µm, a pulsed mode of irradiation with a frequency of 10 Hz, a pulse duration of 150 µs, and an energy density of 955.41 J/cm2. Our results show that the safest protocol for bypassing and/or removing broken instruments involves three series of irradiation of 5 s each with a rest time of 30 s between each series. Furthermore, our results suggest that continuous irradiation for 10 s or more may be harmful for periodontal tissue.

Comparative Evaluation of Solite RS3 and HyFlex Remover Retreatment Files in Conserving Remaining Dentin Thickness During Endodontic Retreatment Using Cone Beam Computed Tomography: An In Vitro Analysis.

Introduction Non-surgical retreatment is seen as a conservative choice for dealing with recurrent infections, instead of opting for periapical surgery. The retreatment processes should be promptly and efficiently carried out, utilizing a suitable armamentarium. The objective of this experiment is to evaluate the quantity of root dentin that remains following the removal of gutta-percha (GP) from the root canal employing two distinct retreatment files. Materials and methods Sixty single-rooted teeth were selected for the examination. The process of shaping and cleaning was performed using the step-back approach, with a master apical file size of 40. The smear layer was effectively eliminated by rinsing with a solution of 3% sodium hypochlorite and 17% ethylenediaminetetraacetic acid. Paper points were employed to desiccate the canals. The obturation process involved the utilization of the lateral compaction technique with the AH Plus sealer (Dentsply Sirona, NC, USA). The teeth were classified into two groups: Group I (n=30) underwent retreatment using HyFlex Remover (Coletene India, Pvt., Ltd.), whereas Group II (n=30) received therapy with Solite RS3 retreatment files (Solite Dental in Chennai, India). The remaining dentin thickness (RDT) was assessed by cone beam computed tomography at levels 3, 6, and 9 mm from the cemento enamel junction after the removal of GP. The acquired data underwent examination using an independent t-test to determine statistical significance. Results The findings demonstrate that the utilization of Solite RS3 files led to a higher level of dentin thickness remaining at 3 mm, 6 mm, and 9 mm on the mesial side in comparison to HyFlex Remover retreatment files. The observed difference was found to be statistically significant at a significance level of p<0.05 on the mesial side. Nevertheless, there was no notable disparity seen between the two file types at these three levels on the distal side (p>0.05). Conclusion Based on the obtained results of the study, it can be concluded that Solite RS3 files show promise in preserving the RDT. However, further studies encompassing diverse parameters are needed to establish a conclusive and definitive conclusion.

Retreatment with immunotherapy in a patient with hepatocellular carcinoma who received immune checkpoint inhibitors after primary curative treatment: a case report.

Hepatocellular carcinoma (HCC) presents a malignant pathology known for its high early recurrence rate following curative treatment, significantly impacting patient prognosis. Currently, effective strategies to mitigate early HCC recurrence remain undetermined. In this report, we document a case of HCC managed with curative radiofrequency ablation (RFA), particularly in a patient facing a high risk of early recurrence due to a substantial tumor size. In an effort to forestall recurrence, immune checkpoint inhibitors (ICIs) were preemptively administered for 6 months post-RFA. Despite this, early recurrence ensued upon ICIs cessation. Traditionally, the approach to advanced HCC has been conservative, yet recent years have seen promising outcomes with ICIs in advanced HCC. However, research on ICIs retreatment is limited. In the short term, this patient experienced widespread metastases post-ICIs discontinuation, yet exhibited prompt regression upon ICIs reinitiation. Notably, this represents the initial documented instance of employing ICIs to forestall recurrence subsequent to curative RFA in HCC. Following ICIs discontinuation, diffuse recurrence with multiple metastases emerged, with successful resolution upon ICIs retreatment.

Benign Prostatic Hyperplasia Surgery: A Snapshot of Trends, Costs, and Surgical Retreatment Rates in the USA.

BACKGROUND: An increasing number of novel surgical treatments (NSTs) for benign prostatic hyperplasia (BPH) have been proposed over time to achieve similar functional outcomes, but better perioperative and sexual outcomes than traditional procedures. OBJECTIVE: To assess the trends in the utilization and costs of BPH surgical procedures over the past decade, and to analyze the need for surgical retreatment after each procedure. DESIGN, SETTING, AND PARTICIPANTS: A retrospective observational population-based analysis was conducted using the PearlDiver Mariner (PearlDiver Technologies, Colorado Springs, CO, USA) database, including all-payer nationally available claims records collected from 2011 to 2022. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number and type of BPH surgical procedures per year, costs associated with each BPH surgical treatment, incidence of BPH surgical retreatment rate, and time to BPH surgical retreatment were assessed. Negative binomial regression and Cochran-Armitage test were used for the temporal trend analysis. A multivariable logistic regression analysis evaluated the predictors of BPH surgical retreatment. RESULTS AND LIMITATIONS: In the study period, 274 808 patients received surgical treatment for BPH. The most common procedure was transurethral resection of the prostate (TURP; 71.7%). The overall utilization of BPH surgical treatment increased over the study period. Traditional surgery remained most performed for the entire period (87.8%), but a statistically significantly rising trend of NSTs was recorded. The mean reimbursements paid per procedure was 1.43 times higher (p < 0.001) for NSTs than for traditional procedures. The surgical retreatment rate was 9.4%. The mean time to surgical retreatment was 25.3 mo, with 85.5% of cases re-treated within 5 yr. At the multivariable analysis, transurethral incision of the prostate, photoselective vaporization of the prostate, prostatic urethral lift, convective water vapor energy, and prostatic artery embolization had a significantly greater likelihood of surgical retreatment than TURP. Holmium/thulium laser enucleation of the prostate (HoLEP/ThuLEP), open simple prostatectomy (SP), and laparoscopic/robot-assisted SP were associated with a lower probability of resurgery than TURP, but a similar probability between these procedures. Retrospective design and a lack of relevant clinical data were the main limitations. CONCLUSIONS: Over the past decade, there has been a progressive increase in the adoption of NSTs. The rate of surgical retreatment appears <10%, with patients undergoing SP and HoLEP/ThuLEP experiencing a statistically significantly lower probability of surgical retreatment. PATIENT SUMMARY: We investigated the trends, costs, and surgical retreatments of benign prostatic hyperplasia surgery. Transurethral resection of the prostate remains the most common procedure. Novel surgical treatments are associated with an upward trend, despite appearing more expensive overall. Retreatment is necessary in <10% of patients and generally within 5 yr.

Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

Successful Management of Ovarian Cancer Progressing on Olaparib by Niraparib Following Cytoreduction: A Case Report.

BACKGROUND: Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. CASE REPORT: A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. CONCLUSION: Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.

Reprint of: The Effect of Mineral Trioxide Aggregate Obturation Levels on the Outcome of Endodontic Retreatment: An Observational Study.

INTRODUCTION: No clinical studies have examined the effect of mineral trioxide aggregate (MTA) obturation levels on the outcome of endodontic retreatment. This retrospective study examined treatment outcomes in three cohorts that compared overfilling, flush filling, and underfilling after orthograde retreatment using MTA. METHODS: Two hundred fifty patients with 264 teeth diagnosed with previously treated root canals and apical periodontitis retreated in a private endodontic practice were included. All teeth received MTA obturation and the extent of the final filling level was measured in relation to the major apical foramen. After 6-month follow-ups, all nonhealing cases were treated surgically. After 24- to 72-month reviews, the effect of preoperative lesion size and the degree of MTA obturation level were assessed. Multiple linear regression and time-to-event analysis using Stata 17 software (StataCorp LLC, College Station, TX) were used to evaluate the data. RESULTS: Within the three cohorts, 99 out of 108 overfilled teeth (91.7%), 90 out of 103 flush fills (87.4%), and 10 out of 53 underfilled teeth (18.9%) healed and were successfully retreated without surgery at 48-months. When surgical outcomes were included, the combined healed proportion was 93.2%. Preoperative lesion size was found to be an important predictor for retreatment nonhealing. A 1-mm increase in lesion size at baseline resulted in an estimated 11% (95% CI 1.04, 1.18)-38% (95% CI 1.22, 1.58) increase in the risk of surgery. Compared to overfilling and flush filling, underfilling was associated with an approximately three-fold increase in requiring surgery and characterized by delayed healing. CONCLUSION: MTA obturation is a viable retreatment option for teeth with nonhealing endodontic treatment. MTA overfills or flush fillings do not adversely affect healing outcomes. However, MTA underfilling increases the chances for nonhealing and surgical intervention.

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report.

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.

Background & Aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts. Methods: Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland. Results: A total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). Conclusions: Infection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective. Impact and implications: Representative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.