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Nonmuscle-Invasive Recurrence and Management During Surveillance in Patients with Muscle-Invasive Bladder Cancer Who Achieve Clinical Complete Response to Neoadjuvant Chemotherapy.

PURPOSE: Many patients are medically unfit for or refuse radical cystectomy. Few postchemotherapy bladder-sparing active surveillance programs have reported on nonmuscle-invasive recurrences and treatment outcomes. In this study, we present data on nonmuscle-invasive recurrences and their management in this population. MATERIALS AND METHODS: This is a retrospective review of a prospectively maintained database. All patients received cisplatin-based neoadjuvant chemotherapy and were determined to have a clinical complete response (cCR) based on negative endoscopic resection, urine cytology, and cross-sectional imaging. Patient data were entered into a strict active surveillance protocol. Primary outcomes of interest were number of nonmuscle-invasive recurrences, grade and stage, and treatment. Secondary outcomes of interest were nonmuscle-invasive treatment response rate and muscle-invasive and metastatic recurrence rate. RESULTS: A total of 61 cCR patients were identified. In total, 28 patients experienced a median of 1 nonmuscle-invasive recurrence over a median follow-up of 28.3 months. There were a total of 46 nonmuscle-invasive recurrences, including 9 (20%) low-grade recurrences and 37 (80%) high-grade recurrences. Of the 37 high-grade recurrences, the majority (60%) were treated with Bacillus Calmette-Guérin induction. Nonmuscle-invasive recurrence was not associated with later muscle-invasive recurrence or metastasis. Genomic analysis of paired tumor samples demonstrated clonal relatedness in one patient sample while another sample demonstrated a likely precancerous urothelial field effect. CONCLUSIONS: There is a high rate of nonmuscle-invasive recurrences in patients who achieve cCR to neoadjuvant chemotherapy. However, most of these patients may be safely managed with bladder-preserving treatments. These findings emphasize the importance of vigilant surveillance protocols and appropriate patient selection.

bladder cancer

TSH Cutoffs and Recurrence Risk in Differentiated Thyroid Carcinomas: A Systematic Review and Meta-Analysis.

CONTEXT: The current American Thyroid Association (ATA) guidelines recommend tailored TSH suppression, considering the recurrence risk of differentiated thyroid cancer (DTC); however, the evidence is limited. OBJECTIVE: This meta-analysis aimed to investigate the risk of recurrence in patients with DTC, stratified by the ATA risk of recurrence, according to variable thyrotropin (TSH) cutoffs (0.1, 0.5, and 2.0 mIU/L). METHODS: We searched Ovid-Medline, EMBASE, and Cochrane databases for studies reporting the recurrence rate of DTCs based on TSH cutoffs through March 2024. The search terms used included "thyroid neoplasm" OR "cancer," "TSH" OR "thyroid stimulating hormone," "suppress" OR "supplementation," and "thyroidectomy". RESULTS: Two randomized controlled trials and 7 observational studies, including 5320 patients, were analyzed, with an overall recurrence rate of 18%. The pooled recurrence risk for DTCs at each TSH cutoff (0.1, 0.5, and 2.0 mIU/L) was not significant. In the subgroup analysis, the pooled hazard ratios (HRs) stratified by the ATA risk of recurrence (low- and high-risk DTCs) did not differ according to TSH levels. However, the risks of recurrence increased at serum TSH of 0.1 mIU/L or greater (HR 2.27; 95% CI, 1.29-3.99) and TSH of 2.0 mIU/L or greater (HR 1.36; 95% CI, 1.001-1.84) in a leave-one-out meta-analysis after removing the study that significantly influenced the analysis. Patients with distant metastases had a higher risk of recurrence (HR 3.3; 95% CI, 1.53-7.10) when maintaining a TSH greater than or equal to 0.1 mIU/L. CONCLUSION: The degree of TSH suppression did not affect the overall risk of DTC recurrence. However, TSH suppression may be beneficial in reducing the recurrence risk in high-risk patients with distant metastases.

Humans

Recurrent myocardial infarction identified by centralized troponin review: Insights from the MINT trial.

BACKGROUND: The utility of routine troponin testing to identify recurrent myocardial infarction (MI) after an incident MI is unclear. We assessed the incidence and prognosis of recurrent MIs identified from centralized troponin review in patients from the Myocardial Ischemia and Transfusion (MINT) trial. METHODS: The MINT trial randomized patients with acute MI and anemia to a liberal vs restrictive red blood cell transfusion strategy. Suspected recurrent MIs were identified through both site-report and centralized review of troponin levels collected for 3 days following randomization. Differences in cardiac, noncardiac, and all-cause death at 30 and 180 days were compared across patients with any site-reported MI, only centrally identified MI, and no recurrent MI. RESULTS: Among 3,504 patients, 275 (7.8%) had a recurrent MI within 30 days; 119 (43.3%) by site-report, and 156 (56.7%) by central troponin review only. Rates of cardiac and all-cause death at 30 and 180 days were highest for patients with site-reported MI, intermediate for centrally identified MI, and lowest for no recurrent MI; rates of noncardiac death did not vary. Patients with only centrally identified recurrent MI had an increased risk of cardiac death at 30 days (RR 1.9, 95% CI 1.0-3.4) and 180 days (RR 1.7, 95% CI 1.1-2.7) compared to those without recurrent MI. CONCLUSIONS: In patients with acute MI and anemia, centralized troponin review identified more than half of all recurrent MI events. Patients with centrally identified MI had a higher risk of cardiac death than those with no recurrent MI. TRIAL REGISTRATION: ClinicalTrials.gov NCT02981407 https://clinicaltrials.gov/study/NCT02619136.

Humans

Mutational signature stratification of recurrent gliomas reveals distinct patterns of genomic traits.

BACKGROUND: Although temozolomide (TMZ) is widely used for glioma treatment, its therapeutic benefit is limited by acquired resistance and recurrence, facilitated by intratumor heterogeneity. Mutational signatures (MSs) inform tumor evolution and reveal alterations associated with treatment response. METHODS: We performed molecular analyses of 96 glioma recurrences with sufficient private single-nucleotide variants relative to their matched primary tumors, stratified by their dominant MS. RESULTS: Four groups were identified: MS11/TMZ-related (n&#x2009;=&#x2009;38), MS1/5/aging-related (n&#x2009;=&#x2009;32), MS6/15/21/26/microsatellite instability (MSI)-related (n&#x2009;=&#x2009;13), and other MS-related recurrences (n&#x2009;=&#x2009;13). MS11/TMZ-related recurrences showed higher acquired mutational counts than the other groups (1338 vs 59 (MS1/5/aging) vs 57 (MS6/15/21/26/MSI) vs 57 (other MSs); P&#x2009;<&#x2009;.01). Mutations in SYNE2, SZT2, and FBN3 were restricted to recurrences with dominant or second-dominant MS11/TMZ-related signature (n&#x2009;=&#x2009;41), and 85% (35/41) harbored mutations in these genes. In MS11/TMZ-related recurrences with RNA sequencing data (n&#x2009;=&#x2009;17), mRNA co-expression analyses identified SYNE2-ATAD5 and SZT2-MAPKBP1 associations. Among MS11/TMZ-related recurrences, MS23 was frequent (44%, 18/41) and associated with higher acquired mutational counts (2089 vs 1188; P&#x2009;=&#x2009;.018) and more IDH-wildtype tumors (67% vs 30%; P&#x2009;=&#x2009;.037). MAPKBP1 mutations were enriched in MS23-positive recurrences (56% (10/18) vs 0% (0/23); P&#x2009;<&#x2009;.001). MS1/5/aging-related recurrences showed more frequent acquired chromosome 16q losses (22% vs 8% (TMZ) vs 0% (MSI) vs 0% (other); P&#x2009;<&#x2009;.05), which were associated with an increased fraction of genome altered relative to 16q-diploid cases (15% vs 7%; P&#x2009;=&#x2009;.01). CONCLUSIONS: These findings show that MS-based stratification of recurrences refines molecular characterization after therapy and nominates candidate biomarkers and pathways for functional studies of treatment-associated glioma evolution.

mutational signatures

Longitudinal ctDNA tracking in early and recurrent breast cancer using an ultrasensitive structural variant-based assay: an extended analysis from the TRACER study.

BACKGROUND: Detection of circulating tumor DNA (ctDNA) following curative-intent therapy is prognostic of disease recurrence in early-stage breast cancer (EBC). An ultrasensitive structural variant (SV)-based ctDNA assay was evaluated previously in a 100-patient EBC cohort treated with neoadjuvant therapy, demonstrating high sensitivity, specificity, and a long lead-time to relapse. The stability of primary tumor-specific SVs at and after metastatic recurrence and their utility for longer-term ctDNA monitoring had not been established. PATIENTS AND METHODS: An updated retrospective analysis of ctDNA dynamics was conducted in an expanded cohort of 121 patients with EBC treated with neoadjuvant therapy. Plasma samples were collected at key clinical timepoints and serially in several patients who experienced metastatic recurrence. Clinical variables were abstracted from medical records. Associations between ctDNA detection, dynamics, and clinical outcomes were evaluated in the early-stage and metastatic settings. RESULTS: Thirty of 121 patients experienced clinical recurrence (28 distant, 2 local) over a median follow-up of 4.2 years (range 0.5-8.8; 25 ctDNA evaluable with adjuvant timepoints). All patients with detectable ctDNA in the adjuvant setting developed metastatic recurrence (22/22). Median lead time from ctDNA detection to metastatic recurrence was 346 days (range 0-1937). Among recurrent cases, 79% of primary tumor-specific SVs (n = 17 patients, tumor fraction &#x2265;0.1%) remained detectable in plasma [range 7% (1/14 SV)-100% (15/15); median: 92%]. ctDNA dynamics in the recurrent metastatic setting demonstrated a strong relationship with radiographic outcomes in evaluable patients (n = 9). CONCLUSION: This SV-based digital PCR assay provided ultrasensitive ctDNA detection in an expanded EBC cohort, maintaining 100% positive predictive value for metastatic recurrence. In patients with recurrence, ctDNA dynamics were concordant with radiographic outcomes. Prospective studies evaluating the clinical utility of longitudinal ctDNA monitoring are warranted.

MRD

Changes in recurrent inhibition during voluntary soleus contractions in man studied by an H-reflex technique.

1. The recurrent inhibition, brought about by a conditioning H-reflex discharge, was estimated in human subjects by the amplitude of a test H-reflex involving only the soleus motoneurones which fired in response to the conditioning volley. The modifications of the recurrent inhibition during contraction were evaluated by comparing the amplitude of the test H-reflex to a reference H-reflex. Both reflexes experienced the excitation underlying the voluntary contraction, but only the test H-reflex was subjected to the recurrent inhibition evoked by the conditioning H-reflex discharge. 2. Distinct differences were observed between the modifications of the test reflex and those of the reference H-reflex during both tonic and phasic voluntary contractions. Evidence is presented that these differences were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 3. The changes in recurrent inhibition were studied while the subjects performed voluntary tonic contractions of various forces. The weakest contractions were accompanied by a decrease in the size of the test reflex. With greater contraction forces, there was no longer an inhibition of the test reflex, but instead a facilitation which grew continuously with increased contraction forces. The test reflex could eventually exceed the reference H-reflex amplitude at the strongest contractions. This is taken to indicate that the recurrent inhibition following the conditioning discharge was progressively decreasing, as the contraction force increased. 4. During ramp contractions, whatever the contraction velocity, the time courses of the variations of the test and reference H reflexes were almost inverse. Evidence is presented that these differential time courses were due to changes in the amount of recurrent inhibition elicited by the conditioning discharge. 5. The possibility of occlusion in the recurrent pathway ;as considered and it was concluded that the decrease in the recurrent inhibition elicited by the conditioning discharge was essentially due to an inhibitory control (spinal and/or suprasegmental) acting on Renshaw cells. This inhibition of Renshaw cells eventually counteracts the increasing excitatory inputs (resulting from the voluntary motor discharge) which they receive via motor axon collaterals during increasing tonic contractions and throughout ramp contractions. 6. The functional significance of the Renshaw cell inhibition during voluntary contraction is discussed in relation to the inhibition exerted through the recurrent pathway on both motoneurones and Ia inhibitory interneurones. It is suggested that the depression of Renshaw cell activity could play an important role during voluntary movements by favouring reciprocal Ia inhibition.

Adult

CT-Derived pelvic morphometry for preoperative risk assessment of recurrent unilateral inguinal hernia.

BACKGROUND: Recurrent inguinal hernia remains a significant challenge in abdominal wall surgery despite advances in mesh-based repair techniques and minimally invasive approaches. Although pelvic skeletal morphology has been implicated in inguinal hernia development, its association with recurrent disease remains incompletely understood. This study aimed to evaluate computed tomography (CT)-derived pelvic morphometric parameters and investigate their potential value in preoperative recurrence risk assessment. METHODS: This retrospective study included 251 male patients with preoperative abdominal CT examinations and complete clinical records who underwent elective inguinal hernia repair at a tertiary referral center. After applying the predefined eligibility criteria, 188 patients with unilateral inguinal hernias constituted the primary study cohort, including 162 primary and 26 recurrent unilateral hernias. The Radoievitch angle and Ami's line were measured independently by two blinded radiology residents using a standardized CT-based pelvic morphometric measurement protocol, and the mean values were used for analysis. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses were performed to evaluate the association between pelvic morphometric parameters and recurrent inguinal hernia. RESULTS: Patients with recurrent unilateral inguinal hernias demonstrated significantly greater affected-side Ami's line measurements (8.27&#x2009;&#xb1;&#x2009;0.63 vs. 7.90&#x2009;&#xb1;&#x2009;0.71&#xa0;cm, p&#x2009;=&#x2009;0.014) and larger Radoievitch angles (40.68&#x2009;&#xb1;&#x2009;4.02&#xb0; vs. 38.80&#x2009;&#xb1;&#x2009;3.68&#xb0;, p&#x2009;=&#x2009;0.018) than patients with primary unilateral hernias. Both the Radoievitch angle (OR 1.14, 95% CI 1.01-1.28, p&#x2009;=&#x2009;0.033) and Ami's line (OR 2.26, 95% CI 1.14-4.49, p&#x2009;=&#x2009;0.020) remained independently associated with recurrent inguinal hernia after adjustment for age and body mass index. ROC analysis demonstrated modest discriminatory performance (AUC 0.634 for the Radoievitch angle and 0.633 for Ami's line), while the multivariable model incorporating age, body mass index, and Ami's line showed slightly improved discrimination (AUC 0.655). CONCLUSION: CT-derived pelvic morphometric parameters were independently associated with recurrent unilateral inguinal hernia. Although their individual discriminatory performance was modest, standardized CT-based pelvimetry may serve as an objective adjunctive tool for individualized preoperative recurrence risk assessment in patients who already undergo CT imaging for unrelated clinical indications. Prospective multicenter studies are warranted to validate these findings and determine their clinical applicability.

Humans

Dynamics of HER2 status in recurrent cervical cancer: Highlighting the clinical value of reassessment.

OBJECTIVE: Human epidermal growth factor receptor 2 (HER2)-directed antibody-drug conjugates have emerged as a promising therapy, making accurate HER2 assessment important. We assessed HER2 expression in recurrent cervical cancer, examined clinicopathological factors associated with HER2 positivity at recurrence, and analyzed HER2 discordance between matched primary and recurrent tumors. METHODS: We retrospectively identified patients with recurrent cervical cancer treated at a single center between 2013 and 2024. HER2 immunohistochemistry was performed on recurrent and matched primary tumors and scored according to the 2017 ASCO/CAP guideline for gastroesophageal adenocarcinoma. Tumors scoring 2+ or 3+ were classified as HER2-positive. Factors associated with HER2 positivity were analyzed by logistic regression. RESULTS: Among 118 patients, the HER2-positive rate in recurrent tumors was 15.3% (18/118). HER2 positivity was higher in endocervical adenocarcinoma than in squamous cell carcinoma (30.6% vs 8.6%, P&#xa0;=&#xa0;0.009). Adenocarcinoma (adjusted odds ratio [OR] 4.80; 95% confidence interval [CI], 1.60-15.66) and recurrence outside the prior radiotherapy field (adjusted OR 7.92; 95% CI, 1.68-77.86) were independently associated with HER2 positivity. Among the 72 matched pairs, HER2 discordance was observed in 7 (9.7%), including HER2 gain in 4 of 61 (6.6%) and HER2 loss in 3 of 11 (27.3%). Adenocarcinoma was the only factor associated with discordance (OR 10.33; 95% CI, 1.99-104.04). CONCLUSIONS: In recurrent cervical cancer, HER2 positivity was associated with endocervical adenocarcinoma and recurrence outside the prior radiotherapy field. Reassessing HER2 by re-biopsy at relapse may inform treatment selection in a subset of patients.

Humans

Association between pembrolizumab-based therapy exposure and survival outcomes in metastatic or recurrent uterine carcinosarcoma: a multi-center real-world study.

OBJECTIVE: To evaluate the association between exposure to pembrolizumab-based therapy in the post-platinum setting and survival outcomes in patients with metastatic or recurrent uterine carcinosarcoma. METHODS: In this retrospective study, patients with metastatic or recurrent uterine carcinosarcoma treated at three tertiary centers between January 2008 and April 2025 were included. Patients received various treatment modalities after recurrence or progression in the post-platinum setting. Survival outcomes were analyzed according to whether patients were exposed to pembrolizumab-based therapy after recurrence or progression. Survival after recurrence and overall survival were evaluated using Kaplan-Meier analyses and Cox proportional hazards models. Additional analyses using inverse probability of treatment weighting, doubly robust methods, and time-dependent Cox models were performed. RESULTS: A total of 147 patients were included, of whom 42 (28.6%) received pembrolizumab-based therapy in the post-platinum setting. In multi-variable analyses, pembrolizumab-based therapy exposure was independently associated with improved survival after recurrence (hazard ratio 0.44, 95% confidence interval 0.24 to 0.83, p = .01) and overall survival (hazard ratio 0.48; 95% confidence interval 0.26 to 0.89, p =.02). Positive peritoneal washing cytology was independently associated with poorer survival outcomes. In time-dependent Cox analyses using inverse probability of treatment weighting, pembrolizumab-based therapy exposure remained significantly associated with improved survival after recurrence (hazard ratio 0.56, 95% confidence interval 0.33 to 0.96, p =.035), whereas the association with overall survival was no longer statistically significant. CONCLUSIONS: Exposure to pembrolizumab-based therapy in the post-platinum setting was associated with improved survival after recurrence in patients with metastatic or recurrent uterine carcinosarcoma. These findings support the potential clinical relevance of pembrolizumab-based therapy in the post-platinum setting and warrant further prospective validation.

Aged

[Recurrence with gonadic localization of acute leukemia. 113 cases].

Amongst 1500 cases of acute lymphoblastic leukaemia, affecting both sexes, the authors noted 111 testicular recurrences and 2 ovarian recurrences, i.e. an incidence of 16 percent. Clinical diagnosis is easy and testicular needle biopsy was reserved for doubtful cases only. Amongst 12 lymphographies, only one showed lumbar node involvement. Testicular involvement may exist before, after or in association with a bone marrow or a meningeal relapse. In 47 cases the first signal recurrence was a testicular tumour. The majority of these recurrences occured during the first two years of the disease, but late recurrences affecting the gonads are possible. Mean survival after an isolated testicular recurrence was 14 months, identical with meningeal recurrences. General chemotherapy and local radiotherapy were in general followed by an in situ or contralateral recurrence. Bilateral irradiation at a dose of 2400 rads is the best local treatment. However, in the light of the frequency of bone marrow recurrences a short time after, intensification of general treatment is necessary.

Biopsy, Needle

LRP4 mutations promote tumor progression and resistance to anti-PD-1 therapy in recurrent hepatocellular carcinoma.

BACKGROUND AND AIMS: HCC recurrence is a major factor limiting long-term survival and the cause of most deaths in patients with HCC. However, molecular characterization and potential therapeutic targets of recurrent HCC remain mostly unknown. APPROACH AND RESULTS: We performed whole-exome sequencing in 63 matched primary and recurrent HCC tumors and combined the data with whole-genome sequencing results in 43 paired samples from our previous study. Sanger sequencing was used to identify all low-density lipoprotein receptor-related protein 4 ( LRP4 ) coding exons in 203 additional patients with recurrent HCC. We identified LRP4 somatic mutations in 7.8% (24/309) of recurrent tumors and only 0.97% (3/309) of primary tumors ( p <0.001). Prognosis after the second liver resection was poorer in patients with an LRP4 mutation. Biofunctional investigations demonstrated that inactivating LRP4 mutations promoted tumor progression and immunosuppression. Mechanistically, mutated LRP4 reduced intratumoral conventional type 1 dendritic cell and CD8 + T cell infiltration by repressing C-C motif chemokine ligand 4 expression and secretion through activation of &#x3b2;-catenin signaling, resulting in resistance to anti-programmed cell death protein-1 therapy. Patients with recurrent HCC carrying an LRP4 mutation did not benefit from anti-programmed cell death protein-1 treatment after their second resection surgery. A &#x3b2;-catenin inhibitor-reversed LRP4-induced resistance to anti-programmed cell death protein-1 therapy in humanized tumor-bearing mice. CONCLUSIONS: Our results identified novel LRP4 mutations important in recurrent HCC. Inactivating LRP4 mutations were associated with resistance to anti-programmed cell death protein-1 therapy and could be useful biomarkers for precision therapy in patients with recurrent HCC.

Humans

Understanding recurrence in Mycobacterium avium complex pulmonary disease: genotypic strategies to support clinical decision-making.

Pulmonary disease caused by Mycobacterium avium complex (MAC-PD) is a chronic, recurrent disease, and its high recurrence rate after treatment makes clinical management difficult. Distinguishing whether recurrence is due to persistence of existing strains or reinfection with new strains is essential for establishing treatment strategies, preventing overuse of antimicrobials, and establishing infection control measures. According to reports, 54%-74% of MAC-PD recurrence is due to reinfection, which may be mainly related to environmental reservoirs such as household water supply. In this review, we present various clinical scenarios in which MAC-PD recurrence may occur and examine genotyping techniques as a strategy to distinguish and respond to them. From traditional methods such as IS1245-based restriction fragment length polymorphism, pulsed-field gel electrophoresis, and hsp65 and rpoB gene sequencing to high-resolution analysis techniques such as multilocus sequence testing and whole-genome sequencing, the latest molecular typing methods are comprehensively summarized. Integrating these genotype data into clinical settings, standardizing single-nucleotide polymorphism-based interpretation thresholds, and promoting the establishment of a global MAC strain database will make a substantial contribution to more accurately distinguishing the recurrence mechanisms of MAC-PD and establishing personalized treatment strategies.IMPORTANCEThe global burden of nontuberculous mycobacterial pulmonary disease (PD) is increasing, with Mycobacterium avium (MAC)-PD being the most prevalent and clinically challenging form. Its low treatment success rates, high frequency of recurrence, and persistent environmental exposure complicate both diagnosis and management. A critical clinical issue is determining whether recurrence represents true relapse, due to persistence of the original strain, or reinfection with a new strain, as this guides treatment and prevents overtreatment. Genotypic strategies capable of resolving strain-level differences can improve diagnostic accuracy, prevent misclassification, and ultimately support more informed treatment decisions. Therefore, integrating genotyping data into clinical workflows, standardizing single-nucleotide polymorphism thresholds, and establishing a global MAC strain database will not only support personalized treatment but also enhance the broader public health response to this disease.

Humans

Long-Term Survey to Assess Recurrence and Complications of Surgically Treated Pleomorphic Adenoma.

OBJECTIVE(S): To (1) report on the long-term recurrence rate of surgically managed pleomorphic adenoma (PA) and (2) assess long-term surgical outcomes after parotidectomyMethods:Cross-sectional survey of all patients with a pathologic diagnosis of PA who underwent surgical management in a tertiary care center from 01/1997 to 12/2023 and had access to an electronic patient portal. Surveys were delivered via electronic patient portal or phone call with 6 questions to assess recurrence and long-term surgical outcomes. Time to first recurrence and recurrence free survival were analyzed using a Kaplan-Meier curve. RESULTS: Seven hundred-forty-five patients met inclusion criteria and received the survey, with a 56% response rate (n&#x2009;=&#x2009;420). The clinical median follow-up length was 51&#x2009;days, which extended to a median length of 6.2&#x2009;years following the survey. The median change in follow-up length was 5.37&#x2009;years (P&#x2009;<&#x2009;.001). The recurrence rate was 1% at 5&#x2009;years, with a median time to first recurrence of 7.54&#x2009;years. 13% and 9% of responders reported facial asymmetry and incisional cosmetic concerns, respectively. 33% of patients reported experiencing Frey syndrome, which increased from 5.2% of survey responders with documented Frey syndrome at their original post-operative assessment. CONCLUSION: Long-term assessment of PA outcomes confirms low recurrence rates, suggesting regular surveillance of recurrence is likely unnecessary. Complaints of Frey syndrome increased in frequency with longer term follow-up, which should be considered during patient counseling. LEVEL OF EVIDENCE: 3.

Humans

Recurrences from malignant parotid salivary gland tumors.

The clinical course of 130 patients treated for malignant parotid tumors at the three institutions have been reviewed. Fifty-six of these 130 patients developed recurrences following their primary treatment by a surgical procedure. There were a total of 109 recurrences among these 56 patients. The average number of recurrences was two per patient. The average survival from first recurrence was 3.7 years, with the median survival 2 years. The range of survival was 0.5 to 17 years. Once recurrence developed, treatment was by surgery, radiation therapy, chemotherapy, or a combination. Of 56 patients with recurrence, 33 are dead and 9 patients are alive with disease. Fourteen patients are alive and well with no evidence of disease. These NED patients had an average number of 1.6 recurrences and a median survival to date of only 3 years. Our study indicates that for the majority of patients who develop recurrence, survival is relatively short and treatment is usually ineffective in three of four patients. The authors conclude that after a surgical procedure for malignant salivary gland tumors, a trial of wide field postoperative radiation therapy to high dose should be considered as part of the initial treatment.

Adenocarcinoma

Recurrent ulcer after proximal gastric vagotomy for duodenal and pre-pyloric ulcer.

Factors thought to be important in the development of recurrent ulcer after proximal gastric vagotomy were investigated 1-4 years after operation in 211 patients with duodenal ulcer and in 49 with pre-pyloric ulcer. Recurrent ulcer was found in 25 patients with duodenal ulcer (12 per cent) and in 6 with pre-pyloric ulcer (12 per cent). Recurrence was not related to age, sex, duration of dyspepsia, radiological findings or peak acid output before and 10 days after vagotomy. Fifty-six patients were operated upon by the method of Amdrup and Jensen (1970), including skeletonization of about 2 cm of the oesophagus. The remaining 204 patients were operated on by a technique in which the dissection of the lesser curve was begun at the 'crow's foot' and the oesophageal dissection was extended, in most cases, to more than 4 cm above the cardia. Recurrence was more frequent among the 56 patients in the first group than among the remaining patients with duodenal ulcer. Recurrence was positively related to basal acid output after vagotomy. An increase of peak acid output of 50 per cent was seen in a smaller group with recurrence and patients with dyspepsia within 18 months of vagotomy. It was concluded that the risk of recurrence is not related to the number of parietal cells, as expressed by peak acid output to histamine. The risk may probably be reduced by extension of the oesophageal skeletonization. A marked increase in peak acid output may be seen during the first year after proximal gastric vagotomy in patients with recurrence or dyspepsia.

Duodenal Ulcer

Recurrent osteoblastoma: a review.

A review of 3 new osteoblastomas and 181 previously reported osteoblastomas revealed 18 recurrences (9.8% recurrence rate). Recurrence was more common in the spine and pelvis. Recurrences were reported as late as 9 years after excision of osteoblastomas and long-term follow-up is indicated in this lesion. Five recurrences were reported to undergo apparent sarcomatous change. Complete en bloc resection is the preferred treatment of osteoblastomas. No recurrence has ever been reported after complete resection, however, apparent incomplete excision has given cures in many cases. Radiotherapy does not appear to prevent recurrence. Its immediate postoperative use is not recommended and may possibly be associated with apparent late sarcomatous change in some cases. Since the efficacy of radiotherapy in the treatment of established recurrence still remains obscure, further surgical intervention is indicated.

Bone Neoplasms

The role of particle therapy in the treatment of locally recurrent rectal cancer: a systematic review.

BACKGROUND: Colorectal cancer is a common malignancy. Advancements in multimodality treatment have improved outcomes. About 2-10% of patients will have a local recurrence even after optimal treatment. Salvage surgical treatment is the treatment of choice, however, in posterior and lateral recurrences, surgery is linked to a high rate of treatment-related morbidity. Some recurrences remain unresectable even after neoadjuvant treatment. MATERIALS AND METHODS: A systematic literature review was performed to search for studies on curative-intent radiation therapy (RT) with photons, stereotactic body radiation therapy (SBRT) and particle beam therapy. The aim of the literature search was to define the role of particle therapy in the treatment of patients with unresectable or inoperable local recurrences of rectal cancer where neoadjuvant treatment is unlikely to result in downstaging, leaving patients with RT as the only curative treatment option. RESULTS: 32 studies which fulfil the criteria were identified. In general, SBRT and particle beam therapy permitted the application of significantly higher doses to the target without a concomitant increase in treatment-related toxicities. CONCLUSIONS: For unresectable and inoperable locally recurrent rectal cancer ablative radiotherapy techniques such as SBRT and particle beam therapy offer a curative treatment approach as an alternative to surgery. SBRT can be offered for small local and nodal recurrences, while particle beam therapy can be offered for larger recurrences and complex shapes spanning several anatomical compartments as well. Further research is needed to stratify patients according to their need and eligibility for the different possible modalities of curative-intent RT.

Humans

Durable burden suppression and recurrence patterns after cryoablation in early persistent AF: 3-year results of COOL-PER trial.

BACKGROUND: Long-term rhythm outcomes following cryoballoon ablation (CBA) in early persistent atrial fibrillation (AF) remain incompletely characterized. OBJECTIVE: To evaluate 3-year atrial fibrillation (AF) burden trajectories, subsequent recurrence patterns detected by implantable loop recorder (ILR), and their association with healthcare resource utilization (HCRU). METHODS: The COOL-PER trial was a prospective, multicenter, single-arm study that enrolled patients with early persistent AF (duration &#x2264; 3 years). An ILR was implanted 7-90 days before CBA for continuous rhythm monitoring. RESULTS: Among 130 enrolled patients, 123 completed the 3-year follow-up (mean age, 60.5 &#xb1; 8.4 years; 25.2% women). Median AF burden decreased from 99.9% (interquartile range, 53.1-100.0) at baseline to 0.1% (0.0-4.2), 0.5% (0.0-9.1), and 0.7% (0.0-9.5) at 1, 2, and 3 years (all P < .001). Of 47 patients who were recurrence-free at 1 year, 25 (53.2%) developed subsequent recurrence, and 20 (80.0%) were detected by ILR alone. Compared with first-year recurrence, subsequent recurrence was less often persistent (4.0% vs 28.9%; P = .001) and was associated with a lower AF burden (0.1% [0.0-1.6] vs 2.8% [0.4-18.7]; P = .010). Both persistent-type recurrence and AF burden &#x2265; 10% were associated with more additional rhythm control interventions (78.3% vs 30.8% vs 0%; 78.6% vs 39.1% vs 0%; both P < .001) and cardiovascular hospitalization (17.4% vs 3.8% vs 0%, P = .045; 14.3% vs 4.3% vs 0%, P = .029). CONCLUSION: CBA achieved durable AF burden suppression over 3 years in early persistent AF. Subsequent recurrence after the first year was common and was predominantly detectable by ILR only. Subsequent recurrences were often paroxysmal, with a lower AF burden and associated with lower HCRU, supporting the value of continuous long-term rhythm monitoring for characterizing rhythm status beyond the first post-ablation year.

Cryoballoon ablation