Growth Rate and Outcomes in Locally Recurrent Extremity and Truncal Soft Tissue Sarcoma.

Importance: Improved prognostic tools are needed for patients with locally recurrent extremity or truncal soft tissue sarcoma (STS). Objective: To examine the association between average local recurrence (LR) growth rate and outcomes following resection of locally recurrent extremity or truncal STS. Design, Setting, and Participants: This retrospective cohort study used a prospectively maintained database from a single high-volume tertiary sarcoma referral center in the US to identify patients 16 years of age or older who underwent repeat resection of a locally recurrent extremity or truncal STS between July 1, 1982, and December 31, 2021. Patients with atypical lipomatous tumors, desmoid tumors, dermatofibrosarcoma protuberans, angiosarcomas, and prior or synchronous distant recurrence were excluded. Data were analyzed from November 1, 2022, to June 17, 2024. Exposure: Average LR growth rate, defined as the sum of recurrent tumor maximal diameters divided by the disease-free interval after index operation. Main Outcomes and Measures: The primary outcomes were cumulative incidences of disease-specific death (DSD), with death from other causes as a competing risk, and second LR, with death from any cause as a competing risk. Results: The study cohort included 253 patients (median [IQR] age, 64 [51-73] years; 140 [55.3%] male). The 5-year cumulative incidence of DSD after repeat resection was 29%. Multivariable analysis indicated that LR growth rate (hazard ratio [HR], 1.12 [95% CI, 1.08-1.18]; P < .001), younger age (HR, 0.98 [95% CI, 0.97-0.99]; P = .002), R1 or R2 margins (HR, 1.71 [95% CI, 1.03-2.84]; P = .04), high LR grade (HR, 2.90 [95% CI, 1.17-7.20]; P = .02), and multifocality (HR, 2.92 [95% CI, 1.70-5.00]; P < .001) were independently associated with higher incidence of DSD. Using the minimum P value method, the optimal cutoff for growth rate was found to be 0.68 cm/mo. Patients with values above this cutoff had higher 5-year incidences of DSD following repeat resection (63% vs 19%; permutation test P < .001) and higher amputation rates (19% vs 7%; P = .008). Only R1 margins were independently associated with higher incidence of second LR (HR, 1.81 [95% CI, 1.19-2.78]; P = .006). Conclusions and Relevance: In this cohort study of patients undergoing resection of a locally recurrent extremity or truncal STS, LR growth rate was independently associated with DSD. These findings suggest that patients with growth rates higher than 0.68 cm/mo who undergo LR resection may have high disease-specific mortality and amputation rates and should be considered for perioperative systemic therapy.

Risk Factors of Oral Squamous Cell Carcinoma with Special Emphasis on Areca Nut Usage and Its Association with Clinicopathological Parameters and Recurrence.

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent type of head and neck cancer and is associated with high mortality, particularly in Southeast Asian countries. Areca nut usage, smoking, and alcohol consumption are the most common risk factors for OSCC. Areca nut chewing is highly prevalent in Pakistan and has been attributed to an increase in OSCC cases. This study aimed to determine the association between areca nut usage and various clinicopathological features of OSCC and further evaluate the association of clinicopathological parameters of OSCC with tumor recurrence. Materials and Methods: The study was conducted using the data of 228 patients with OSCC resected at Liaquat National Hospital, Karachi, Pakistan, over 5 years between 2018 and 2022. Clinicopathological data were collected from hospital archives, and associations between various risk factors and clinicopathological parameters were determined. Results: Males were more commonly affected (77.2%), and the most common age group was <50 years (54.4%). Areca nut usage was reported in 59.6% of cases, and the buccal mucosa was the most common site (62.7%). Areca nut usage was significantly associated with male gender, greater tumor size, greater depth of invasion (DOI), higher tumor stage, nodal stage, presence of perineural invasion (PNI), and recurrence. In addition, multivariate analysis revealed that OSCC recurrence was significantly associated with older age, larger tumor size and DOI, nodal metastasis, and areca nut usage. Conclusion: Areca nut-related OSCCs were associated with poor prognosis and recurrence in our study population. Furthermore, OSCC recurrence was associated with various clinicopathological parameters, such as larger tumor size, a higher DOI, and nodal metastasis.

Metastatic disease and major adverse cardiovascular events preceding diagnosis are the main determinants of disease-specific survival of pheochromocytoma/paraganglioma: long-term follow-up of 303 patients.

Purpose: The natural history in unselected cohorts of patients with pheochromocytoma/ paraganglioma (PPGL) followed for a period >10 years remains limited. We aimed to describe baseline characteristics and outcome of a large cohort and to identify predictors of shorter survival. Methods: This retrospective single-center study included 303 patients with newly diagnosed PPGL from 1968 to December 31, 2023, in 199 prospectively supplemented since July 2020. Mean follow-up was 11.4 (range 0.3-50) years, germline genetic analyses were available in 92.1%. The main outcome measures were overall (OAS), disease-specific (DSS), recurrence-free (RFS) survival and predictors of shorter survival evaluated in patients with metastases at first diagnosis (n=12), metastatic (n=24) and nonmetastatic (n=33) recurrences and without evidence of PPGL after first surgery (n=234). Results: Age at study begin was 49.4 ± 16.3 years. There were 72 (23.8%) deaths, 15 (5.0%), 29 (9.6%) and 28 (9.2%) due to PPGL, cardiovascular disease (CVD) and malignant or other diseases, respectively. Median OAS, DSS1 (tumor-related) and DSS2 (DSS1 and death caused by CVD) were 4.8, 5.9 and 5.2 years (patients with metastases at first diagnosis), 21.2, 21.2 and 19.9 years, and 38.0, undefined and 38.0 years (patients with metastatic and with nonmetastatic recurrences, respectively). Major adverse cardiovascular events (MACE) preceded the first diagnosis in 15% (n=44). Shorter DSS2 correlated with older age (P ≤ 0.001), male sex (P ≤ 0.02), MACE (P ≤ 0.01) and primary metastases (P<0.0001, also for DSS1). Conclusion: The clinical course of unselected patients with PPGL is rather benign. Survival rates remain high for decades, unless there are MACE before diagnosis or metastatic disease.

[Epidemiological features of laryngeal papillomatosis in adults in Moscow]. / Epidemiologicheskie osobennosti papillomatoza gortani u vzroslykh v Moskve.

OBJECTIVE: To evaluate the incidence of laryngeal papillomatosis (LP) and LP recurrence in adults and to determine the risk factors for the development of LP recurrence in adults in Moscow. To solve the tasks set, a survey of patients carried out, including the collection of complaints and anamnesis, a standard examination of the ENT organs, an assessment of the condition of the larynx, and a histological examination. MATERIAL AND METHODS: We conducted a retrospective analysis of the case histories of 299 patients with LP observed and treated at the Sverzhevsky Research and Clinical Institute of Otorhinolaryngology in the period 2010-2020. RESULTS: On average, over the entire study period, the prevalence of PG was 17.80%. It was found that out of 299 patients, 69.6% (n=208) had a relapse of LP. Papilloma of the larynx were more often localized in the glottis. 275 (92%) patients had a widespread form of LP. LP recurrences were significantly more common in women and in patients with an existing cicatricle process in the larynx. The relapse rate was higher in non-smokers (73.5% vs 47.8%; p<0.001). Although the recurrence rate was higher in patients with non-voice occupations (70.6% vs. 52.9%), there was no statistically significant association between relapses and the vocal professions (p=0.125). CONCLUSION: As a result of the study, a number of risk factors for laryngeal papillomatosis recurrent have been identified, and their study should be continued.

No difference in oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving radical nephroureterectomy.

Patients with end stage renal disease (ESRD) are at high risk of developing upper tract urothelial carcinoma (UTUC). Due to high recurrence rate of UTUC in contralateral kidney and ureter, and high risk of complications related to surgery and anesthesia, whether it's necessary to remove both kineys and ureters at one time remains in debate. We utilized Taiwanese UTUC Registry Database to valuate the difference of oncological outcomes and perioperative complications between patients with ESRD with unilateral and bilateral UTUC receiving surgical resection. Patients with ESRD and UTUC were divided into three groups, unilateral UTUC, previous history of unilateral UTUC with metachronous contralateral UTUC, and concurrent bilatetral UTUC. Oncological outcomes, perioperative complications, and length of hospital stays were investiaged. We found that there is no diffence of oncological outcomes including overall survival, cancer specific survival, disease free survival and bladder recurrence free survival between these three groups. Complication rate and length of hospital stay are similar. Adverse oncological features such as advanced tumor stage, lymph node involvement, lymphovascular invasion, and positive surgical margin would negatively affect oncological outcomes.

Recurrences after nephron-sparing treatments of renal cell carcinoma: a competing risk analysis.

PURPOSE: To examine associations between ablative therapy (AT) and partial nephrectomy (PN) and the occurrence of local recurrence (LR), distant metastatic recurrence (DMR) and all-cause mortality in a nation-wide real-world population-based cohort of patients with nonmetastatic renal cell carcinoma (nmRCC). METHODS: Data on 2751 AT- or PN-treated nmRCC tumours diagnosed during 2005-2018, representing 2701 unique patients, were obtained from the National Swedish Kidney Cancer Register. Time to LR/DMR or death with/without LR/DMR was analysed using Cox regression models. RESULTS: During a mean of 4.8 years follow-up, LR was observed for 111 (4.0%) tumours, DMR for 108 (3.9%) tumours, and death without LR/DMR for 206 (7.5%) tumours. AT-treated tumours had a 4.31 times higher risk of LR (P < 0.001) and a 1.91 times higher risk of DMR (P = 0.018) than PN-treated, with no significant differences in risk of death without LR/DMR. During a mean of 3.2 and 2.5 years of follow-up after LR/DMR, respectively, 24 (21.6%) of the LR cases and 56 (51.9%) of the DMR cases died, compared to 7.5% in patients without LR/DMR. There were no significant differences between AT- and PN-treated regarding risks of early death after occurrence of LR or DMR. CONCLUSION: AT treatment of patients with nmRCC implied significantly higher risks of LR and DMR compared with PN treatment. To minimize the risks of LR and DMR, these results suggest that PN is preferred over AT as primary treatment, supporting the EAU guidelines to recommended AT mainly to frail and/or comorbid patients.

Evaluation of different methods of transoral minimally invasive surgery for supraglottic laryngeal carcinoma.

BACKGROUND AND OBJECTIVES: To analyze oncological and functional results of transoral minimally invasive surgery (TMIS) for supraglottic laryngeal carcinoma (SGLC), and investigate independent prognostic factors. METHODS: Seventy SGLC patients treated with TMIS were included. The overall survival (OS), recurrence-free survival (RFS), and postoperative functions were analyzed. RESULTS: Sixty-two patients were early-stage (Tis, T1, and T2) and eight patients were T3. Eleven patients received preoperative induction chemotherapy (IC). Sixty patients received transoral laser microsurgery (TLM), and 10 patients received transoral robotic surgery (TORS). Fifty-eight patients were scored Grade-1 by water swallow test, and 49 patients were scored Grade 0 by grade, roughness, breathiness, asthenia, strain. The 1, 3, and 5 year OS of all were 95.450%, 84.877%, and 78.026%, and RFS were 89.167%, 78.052%, and 75.451% respectively. Kaplan-Meier survival analysis showed N stage and clinical stage were associated with OS, smoking, clinical stage, surgical margins, and Ki-67 index were associated with RFS. There were no significant differences in preoperative IC or direct surgery, TLM, or TORS. Cox analyses showed smoking and surgical margins were independent prognosis factors for RFS. CONCLUSIONS: The positive margin, Ki-67 index ≥40% and P53(+)&Ki-67 index ≥40% are worse factors affecting recurrence for SGLC patients. Both smoking and surgical margins are independent prognostic factors affecting recurrence.

Differential effect of surgical technique on intravesical recurrence after radical nephroureterectomy in patients with upper tract urothelial cancer: a systematic review and Meta-analysis.

CONTEXT: Radical nephroureterectomy (RNU) with bladder cuff resection is the standard treatment in patients with high-risk upper tract urothelial cancer (UTUC). However, it is unclear which specific surgical technique may lead to improve oncological outcomes in term of intravesical recurrence (IVR) in patients with UTUC. OBJECTIVE: To evaluate the efficacy of surgical techniques and approaches of RNU in reducing IVR in UTUC patients. EVIDENCE ACQUISITION: Three databases were queried in January 2024 for studies analyzing UTUC patients who underwent RNU. The primary outcome of interest was the rate of IVR among various types of surgical techniques and approaches of RNU. EVIDENCE SYNTHESIS: Thirty-one studies, comprising 1 randomized controlled trial and 1 prospective study, were included for a systematic review and meta-analysis. The rate of IVR was significantly lower in RNU patients who had an early ligation (EL) of the ureter compared to those who did not (HR: 0.64, 95% CI: 0.44-0.94, p = 0.02). Laparoscopic RNU significantly increased the IVR compared to open RNU (HR: 1.28, 95% CI: 1.06-1.54, p < 0.001). Intravesical bladder cuff removal significantly reduced the IVR compared to both extravesical and transurethral bladder cuff removal (HR: 0.65, 95% CI: 0.51-0.83, p = 0.02 and HR: 1.64, 95% CI: 1.15-2.34, p = 0.006, respectively). CONCLUSIONS: EL of the affected upper tract system, ureteral management, open RNU, and intravesical bladder cuff removal seem to yield the lowest IVR rate in patients with UTUC. Well-designed prospective studies are needed to conclusively elucidate the optimal surgical technique in the setting of single post-operative intravesical chemotherapy.

Evaluating the effect of histopathological parameters of prostate adenocarcinoma on prognosis in radical prostatectomy specimens.

BACKGROUND: Over the past decade, significant updates have been made regarding the classification and grading of prostate adenocarcinoma in radical prostatectomy specimens, following decisions reached in international conferences and through impactful publications. These alterations are closely linked to patient prognosis. OBJECTIVES: Observe the incidence of these changes and their impact on patient prognosis. Additionally, investigate the relationship between histopathological and clinical parameters to assist in multidisciplinary treatment planning. DESIGN: Retrospective cohort study. SETTING: Tertiary university hospital. METHODS: Hematoxylin and eosin, along with immunohistochemistry stained sections, were reevaluated, and clinical information, including patient demographics, preoperative PSA levels, and patient follow-up were collected from patients who underwent radical prostatectomy at our center. SAMPLE SIZE: 182 patients. MAIN OUTCOME MEASURES: Biochemical recurrence. RESULTS: The study highlighted the negative prognostic effects of factors such as Gleason grade group, lymphovascular invasion, intraductal carcinoma, positive surgical margins, extraprostatic extension, pathological T stage, and seminal vesicle invasion. These factors are important determinants of recurrence-free survival in prostate adenocarcinoma patients. CONCLUSION: This study identified comedonecrosis and intraductal carcinoma as independent negative prognostic factors. A 3-mm cutoff for positive surgical margins was supported, while the current cutoff for extraprostatic extension may require reevaluation. The impact of cribriform pattern and ductal carcinoma appears to be influenced by the grade group. No independent relationship was found between the Gleason score/pattern on positive surgical margins or extraprostatic extension and prognosis. Further, large-scale studies with long-term follow-up are needed. LIMITATIONS: The study is limited by the relatively small number of patients for certain parameters.

Appendiceal neoplasms in Saudi Arabia: prevalence and clinicopathological profile.

BACKGROUND: The appendix is a small organ with no particular known function. Primary appendiceal neoplasms (ANs) are rare. While the prevalence is increasing worldwide over the past two decades, no apparent increase in the prevalence of ANs has been reported in the Arabian Gulf States. Recently, a significant decline in the age at diagnosis of some types of ANs has been reported worldwide, with a female predominance. OBJECTIVES: Evaluate the prevalence and clinicopathological characteristics of ANs within our institution in Saudi Arabia and compare them to limited existing studies from different regions as well as the Arabian Gulf States. DESIGN: Retrospective cohort. SETTING: Tertiary care center in Riyadh. PATIENTS AND METHODS: All patients who underwent appendectomy and had the appendix submitted for histopathological evaluation between May 2015 and June 2020 were included to allow for a follow-up of 5 years or more at the time of data collection. MAIN OUTCOME MEASURES: Demographics, clinical presentations, surgical interventions, histopathological findings, complications, and recurrence rates. SAMPLE SIZE: 25 AN patients. RESULTS: Of 1110 patients, 25 had ANs (13 female and 12 male participants) with a mean (standard deviation) age of 54.6 (14.1) years. Only 40% presented with acute appendicitis, 64% had comorbidities, and less than 50% underwent laparoscopic appendectomy. Histopathologically, 72% were low-grade appendiceal mucinous neoplasms (LAMNs). Complications were minimal grades (Clavien-Dindo classification), with 80% experiencing none. The mean hospital stay was 9.96 days. Local recurrence occurred in 8% of cases, and distant metastasis was documented in one adenocarcinoma case. However, the 5-year overall and disease-free survival rates were 88% and 80%, respectively. CONCLUSIONS: The incidence of ANs is increasing in Saudi Arabia with the higher prevalence of LAMNs. The pathological examination of the resected appendix played a pivotal role in the diagnosis of ANs. LIMITATIONS: Data collected retrospectively, a single institution, and a small population.

Prediction of non-muscle invasive bladder cancer recurrence using deep learning of pathology image.

We aimed to build a deep learning-based pathomics model to predict the early recurrence of non-muscle-infiltrating bladder cancer (NMIBC) in this work. A total of 147 patients from Xuzhou Central Hospital were enrolled as the training cohort, and 63 patients from Suqian Affiliated Hospital of Xuzhou Medical University were enrolled as the test cohort. Based on two consecutive phases of patch level prediction and WSI-level predictione, we built a pathomics model, with the initial model developed in the training cohort and subjected to transfer learning, and then the test cohort was validated for generalization. The features extracted from the visualization model were used for model interpretation. After migration learning, the area under the receiver operating characteristic curve for the deep learning-based pathomics model in the test cohort was 0.860 (95% CI 0.752-0.969), with good agreement between the migration training cohort and the test cohort in predicting recurrence, and the predicted values matched well with the observed values, with p values of 0.667766 and 0.140233 for the Hosmer-Lemeshow test, respectively. The good clinical application was observed using a decision curve analysis method. We developed a deep learning-based pathomics model showed promising performance in predicting recurrence within one year in NMIBC patients. Including 10 state prediction NMIBC recurrence group pathology features be visualized, which may be used to facilitate personalized management of NMIBC patients to avoid ineffective or unnecessary treatment for the benefit of patients.

The Recurrence Rate of Colorectal Polyps among Patients with Average Risk of Colorectal Cancer.

BACKGROUND: CRC is going to be an important issue in Middle East countries. Also, the main parts of this cancer develop from benign adenomas. AIM: To understand the recurrence rate of colorectal polyps among average-risk subjects. METHOD: In a prospective study, the average-risk patients with colorectal adenoma were enrolled in this study based on inclusion criteria. The patients were consulted annually by an expert gastroenterologist. A control colonoscopy was programmed after three years of follow-up. It was not an obligation to follow our program, and each patient could exit the study at any time. The patient who developed one of the exclusion criteria was also withdrawn from the study by the gastroenterologist of this study. RESULTS: 237 patients were enrolled in this study. Of them, 102 patients completed their 3-year follow-up. Among these participants, 62 (60.8%) were male and 40 (39.2%) were female, with a mean age of 57.05 ± 12.87 years. Additionally, 20 (19.6%) subjects had adenomatous polyps at the end of the study. Patients with recurrent colorectal polyps tend to be raised in large ones with a tubulovillous morphology. The polyps were more commonly located in the sigmoid colon, rectum. Furthermore, high-grade dysplasia was recorded in 5 patients. Tubulovillous polyp had higher chance of recurrence than patients with tubular polyp. CONCLUSION: We believe the colonoscopy screening needs to be set up in regions previously considered low-risk for CRC. Also, it may be valuable to control colonoscopy for less than three years in patients with dysplasia.

Radicality and safety of total mesopancreatic excision in pancreatoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Pancreatic head cancer patients who undergo pancreatoduodenectomy (PD) often experience disease recurrence, frequently associated with a positive margin status (R1). Total mesopancreas excision (TMpE) has emerged as a potential approach to increase surgical radicality and minimize locoregional recurrence. However, its effectiveness and safety remain under evaluation. METHODS: We conducted a systematic review and meta-analysis to synthesize current evidence on TMpE outcomes. A systematic search of MEDLINE, EMBASE, Cochrane, and Web of Science databases was conducted up to March 2024 to identify studies comparing TMpE with standard pancreatoduodenectomy (sPD). The risk ratio (RR) or mean difference (MD) was pooled using a random effects model. RESULTS: From 452 studies identified, 9 studies with a total of 738 patients were included, with 361 (49%) undergoing TMpE. TMpE significantly improved the R0 resection rate (RR 1.24; 95% CI 1.11-1.38; P < 0.05), reduced blood loss (MD -143.70 ml; 95% CI -247.92, -39.49; P < 0.05), and increased lymph node harvest (MD 7.27 nodes; 95% CI 4.81, 9.73; P < 0.05). No significant differences were observed in hospital stay, postoperative complications, or mortality between TMpE and sPD. TMpE also significantly reduced overall recurrence (RR 0.53; 95% CI 0.35-0.81; P < 0.05) and local recurrence (RR 0.39; 95% CI 0.24-0.63; P < 0.05). Additionally, the risk of pancreatic fistula was lower in the TMpE group (RR 0.66; 95% CI 0.52-0.85; P < 0.05). CONCLUSION: Total mesopancreas excision significantly increases the R0 resection rate and reduces locoregional recurrence while maintaining an acceptable safety profile when compared with standard pancreatoduodenectomy. Further prospective randomized studies are warranted to determine the optimal surgical approach for total mesopancreatic resection.

Factors Associated with Recurrence of Ameloblastoma: A Scoping Review.

PURPOSE: This scoping review aimed to identify factors associated with the recurrence of ameloblastoma. METHODS: Systematic searches were conducted in PubMed, Scopus, and EMBASE, based on the board research question: "What factors are related to the recurrence of ameloblastoma?". English-language observational studies addressing the risk and preventive factors associated with recurrent ameloblastoma were included and data were extracted. RESULTS: Eighty-three retrospective observational studies met the inclusion criteria. The identified prognostic factors for recurrence included: (1) Tumor size/diameter/volume, (2) cortical bone perforation/ soft tissue invasion, (3) multilocular radiolucency, (4) impacted tooth-involving lesions, (5) root resorption, (6) WHO classification - conventional (solid/multicystic) ameloblastoma, (7) histological subtype - mural invasion of unicystic ameloblastoma, (8) conservative treatment modalities - simple enucleation, curettage, and marsupialization, and (9) non-extraction/preservation of involved teeth. No strong evidence linked immunohistochemical expression to recurrence. Interestingly, BRAF p.V600E remained controversial in terms of recurrence, despite being a frequent finding in ameloblastoma. CONCLUSION: Certain clinical characteristics, radiographic findings, histological subtypes, and treatment choices of ameloblastoma can help identify patients at high risk of recurrence. Further prospective studies to evaluate the prognostic factor model and research on immunohistochemistry are required.

Temporal trends and long-term outcomes of radiofrequency ablation for hepatocellular carcinoma within the Milan criteria.

No study has analysed the temporal trends of the long-term results and clinical characteristics of patients with hepatocellular carcinoma (HCC) treated using radiofrequency ablation (RFA). Therefore, we examined temporal trends of characteristics of patients and treatment-naïve HCCs within the Milan criteria treated by RFA over 20 years. We retrospectively analysed 1099 patients with HCC within the Milan criteria treated with percutaneous RFA from January 2000 to December 2019. The overall survival (OS), recurrence-free survival (RFS), and factors affecting survival and local tumor progression were analysed using the Kaplan‒Meier method and Cox proportional hazards model. A trend test was performed to analyse the changing trends in participants and treatment outcomes. The overall and RFS of patients improved during the later period. In addition, viral hepatitis-related HCC incidence decreased, whereas that of alcohol- or non-alcoholic fatty liver disease-related HCC increased from the earlier to the later period (P for trend < 0.001). HBV antiviral therapy was increased and improved OS and RFS in patients treated using RFA. The outcomes after RFA over a 20-year period improved due to changes over time in target tumors and patients. The results could be useful for selecting patients who will benefit from RFA.

The Population-level Effect of Adjuvant Therapies on Breast Cancer Recurrence: Application of the Trend-in-Trend Design.

PURPOSE: Breast cancer has an average 10-year relative survival reaching 84%. This favorable survival is due, in part, to the introduction of biomarker-guided therapies. We estimated the population-level effect of the introduction of two adjuvant therapies-tamoxifen and trastuzumab-on recurrence using the trend-in-trend pharmacoepidemiologic study design. METHODS: We ascertained data on women diagnosed with nonmetastatic breast cancer who were registered in the Danish Breast Cancer Group clinical database. We used the trend-in-trend design to estimate the population-level effect of the introduction of (1) tamoxifen for postmenopausal women with estrogen receptor (ER)-positive breast cancer in 1982, (2) tamoxifen for premenopausal women diagnosed with ER-positive breast cancer in 1999, and (3) trastuzumab for women <60 years diagnosed with human epidermal growth factor receptor 2-positive breast cancer in 2007. RESULTS: For the population-level effect of the introduction of tamoxifen among premenopausal women diagnosed with ER-positive breast cancer in 1999, the risk of recurrence decreased by nearly one-half (OR = 0.52), consistent with evidence from clinical trials; however, the estimate was imprecise (95% confidence interval [CI] = 0.25, 1.85). We observed an imprecise association between tamoxifen use and recurrence from the time it was introduced in 1982 (OR = 1.24 95% CI = 0.46, 5.11), inconsistent with prior knowledge from clinical trials. For the introduction of trastuzumab in 2007, the estimate was also consistent with trial evidence, though imprecise (OR = 0.51; 95% CI = 0.21, 22.4). CONCLUSIONS: We demonstrated how novel pharmacoepidemiologic analytic designs can be used to evaluate the routine clinical care and effectiveness of therapeutic advancements in a population-based setting while considering some limitations of the approach.

PRAP study-partial versus radical adrenalectomy in hereditary pheochromocytomas.

OBJECTIVE: Hereditary pheochromocytoma (hPCC) commonly develops bilaterally, causing adrenal insufficiency when standard treatment, radical adrenalectomy (RA), is performed. Partial adrenalectomy (PA) aims to preserve adrenal function, but with higher recurrence rates. This study compares outcomes of PA versus RA in hPCC. METHODS: Patients with hPCC due to pathogenic variants in RET, VHL, NF1, MAX, and TMEM127 from 12 European centers (1974-2023) were studied retrospectively. Stratified analysis based on surgery type and initial presentation was conducted. The main outcomes included recurrence, adrenal insufficiency, metastasis, and mortality. RESULTS: The study included 256 patients (223 RA, 33 PA). Ipsilateral recurrence rates were 9/223 (4%) after RA versus 5/33 (15%) after PA (P = 0.02). Metastasis and mortality did not differ between groups. Overall, 103 patients (40%) underwent bilateral adrenalectomy either synchronously or metachronously (75 RA, 28 PA). Of these, 46% developed adrenal insufficiency after PA.In total, 191 patients presented with initial unilateral disease, of whom 50 (26%) developed metachronous contralateral disease, most commonly in RET, VHL, and MAX. In patients with metachronous bilateral disease, adrenal insufficiency developed in 3/4 (75%) when PA was performed as the first operation followed by RA, compared to 1/7 (14%) when PA was performed as the second operation after prior RA (P = 0.09). CONCLUSION: In patients with hPCC undergoing PA, local recurrence rates are higher than after RA, but metastasis and disease-specific mortality are similar. Therefore, PA seems a safe method to preserve adrenal function in patients with hPCC, in cases of both synchronous and metachronous bilateral disease, when performed as a second operation.

Clinical Treatment Score Post-5 Years (CTS5) and Late Recurrence Risk in Hormone Receptor-Positive, HER2-Positive Breast Cancer.

BACKGROUND: The Clinical Treatment Score post-5 years (CTS5) is a risk stratification tool used to determine the risk of late recurrence in hormone receptor-positive (HR+), HER2-negative breast cancer (BC). Limited data exist on its use in HR+, HER2-positive (HER2+) BC. PATIENTS AND METHODS: CTS5 was evaluated in HR+, HER2+ BC in the North Central Cancer Treatment Group (NCCTG) N9831 (Alliance) and NSABP B-31 (NRG) trials. RESULTS: A total of 1,862 patients with HR+, HER2+ BC without recurrence 5 years after enrollment were included. Overall, the CTS5 score was significantly associated with recurrence-free survival (RFS), with a hazard ratio (HR) of 1.35 (95% CI, 1.12-1.63; P=.002), but did not reach statistical significance in patients who received trastuzumab (n=829; HR, 1.29; 95% CI, 0.98-1.71; P=.07). CTS5 risk category was not significantly associated with RFS. In patients who received trastuzumab, other variables used in CTS5, including patient age and tumor size, were not significantly associated with RFS. N3 was significantly associated with worse outcomes (HR, 1.86; 95% CI, 1.09-3.17; P=.02) compared with N0-N1. Paradoxically, higher tumor grade was associated with better outcomes after 5 years in the multivariate analysis (HR, 0.71; 95% CI, 0.50-1.00; P=.05). The incidence of recurrences or deaths between years 5 to 10 was 10.6% in the CTS5 low-risk category, 5.6% in the intermediate-risk category, and 9.8% in the high-risk category. CONCLUSIONS: The CTS5 model does not accurately predict the risk of late recurrence in HR+, HER2+ BC treated with adjuvant trastuzumab in the N9831 and B-31 trials. This study underlines the need to develop a new prognostic model to better delineate the risk of late recurrence in patients with HR+, HER2+ BC receiving adjuvant trastuzumab. CLINICALTRIALS: gov identifiers: NCT00005970 (NCCTG N9831) and NCT00004067 (NRG/NSABP B-31).

Postoperative venous thromboembolism after surgery for locally recurrent rectal cancer.

BACKGROUND: Local recurrence is common after curative resections of rectal cancer. Surgical resection is considered a primary curative treatment option for patients with locally recurrent rectal cancer (LRRC). LRRC often requires a combined resection of other organs, especially in the case of posterior recurrence, which requires a combined resection of the sacrum, making the surgery highly invasive. Venous thromboembolism (VTE) is one of the lethal complications in the postoperative period, particularly in the field of pelvic surgery. We found no reports regarding the risks of postoperative VTE in surgery for LRRC, a typical highly invasive procedure in the field of colorectal surgery. This study aims to evaluate the risk of postoperative VTE in surgery for LRRC patients. METHODS: From April 2010 to March 2022, a total of 166 patients underwent surgery for LRRC in the pelvic region at our institutions. Clinicopathological background and VTE incidence were compared retrospectively. RESULTS: Among the 166 patients included in the study, 55 patients (33.1%) needed sacral resection. Pharmacological prophylaxis for prevention of VTE was performed in 121 patients (73.3%), and the incidence of VTE was 9.09% (5/55 patients) among those who underwent surgery for LRRC with sacral resection, while it was 1.8% (2/111 patients) in those without sacral resection. In univariate analysis, the combination with sacral resection was identified as a risk factor for VTE in surgery for LRRC (p = 0.047). CONCLUSIONS: This study demonstrates that surgery for LRRC combined with sacral resection could be a significant risk factor for VTE.

Natural history and surgical outcomes of Rathke's cleft cysts: a Spanish multicenter study.

Rathke's cleft cysts (RCC) are a common type of lesion found in the sellar or suprasellar area. They are usually monitored clinically, but in some cases, surgery may be required. However, their natural progression is not yet well understood, and the outcomes of surgery are uncertain. The objective of this study is to evaluate the natural history of Rathke's cleft cysts in patients who are clinically monitored without treatment, and to determine the outcomes of surgery and the incidence of recurrences over time. Design and patients: National multicentric study of patients diagnosed of Rathke's cleft cyst (RCC- Spain) from 2000 onwards and followed in 15 tertiary centers of Spain. A total of 177 patients diagnosed of RCC followed for 67.3 months (6-215) and 88 patients who underwent surgery, (81 patients underwent immediate surgery after diagnosis and 7 later for subsequent growth) followed for 68.8 months (3-235). Results: The cyst size remained stable or decreased in 73.5% (133) of the patients. Only 44 patients (24.3%) experienced a cyst increase and 9 of them (5.1%) experienced an increase greater than 3 mm. In most of the patients who underwent surgery headaches and visual alterations improved, recurrence was observed in 8 (9.1%) after a median time of 96 months, and no predictors of recurrence were discovered. Conclusions: Rathke's cleft cysts without initial compressive symptoms have a low probability of growth, so conservative management is recommended. Patients who undergo transsphenoidal surgery experience rapid clinical improvement, and recurrences are infrequent. However, they can occur after a long period of time, although no predictors of recurrence have been identified.