Acute appendicitis has traditionally been seen as a progressive disease that necessitates surgery to prevent complications like perforation. However, recent studies emphasize the importance of distinguishing between complicated and uncomplicated appendicitis, rather than treating all cases the same. This evolving understanding has led to a paradigm shift in how uncomplicated appendicitis is diagnosed and treated, with options like antibiotic therapy being considered alternatives to immediate surgery. This shift challenges the long-held belief that surgery is always required, and instead encourages more personalized treatment approaches and shared decision-making between clinicians and patients.

Background:Surgical site infections (SSI) are common. We selected five interventions from recent SSI prevention guidelines, to form the Enhanced PeriOperative Care and Health program (EPO2CH), a perioperative care bundle. We aimed to investigate the effect of the EPO2CH bundle on the incidence of SSI. Methods:The EPO2CH trial concerns an open label, pragmatic, randomised controlled parallel-group multicentre trial, in which we assigned patients, scheduled for elective abdominal surgery with incisions larger than five centimetres, to either standard care or standard care plus the EPO2CH bundle consisting of intraoperative high fraction of inspired oxygen; Goal-Directed Fluid Therapy; normothermia; perioperative glucose control; and incisional wound irrigation. The study was conducted in seven hospitals in the Netherlands. Patients were randomised per hospital per day in a 1:1 ratio with variable block sizes using an internet-based automated assignment system. The primary outcome was the incidence of SSI within 30 days in the intention-to-treat population. This study is registered at CCMO register (NL-OMON50566). Findings:Between March 1st, 2016, and March 26th, 2020, 1777 patients were included. The intervention group included 869 patients (mean age 63.1, 467 female and 402 male) versus 908 in the control group (mean age 64.0, 530 female and 378 male). The incidence of SSI was 18.4% (160/869) in the intervention and 18.9% (172/908) in the control group; relative risk 0.98 (95% CI: 0.81-1.18) in the intention-to-treat analysis and 0.91 (95% CI: 0.60-1.37) in the per-protocol analysis. The percentage of patients with a serious adverse event was 33.3% (289/869) versus 33.5% (304/908), RR 0.99, 95% CI 0.87-1.23. Interpretation:In a high-income health care setting, a care bundle did not lead to a lower incidence of surgical site infections when added to standard care including preoperative systemic antibiotic prophylaxis and alcohol-based surgical skin preparation. Considering the persistent high risk of SSI, research into interventions that may help to reduce this risk remains urgently needed. Funding:The Netherlands Organisation for Health Research and Development (ZonMW), and co-financed by Innovatiefonds Zorgverzekeraars, and Ethicon.

BACKGROUND:Randomised controlled trials (RCTs) have found antibiotics to be a feasible and safe alternative to appendicectomy in adults with imaging-confirmed acute appendicitis. However, patient inclusion criteria and outcome definitions vary greatly between RCTs. We aimed to compare antibiotics with appendicectomy for the treatment of acute appendicitis using individual patient data and uniform outcome definitions. METHODS:In this individual patient data meta-analysis, we searched PubMed, Embase, and the Cochrane Central Register of Controlled Trials without language restrictions between database inception and June 6, 2023, for RCTs comparing appendicectomy with antibiotics for the treatment of adults (≥18 years) with imaging-confirmed acute appendicitis. Studies without 1-year follow-up data on complications were excluded, as were patients. Corresponding authors of eligible studies were contacted and invited to share data; individual patient data were merged after validation. One-stage meta-analyses were conducted using a generalised, mixed-effects linear regression model, accounting for clustering of patients within studies. The primary outcome was the complication rate at 1-year follow-up, uniformly harmonised across trials using the Clavien-Dindo classification. Complications were further divided into minor (grade 1-2 or equivalent) and major (grade 3-5 or equivalent) complications. Appendicectomy rate during 1 year was a key secondary outcome but not considered a complication for the antibiotics group. Outcomes were described separately for patients with and without an appendicolith. This study is registered with PROSPERO, CRD42023391676. FINDINGS:Of 887 potentially relevant articles, eight were eligible for inclusion, of which six RCTs could provide data for 2101 eligible patients (1050 assigned to antibiotics and 1051 assigned to appendicectomy; 830 [39·5%] women and 1271 [60·5%] men). All studies raised some bias concerns due to absence of blinding. One study was judged to have a high risk of bias due to the exclusion of eligible patients after randomisation, but these patients were eligible for inclusion in our meta-analysis. At 1 year, 57 (5·4%) of 1050 patients randomly assigned to antibiotics had a complication compared with 87 (8·3%) of 1051 patients randomly assigned to appendicectomy (odds ratio [OR] 0·49 [95% CI 0·20 to 1·20]; risk difference -4·5 percentage points [95% CI -11·6 to 2·6]). At 1 year, 1025 (97·5%) patients in the appendicectomy group had undergone appendicectomy compared with 356 (33·9%) patients in the antibiotics group. In patients with an appendicolith at pre-interventional imaging, there were more complications at 1 year among patients who received antibiotic treatment than among those who underwent appendicectomy (29 [15·0%] of 193 patients vs 12 [6·3%] of 190 patients; OR 2·82 [95% CI 1·11 to 7·18]; risk difference 13·2 percentage points [95% CI 2·3 to 24·2]). In the antibiotics group, 94 (48·7%) of 193 patients with an appendicolith underwent appendicectomy within 1 year versus 262 (30·6%) of 857 patients without an appendicolith. INTERPRETATION:This meta-analysis showed that antibiotic treatment in adults with imaging-confirmed acute appendicitis was a safe alternative to surgery and resulted in around two-thirds of patients avoiding appendicectomy during the first year. In patients with an appendicolith, initial antibiotic treatment increased the risk of complications compared with appendicectomy, and around half of these patients assigned to antibiotics underwent step-up appendicectomy within 1 year. These data should be key components in shared decision making. FUNDING:None.

PURPOSE:To determine the accuracy of final judgements of doctors at the emergency department (ED) and radiologists to differentiate between complicated and uncomplicated acute appendicitis, because these have different treatment options. METHODS:This prospective, multicenter study included adult patients with imaging-confirmed acute appendicitis, operated with intention to appendectomy. Both doctors at ED and radiologists assessed appendicitis severity as a final judgement of "uncomplicated" or "complicated" appendicitis. Doctors at ED integrated clinical, laboratory, and imaging findings. Radiologists relied solely on imaging findings. Outcomes were accuracy of these judgements for diagnosis of complicated appendicitis compared to the reference standard by an adjudication committee. RESULTS:After imaging, 1070 patients with confirmed acute appendicitis were included. Doctors at ED accurately labelled 656 of 701 (93.6%) patients with true uncomplicated appendicitis as uncomplicated, and 163 of 369 (44.2%) patients with true complicated appendicitis were labelled as complicated. Sensitivity, specificity, and positive and negative predictive values (PPV and NPV) for complicated appendicitis were 44.2%, 93.6%, and 78.4% and 76.1%, respectively. Comparable accuracy was found for the radiologist's assessment in 941 patients, with true positive rates of 92.2% (581 of 630 patients) for uncomplicated appendicitis and 46.6% (145 of 311 patients) for complicated appendicitis. CONCLUSION:More than half of all patients with true complicated appendicitis is incorrectly classified as uncomplicated appendicitis according to the judgements of doctors at ED, integrating clinical, laboratory, and imaging results, and of radiologists assessing diagnostic imaging. These judgements are thereby not sufficiently reliable in ruling out complicated appendicitis.

ImportanceWhen considering nonoperative treatment in a patient with acute appendicitis, it is crucial to accurately rule out complicated appendicitis. The Atema score, also referred to as the Scoring System of Appendicitis Severity (SAS), has been designed to differentiate between uncomplicated and complicated appendicitis but has not been prospectively externally validated.ObjectiveTo externally validate the SAS and, in case of failure, to develop an improved SAS (2.0) for estimating the probability of complicated appendicitis.Design, Setting, and ParticipantsThis prospective study included adult patients who underwent operations for suspected acute appendicitis at 11 hospitals in the Netherlands between January 2020 and August 2021.Main Outcomes and MeasuresAppendicitis severity was predicted according to the SAS in 795 patients and its sensitivity and negative predictive value (NPV) for complicated appendicitis were calculated. Since the predefined targets of 95% for both were not met, the SAS 2.0 was developed using the same cohort. This clinical prediction model was developed with multivariable regression using clinical, biochemical, and imaging findings. The SAS 2.0 was externally validated in a temporal validation cohort consisting of 565 patients.ResultsIn total, 1360 patients were included, 463 of whom (34.5%) had complicated appendicitis. Validation of the SAS resulted in a sensitivity of 83.6% (95% CI, 78.8-87.6) and an NPV of 85.0% (95% CI, 80.6-88.8), meaning that the predefined targets were not achieved. Therefore, the SAS 2.0 was developed, internally validated (C statistic, 0.87; 95% CI, 0.84-0.89), and subsequently externally validated (C statistic, 0.86; 95% CI, 0.82-0.89). The SAS 2.0 was designed to calculate a patient’s individual probability of having complicated appendicitis along with a 95% CI.Conclusions and RelevanceIn this study, external validation of the SAS fell short in accurately distinguishing complicated from uncomplicated appendicitis. The newly developed and externally validated SAS 2.0 was able to assess an individual patient’s probability of having complicated appendicitis with high accuracy in patients with acute appendicitis. Use of this patient-specific risk assessment tool can be helpful when considering and discussing nonoperative treatment of acute appendicitis with patients.

Abdominal pain can be part of a variety of abdominal and non-abdominal conditions. Individual symptoms and signs from history taking and physical examination have limited discriminatory value for a clear diagnosis. Additional laboratory testing strategies and imaging techniques can provide more guidance in this respect. In this article, we will answer specific practical questions with respect to abdominal pain. Topics discussed include various abdominal conditions, diagnostic markers, the diagnostic value of imaging techniques and the most recent changes in the policies for the diagnosis of appendicitis, cholecystitis and diverticulitis.

Abdominal pain can be part of a variety of abdominal and non-abdominal conditions. Individual symptoms and signs from history taking and physical examination have limited discriminatory value for a clear diagnosis. Additional laboratory testing strategies and imaging techniques can provide more guidance in this respect. In this article, we will answer specific practical questions with respect to abdominal pain. Topics discussed include various abdominal conditions, diagnostic markers, the diagnostic value of imaging techniques and the most recent changes in the policies for the diagnosis of appendicitis, cholecystitis and diverticulitis.

Background Radiologic imaging can accurately diagnose acute appendicitis, but little is known about its discriminatory capacity between complicated and uncomplicated appendicitis. Objective This study aims to investigate the accuracy of imaging in discriminating complicated from uncomplicated appendicitis. Methods Data was used from the prospective, nationwide, observational SNAPSHOT appendicitis database, including patients with suspected acute appendicitis who were planned for an appendectomy. Usage of ultrasound (US), CT, MRI or a combination was recorded. Radiological reports were used to group for complicated or uncomplicated appendicitis. The reference standard was based on operative and pathological findings. Primary outcomes were sensitivity and specificity in discriminating complicated from uncomplicated appendicitis. Secondary outcomes were diagnostic accuracy results per imaging modality and for the subgroups age, BMI, and sex. Results Preoperative imaging was performed in 1964 patients. In 1434 patients (73%), only US was used; in 109 (6%) patients, only CT was used; and 421 (21%) patients underwent US followed by CT or MRI. Overall, imaging workup as practiced, following the national guideline, had a poor sensitivity for complicated appendicitis of only 35%, although specificity was as high as 93%. For US, accuracy for complicated appendicitis was higher in children than in adults; sensitivity 41.2% vs. 26.4% and specificity 94.6% vs. 93.4%, respectively, p = 0.003. For relevant subgroups such as age, sex and BMI, no other differences in the discriminatory performance were found. Conclusion A diagnostic workup with stepwise imaging, using a conditional CT or MRI strategy, poorly discriminates between complicated and uncomplicated appendicitis in daily practice.

Background: Little is known about patients with appendicitis presenting at nighttime. It is hypothesized that patients presented at night more frequently have a complicated (gangrenous or perforated) appendicitis and therefore develop more postoperative complications. Methods: In this study data were used from the nationwide, prospective SNAPSHOT study appendicitis, including 1975 patients undergoing surgery for suspected appendicitis. This study included only adults. Two primary outcomes were defined: (A) The proportion of patients with complicated appendicitis and (B) the proportion of patients with a complication postoperatively presenting during daytime versus nighttime period. Analysis for both complicated and uncomplicated appendicitis was performed, and a multivariate model was used to correct for baseline characteristics and time to surgery. Results: In total, 1361 adult patients with appendicitis were analyzed. Both at nighttime and at daytime, 34% had complicated appendicitis. In patients presenting in the daytime, 12.1% developed a postoperative complication versus 18.6% for presentation at night (p = 0.008). In a multivariate analysis, the risk for a postoperative complication when presenting at night was significantly increased (adjusted OR 1.74; 95% CI 1.14–2.66, p = 0.01). Surgery within eight hours after presentation does not lower this risk (adjusted OR 1.37; 95% CI 0.97–1.95, p = 0.078). Conclusion: Complicated appendicitis is seen as frequently during the day as at nighttime. For patients who present at nighttime with acute appendicitis, the risk of a postoperative complication is higher compared with a presentation at daytime. In multivariate analysis, nighttime presentation but not surgery within 8 h after presentation is independently associated with postoperative complication risk.

Present theory is that uncomplicated and complicated appendicitis are different entities. Recent studies suggest it is safe to delay surgery in patients with uncomplicated appendicitis. We hypothesize that patients with complicated appendicitis are at higher risk for postoperative complications when surgery is delayed. Data was used from the multicenter, prospective SNAPSHOT appendicitis study of 1975 patients undergoing surgery for suspected appendicitis. Adult patients (≥ 18 years) who underwent appendectomy for appendicitis were included in this study. The primary outcome was the difference in postoperative complications between patients with complicated appendicitis who were operated within and after 8 h after hospital presentation. Secondary outcomes were the incidence of both uncomplicated and complicated appendicitis in relationship to delay of appendectomy. Follow-up was 30 days. A multivariable analysis was performed. Of 1341 adult patients with appendicitis, 34.3% had complicated appendicitis. In patients with complicated appendicitis, 22.8% developed a postoperative complication compared to 8.2% for uncomplicated appendicitis (P < 0.001). Delay in surgery (> 8 h) increased the complication rate in patients with complicated appendicitis (28.1%) compared to surgery within 8 h (18.3%; P = 0.01). Multivariate analysis showed a delay in surgery as an independent predictor for a postoperative complication in patients with complicated appendicitis (OR 1.71; 95%CI 1.01–2.68, P = 0.02). In-hospital delay of surgery (> 8 h) in patients with complicated appendicitis is associated with a higher risk of a postoperative complication. It is important that we recognize and treat these patients early.

IntroductionGrowing evidence is showing that complicated and uncomplicated appendicitis are two different entities that may be treated differently. A correct diagnosis of the type of appendicitis is therefore essential. The Scoring system of Appendicitis Severity (SAS) combines clinical, laboratory and imaging findings. The SAS rules out complicated appendicitis in 95% (negative predictive value, NPV) and detects 95% (sensitivity) of patients with complicated appendicitis in adults suspected of acute appendicitis. However, this scoring system has not yet been validated externally. In this study, we aim to provide a prospective external validation of the SAS in a new cohort of patients with clinical suspicion of appendicitis. We will optimise the score when necessary.Methods and analysisThe SAS will be validated in 795 consecutive adult patients diagnosed with acute appendicitis confirmed by imaging. Data will be collected prospectively in multiple centres. The predicted diagnosis based on the SAS score will be compared with the combined surgical and histological diagnosis. Diagnostic accuracy for ruling out complicated appendicitis will be calculated. If the SAS does not reach a sensitivity and NPV of 95% in its present form, the score will be optimised. After optimisation, a second external validation will be performed in a new group of 328 patients. Furthermore, the diagnostic accuracy of the clinical perspective of the treating physician for differentiation between uncomplicated and complicated appendicitis and the patient’s preferences for different treatment options will be assessed.Ethics and disseminationEthical approval was granted by the Amsterdam UMC Medical Ethics Committee (reference W19_416 # 19.483). Because of the observational nature of this study, the study does not fall under the scope of the Medical Research Involving Human Subjects Act. Results will be presented in peer-reviewed journals. This protocol is submitted for publication before analysis of the results.

Background During the COVID-19 pandemic, a decrease in the number of patients presenting with acute appendicitis was observed. It is unclear whether this caused a shift towards more complicated cases of acute appendicitis. We compared a cohort of patients diagnosed with acute appendicitis during the 2020 COVID-19 pandemic with a 2019 control cohort. Methods We retrospectively included consecutive adult patients in 21 hospitals presenting with acute appendicitis in a COVID-19 pandemic cohort (March 15 – April 30, 2020) and a control cohort (March 15 – April 30, 2019). Primary outcome was the proportion of complicated appendicitis. Secondary outcomes included prehospital delay, appendicitis severity, and postoperative complication rates. Results The COVID-19 pandemic cohort comprised 607 patients vs. 642 patients in the control cohort. During the COVID-19 pandemic, a higher proportion of complicated appendicitis was seen (46.9% vs. 38.5%; p = 0.003). More patients had symptoms exceeding 24 h (61.1% vs. 56.2%, respectively, p = 0.048). After correction for prehospital delay, presentation during the first wave of the COVID-19 pandemic was still associated with a higher rate of complicated appendicitis. Patients presenting > 24 h after onset of symptoms during the COVID-19 pandemic were older (median 45 vs. 37 years; p = 0.001) and had more postoperative complications (15.3% vs. 6.7%; p = 0.002). Conclusions Although the incidence of acute appendicitis was slightly lower during the first wave of the 2020 COVID-19 pandemic, more patients presented with a delay and with complicated appendicitis than in a corresponding period in 2019. Spontaneous resolution of mild appendicitis may have contributed to the increased proportion of patients with complicated appendicitis. Late presenting patients were older and experienced more postoperative complications compared to the control cohort.

Background: The effect of diagnosing appendicitis at re-assessment on post-operative outcomes is not clear. This study aims to compare patients diagnosed with appendicitis at initial presentation versus patients who were diagnosed at re-assessment. Patients and Methods: Data from the Dutch SNAPSHOT appendicitis collaborative was used. Patients with appendicitis who underwent appendectomy were included. Effects of diagnosis at re-assessment were compared with diagnosis at initial presentation. Primary outcomes were the proportion of patients with complicated appendicitis and the post-operative complication rate. Results: Of 1,832 patients, 245 (13.4%) were diagnosed at re-assessment. Re-assessed patients had a post-operative complication rate comparable to those diagnosed with appendicitis at initial presentation (15.1% vs. 12.7%; p = 0.29) and no substantial difference was found in the proportion of patients with complicated appendicitis (27.9% vs. 33.5%; p = 0.07). For patients with complicated appendicitis, more post-operative complications were seen if diagnosed at re-assessment than if diagnosed initially (38.2% vs. 22.9%; p = 0.006). Conclusions: For patients in whom appendicitis was not diagnosed at first presentation, but at re-assessment, both the proportion of complicated appendicitis and the post-operative complication rate were comparable to those who were diagnosed with appendicitis at initial presentation. However, re-assessed patients with complicated appendicitis encountered more post-operative complications.

Abstract Background Non-operative treatment of uncomplicated appendicitis is safe and increasing in popularity, but has other risks and benefits compared with appendicectomy. This study aimed to explore the preference of the general population regarding operative or antibiotic treatment of uncomplicated appendicitis. Methods In this prospective study, a clinical scenario and questionnaire were submitted to a panel comprising a sample of an average adult population. The survey was distributed by an independent, external research bureau, and included a comprehensive explanation of the risks and benefits of both treatment options. The primary outcome was the proportion of participants who would prefer antibiotics over surgery. Secondary outcomes were reasons for this preference and the accepted recurrence rate within 1 year when treated with antibiotics only. All outcomes were weighted for the average Dutch population. Results Of 254 participants, 49.2 per cent preferred antibiotic treatment for uncomplicated appendicitis, 44.5 per cent preferred surgery, and 6.3 per cent could not make a decision. About half of the participants preferring antibiotics would accept a recurrence risk of more than 50 per cent within 1 year. Avoiding surgery was their main reason. In participants preferring surgery, many tolerated a recurrence risk of no more than 10 per cent when treated with antibiotics. Removal of the cause of appendicitis was their main reason. Conclusion Around half of the average population sample preferred antibiotics over surgical treatment of uncomplicated appendicitis and were willing to accept a high recurrence risk to avoid surgery initially. Participants who preferred surgery tolerated only a very low recurrence risk with antibiotic treatment.

BACKGROUND:Diagnostic work-up of acute appendicitis remains challenging. While some guidelines advise to use a risk stratification based on clinical parameters, others use standard imaging in all patients. As non-operative management of uncomplicated appendicitis has been identified as feasible and safe, differentiation between uncomplicated and complicated appendicitis is of paramount importance. We reviewed the literature to describe the optimal strategy for diagnosis of acute appendicitis.METHODS:A narrative review about the diagnosis of acute appendicitis in adult patients was conducted. Both diagnostic strategies and goals were analyzed.RESULTS:For diagnosing acute appendicitis, both ruling in and ruling out the disease are important. Clinical and laboratory findings individually do not suffice, but when combined in a diagnostic score, a better risk prediction can be made for having acute appendicitis. However, for accurate diagnosis imaging seems obligatory in patients suspected for acute appendicitis. Scoring systems combining clinical and imaging features may differentiate between uncomplicated and complicated appendicitis and may enable ruling out complicated appendicitis. Within conservatively treated patients with uncomplicated appendicitis, predictive factors for non-responsiveness to antibiotics and recurrence of appendicitis need to be defined in order to optimize treatment outcomes.CONCLUSION:Standard imaging increases the diagnostic power for both ruling in and ruling out acute appendicitis. Incorporating imaging features in clinical scoring models may provide better differentiation between uncomplicated and complicated appendicitis. Optimizing patient selection for antibiotic treatment of appendicitis may minimize recurrence rates, resulting in better treatment outcomes.

Abstract Background Discriminating complicated from uncomplicated appendicitis is crucial. Patients with suspected complicated appendicitis are best treated by emergency surgery, whereas those with uncomplicated appendicitis may be treated with antibiotics alone. This study aimed to obtain summary estimates of the accuracy of ultrasound imaging, CT and MRI in discriminating complicated from uncomplicated appendicitis Methods A systematic literature review was conducted by an electronic search in PubMed, Embase and the Cochrane Library for studies describing the diagnostic accuracy of complicated versus uncomplicated appendicitis. Studies were included if the population comprised adults, and surgery or pathology was used as a reference standard. Risk of bias and applicability were assessed with QUADAS-2. Bivariable logitnormal random-effect models were used to estimate mean sensitivity and specificity. Results Two studies reporting on ultrasound imaging, 11 studies on CT, one on MRI, and one on ultrasonography with conditional CT were included. Summary estimates for sensitivity and specificity in detecting complicated appendicitis could be calculated only for CT, because of lack of data for the other imaging modalities. For CT, mean sensitivity was 78 (95 per cent c.i. 64 to 88) per cent, and mean specificity was 91 (85 to 99) per cent. At a median prevalence of 25 per cent, the positive predictive value of CT for complicated appendicitis would be 74 per cent and its negative predictive value 93 per cent. Conclusion Ultrasound imaging, CT and MRI have limitations in discriminating between complicated and uncomplicated appendicitis. Although CT has far from perfect sensitivity, its negative predictive value for complicated appendicitis is high.

Objective: Radiofrequency ablation (RFA) is increasingly considered the prime option for treating symptomatic, benign, non-functioning thyroid nodules (NFTN). However, little is known about the degree of operator experience required to achieve optimal results. This study describes the RFA learning curve of a single-center team. Methods: A retrospective cohort study of the first 103 patients receiving RFA treatment for a single, symptomatic, and benign NFTN, with a follow-up of at least 1 year. The primary outcome measure was technique efficacy, defined as the percentage of patients with a 6-month nodal volume reduction ratio (VRR) >50% after single-session RFA. Optimal treatment efficacy was defined as a 6-month VRR >50% achieved in at least 75% of patients. Secondary outcomes were complications of RFA and indications of secondary interventions. Results: Median nodal volume at baseline was 12.0 mL (range 2.0-58.0 mL). A 6-month VRR >50% was achieved in 45% of the first 20 patients, 75% of the next 20, and 79% of the following 63 patients. Complications included minor bleeding (N = 4), transient hyperthyroidism (N = 4), and transient loss of voice (N = 1). Poor volume reduction or nodular regrowth led to diagnostic lobectomy in 11 patients and a second RFA in 5. Lobectomy revealed a follicular carcinoma (T2N0M0) in 2 patients. In 1 patient, nodule regrowth was caused by an intranodular solitary B-cell lymphoma. Conclusion: About 40 procedures are required to achieve a 6-month VRR >50% in the majority of patients. Appropriate follow-up with re-evaluation is recommended for all patients with a VRR <50% and in those with regrowth to exclude underlying malignancy.