Optimal Follow-up Of Patients Research Articles

Genetic predisposition to pheochromocytoma and paraganglioma: 21 years of experience in the field

ContextPheochromocytoma and paraganglioma (PPGL) are rare neuroendocrine tumors with high heritability, justifying systematic genetic screening for a germline variant in one of the twenty predisposing genes described to date. PurposeTo describe the experience of one endocrine oncogenetic laboratory over a period of 21 years (2001–2022), from the beginning of PPGL genotyping with Sanger sequencing in 2001 to the implementation of next-generation sequencing (NGS). MethodThe activity database of an academic oncogenetic laboratory was searched to extract patients/relatives identified with a pathogenic variant/likely pathogenic variant (PV/LPV) over a period of 21 years. Clinical and genetic data were compared. ResultsIn total, 606 index cases with PPGL and 444 relatives were genotyped. Genotyping of index cases was performed by Sanger sequencing and gene deletion analysis in 327 cases and by NGS in 279. Germline PV/LPV spanning 10 genes was identified in 165 index cases (27.2%). Several recurrent PV/LPVs in SDHx were observed in non-related index cases, the most frequent being SDHD, c.170-1G>T (n=28). This subgroup showed great phenotypic variability both between and within families in terms of both tumor location and number. Four patients (1.1%) with PV/LPV in SDHx had 3PA (Pituitary Adenoma and pheochromocytoma/paraganglioma) syndrome. 258 relatives (58.1%) had inherited a PV/LPV in one driver gene. The rate of PV/LPV carriers who were symptomatic at first imaging evaluation was 32%, but varied between<20% in SDHB and SDHC and >50% in SDHD, VHL and MAX. ConclusionOur experience confirmed previously established genotype-phenotype correlations, but also highlights atypical clinical presentations, even for the same genetic variant. These data must be taken into account for optimal patient follow-up and management.

Strategies and resources to optimise the management of Psoriatic Arthritis patients: The CREA Project

Background and aimPsoriatic arthritis (PsA) is a chronic immune-mediated inflammatory disease that affects the musculoskeletal system and skin, and manifests heterogeneously, with a variable course. In current clinical practice, variability and limitations in its follow-up have been observed. The aim of the CREA project was to agree on strategies to improve the initial assessment and follow-up of patients with PsA in Spain. Materials and methodsA survey was conducted among a representative sample of expert rheumatologists in Spain, containing 33 questions on current clinical practice, available resources, and current limitations in the follow-up of patients with PsA. The results were discussed in regional meetings and 105 strategies were proposed and finally evaluated by 85 experts in a Delphi consensus. ResultsThe most important limitations in the follow-up of PsA were lack of consultation time, lack of nursing staff, and delays in performing imaging tests. A total of 108 strategies were proposed related to the assessment of quality of life and disease-impact indices; comorbidities and extra-articular manifestations; laboratory tests; imaging tests; physical examination and metrology; and activity and function indices. Of the total, 53 were considered highly advisable, with no regional differences in consensus values. Discussion and ConclusionsThe proposals offered in the current study are applicable to the entire country, respond to the unmet needs detected in the initial survey, form a minimum action framework, and ensure optimal follow-up of patients with PsA.

The Impact of Clinical Follow-Up After Revascularization on the Outcomes of Patients with Chronic Limb Threatening Ischemia

Guidelines for optimal follow-up for patients undergoing lower extremity revascularization (LER) for peripheral arterial disease recommend multiple visits with imaging during the first year followed by yearly monitoring thereafter. Critical limb-threatening ischemia (CLTI) patients are at a greater risk for mortality and limb amputation than claudicants and thus necessitate closer monitoring. The goal of this article is to study the effects of compliance with follow-up after revascularization for patients with CLTI on major amputation rates and mortality. A single-center retrospective chart review of consecutive patients undergoing LER for CLTI was performed. Patients were stratified based on compliance with follow-up to compliant or noncompliant cohorts. Patient characteristics, reinterventions, and perioperative and long-term outcomes were compared between the 2 groups. There were 356 patients undergoing LER and 61% (N=218) were compliant. There was no significant difference in baseline characteristics between the 2 groups. Noncompliant patients were more likely to undergo endovascular interventions compared to compliant patients (92.8% vs. 79.4%, P=0.03). There was no difference in perioperative outcomes between the 2 groups with overall 30-day mortality of 0.6%. After mean follow-up of 2.7years, compliant patients had greater ipsilateral reintervention rates (49.1% vs. 34.1%, P=0.005) and overall reintervention rates (61% vs. 44.2%, P=0.002) compared to noncompliant patients. There was no significant difference in mortality or ipsilateral major amputations between the 2 groups. Patients who were compliant with follow-up after LER for CLTI underwent more reinterventions with no difference in mortality or major limb amputation. Further research regarding the threshold for reintervention and the optimal schedule for follow-up in patients with CLTI is needed.

P1423: CIRCULATING CELL-FREE DNA KINETICS MEASURED BY DIGITAL PCR IN LYMPHOMA PATIENTS UNDERGOING CD19-CAR-T THERAPY

Background: Monitoring of CD19-targeted chimeric antigen receptor (CAR)-T cell levels is essential for an optimal follow-up of patients. In this regard, methodologies such as multiparametric flow cytometry (MFC) or qPCR are commonly performed. In addition, the use of new approaches, such as digital PCR (dPCR), has improved the analysis of cell kinetics. Nevertheless, the role of CAR circulating cell-free DNA (ccfDNA) dynamics during CAR-T cell treatment is not clear. Aims: To evaluate the usefulness of CAR ccfDNA measurement by dPCR in patients treated with CD19-CAR-T cell therapy and its correlation with CAR-T cell levels measured by MFC and dPCR. Methods: Forty patients diagnosed with a B-cell lymphoma who underwent CAR-T therapy (28 Axicabtagen Ciloleucel and 12 Tisagenlecleucel) between May 2019 and May 2021 were included in the analysis. One hundred and five peripheral blood (PB) samples were collected in EDTA tubes at days +1, +7, +14, +30 (10, 31, 33, and 31 samples, respectively) after CAR-T administration. Plasma was obtained from 20 mL of PB by centrifugation at 2500g for 30 minutes at 4°C. DNA was purified from PB samples using the Maxwell 16 Blood DNA Purification Kit (Promega) and ccfDNA was extracted from 5 mL of plasma, using QIAamp® Circulating Nucleic Acid (Qiagen). dPCR was carried out in DNA and ccfDNA samples, using specific primers and probes for FMC63 and a reference gene. MFC was performed on a DxFLEX cytometer (Beckman Coulter), using CD19 (20-291) protein-FITC (ACRO Biosystems). Continuous variables were expressed as median and range. Correlations between CAR copies in plasma determined by dPCR and CAR-T cells measured in PB by MFC and dPCR were analyzed using Pearson’s test. Comparison between number of copies and clinical variables (cytokine release syndrome -CRS-, immune effector-cell associated neurotoxicity syndrome -ICANS-, and relapse) was analyzed using Mann-Whitney U test. All statistical analyses were performed using GraphPad Prism 8.0.1. Results: Median values of CAR copies of ccfDNA per milliliter measured by dPCR were 39, 38, 25 and 2 at days +1, +7, +14 and +30. Similarly, median reference gene values were 3079, 1799, 2588 and 2183 (Figure 1). Thus, we validate previous observations of an initial peak concentration followed by a constant decrease in plasma CAR copies kinetics. Moderate correlation was found between CAR copies/mL of plasma and CAR-T cells in PB determined by MFC and dPCR (R=0.49, p<0.001, Figure 2A; R=0.51, p<0.001, Figure 2B, respectively). So, although a part of plasma CAR copies variation is explained by changes in whole blood CAR content, there might be other influencing factors. Regarding the association between CAR copies in plasma at +7 and clinical variables, an association was only found in the case of development of CRS<2 and CRS grade ≥2 (28 [0-220] vs 168 [11-1479], p<0.01, Figure 3). Further experiments are needed to evaluate whether this reflects the overall CAR-T cell kinetics. Image:Summary/Conclusion: The analysis of multiple variables is important for an optimal monitoring of patients undergoing CAR-T cell therapy. In this sense, ccfDNA dynamics may play an important role during the follow-up and even have relevant clinical implications as we have demonstrated in the present study. However, more studies are necessary for validating our data.

Practical diagnostic tips for the Sjögren Clinic: pearls, myths and mistakes.

More than 90 years have passed since Hendrik Sjögren began to consider that behind the dryness that several of his patients presented, there could be a systemic disease potentially linked to abnormal immune responses. For many years, the disease was mostly considered a minor syndrome compared with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and vasculitis, and advances in its understanding were slow and little recognised. The irruption of new technologies at the end of the 20th century rapidly promoted the development of international projects with a wide impact and diffusion. In the last 20 years, a significant improvement has been achieved in epidemiological determinants, pathogenic mechanisms, diagnostic accuracy, and a standardised therapeutic approach for patients with Sjögren's syndrome (SS). These developments have provided the tools for an early diagnosis and personalised management for most patients. However, a significant number of early myths and ongoing controversies are still making the appropriate management of SS difficult in daily clinical practice. This review provides a selection of pearls, myths, and mistakes that may serve as practical diagnostic tips for the Sjögren Clinic in four specific scenarios: defining the appropriate epidemiological background, enabling the earliest diagnostic suspicion as possible, improving the systemic characterisation of the disease, and designing an optimal follow-up of patients.

Optimal follow-up after acute pulmonary embolism: a position paper of the European Society of Cardiology Working Group on Pulmonary Circulation and Right Ventricular Function, in collaboration with the European Society of Cardiology Working Group on Atherosclerosis and Vascular Biology, endorsed by the European Respiratory Society.

This position paper provides a comprehensive guide for optimal follow-up of patients with acute pulmonary embolism (PE), covering multiple relevant aspects of patient counselling. It serves as a practical guide to treating patients with acute PE complementary to the formal 2019 European Society of Cardiology guidelines developed with the European Respiratory Society. We propose a holistic approach considering the whole spectrum of serious adverse events that patients with acute PE may encounter on the short and long run. We underline the relevance of assessment of modifiable risk factors for bleeding, of acquired thrombophilia and limited cancer screening (unprovoked PE) as well as a dedicated surveillance for the potential development of chronic thromboembolic pulmonary hypertension as part of routine practice; routine testing for genetic thrombophilia should be avoided. We advocate the use of outcome measures for functional outcome and quality of life to quantify the impact of the PE diagnosis and identify patients with the post-PE syndrome early. Counselling patients on maintaining a healthy lifestyle mitigates the risk of the post-PE syndrome and improves cardiovascular prognosis. Therefore, we consider it important to discuss when and how to resume sporting activities soon after diagnosing PE. Additional patient-relevant topics that require Focused counselling are travel and birth control.

Prediction of age-related macular degeneration disease using a sequential deep learning approach on longitudinal SD-OCT imaging biomarkers

We propose a hybrid sequential prediction model called “Deep Sequence”, integrating radiomics-engineered imaging features, demographic, and visual factors, with a recursive neural network (RNN) model in the same platform to predict the risk of exudation within a future time-frame in non-exudative AMD eyes. The proposed model provides scores associated with risk of exudation in the short term (within 3 months) and long term (within 21 months), handling challenges related to variability of OCT scan characteristics and the size of the training cohort. We used a retrospective clinical trial dataset that includes 671 AMD fellow eyes with 13,954 observations before any signs of exudation for training and validation in a tenfold cross validation setting. Deep Sequence achieved high performance for the prediction of exudation within 3 months (0.96 ± 0.02 AUCROC) and within 21 months (0.97 ± 0.02 AUCROC) on cross-validation. Training the proposed model on this clinical trial dataset and testing it on an external real-world clinical dataset showed high performance for the prediction within 3-months (0.82 AUCROC) but a clear decrease in performance for the prediction within 21-months (0.68 AUCROC). While performance differences at longer time intervals may be derived from dataset differences, we believe that the high performance and generalizability achieved in short-term predictions may have a high clinical impact allowing for optimal patient follow-up, adding the possibility of more frequent, detailed screening and tailored treatments for those patients with imminent risk of exudation.

Machine learning and treatment outcome prediction for oral cancer.

The natural history of oral squamous cell carcinoma (OSCC) is complicated by progressive disease including loco-regional tumour recurrence and development of distant metastases. Accurate prediction of tumour behaviour is crucial in delivering individualized treatment plans and developing optimal patient follow-up and surveillance strategies. Machine learning algorithms may be employed in oncology research to improve clinical outcome prediction. Retrospective review of 467 OSCC patients treated over a 19-year period facilitated construction of a detailed clinicopathological database. 34 prognostic features from the database were used to populate 4 machine learning algorithms, linear regression (LR), decision tree (DT), support vector machine (SVM) and k-nearest neighbours (KNN) models, to attempt progressive disease outcome prediction. Principal component analysis (PCA) and bivariate analysis were used to reduce data dimensionality and highlight correlated variables. Models were validated for accuracy, sensitivity and specificity, with predictive ability assessed by receiver operating characteristic (ROC) and area under the curve (AUC) calculation. Out of 408 fully characterized OSCC patients, 151 (37%) had died and 131 (32%) exhibited progressive disease at the time of data retrieval. The DT model with 34 prognostic features was most successful in identifying "true positive" progressive disease, achieving 70.59% accuracy (AUC 0.67), 41.98% sensitivity and a high specificity of 84.12%. Machine learning models assist clinicians in accessing digitized health information and appear promising in predicting progressive disease outcomes. The future will see increasing emphasis on the use of artificial intelligence to enhance understanding of aggressive tumour behaviour, recurrence and disease progression.

Use of PROM during follow-up of patients with ovarian cancer: the PROMova study protocol

BackgroundThere is a paucity of high-level evidence on the optimal follow-up of patients with ovarian cancer after primary treatment. A debate is ongoing on the extent to which follow-up should...

Determining Optimal Follow-up for Patients With Anal Cancer Following Chemoradiation.

US health care is increasingly defined by over expenditure and inefficiency. Optimizing patient follow-up is critical, especially in cancers treated with high control rates. To optimize patient care, this study assessed time to disease recurrence or toxicity in patients with anal carcinoma. In total, 140 patients with biopsy-proven, nonmetastatic anal carcinoma, treated with chemoradiation utilizing intensity-modulated radiation therapy, were identified from our institutional database. This retrospective study evaluated local recurrence (LR), distant metastasis (DM), overall survival (OS), and late ≥grade 3 toxicity (LG3T). Patients were followed posttreatment every 3 months for 2 years, every 6 months in years 3 to 5, then yearly thereafter per NCCN recommendations. The median age and follow-up was 58 years and 27 months, respectively. Patients were categorized into high (n=61; 44%) and low (n=77; 55%) risk groups based on stage. The 2-year LC, DMFS, and OS were 93%, 94%, and 89% and 5-year LC, DMFS, OS were 92%, 87%, and 85%, respectively. Overall, there were 29 events (9 LR, 11 DM, and 9 LG3T), with 62% of events occurring within year 1 and 79% within 2 years. Stratified by event type, at 2 years 89% of LR, 64% of DM, and 89% LG3T were identified. At the remaining follow-up points, the event incidence rate was 1.3%. With the majority of recurrences/toxicities occurring within the first 2 years, a reduction in follow-up during years 3 to 5 may provide adequate surveillance. Revisions of the current recommendations could maximize resources while improving patient quality of life.

A natural history of carcinoid heart disease in the modern management era

The development of carcinoid heart disease (CaHD) is still relatively unknown at present. It is difficult to define an optimal follow-up for patients initially free from cardiac involvement. The aim of this study was to assess the prevalence and the evolution of CaHD using annual echocardiographic follow-up. We reviewed from our database 137 patients (61 ± 12 years, 53% men) with histologically proven neuroendocrine tumor between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right-sided and left-sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CHD. An increase of 25% of the score was considered as significant. Mean follow-up was 2.6 ± 3.5 years [0;16]. Prevalence of CaHD was 27% (37 pts) at baseline and 36% (49 pts) at the end of follow-up. Among patients with initial CaHD followed for more than one year, disease progression was observed in 28% of cases. Among the patients free from initial cardiac involvement, an onset of the disease was observed during follow-up in 21% of cases. The onset of CHD could be very late, more than 5 years from the initial echocardiographic examination in 42% of our cases ( Fig. 1 ). This late occurrence of CaHD was only observed in patients presenting with new resumption of neuroendocrine tumor (symptoms, increased of 5-HIAA, occurrence of new metastasis). Our study demonstrated that in patients without initial CaHD, cardiac involvement may occur tardily after a normal initial assessment. Our data suggest the need for prolonged echocardiographic follow-up in patients presenting with a resumption of tumor process.

P4653A natural history of carcinoid heart disease in the modern management era

Abstract Background The development of carcinoid heart disease (CaHD) is still relatively unknown at present. It is difficult to define an optimal follow-up for patients initially free from cardiac involvement. The aim of this study was to assess the prevalence and the evolution of CaHD using annual echocardiographic follow-up. Methods We reviewed from our database 137 patients (61±12 years, 53% men) with histologically proven neuroendocrine tumor between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right-sided and left-sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CHD. An increase of 25% of the score was considered as significant. Results Mean follow-up was 2.6±3.5 years [0; 16]. Prevalence of CaHD was 27% (37 pts) at baseline and 36% (49 pts) at the end of follow-up. Among patients with initial CaHD followed for more than one year, disease progression was observed in 28% of cases. Among the patients free from initial cardiac involvement, an onset of the disease was observed during follow-up in 21% of cases. The onset of CHD could be very late, more than 5 years from the initial echocardiographic examination in 42% of our cases (Figure). This late occurrence of CaHD was only observed in patients presenting with new resumption of neuroendocrine tumor (symptoms, increased of 5-HIAA, occurrence of new metastasis). Conclusion Our study demonstrated that in patients without initial CaHD, cardiac involvement may occur tardily after a normal initial assessment. Our data suggest the need for prolonged echocardiographic follow-up in patients presenting with a resumption of tumor process.

A natural history of carcinoid heart disease in the modern management era

The development of carcinoid heart disease (CaHD) is still relatively unknown at present. It is difficult to define an optimal follow-up for patients initially free from cardiac involvement. The aim of this study was to assess the prevalence and the evolution of CaHD using annual echocardiographic follow-up. We reviewed from our database 137 patients (61 ± 12 years, 53% men) with histologically proven neuroendocrine tumor between 1997 and 2017. All patients underwent serial conventional transthoracic echocardiographic studies. Right-sided and left-sided CaHD were systematically assessed. We used a previous validated echocardiographic scoring system of severity for the assessment of CHD. An increase of 25% of the score was considered as significant. Mean follow-up was 2.6 ± 3.5 years [0;16]. Prevalence of CaHD was 27% (37 pts) at baseline and 36% (49 pts) at the end of follow-up. Among patients with initial CaHD followed for more than one year, disease progression was observed in 28% of cases. Among the patients free from initial cardiac involvement, an onset of the disease was observed during follow-up in 21% of cases. The onset of CHD could be very late, more than 5 years from the initial echocardiographic examination in 42% of our cases ( Figure 1 ). This late occurrence of CaHD was only observed in patients presenting with new resumption of neuroendocrine tumor (symptoms, increased of 5-HIAA, occurrence of new metastasis). Our study demonstrated that in patients without initial CaHD, cardiac involvement may occur tardily after a normal initial assessment. Our data suggest the need for prolonged echocardiographic follow-up in patients presenting with a resumption of tumor process ( Figure 1 ).

Le point sur les dosages de l’hormone gonadotrophine chorionique : lequel prescrire pour quelle prise en charge ?

The point on chorionic gonadotropin assays: which tests prescribe for the best take care? hCG assays are very often prescribed for biological investigations or before medical investigations. Physicians and biologists have to discuss about these different available hCG assays for an optimal patient's follow-up. Patients must be advised to have blood sample in the same laboratory to avoid analytical variations, possibly prejudiciable in case of cinetic observations.

Echocardiography in functional midgut neuroendocrine tumors: When and how often.

The management of patients with midgut neuroendocrine tumors (MNET) is rapidly evolving. Current preoperative detection rates of primary tumor sites are higher than ever and progression-free survival in patients with already advanced disease is expanding due to the implementation of novel efficacious treatment strategies. This survival benefit may potentially translate into a need for a multidisciplinary approach to an even more heterogenous variety of clinical conditions, among these, carcinoid syndrome (CS) and carcinoid heart disease (CHD). The latter often triggers substantial morbidity and mortality, hence a systematic screening, an accurate diagnosis, as well as effective interventions are critically important. The rarity of the disease has result in a relative lack of statistically powerful evidence, which in turn may have rendered significant variability between practices. In this regard, despite recent guidelines, the optimal follow-up of patients with CHD remain debatable to some authors, perhaps due to the preponderance of certain schools throughout the manuscript. Herein, we present a concise and practical guidance document on clinical screening and echocardiographic surveillance of patients with CHD based on a comprehensive review of the literature, and complemented by our experience at the Center for Carcinoid and Neuroendocrine Tumors at The Mount Sinai Hospital.

Optimal Follow-up of Patients with Viral Hepatitis Improves the Detection of Early-stage Hepatocellular Carcinoma and the Prognosis of Survival.

Objective To manage patients with viral hepatitis, it is important to screen for hepatitis, conduct a comprehensive examination if such screening is positive, administer antiviral treatment, and conduct surveillance for hepatocellular carcinoma (HCC). The proper execution of this strategy is expected to effectively reduce the number of deaths from viral hepatitis. Such an "optimal" follow-up for HCC surveillance is therefore important. This study aimed to determine the benefits of performing an optimal follow-up of patients with viral hepatitis. Methods The subjects were infected with the hepatitis virus and were initially diagnosed with or treated for HCC from 2004-2012. We retrospectively analyzed the history of a patient's current illness using the hospital discharge summary. To minimize any lead-time bias, we calculated the corrected survival for patients who received an optimal follow-up. Results Of 333 patients, 107 (32.1%) did not receive an optimal follow-up and thus had low cumulative survival rates in comparison to those who did. The median corrected survival was 51.5 months for patients with an optimal follow-up compared with 31.4 months for those without (p=0.011). A multivariate analysis revealed that AFP <35 [odds ratio (OR), 2.054], Child-Pugh A (OR, 2.488), and an optimal follow-up (OR, 4.539) were independent factors associated with the detection of early-stage HCC. Age (OR, 0.939), tumor stage I/II (OR, 6.918), and an optimal follow-up (OR, 3.213) were found to be independent factors associated with receiving curative treatment. Conclusion An optimal follow-up of patients with viral hepatitis independently increased the detection of early-stage HCC and the administration of curative treatment. Patients with an optimal follow-up survived longer than those without.

Determining optimal follow-up in the management of human papillomavirus-positive oropharyngeal cancer.

Determining the optimal follow-up for patients can help maximize the use of health care resources. This is particularly true in a growing epidemic such as human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV+OPSCC). The objective of the current study was to evaluate time to disease recurrence or late toxicity in this cohort of patients to optimize patient management. An institutional database identified 232 patients with biopsy-proven, nonmetastatic HPV+OPSCC who were treated with radiotherapy. A retrospective review was conducted in patients who were followed every 3 months for the first year, every 4 months in year 2, and every 6 months in years 3 to 5. Late toxicity (grade ≥ 3; toxicity was scored based on National Cancer Institute Common Terminology Criteria for Adverse Events [version 4]), locoregional control, distant control, and overall survival were assessed. The median follow-up was 33 months. Based on Radiation Therapy Oncology Group (RTOG) 0129 study risk groupings, patients were either considered to be at low (162 patients; 70%) or intermediate (70 patients; 30%) risk. Concurrent systemic therapy was used in 85% of patients (196 patients). The 3-year locoregional control, distant control, and overall survival rates were 94%, 91%, and 91%, respectively. Late toxicity occurred in 9% of patients (21 patients). Overall, 64% of toxicity and failure events occurred within the first 6 months of follow-up, with a < 2% event incidence noted at each subsequent follow-up. Only 4 patients experienced their first event after 2 years. HPV+OPSCC has a low risk of disease recurrence and late toxicity after treatment; approximately two-thirds of events occur within the first 6 months of follow-up. These data suggest that it may be reasonable to reduce follow-up in patients with HPV+OPSCC to every 3 months for the first 6 months, every 6 months for the first 2 years, and annually thereafter.

Reproducibility of Volumetric Computed Tomography of Stable Small Pulmonary Nodules with Implications on Estimated Growth Rate and Optimal Scan Interval.

PurposeTo use clinically measured reproducibility of volumetric CT (vCT) of lung nodules to estimate error in nodule growth rate in order to determine optimal scan interval for patient follow-up.MethodsWe performed quantitative vCT on 89 stable non-calcified nodules and 49 calcified nodules measuring 3–13 mm diameter in 71 patients who underwent 3–9 repeat vCT studies for clinical evaluation of pulmonary nodules. Calculated volume standard deviation as a function of mean nodule volume was used to compute error in estimated growth rate. This error was then used to determine the optimal patient follow-up scan interval while fixing the false positive rate at 5%.ResultsLinear regression of nodule volume standard deviation versus the mean nodule volume for stable non-calcified nodules yielded a slope of 0.057±0.002 (r2 = 0.79, p<0.001). For calcified stable nodules, the regression slope was 0.052±0.005 (r2 = 0.65, p = 0.03). Using this with the error propagation formula, the optimal patient follow-up scan interval was calculated to be 81 days, independent of initial nodule volume.ConclusionsReproducibility of vCT is excellent, and the standard error is proportional to the mean calculated nodule volume for the range of nodules examined. This relationship constrains statistical certainty of vCT calculated doubling times and results in an optimal scan interval that is independent of the initial nodule volume.

Durability of antiviral therapy for chronic hepatitis C after achieving sustained virological response

See Article on Page 183 Hepatitis C virus (HCV) causes various liver diseases including acute hepatitis, chronic hepatitis, health-holders, liver cirrhosis and hepatocellular carcinoma.1 Acute hepatitis C progresses to chronic hepatitis from 75 to 85% and cirrhosis after 20-25 years later. In patients with HCV-positive cirrhosis, the annual incidence of hepatocellular carcinoma has been reported as 5% approximately.1 The current standard antiviral treatment with peginterferon and ribavirin combination therapy is effective in about 50% of patients with chronic hepatitis C. It is assumed that achievement of sustained virological response (SVR) after the combination therapy, confirmed by means of commercial HCV RNA detection assays is regarded as a cure for chronic hepatitis C (Table 1). It is associated with histological improvement, reduced the risk of hepatocellular carcinoma and liver related mortality, and improved quality of life. Table 1 Commercially available HCV RNA detection assays For the respect of the durability of SVR, several studies have been reported. Marcellin et al2 reported that an SVR after antiviral therapy was associated with long-term biochemical and virological responses as well as histologic improvement. Eighty-patients who had SVR after interferon-alpha monotherapy, mean follow-up of 4 years showed that 96% had undetectable serum HCV RNA. In a large-scale clinical trials, 7 (2%) among 400 sustained virological responder had detectable hepatic HCV RNA during follow-up; 5 have been followed and 2 (0.5%) were reappearance of serum HCV RNA at 12 months after therapy.3 Many other reports including the study of Choi et al4 confirmed that late relapse is rare after achievement of an SVR with completion of interferon without or with ribavirin therapy (Table 2).5-13 On the other hand, earlier reports showed higher rate of late relapse.14-16 These discrepancies may be resulted from use of HCV polymerase chain reaction (PCR) assays with varying degrees of sensitivity and a range of patient populations. As a result, the true durability of the response remains unclear, and the optimal follow-up for patients who have achieved an SVR is unknown. Table 2 Reappearance rates of serum HCV RNA after achieving SVR Even then achievement of an SVR, there are many evidences that HCV can persist and replicate in peripheral blood mononuclear cells, hepatic tissue and other organs including kidney, heart, pancreas, intestine, adrenal gland, lymph node and gallbladder in spite of still undetectable serum HCV RNA.3,17-21 It is so called HCV, which can be reservoir of reappearance HCV RNA in serum3,21 and thus play a role in the persistence and reactivation of infection. Highly sensitive reverse transcription and nested PCR assays detected residual HCV RNA in case of occult HCV. However, these assays are not currently standard diagnostic procedures and whether these findings actually represent a replication-competent virus or have any clinical significance is not clear. The immunologic mechanism of HCV recurrence after SVR is also not well investigated. Quiroga et at22 reported HCV-specific cellular immune responses are stronger in occult HCV infection than in chronic hepatitis C and it would be the cause of the rare incidence of late relapse. For the factors affecting the durability of SVR, no distinct pattern of baseline characteristics could be identified. Several studies with small number of patients reported the transfusion, injection drug use or dose reduction as a risk factor. However, it was unknown whether these cases reflect relapse or re-infection because of the paucity of paired samples. Although there is reappearance of serum HCV RNA in approximate 1% of patients with an SVR, individuals who have achieved an SVR should have a single additional follow-up HCV RNA measurement performed to ensure that the negative HCV RNA result at 6 months posttreatment was not a false negative possibly due to faulty sample collection. If the second posttreatment HCV RNA measurement is negative, the SVR appears to be durable and a reliable sign of cure after antiviral therapy in chronic hepatitis C. However, it is recommended to follow up serum HCV RNA for a long time after an SVR for those individuals who show intermittent viral breakthrough during treatment or who may be considered at risk for reinfection or late relapse.

Secondary Prevention of Colorectal Cancer: Is There an Optimal Follow-up for Patients with Colorectal Cancer?

Secondary prevention of colorectal cancer, as opposed to primary prevention, indicates that a person has already had the disease and there are steps being taken to prevent cancer recurrence, usually as metachronous tumors. This generally involves annual surveillance with colonoscopy after surgical removal of the initial cancer if some aspect of the colon remains. However, some familial cases may involve other modalities, such as cyclooxygenase inhibitors, as an adjunct after the initial operation. Genetic testing in suspected familial cases may identify candidates for secondary prevention. The timing for secondary prevention is critical to prevent recurrent advanced disease, which is detrimental to patient survival. Recommendations are often empiric, but some cases are based on the biological behavior of the tumor. Close follow-up with a competent health care provider, such as a gastroenterologist, is necessary to help prevent recurrence.