Anatomic Staging Research Articles

Non-Invasive and Real-Time Monitoring of the Breast Cancer Metastasis Degree via Metabolomics.

Breast cancer (BC) is a serious threat to women's health and metastasis is the major cause of BC-associated mortality. Various techniques are currently used to preoperatively describe the metastatic status of tumors, based on which a comprehensive treatment protocol was determined. However, accurately staging a tumor before surgery remains a challenge, which may lead to the miss of optimal treatment options. More severely, the failure to detect and remove occult micrometastases often causes tumor recurrences. There is an urgent need to develop a more precise and non-invasive strategy for the detection of the tumor metastasis in lymph nodes and distant organs. Based on the facts that tumor metastasis is closely related to the primary tumor microenvironment (TME) evolutions and that metabolomics profiling of the circulatory system can precisely reflect subtle changes within TME, we suppose whether metabolomic technology can be used to achieve non-invasive and real-time monitoring of BC metastatic status. In this study, the metastasis status of BC mouse models with different tumor-bearing times was firstly depicted to mimic clinical anatomic TNM staging system. Metabolomic profiling together with metastasis-related changes in TME among tumor-bearing mice with different metastatic status was conducted. A range of differential metabolites reflecting tumor metastatic states were screened and in vivo experiments proved that two main metastasis-driving factors in TME, TGF-β and hypoxia, were closely related to the regular changes of these metabolites. The differential metabolites level changes were also preliminarily confirmed in a limited number of clinical BC samples. Metabolite lysoPC (16:0) was found to be useful for clinical N stage diagnosis and the possible cause of its changes was analyzed by bioinformatics techniques.

Relationship between peripheral arterial disease severity determined by the Glass classification and triglyceride-glucose index; novel association and novel classification system.

Peripheral arterial disease is a serious clinical manifestation caused by atherosclerosis. It is one common cause of morbidity and mortality worldwide. It is commonly seen in males, and its (prevelance) increases with age. It is most prevalent with smoking, hypertension, diabetes mellitus and hyperlip-idemia. Novel studies investigate the relationship between triglyceride-glucose index (TyG) and cardiovascular diseases. Studies investigating the association of this index and peripheral arterial disease and disease severity are generally done by using The Trans-Atlantic Inter-Society Consensus (TASC) classification. We aimed to study this association by using the new Global Limb Anatomic Staging System (GLASS) classification. Two hundred patients between 25 to 90 years old diagnosed with peripheral arterial disease and admitted to the hospital for peripheral arterial angiography between July 2021 and December 2021, were evaluated retrospectively with blood parameters and angiographic images. Patients were divided into two groups: moderate (group 1; n=58) and severe (group 2; n=142) according to the GLASS classification. No statistical differences were observed for comorbidities and repeated interventional pro-cedure rates (p=0.164). Triglyceride values were found to be statistically dif-ferent between groups (p=0.040). TyG was found higher in group 2 (p= 0.04). According to the binary logistic regression model, only TyG was found to have a significant effect as a diagnostic factor (p=0.011). TyG was also significantly correlated with the Rutherford (p=0.012) and GLASS classification severity (p<0.001). Peripheral arterial disease and disease severity could be easily moni-tored with simple calculable TyG. In this way, precautions could be taken, and morbidities could be prevented.

Surgical resection rates after neoadjuvant therapy for localized pancreatic ductal adenocarcinoma: meta-analysis.

Neoadjuvant therapy is increasingly being used before surgery for localized pancreatic cancer. Given the importance of completing multimodal therapy, the aim of this study was to characterize surgical resection rates after neoadjuvant therapy as well as the reasons for, and long-term prognostic impact of, not undergoing resection. A systematic review and meta-analysis of prospective trials and high-quality retrospective studies since 2010 was performed to calculate pooled resection rates using a generalized random-effects model for potentially resectable, borderline resectable, and locally advanced pancreatic cancer. Median survival times were calculated using random-effects models for patients who did and did not undergo resection. In 125 studies that met the inclusion criteria, neoadjuvant therapy consisted of chemotherapy (36.8 per cent), chemoradiation (15.2 per cent), or chemotherapy and radiation (48.0 per cent). Among 11 713 patients, the pooled resection rates were 77.4 (95 per cent c.i. 71.3 to 82.5), 60.6 (54.8 to 66.1), and 22.2 (16.7 to 29.0) per cent for potentially resectable, borderline resectable, and locally advanced pancreatic cancer respectively. The most common reasons for not undergoing resection were distant progression for resectable and borderline resectable cancers, and local unresectability for locally advanced disease. Among 42 studies with survival data available, achieving surgical resection after neoadjuvant therapy was associated with improved survival for patients with potentially resectable (median 38.5 versus 13.3 months), borderline resectable (32.3 versus 13.9 months), and locally advanced (30.0 versus 14.6 months) pancreatic cancer (P < 0.001 for all). Although rates of surgical resection after neoadjuvant therapy vary based on anatomical stage, surgery is associated with improved survival for all patients with localized pancreatic cancer. These pooled resection and survival rates may inform patient-provider decision-making and serve as important benchmarks for future prospective trials.

Evaluation of global limb anatomic staging system for patients with chronic limb-threatening ischemia treated with autogenous bypass grafts.

We evaluated the relationship of the global limb anatomic staging system (GLASS) stage with the clinical outcomes for patients with chronic limb-threatening ischemia (CLTI) who had undergone distal bypass with vein grafting. We performed a single-center, retrospective analysis of patients with CLTI who had undergone distal bypass with vein grafting from January 2012 to December 2019. The primary end point was freedom from CLTI, including amputation-free survival, complete wound healing, and no ischemic rest pain. The secondary end points included a composite outcome of recurrence (patients who had achieved freedom from CLTI but had developed a new wound or ischemic rest pain), major limb amputation, amputation free-survival, overall survival, major adverse limb events, limb-based patency, and primary and secondary patency rates. A total of 190 patients had undergone 211 distal bypasses with a median follow-up of 30months. Of these patients, 80% had had diabetes or end-stage renal disease requiring dialysis. Most patients (63%) had experienced major or extensive tissue loss (WIfI [wound, ischemia, foot infection] wound class ≥2), and more than one half of these had had some degree of infection of the foot. A severe anatomic pattern (GLASS stage III) was predominant, with a prevalence of 78%. No significant differences were found between GLASS stage I and II and GLASS stage III groups for all the outcomes analyzed. Approximately 80% of the 211 revascularized limbs were free of CLTI at 12months after treatment. At 4years of follow-up, we observed that 25% of the patients had had CLTI recurrence, 83% were free from major amputation, and 61% were free from major adverse limb events. Limb-based patency, primary patency, and secondary patency were 79%, 80%, and 93% at 1year and 64%, 65%, and 81% at 4years, respectively. The GLASS stage was not related to patency or the clinical outcomes after distal bypass with vein grafting. Distal open revascularization resulted in excellent rates of freedom from CLTI with low rates of CLTI recurrence, two key time-integrated outcomes of clinical disease severity for patients with CLTI.

The Value of the 8th Edition of American Joint Committee on Cancer Pathological Prognostic Staging on the Selection of Postmastectomy Radiotherapy for T1-2N1 Breast Cancer.

Patients diagnosed with pT1-2N1M0 breast cancer between 2008 and 2018 in West China Hospital, Sichuan University were included. Locoregional-free survival (LRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), breast cancer-specific survival (BCSS), and overall survival (OS) were defined as endpoints. The propensity score matching (PSM), receiver operating characteristic (ROC) curve, the Kaplan-Meier analysis, and the Cox multivariable model were used for data analysis. We identified 1,615 patients with T1-2N1M0 breast cancer, and 44.9% (n = 744) of them were treated with PMRT. With a median follow-up of 76 months, 46 (2.8%) recurrences, 96 (5.9%) deaths, and 80 (5.0%) breast cancer-related deaths occurred. The 5-year LRFS, DMFS, DFS, BCSS, and OS were 98.6%, 95.3%, 93.7%, 96.5%, and 96.0%, respectively. PMRT could not improve 5-year LRFS, DMFS, DFS, BCSS, and OS compared with non-PMRT neither before nor after PSM in the era of contemporary systemic treatment. ROC curve showed that the 8th pathological prognostic staging had better discriminative ability compared with the 7th anatomical staging [the area under the curve (AUC) 0.653 vs. 0.546, P < 0.001]. In the anatomical staging system, PMRT had comparable 5-year BCSS in comparison with non-PMRT both in stages IIA (97.4% vs. 96.8%, P = 0.799) and IIB (95.3% vs. 97.0%, P = 0.071). When stratified according to the pathological staging, PMRT was associated with better 5-year BCSS in stage IIB (97.1% vs. 90.7%, P = 0.039), while not in stages IA, IB, IIA, and IIIA. Multivariate analysis demonstrated that PMRT was a significantly protective factor for BCSS in stage IIB (HR 0.331, 95% CI: 0.100-0.967, P = 0.044). The new staging could better select high-risk patients with T1-2N1 breast cancer for radiotherapy compared with the 7th staging, and PMRT might be exempted except the 8th staging of IIB in the era of contemporary systemic therapy in this disease.

Pulmonary Function Testing (PFT) after Photon and Proton Radiotherapy for Stage II-III Breast Cancer

<h3>Purpose/Objective(s)</h3> The Breast Cancer Lung Late Effects (BELLE) study prospectively enrolled patients with breast cancer who received adjuvant photon (XRT) or proton (PT) radiotherapy (RT) to evaluate potential early markers of induced lung injury, including pulmonary function tests (PFTs). <h3>Materials/Methods</h3> Patients ≥18 years with AJCC 8^th edition anatomic stage II-III or greater breast cancer were enrolled into the BELLE study between May 27, 2016 and May 26, 2020. All patients underwent clinical evaluation, computed tomography imaging, PFTs, and QoL questionnaires at baseline, 6 months, and 12 months relative to RT start. Fisher's exact tests and Kruskal-Wallis rank sum tests were used to compare the XRT and PT groups. <h3>Results</h3> A total of 37 patients were included in the final analysis (XRT, n=21; PT, n=16). Median age at diagnosis was 51 years (range, 31-76); 26 patients identified as white (70.3%), 8 as Black (21.6%), and 3 other (7.1%). Most patients did not have pre-existing respiratory disease (83.8%) or prior smoking history (62.2%), while 35.1% were former smokers and 1 was a current smoker (2.7%). The median BMI was 29.4 (range, 18.9-44.2). Most patients received chemotherapy (75.7%) and regional nodal irradiation (RNI; 78.4%). Median lung V20 was 25.3% (range, 5.6-39.7) and median lung V5 was 59.6% (range, 29.7-86.4). XRT patients had more pre-existing respiratory disease and were less likely to receive RNI (p=0.027 and p=0.006, respectively). There was no statistically significant difference between the XRT and PT cohorts for median lung V20 or V5. The median FEV1/FVC ratio at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (80.2 % vs 81.5%, p=0.81; 79.3% vs 81.3%, p=0.95; and 80.6% vs 79.4% p>0.99, respectively). Similarly, the median FVC values at baseline, 6 months, and 12 months were not significantly different between the XRT and PT cohorts (3.4 L vs 3.1 L, p=0.76; 3.2 L vs 3.0 L, p=0.38; and 3.5 L vs 3.0 L, p=0.23, respectively). While the median DLCO at baseline was significantly worse for the PT cohort (91% vs 76%, p=0.005), there was no difference between cohorts at 6 and 12 months (79.0% vs 78.0%, p=0.38; 89.0% vs 84.0%, p=0.80, respectively). Four patients developed radiation pneumonitis (RP) within a year of RT including 3 with transient grade 1 (n=1 PT; n=2 XRT) and 1 with grade 3 (XRT). <h3>Conclusion</h3> Despite high variability among patients across all PFT parameters, the median FEV1/FVC ratio and FVC were stable over time and did not cross the threshold for concern of restrictive lung disease in either cohort. Although DLCO decreased at 6 months in the XRT cohort, both cohorts showed improvement at one year without diagnosis of restrictive lung disease. Utilizing PFTs as an early marker of RT-induced lung injury, neither patients treated with XRT nor PT exhibited sustained PFT abnormalities with 1 year of follow-up.

Relationship between left ventriculoarterial coupling and damage stage in severe aortic stenosis

Abstract Background In patients with severe aortic stenosis (AS), an anatomic and functional staging classification has been proposed to assess extent of cardiac chambers damage to improve the decision of aortic valve replacement based only in symptoms or ejection fraction (EF) &amp;lt;50%. This staging relies on the concept that left ventricular (LV) afterload secondary to AS induce LV dysfunction with progression to LV and right ventricular damage. However, afterload has valvular and vascular components, and the latter is not evaluated by the classification of stages. Characteristics of arterial vasculature can impact on LV function through the alteration in LV-VA coupling which is the relationship between effective arterial elastance (Ea) and LV end-systolic elastance (Emax). Objective To evaluate the relationship between LV-VA coupling and the different stages of cardiac damage in severe AS. Methods We studied 205 patients, age average 70±11 years, 117 men, with severe AS (AVA &amp;lt;1 cm2) with Doppler echocardiography. Measurements of cardiac chambers were made according to ASE/EACVI Guidelines. Ea was calculated as end-systolic pressure divided by stroke volume. End-systolic pressure was obtained from tonometry of carotid pulse. Emax was estimated by the method of Senzaki (1) as an index of LV contractility. Ea / Emax ratio was used to assess LV-VA coupling. Patients were divided in five groups according to the classification of staging cardiac damage proposed by Tasted (2): stage 0, no valvular cardiac damage; stage 1, LV damage (EF &amp;lt;60%); stage 2, left atrial or mitral valve damage; stage 3, pulmonary vasculature or tricuspid valve damage and stage 4, right ventricular damage, or subclinical heart failure (LV stroke volume index &amp;lt;30 ml/m2). Results Mean ± standard deviation (see Table 1). No patient was in stage 0. Symptoms was present in 40% of stage 1, 85% of stage 2 and 100% of stage 3 and 4. Ea increases from stage 2 to stage 4 while Emax did not change in those groups but decreased from stage 1 to 2. Consequently, LV-VA coupling progressively decreased from stage 1 to 4. Conclusions Worsening of LV-VA coupling increase with staging cardiac damage. The alteration of LV-VA coupling from stage 2 to 4 is due to an increase in Ea without significant changes in level of contractility (Emax). The progression of cardiac damage appears to be related not only to valve disease but also to the characteristics of arterial vasculature. Funding Acknowledgement Type of funding sources: None.

Evaluating The Use Of Glass, Wifi And Mac Scores As Predictors Of Limb Salvage Success In Patients Receiving Free Tissue Transfer For Chronic Lower Extremity Wounds

The WIfI (wound, ischemia, and foot infection), MAC (medial arterial calcification), and GLASS (global limb anatomic staging system) grading scales have recently been adopted by the Society of Vascular Surgery as predictors of amputation rates and failure of revascularization in patients with chronic limb-threatening ischemia (CLTI). However, these metrics have not taken into account the ability of free tissue transfer (FTT) to shift these outcomes. This study seeks to characterize whether the addition of free tissue transfer can facilitate limb salvage in patients who would otherwise be deemed as high risk for failure using these grading systems.

A Review of Current Management of Gestational Trophoblastic Disease

A set of conditions connected to pregnancy and caused by trophoblast cells are known as gestational trophoblastic diseases. There are benign and malignant cancers, including invasive moles, choriocarcinomas, placental site trophoblastic tumors (PSTT), and epithelioid trophoblastic tumors (ETT). These cancers are classified as gestational trophoblastic neoplasms (GTN), which are less common but more serious. Most often, monitoring serum human chorionic gonadotropin (hCG) with histological confirmation is used to diagnose GTN. As a differential diagnosis, certain tissue biomarkers have grown in popularity. This has produced more accurate results and various treatment regimens and prognoses for each GTN. The World Health Organization's prognostic score system and the International Federation of Gynecology and Obstetrics anatomical staging system are the foundations for the treatment. Suppose the proper diagnosis is made and the instructions are followed. In that case, choriocarcinoma and invasive mole cases can be cured in 98 percent of instances, whereas PSTT and ETT still have only moderate success rates. The increased understanding of GTN and its characteristics enables medical professionals to rapidly make a differential diagnosis and select the appropriate treatment option, thus improving the overall survival of affected women. Nevertheless, epidemiological data collection and knowledge advancement through basic and translational research are crucial to address issues regarding GTN pathophysiology, their origins, and cellular behaviour.

Hodgkin lymphoma: 2023 update on diagnosis, risk-stratification, and management.

Hodgkin lymphoma (HL) is an uncommon B-cell lymphoid malignancy affecting 8540 new patients annually and representing approximately 10% of all lymphomas in the United States. HL is composed of two distinct disease entities: classical HL and nodular lymphocyte-predominant HL. Nodular sclerosis, mixed cellularity, lymphocyte depletion, and lymphocyte-rich HL are subgroups of classical HL. An accurate assessment of the stage of disease in patients with HL is critical for the selection of the appropriate therapy. Prognostic models that identify patients at low or high risk for recurrence, as well as the response to therapy as determined by positron emission tomography scan, are used to optimize therapy. Initial therapy for HL patients is based on the histology of the disease, the anatomical stage, and the presence of poor prognostic features. Patients with early-stage disease are typically treated with combined modality strategies utilizing abbreviated courses of combination chemotherapy followed by involved-field radiation therapy, while those with advanced-stage disease receive a longer course of chemotherapy, often without radiation therapy. However, newer agents, including brentuximab vedotin and anti-programmed death-1 (PD-1) antibodies, are now being incorporated into frontline therapy. High-dose chemotherapy (HDCT) followed by an autologous stem cell transplant (ASCT) is the standard of care for most patients who relapse following initial therapy. For patients who fail HDCT with ASCT, brentuximab vedotin, PD-1 blockade, non-myeloablative allogeneic transplant, or participation in a clinical trial should be considered.

Evaluation of the Global Limb Anatomic Staging System in patients with chronic limb-threatening ischemia undergoing endovascular intervention for femoropopliteal disease

BackgroundThe Global Limb Anatomic Staging System (GLASS) is a new method of quantifying the anatomic severity of infrainguinal disease in patients with chronic limb-threatening ischemia. However, because GLASS has undergone limited validation, its value as an aid to shared decision-making regarding the choice of revascularization strategy remains incompletely defined. Here we report the relationship between GLASS and outcomes in a contemporary series comprising all 309 patients who underwent an attempt at femoropopliteal and/or infrapopiteal endovascular therapy for chronic limb-threatening ischemia in our unit between 2009 and 2014. MethodsBaseline patient characteristics and outcome data including immediate technical success (ITS), amputation-free survival (AFS), overall survival, limb salvage, freedom from reintervention (FF-R), and freedom from major adverse limb events (FF-MALE) were obtained from hospital databases. GLASS grades and stage were obtained from pre-endovascular therapy angiographic imaging. Outcome data were censored on May 31, 2017. ResultsBaseline patient characteristics were similar across different GLASS femoropopliteal and IP grades and overall limb stages. Worsening GLASS stage was associated with a significant reduction in ITS (97.5% vs 91.5% vs 84.0%; P = .029). At 72 months FF-R (hazard ratio, 2.00; 95% confidence interval, 1.11-3.57; P = .020) and FF-MALE (hazard ratio, 1.76, 95% confidence interval, 1.10-2.81; P = .019) were significant worse in GLASS stage 3 than in stage 2 limbs. ConclusionsIn our study, there were significant differences in ITS, FF-R and FF-MALE between limbs with GLASS stage 2 and 3 disease. However, further GLASS refinement seems likely to be required if its usefulness in everyday clinical practice as an aid to shared decision-making regarding the choice of revascularization strategy is to be maximized.

Added value of quantitative, multiparametric 18F-FDG PET/MRI in the locoregional staging of rectal cancer

PurposeThe purpose of this study was to determine whether multiparametric positron emission tomography/magnetic resonance imaging (mpPET/MRI) can improve locoregional staging of rectal cancer (RC) and to assess its prognostic value after resection.MethodsIn this retrospective study, 46 patients with primary RC, who underwent multiparametric 18F-fluorodeoxyglucose (FDG) PET/MRI, followed by surgical resection without chemoradiotherapy, were included. Two readers reviewed T- and N- stage, mesorectal involvement, sphincter infiltration, tumor length, and distance from anal verge. In addition, diffusion-weighted imaging (DWI) and PET parameters were extracted from the multiparametric protocol and were compared to radiological staging as well as to the histopathological reference standard. Clinical and imaging follow-up was systematically assessed for tumor recurrence and death.ResultsLocally advanced rectal cancers (LARC) exhibited significantly higher metabolic tumor volume (MTV, AUC 0.74 [95% CI 0.59–0.89], p = 0.004) and total lesion glycolysis (TLG, AUC 0.70 [95% CI 0.53–0.87], p = 0.022) compared to early tumors. T-stage was associated with MTV (AUC 0.70 [95% CI 0.54–0.85], p = 0.021), while N-stage was better assessed using anatomical MRI sequences (AUC 0.72 [95% CI 0.539–0.894], p = 0.032). In the multivariate regression analysis, depending on the model, both anatomical MRI sequences and MTV/TLG were capable of detecting LARC. Combining anatomical MRI stage and MTV/TLG led to a superior diagnostic performance for detecting LARC (AUC 0.81, [95% CI 0.68–0.94], p < 0.001). In the survival analysis, MTV was independently associated with overall survival (HR 1.05 [95% CI 1.01–1.10], p = 0.044).ConclusionMultiparametric PET-MRI can improve identification of locally advanced tumors and, hence, help in treatment stratification. It provides additional information on RC tumor biology and may have prognostic value.

Transcriptomics in Tumor and Normal Lung Tissues Identify Patients With Early-Stage Non-Small-Cell Lung Cancer With High Risk of Postsurgery Recurrence Who May Benefit From Adjuvant Therapies.

PURPOSEThe prognosis of patients with non–small-cell lung cancer (NSCLC), traditionally determined by anatomic histology and TNM staging, neglects the biological features of the tumor that may be important in determining patient outcome and guiding therapeutic interventions. Identifying patients with NSCLC at increased risk of recurrence after curative-intent surgery remains an important unmet need so that known effective adjuvant treatments can be offered to those at highest risk of recurrence.METHODSRelative gene expression level in the primary tumor and normal bronchial tissues was used to retrospectively assess their association with disease-free survival (DFS) in a cohort of 120 patients with NSCLC who underwent curative-intent surgery.RESULTSLow versus high Digital Display Precision Predictor (DDPP) score (a measure of relative gene expression) was significantly associated with shorter DFS (highest recurrence risk; P = .006) in all patients and in patients with TNM stages 1-2 (P = .00051; n = 83). For patients with stages 1-2 and low DDPP score (n = 29), adjuvant chemotherapy was associated with improved DFS (P = .0041). High co-overexpression of CTLA-4, PD-L1, and ICOS in normal lung (28 of 120 patients) was also significantly associated with decreased DFS (P = .0013), suggesting an immune tolerance to tumor neoantigens in some patients. Patients with DDPP low and immunotolerant normal tissue had the shortest DFS (P = 2.12E–11).CONCLUSIONTNM stage, DDPP score, and immune competence status of normal lung are independent prognostic factors in multivariate analysis. Our findings open new avenues for prospective prognostic assessment and treatment assignment on the basis of transcriptomic profiling of tumor and normal lung tissue in patients with NSCLC.

The Infrapopliteal Global Limb Anatomic Staging System Predicts Wound Healing and Pain Relief after Partial Revascularization

Chronic limb-threatening ischemia (CLTI) is frequently associated with crural artery occlusion. Complete revascularization beyond the diseased crural artery is preferable; however, complete revascularization is challenging in many cases for various reasons. On the other hand, partial reconstruction for inflow disease sometimes leads to complete relief of symptoms. It is not elucidated which patients may recover from CLTI with partial revascularization (PR). Therefore, we aimed to evaluate the factors affecting outcomes after PR. We retrospectively reviewed the medical records of patients who underwent first-attempt PR, for CLTI, for limb salvage, in our institution, between April 2012 and December 2020. We divided these 103 cases into 2 groups: the salvage group (who achieved wound healing or relief from rest pain with PR; n=81) and the nonsalvage group (who ended with major amputation or additional distal revascularization; n=22). We evaluated the factors affecting the outcome of PR in terms of patient risk, limb severity (Society for Vascular Surgery Lower Extremity Threatened Limb Classification System; wound, ischemia, and foot infection [WIfI] classification), and anatomical pattern (Global Limb Anatomic Staging System; GLASS classification). Although patient risk between the 2 groups was not statistically significant, hypoalbuminemia (< 3.0mg/dL) was more prevalent in the nonsalvage group without significance (P=0.068). Regarding limb severity status, there was no significant difference in WIfI grades. Wound grade showed the strongest correlation (P=0.11) and reduced wound grade suggested future wound healing. In terms of GLASS, infrapopliteal grade was statistically significant (P=0.033). Upon a multivariate analysis, among infrapopliteal grade, hypoalbuminemia, and wound grade, infrapopliteal grade (P=0.0096) and hypoalbuminemia (P=0.2512) revealed significant differences. Wound grade also showed correlation (P=0.085). The usefulness of the WIfI classification and GLASS classification to predict wound healing after PR for CLTI was validated.

Predictors of infrapopliteal vein bypass graft revision in patients with chronic limb-threatening ischemia.

Surgical revascularization is the standard treatment for chronic limb-threatening ischemia (CLTI). However, some patients may require reintervention. The Global Anatomic Staging System (GLASS), which evaluates the complexity of infrainguinal lesions, was proposed. This study aimed to identify predictors for graft revision and evaluate whether GLASS impacts vein graft revision. Between 2011 and 2018, CLTI patients who underwent de novo infrapopliteal bypass using autogenous veins were retrospectively analyzed. To assess anatomic complexity with GLASS, femoropopliteal, infrapopliteal, and inframalleolar/pedal (IM) disease grades were determined. The outcomes of patients with or without graft revision were compared. Cox regression analysis was performed. Thirty-six of the 80 patients underwent reintervention for graft revision. Compared to the non-graft revision group, the graft revision group exhibited significantly higher rates of GLASS stage III (66% vs 81%, p = 0.046) and grade P2 IM disease (25% vs 58%, p = 0.009). Multivariate analysis revealed that IM grade P2 (hazard ratio [HR], 3.35; 95% confidence interval [CI], 1.66-6.75; p = 0.001) and spliced vein grafts (HR, 3.18; 95% CI, 1.43-7.06; p = 0.005) were significantly associated with graft revision. This study demonstrated that IM grade P2 and spliced vein grafts were predictors of graft revision. The GLASS stratification of IM disease grade may be useful in optimizing treatment for CLTI.

Predictability of the Global Limb Anatomic Staging System (GLASS) for Technical and Limb Related Outcomes: A Systematic Review and Meta-Analysis

The newly proposed Global Limb Anatomic Staging System (GLASS), a categorical staging of infrainguinal artery disease complexity, is expected to correlate with clinical outcomes in patients with chronic limb threatening ischaemia (CLTI). This study aimed to verify the relationship between GLASS stages and clinical outcomes after endovascular treatment (EVT) and bypass surgery (BS).

Tryptophan: Its Metabolism along the Kynurenine, Serotonin, and Indole Pathway in Malignant Melanoma.

(1) Background: Tryptophan metabolism is known to be one of the important mechanisms used by cancer to evade immune surveillance. Altered tryptophan metabolism was studied in patients with pigmented malignant melanoma confirmed histologically by the anatomic stage grouping for cutaneous melanoma using clinical staging on the basis of the Breslow thickness of the melanoma, the degree of spread to regional lymph nodes, and by the presence of distant metastasis. (2) Methods: Urinary tryptophan metabolites were detected by RP-HPLC method. (3) Results: In the present work, we provided evidence of altered metabolism of all tryptophan pathways in melanoma patients. (4) Conclusions: Knowledge of the shifted serotonin pathway toward DHICA formation and kynurenine pathway shifted toward NAD+ production could serve in the early detection of the disease and the initiation of early treatment of malignant melanoma.

Real-life long-term outcomes of upfront surgery in patients with resectable stage I-IIIA non-small cell lung cancer.

BackgroundTreatment of early-stage non-small cell lung cancer (NSCLC) is rapidly evolving. When introducing novelties, real-life data on effectiveness of currently used treatment strategies are needed. The present study evaluated outcomes of stage I–IIIA NSCLC patients treated with upfront radical surgery in everyday clinical practice, between 2010–2017.Patients and methodsData of 539 consecutive patients were retrieved from a prospective hospital-based registry. All diagnostic, treatment and follow-up procedures were performed at the same thoracic oncology centre according to the valid guidelines. The primary outcome was overall survival (OS) analysed by clinical(c) and pathological(p) TNM (tumour, node, metastases) stage. The impact of clinicopathological characteristics on OS was evaluated using univariable (UVA) and multivariable regression analysis (MVA).ResultsWith a median follow-up of 53.9 months, median OS and 5-year OS rate in the overall population were 90.4 months and 64.4%. Five-year OS rates by pTNM stage I, II and IIIA were 70.2%, 60.21%, and 49.9%, respectively. Both cTNM and pTNM stages were associated with OS; but only pTNM retained its independent prognostic value (p = 0.003) in MVA. Agreement between cTNM and pTNM was 69.0%. Next to pTNM, age (p = 0.001) and gender (p = 0.004) retained their independent prognostic value for OS.ConclusionsThe study showed favourable outcomes of resectable stage I–IIIA NSCLC treated with upfront surgery in real-life. Relatively low agreement between cTNM and pTNM stages and independent prognostic value of only pTNM, observed in real-life data, suggest that surgery remains the most accurate provider of the anatomical stage of disease and important upfront therapy.

Role of dynamic and parametric whole-body FDG PET/CT imaging in molecular characterization of primary breast cancer: a single institution experience.

The aim of this pilot study was to assess the role of dynamic whole-body PET and parametric imaging in the biological characterization of primary breast cancer. In total 24 histologically proven primary breast cancer lesions in 21 consecutive patients were retrospectively analyzed. Each patient underwent 18F-fluoro-deoxyglucose whole-body dynamic PET-CT before any treatment. Dynamic PET images were acquired in the list mode for a total duration of 70 min. The reconstructed parametric imaging generated Patlak plot-based 'Slope' and 'Intercept' images, from which parametric indices ki and DV were obtained. The standard uptake value (SUV) metric was also obtained by summing the last few frames of the dynamic study. ki, distribution volume (DV) and SUV were correlated with the histological tumor grade, biomarkers [hormone receptors and human epidermal growth factor receptor 2 (HER-2) neu expression] and molecular subtypes (A, B and C) as well as with tumor size, regional nodal metastases and distant metastases. The mean ki was found to be significantly higher in grade III than II lesions (P = 0.005), HER-2 neu positive status (P = 0.04) and molecular subtype B (P = 0.04) as well as in greater than T1 lesions(P = 0.0003 and P = 0.04, respectively) and node-positive lesions (P = 0.009). Though mean ki was not found to be significant for the hormone receptors status (P = 0.08), it showed the best correlation compared to the other parameters (P = 0.8 for DV and P = 0.1 for SUV). Spearman's correlation test, area under the curve (AUC) and mismatch percentage also revealed ki to predict tumor grade (AUC, 0.95; r = 0.7; P = 0.0001), HER-2 neu status and molecular subtypes (AUC, 0.81; r = 0.49 and P = 0.01) along with the hormone receptors status (AUC, 0.83; r = 0.32; P = 0.1). The mean DV failed to show any association with any of the biological or anatomical staging parameters. Though ki was found to be comparable to that of SUV in almost all the assessed parameters, it appeared to be better for predicting hormone receptors status even though both parameters were not statistically significant. Our initial observation in a small cohort of breast cancer patients suggests that ki is promising in stratifying primary breast cancer lesions according to the tumor grade and biological characteristics.

Quantifying the relationship of HIV infection with clinicopathological spectrum and outcome among patients with colorectal cancer in a South African population

Literature is limited on HIV and colorectal cancer (CRC) in sub-Saharan Africa despite it being the epicentre of the HIV epidemic. To compare clinicopathological features and outcome of CRC in HIV-negative and HIV-positive patients. Retrospective analysis of a prospective CRC database. Demographic details, HIV status, anatomical site, disease stage, treatment and follow-up were documented. Of 715 patients with CRC, 145 and 570 tested positive and negative respectively for HIV. Median age was 45 (IQR 36-53 and 57 (IQR 45-66) years among HIV-positive and HIV-negative patients respectively (p<0.0001). Tumour differentiation differed between the two groups (p=0.003) but staging was not different (p=0.6). Surgical resection rate was 52% for HIV-positive patients versus 59% for HIV-negative patients (p=0.07). Median follow-up was 9 (IQR 2-20.5) months for HIV-positive patients and 12 (IQR 6-29) months for HIV-negative patients (p=0.154). Recurrence rate was 14.7% among HIV positive patients and 6.8% in HIV negative patients (p=0.089). When compared with HIV-negative patients, HIV-positive patients with CRC presented at a younger age and tended to have lower surgical resection rates. There was no difference between the two groups with CRC in terms of anatomical sub-site distribution, disease staging and recurrence rates.