Improvements and future perspective in diagnostic tools for neuroendocrine neoplasms.

INTRODUCTION: Neuroendocrine neoplasms (NENs) represent a complex group of tumors arising from neuroendocrine cells, characterized by heterogeneous behavior and challenging diagnostics. Despite advancements in medical technology, NENs present a major challenge in early detection, often leading to delayed diagnosis and variable outcomes. This review aims to provide an in-depth analysis of current diagnostic methods as well as the evolving and future directions of diagnostic strategies for NENs. AREA COVERED: The review extensively covers the evolution of diagnostic tools for NENs, from traditional imaging and biochemical tests to advanced genomic profiling and next-generation sequencing. The emerging role of technologies such as artificial intelligence, machine learning, and liquid biopsies could improve diagnostic precision, as could the integration of imaging modalities such as positron emission tomography (PET)/magnetic resonance imaging (MRI) hybrids and innovative radiotracers. EXPERT OPINION: Despite progress, there is still a significant gap in the early diagnosis of NENs. Bridging this diagnostic gap and integrating advanced technologies and precision medicine are crucial to improving patient outcomes. However, challenges such as low clinical awareness, limited possibility of noninvasive diagnostic tools and funding limitations for rare diseases like NENs are acknowledged.

Cross-sectional imaging after pancreatic surgery: The dialogue between the radiologist and the surgeon.

Pancreatic surgery is nowadays considered one of the most complex surgical approaches and not unscathed from complications. After the surgical procedure, cross-sectional imaging is considered the non-invasive reference standard to detect early and late compilations, and consequently to address patients to the best management possible. Contras-enhanced computed tomography (CECT) should be considered the most important and useful imaging technique to evaluate the surgical site. Thanks to its speed, contrast, and spatial resolution, it can help reach the final diagnosis with high accuracy. On the other hand, magnetic resonance imaging (MRI) should be considered as a second-line imaging approach, especially for the evaluation of biliary findings and late complications. In both cases, the radiologist should be aware of protocols and what to look at, to create a robust dialogue with the surgeon and outline a fitted treatment for each patient.

Radiomics and liver: Where we are and where we are headed?

Hepatic diffuse conditions and focal liver lesions represent two of the most common scenarios to face in everyday radiological clinical practice. Thanks to the advances in technology, radiology has gained a central role in the management of patients with liver disease, especially due to its high sensitivity and specificity. Since the introduction of computed tomography (CT) and magnetic resonance imaging (MRI), radiology has been considered the non-invasive reference modality to assess and characterize liver pathologies. In recent years, clinical practice has moved forward to a quantitative approach to better evaluate and manage each patient with a more fitted approach. In this setting, radiomics has gained an important role in helping radiologists and clinicians characterize hepatic pathological entities, in managing patients, and in determining prognosis. Radiomics can extract a large amount of data from radiological images, which can be associated with different liver scenarios. Thanks to its wide applications in ultrasonography (US), CT, and MRI, different studies were focused on specific aspects related to liver diseases. Even if broadly applied, radiomics has some advantages and different pitfalls. This review aims to summarize the most important and robust studies published in the field of liver radiomics, underlying their main limitations and issues, and what they can add to the current and future clinical practice and literature.

Liver metastases: The role of magnetic resonance imaging.

The liver is one of the organs most commonly involved in metastatic disease, especially due to its unique vascularization. It's well known that liver metastases represent the most common hepatic malignant tumors. From a practical point of view, it's of utmost importance to evaluate the presence of liver metastases when staging oncologic patients, to select the best treatment possible, and finally to predict the overall prognosis. In the past few years, imaging techniques have gained a central role in identifying liver metastases, thanks to ultrasonography, contrast-enhanced computed tomography (CT), and magnetic resonance imaging (MRI). All these techniques, especially CT and MRI, can be considered the non-invasive reference standard techniques for the assessment of liver involvement by metastases. On the other hand, the liver can be affected by different focal lesions, sometimes benign, and sometimes malignant. On these bases, radiologists should face the differential diagnosis between benign and secondary lesions to correctly allocate patients to the best management. Considering the above-mentioned principles, it's extremely important to underline and refresh the broad spectrum of liver metastases features that can occur in everyday clinical practice. This review aims to summarize the most common imaging features of liver metastases, with a special focus on typical and atypical appearance, by using MRI.

Gynaecological Causes of Acute Pelvic Pain: Common and Not-So-Common Imaging Findings.

In female patients, acute pelvic pain can be caused by gynaecological, gastrointestinal, and urinary tract pathologies. Due to the variety of diagnostic possibilities, the correct assessment of these patients may be challenging. The most frequent gynaecological causes of acute pelvic pain in non-pregnant women are pelvic inflammatory disease, ruptured ovarian cysts, ovarian torsion, and degeneration or torsion of uterine leiomyomas. On the other hand, spontaneous abortion, ectopic pregnancy, and placental disorders are the most frequent gynaecological entities to cause acute pelvic pain in pregnant patients. Ultrasound (US) is usually the first-line diagnostic technique because of its sensitivity across most common aetiologies and its lack of radiation exposure. Computed tomography (CT) may be performed if ultrasound findings are equivocal or if a gynaecologic disease is not initially suspected. Magnetic resonance imaging (MRI) is an extremely useful second-line technique for further characterisation after US or CT. This pictorial review aims to review the spectrum of gynaecological entities that may manifest as acute pelvic pain in the emergency department and to describe the imaging findings of these gynaecological conditions obtained with different imaging techniques.

Radiomics in colorectal cancer patients.

The main therapeutic options for colorectal cancer are surgical resection and adjuvant chemotherapy in non-metastatic disease. However, the evaluation of the overall adjuvant chemotherapy benefit in patients with a high risk of recurrence is challenging. Radiological images can represent a source of data that can be analyzed by using automated computer-based techniques, working on numerical information coded within Digital Imaging and Communications in Medicine files: This image numerical analysis has been named "radiomics". Radiomics allows the extraction of quantitative features from radiological images, mainly invisible to the naked eye, that can be further analyzed by artificial intelligence algorithms. Radiomics is expanding in oncology to either understand tumor biology or for the development of imaging biomarkers for diagnosis, staging, and prognosis, prediction of treatment response and diseases monitoring and surveillance. Several efforts have been made to develop radiomics signatures for colorectal cancer patient using computed tomography (CT) images with different aims: The preoperative prediction of lymph node metastasis, detecting BRAF and RAS gene mutations. Moreover, the use of delta-radiomics allows the analysis of variations of the radiomics parameters extracted from CT scans performed at different timepoints. Most published studies concerning radiomics and magnetic resonance imaging (MRI) mainly focused on the response of advanced tumors that underwent neoadjuvant therapy. Nodes status is the main determinant of adjuvant chemotherapy. Therefore, several radiomics model based on MRI, especially on T2-weighted images and ADC maps, for the preoperative prediction of nodes metastasis in rectal cancer has been developed. Current studies mostly focused on the applications of radiomics in positron emission tomography/CT for the prediction of survival after curative surgical resection and assessment of response following neoadjuvant chemoradiotherapy. Since colorectal liver metastases develop in about 25% of patients with colorectal carcinoma, the main diagnostic tasks of radiomics should be the detection of synchronous and metachronous lesions. Radiomics could be an additional tool in clinical setting, especially in identifying patients with high-risk disease. Nevertheless, radiomics has numerous shortcomings that make daily use extremely difficult. Further studies are needed to assess performance of radiomics in stratifying patients with high-risk disease.

Association of chronic statin use, myopenia, myosteatosis and major morbidity in surgical patients with upper gastrointestinal cancer.

Derangements of body composition affect surgical outcomes. Chronic statin use may induce muscle wasting and impair muscle tissue quality. Aim of this study was to evaluate the association of chronic statin use, skeletal muscle area (SMA), myosteatosis and major postoperative morbidity. Between 2011 and 2021, patients undergoing pancreatoduodenectomy or total gastrectomy for cancer, and using statins since at least 1 year, were retrospective studied. SMA and myosteatosis were measured at CT scan. The cut-off for SMA and myosteatosis were determined using ROC curve and considering severe complications as the binary outcome. The presence of myopenia was defined when SMA was lower that the cut-off. A multivariable logistic regression was applied to assess the association between several factors and severe complications. After a matching procedure (1:1) for key baseline risk factors (ASA; age; Charlson comorbidity index; tumor site; intraoperative blood loss), a final sample of 104 patients, of which 52 treated and 52 not treated with statins, was obtained. The median age was 75 years, with an ASA score ≥ 3 in 63% of the cases. SMA (OR 5.119, 95% CI 1.053-24.865) and myosteatosis (OR 4.234, 95% CI 1.511-11.866) below the cut-off values were significantly associated with major morbidity. Statin use was predictive of major complication only in patients with preoperative myopenia (OR 5.449, 95% CI 1.054-28.158). Myopenia and myosteatosis were independently associated with an increased risk of severe complications. Statin use was associated with a higher risk of having major morbidity only in the subgroup of patients with myopenia.

Imaging in Gastric Cancer: Current Practice and Future Perspectives.

Gastric cancer represents one of the most common oncological causes of death worldwide. In order to treat patients in the best possible way, the staging of gastric cancer should be accurate. In this regard, endoscopy ultrasound (EUS) has been considered the reference standard for tumor (T) and nodal (N) statuses in recent decades. However, thanks to technological improvements, computed tomography (CT) has gained an important role, not only in the assessment of distant metastases (M status) but also in T and N staging. In addition, magnetic resonance imaging (MRI) can contribute to the detection and staging of primary gastric tumors thanks to its excellent soft tissue contrast and multiple imaging sequences without radiation-related risks. In addition, MRI can help with the detection of liver metastases, especially small lesions. Finally, positron emission tomography (PET) is still considered a useful diagnostic tool for the staging of gastric cancer patients, with a focus on nodal metastases and peritoneal carcinomatosis. In addition, it may play a role in the treatment of gastric cancer in the coming years thanks to the introduction of new labeling peptides. This review aims to summarize the most common advantages and pitfalls of EUS, CT, MRI and PET in the TNM staging of gastric cancer patients.

Radiological findings in non-surgical recurrent hepatocellular carcinoma: From locoregional treatments to immunotherapy.

Since hepatocellular carcinoma (HCC) represents an important cause of mortality and morbidity all over the world. Currently, it is fundamental not only to achieve a curative treatment but also to manage in the best way any possible recurrence. Even if the latest update of the Barcelona Clinic Liver Cancer guidelines for HCC treatment has introduced new locoregional techniques and confirmed others as well-established clinical practices, there is still no consensus about the treatment of recurrent HCC (RHCC). Locoregional treatments and medical therapy represent two of the most widely accepted approaches for disease control, especially in the advanced stage of liver disease. Different medical treatments are now approved, and others are under investigation. On this basis, radiology plays a central role in the diagnosis of RHCC and the assessment of response to locoregional treatments and medical therapy for RHCC. This review summarized the actual clinical practice by underlining the importance of the radiological approach both in the diagnosis and treatment of RHCC.

The usefulness of preoperative CT in colon cancer staging: impact of radiologists' experience.

PURPOSE: To assess the agreement between radiologists in the detection of specific features related to T- and N-stage and evaluate accuracy in colon cancer staging. METHODS: Patients who underwent contrast-enhanced computed tomography (CECT) before surgery were enrolled and evaluated by three radiologists with different experience. Pathological data were used as the reference standard. Tumor location, presence of tumor bulging, fat stranding, lateroconal fascia invasion, enlarged vessels, axial short diameter of the biggest node, shape, enhancement pattern, intranodal necrosis, and cluster were collected. Reliability analysis was performed with κ statistics and intraclass correlation coefficients (ICCs). Logistic regressions were used to determine independent predictors associated with staging. RESULTS: Seventy five patients were evaluated. The reliability analysis was moderate to substantial for tumor location (κ = 0.853), T staging (κ = 0.531), tumor bulging (κ = 0.478), fat stranding (κ = 0.490), lateroconal fascia invasion (κ = 0.436), enlarged vessels (κ = 0.401), the axial short diameter of the biggest node (ICC = 0.732), shape (κ = 0.484), enhancement pattern (κ = 0.431), intranodal necrosis (κ = 0.606), and cluster (κ = 0.358). For all readers, sensitivity was higher for T3 lesions (60-69%) and specificity was higher for T2 and T4 lesions (84.5-90.0% and 82.4-85.1%). The diagnostic accuracy was acceptable for all lesions and among all readers (50.7-92.1%). The lateroconal fascia invasion and enlarged vessels resulted as independent predictor factors (OR = 3.292 and OR = 2.651) for T staging, while nodes' cluster and dimension as independent predictor factors of N staging [OR = 3.798 and OR = 1.083]. CONCLUSION: Reader's experience is one of the most important factors associated with the correct classification of colon cancer. Moreover, CECT can help depict radiological features independently associated with the T and N stages.

Radiomics in PI-RADS 3 Multiparametric MRI for Prostate Cancer Identification: Literature Models Re-Implementation and Proposal of a Clinical-Radiological Model.

PI-RADS 3 prostate lesions clinical management is still debated, with high variability among different centers. Identifying clinically significant tumors among PI-RADS 3 is crucial. Radiomics applied to multiparametric MR (mpMR) seems promising. Nevertheless, reproducibility assessment by external validation is required. We retrospectively included all patients with at least one PI-RADS 3 lesion (PI-RADS v2.1) detected on a 3T prostate MRI scan at our Institution (June 2016-March 2021). An MRI-targeted biopsy was used as ground truth. We assessed reproducible mpMRI radiomic features found in the literature. Then, we proposed a new model combining PSA density and two radiomic features (texture regularity (T2) and size zone heterogeneity (ADC)). All models were trained/assessed through 100-repetitions 5-fold cross-validation. Eighty patients were included (26 with GS ≥ 7). In total, 9/20 T2 features (Hector's model) and 1 T2 feature (Jin's model) significantly correlated to biopsy on our dataset. PSA density alone predicted clinically significant tumors (sensitivity: 66%; specificity: 71%). Our model obtained a sensitivity of 80% and a specificity of 76%. Standard-compliant works with detailed methodologies achieve comparable radiomic feature sets. Therefore, efforts to facilitate reproducibility are needed, while complex models and imaging protocols seem not, since our model combining PSA density and two radiomic features from routinely performed sequences appeared to differentiate clinically significant cancers.

Liver magnetic resonance imaging for evaluation of response to treatment after stereotactic body radiation therapy of hepatocellular carcinoma.

BACKGROUND: Although stereotactic body radiation therapy (SBRT) is increasingly used, its application has not yet been regulated by the main international guidelines, leaving the decision to multidisciplinary teams. AIM: To assess magnetic resonance imaging (MRI) features of hepatocellular carcinoma (HCC) treated with SBRT, highlighting the efficacy of the treatment and the main aspects of the lesion before and after the procedure. METHODS: As part of a retrospective study, 49 patients who underwent SBRT for HCC between January 2013 and November 2019 were recruited. Each patient underwent a pre-treatment MRI examination with a hepatospecific contrast agent and a similar follow-up examination within 6 mo of therapy. In addition, 22 patients underwent a second follow-up examination after the first 6 mo. The following characteristics were analysed: Features analysed compared to pre-treatment MRI examination, presence or absence of infield and outfield progression, ring-like enhancement, signal hyperintensity in T2-weighted sequences in the perilesional parenchyma, capsular retraction, and "band" signal hypointensity in T1-weighted gradient echo fat saturated sequences obtained during hepatobiliary excretion. RESULTS: Signal hyperintensity in the T2-weighted sequences showed a statistically significant reduction in the number of lesions at the post-SBRT first control (P = 0.0006). Signal hyperintensity in diffusion-weighted imaging-weighted sequences was decreased at MRI first control (P < 0.0001). A statistically significant increase of apparent diffusion coefficient values from a median of 1.01 to 1.38 at the first post-control was found (P < 0.0001). Capsular retraction was increased at the late evaluation (P = 0.006). Band-like signal hypointensity in the hepatobiliary phase was present in 94% at the late control (P = 0.006). The study of the risk of outfield progression vs infield progression revealed a hazard ratio of 9. CONCLUSION: The efficacy of SBRT should be evaluated not in the first 6 mo, but at least 9 mo post-SBRT, when infield progression persists at very low rates while the risk of outfield progression increases significantly.

Role of gadoxetic acid-enhanced liver magnetic resonance imaging in the evaluation of hepatocellular carcinoma after locoregional treatment.

Locoregional treatments, as alternatives to surgery, play a key role in the management of hepatocellular carcinoma (HCC). Liver magnetic resonance imaging (MRI) enables a multiparametric assessment, going beyond the traditional dynamic computed tomography approach. Moreover, the use of hepatobiliary agents can improve diagnostic accuracy and are becoming important in the diagnosis and follow-up of HCC. However, the main challenge is to quickly identify classical responses to loco-regional treatments in order to determine the most suitable management strategy for each patient. The aim of this review is to provide a summary of the most common and uncommon liver MRI findings in patients who underwent loco-regional treatments for HCC, with a special focus on ablative therapies (radiofrequency, microwaves and cryoablation), trans-arterial chemoembolization, trans-arterial radio-embolization and stereotactic ablative radiotherapy techniques, considering the usefulness of gadoxetate disodium (Gd-EOB-DTPA) contrast agent.

Computation of contrast-enhanced perfusion using only two CT scan phases: a proof-of-concept study on abdominal organs.

BACKGROUND: Computed tomography perfusion imaging (CTPI) by repeated scanning has clinical relevance but implies relatively high radiation exposure. We present a method to measure perfusion from two CT scan phases only, considering tissue enhancement, feeding vessel (aortic) peak enhancement, and bolus shape. METHODS: CTPI scans (each with 40 frames acquired every 1.5 s) of 11 patients with advanced hepatocellular carcinoma (HCC) enrolled between 2012 and 2016 were retrospectively analysed (aged 69 ± 9 years, 8/11 males). Perfusion was defined as the maximal slope of the time-enhancement curve divided by the peak enhancement of the feeding vessel (aorta). Perfusion was computed two times, first using the maximum slope derived from all data points and then using the peak tissue enhancement and the bolus shape obtained from the aortic curve. RESULTS: Perfusion values from the two methods were linearly related (r2 = 0.92, p < 0.001; Bland-Altman analysis bias -0.12). The mathematical model showed that the perfusion ratio of two ROIs with the same feeding vessel (aorta) corresponds to their peak enhancement ratio (r2 = 0.55, p < 0.001; Bland-Altman analysis bias -0.68). The relationship between perfusion and tissue enhancement is predicted to be linear in the clinical range of interest, being only function of perfusion, peak feeding vessel enhancement, and bolus shape. CONCLUSIONS: This proof-of-concept study showed that perfusion values of HCC, kidney, and pancreas could be computed using enhancement measured only with two CT scan phases, if aortic peak enhancement and bolus shape are known.

Estimating Fatty Pancreas-A Preoperative Bedside Assessment by Bioelectric Impedance Analysis: Implications for Pancreatic Surgery.

OBJECTIVE: The aim of the study was to evaluate whether fatty pancreas could be estimated by fat mass measurement by preoperative bioelectric impedance analysis. Preoperative computed tomography scan and pathologic evaluation were used as validation methods. Moreover, the 3 methodologies were tested for their ability in predicting postoperative pancreatic fistula. METHODS: Seventy-five patients who underwent pancreatic resection were analyzed. Preoperative computed tomography attenuation in Hounsfield unit (CT-HU) was used to assess fatty pancreas. Bioelectric impedance analysis was performed the day before surgery and fat mass index (FMI) was calculated. Pancreatic steatosis was assessed by pathologists at the line of surgical transection. The ability of the methods in predicting postoperative pancreatic fistula was evaluated by the area under the receiver operating characteristics curves. RESULTS: There was a strong correlation between CT-HU values and grade of pancreatic steatosis evaluated at histology ( r = -0.852, P < 0.001) and a moderate correlation between FMI and histologic pancreatic steatosis ( r = 0.612, P < 0.001) and between CT-HU value and FMI ( r = -0.659, P < 0.001) values. The area under the curve (95% confidence interval) was 0.942 (0.879-1) for histology, 0.924 (0.844-1) for CT-HU, and 0.884 (0.778-0.990) for FMI. CONCLUSIONS: Bioelectric impedance analysis represents a valid alternative to assess pancreatic steatosis.

Benign focal liver lesions: The role of magnetic resonance imaging.

Liver lesions are common findings in radiologists' daily routine. They are a complex category of pathology that range from solitary benign lesions to primary liver cancer and liver metastases. Benign focal liver lesions can arise from different liver cell types: Epithelial (hepatocytes and biliary cells) and nonepithelial (mesenchymal cells). Liver magnetic resonance imaging (MRI) is a fundamental radiological method in these patients as it allows with its multiparametric approach optimal non-invasive tissue characterization. Furthermore, advanced liver MRI techniques such as diffusion-weighted imaging and hepatobiliary contrast agents have improved the detection of focal liver lesions and can be highly effective in differentiating pseudotumor from tumors, as well as benign from malignant lesions, and can also be used for differential diagnosis. Although histological examination can be useful in making a definitive diagnosis, MRI is an important modality in the diagnosis of liver lesions with a significant impact on patient care. This aim of this review is to provide a comprehensive overview of benign liver lesions on MRI.

Low skeletal muscle index and myosteatosis as predictors of mortality in critically ill surgical patients.

OBJECTIVES: After elective surgeries, low muscle mass and other specific body composition indexes, assessed by computed tomography (CT), are associated with adverse outcomes such as an increased risk for postoperative complications and higher mortality. However, limited information is available about the role of these indexes on short- and long-term outcomes in surgical patients admitted to the intensive care unit (ICU). The aim of this study was to assess the association of body composition indexes with 90-d mortality in this specific patient cohort. METHODS: This was a retrospective study including adult surgical patients admitted to the ICU between 2014 and 2018 who underwent a CT scan at the time of admission. Total muscle area (TMA), total fat area (TFA), visceral fat area (VFA), and intramuscular fat area (IMFA) were measured. We then calculated skeletal muscle index (SMI; TMA/m2), myosteatosis (IMFA/TMA), and visceral fat-to-muscle ratio (VFA/TMA). We analyzed the effects of these indexes on mortality. RESULTS: The study included 204 patients. Overall, 90-d mortality was 28%. Log-rank test and Cox multivariate analysis on 90-d mortality showed a significant association of low SMI and myosteatosis with 90-d mortality. Myosteatosis was also significantly associated with prolonged mechanical ventilation and increased ICU length of stay. CONCLUSIONS: Specific body composition indexes may predict mortality in surgical patients admitted to the ICU. Low SMI and myosteatosis were independently associated with increased 90-d mortality.

Skeletal muscle wasting and long-term prognosis in patients undergoing rectal cancer surgery without neoadjuvant therapy.

BACKGROUND: Derangement of body composition has been associated with dismal long-term survival in several gastrointestinal cancers including rectal tumors treated with neoadjuvant therapies. The role of specific preoperative anthropometric indexes on the oncologic outcomes of patients undergoing upfront surgery for rectal cancer has not been investigated. The aim of the study is to evaluate the association of body composition and overall survival in this specific cohort. METHODS: Lumbar computed tomography images, obtained within the 30 days previous to surgery, between January 2009 and December 2016, were used to calculate population-specific thresholds of muscle mass (sarcopenia), subcutaneous and visceral adiposity, visceral obesity, sarcopenic obesity, and myosteatosis. These body composition variables were related with overall survival (OS), tumor-specific survival (TSS), and disease-free survival (DFS). OS, TSS, and DFS were evaluated by the Kaplan-Meier method. Cox regression analysis was used to identify independent predictors of mortality, tumor-specific mortality, and recurrence, and data were presented as hazard ratio (HR) and 95% confidence interval (CI). RESULTS: During the study period, 411 patients underwent rectal resection for cancer, and among these, 129 were without neoadjuvant chemoradiation. The median follow-up was 96.7 months. At the end of the follow-up, 41 patients (31.8%) had died; of these, 26 (20.1%) died for tumor-related reasons, and 36 (27.1%) experienced disease recurrence. One-, three-, and five-year OS was 95.7%, 86.0%, and 76.8% for non-sarcopenic patients versus 82.4%, 58.8%, and 40.0% for sarcopenic ones respectively (p < 0.001). Kaplan-Meier survival curves comparing sarcopenic and non-sarcopenic patients showed a significant difference in terms of OS (log-rank < 0.0001). Through multivariate Cox regression, overall mortality risk was associated only with sarcopenia (HR 1.96; 95%CI 1.03-3.74; p = 0.041). Disease stage IV and III (HR 13.75; 95% CI 2.89-65.6; p < 0.001 and HR 4.72; 95% CI 1.06-21.1; p = 0.043, respectively) and sarcopenia (HR 2.62; 95% CI 1.22-5.6; p = 0.013) were independently associated with TSS. The other body composition indexes investigated showed no significant association with prognosis. CONCLUSIONS: These results support the inclusion of body composition assessment for prognostic stratification of rectal cancer patients undergoing upfront resection.