Interstitial Lung Abnormalities: Current Understanding.

Interstitial lung abnormalities (ILAs) are incidental findings on computed tomography scans, characterized by nondependent abnormalities affecting more than 5% of any lung zone. They are associated with factors such as age, smoking, genetic variants, worsened clinical outcomes, and increased mortality. Risk stratification based on clinical and radiological features of ILAs is crucial in clinical practice, particularly for identifying cases at high risk of progression to pulmonary fibrosis. Traction bronchiectasis/bronchiolectasis index has emerged as a promising imaging biomarker for prognostic risk stratification in ILAs. These findings suggest a spectrum of fibrosing interstitial lung diseases, encompassing from ILAs to pulmonary fibrosis.

Multiparametric assessment of microvascular invasion in hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

PURPOSE: To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. METHODS: In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. RESULTS: A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). CONCLUSION: Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Effect of lipiodol marking before CT-guided cryoablation on the outcome of sporadic renal cell carcinoma.

PURPOSE: This retrospective study evaluates the impact of preoperative lipiodol marking on the outcomes of computed tomography (CT)-guided cryoablation for histologically diagnosed sporadic renal cell carcinoma (RCC). METHODS: This study analyzed the data of 173 patients who underwent CT-guided cryoablation for histologically proven sporadic RCC at a single institution between April 2014 and December 2020. The local control rate (LCR), recurrence-free survival rate (RFSR), overall survival rate (OSR), changes in renal function, and complications in patients with (n = 85) and without (n = 88) preoperative lipiodol marking were compared. RESULTS: The 5-year LCR and 5-year RFSR were significantly higher in patients with lipiodol marking (97.51% and 93.84%, respectively) than in those without (72.38% and 68.10%, respectively) (P value <0.01, log-rank test). There were no significant differences between the two groups regarding the 5-year OSR (97.50% vs. 86.82%) or the deterioration in chronic kidney disease stage (12.70% vs. 16.43%). Grade ≥3 complications occurred in patients with lipiodol marking (n = 2, retroperitoneal hematoma and cerebral infarction in 1 patient each) and without (n = 5; urinary fistula in 2, colonic perforation in 2, urinary infection in 1). CONCLUSION: Lipiodol marking before CT-guided cryoablation for sporadic RCC is a feasible approach to improving local control and RFS while mitigating the decline in renal function. Additionally, it may help reduce complications.

Imaging of Pulmonary Fibrosis: An Update, From the AJR Special Series on Imaging of Fibrosis.

Pulmonary fibrosis is recognized as occurring in association with a wide and increasing array of conditions, and it presents with a spectrum of chest CT appearances. Idiopathic pulmonary fibrosis (IPF), which corresponds histologically with usual interstitial pneumonia and represents the most common idiopathic interstitial pneumonia, is a chronic progressive fibrotic interstitial lung disease (ILD) of unknown cause. Progressive pulmonary fibrosis (PPF) describes the radiologic development of pulmonary fibrosis in patients with ILD of a known or unknown cause other than IPF. The recognition of PPF impacts management of patients with ILD-for example, in guiding initiation of antifibrotic therapy. Interstitial lung abnormalities are an incidental CT finding in patients without suspected ILD and may represent an early intervenable form of pulmonary fibrosis. Traction bronchiectasis and/or bronchiolectasis, when detected in the setting of chronic fibrosis, is generally considered evidence of irreversible disease, and progression predicts worsening mortality risk. Awareness of the association between pulmonary fibrosis and connective tissue diseases, particularly rheumatoid arthritis, is increasing. This review provides an update on the imaging of pulmonary fibrosis, with attention given to recent advances in disease understanding with relevance to radiologic practice. The essential role of a multidisciplinary approach to clinical and radiologic data is highlighted.

Incidence and severity of pulmonary embolism in COVID-19 infection: Ancestral, Alpha, Delta, and Omicron variants.

Little information is available regarding incidence and severity of pulmonary embolism (PE) across the periods of ancestral strain, Alpha, Delta, and Omicron variants. The aim of this study is to investigate the incidence and severity of PE over the dominant periods of ancestral strain and Alpha, Delta, and Omicron variants. We hypothesized that the incidence and the severity by proximity of PE in patients with the newer variants and vaccination would be decreased compared with those in ancestral and earlier variants. Patients with COVID-19 diagnosis between March 2020 and February 2022 and computed tomography pulmonary angiogram performed within a 6-week window around the diagnosis (-2 to +4 weeks) were studied retrospectively. The primary endpoints were the associations of the incidence and location of PE with the ancestral strain and each variant. Of the 720 coronavirus disease 2019 patients with computed tomography pulmonary angiogram (58.6 ± 17.2 years; 374 females), PE was diagnosed among 42/358 (12%) during the ancestral strain period, 5/60 (8%) during the Alpha variant period, 16/152 (11%) during the Delta variant period, and 13/150 (9%) during the Omicron variant period. The most proximal PE (ancestral strain vs variants) was located in the main/lobar arteries (31% vs 6%-40%), in the segmental arteries (52% vs 60%-75%), and in the subsegmental arteries (17% vs 0%-19%). There was no significant difference in both the incidence and location of PE across the periods, confirmed by multivariable logistic regression models. In summary, the incidence and severity of PE did not significantly differ across the periods of ancestral strain and Alpha, Delta, and Omicron variants.

Extracellular volume fraction determined by dual-layer spectral detector CT: Possible role in predicting the efficacy of preoperative neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma.

PURPOSE: To clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). METHODS: We enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. RESULTS: Tumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV (<26.0 %), sensitivity, specificity, accuracy, positive predictive value, and negative value for predicting response group were 71.4 %, 85.0 %, 83.6 %, 35.7 % and 96.2 %, respectively. CONCLUSION: PDAC with lower DECT-ECV can potentially show better response to NAC. DECT-ECV might be a useful biomarker for predicting response to NAC in patients with PDAC.

Severe COVID-19 pneumonia leads to post-COVID-19 lung abnormalities on follow-up CT scans.

Purpose: To investigate the association of the maximal severity of pneumonia on CT scans obtained within 6-week of diagnosis with the subsequent development of post-COVID-19 lung abnormalities (Co-LA). Methods: COVID-19 patients diagnosed at our hospital between March 2020 and September 2021 were studied retrospectively. The patients were included if they had (1) at least one chest CT scan available within 6-week of diagnosis; and (2) at least one follow-up chest CT scan available ≥ 6 months after diagnosis, which were evaluated by two independent radiologists. Pneumonia Severity Categories were assigned on CT at diagnosis according to the CT patterns of pneumonia and extent as: 1) no pneumonia (Estimated Extent, 0%); 2) non-extensive pneumonia (GGO and OP, <40%); and 3) extensive pneumonia (extensive OP and DAD, >40%). Co-LA on follow-up CT scans, categorized using a 3-point Co-LA Score (0, No Co-LA; 1, Indeterminate Co-LA; and 2, Co-LA). Results: Out of 132 patients, 42 patients (32%) developed Co-LA on their follow-up CT scans 6-24 months post diagnosis. The severity of COVID-19 pneumonia was associated with Co-LA: In 47 patients with extensive pneumonia, 33 patients (70%) developed Co-LA, of whom 18 (55%) developed fibrotic Co-LA. In 52 with non-extensive pneumonia, 9 (17%) developed Co-LA: In 33 with no pneumonia, none (0%) developed Co-LA. Conclusions: Higher severity of pneumonia at diagnosis was associated with the increased risk of development of Co-LA after 6-24 months of SARS-CoV-2 infection.

Right adrenal vein identification using unenhanced magnetic resonance imaging.

Purpose: Unenhanced magnetic resonance imaging (MRI) is known to be useful in characterizing adrenal adenomas through the implementation of in-phase (IPI) and opposed-phase imaging (OPI) based on chemical shift artifacts. However, whether unenhanced MRI can contribute to the identification of right adrenal vein (RAV) remains unclear. The aim of this study was to evaluate the feasibility of unenhanced MRI for the identification of RAV. Material and methods: This retrospective study reviewed 30 patients (16 men; median age 60 years; range 34-76 years) who underwent MRI and subsequent adrenal venous sampling (AVS). Chemical shift MRI was acquired using echo times of 2.3 ms (OPI) and 4.6 ms (IPI) with a slice thickness of 3 mm and a gap of 1 mm. T2-weighted imaging (T2WI) was also performed. Identification of RAVs was performed by 2 independent radiologists. Inter-observer agreement on a 3-point rating scale was evaluated using κ statistics. The identification rate of RAVs was compared between OPI, IPI, and T2WI using McNemar's test. Results: Good inter-observer agreement was found for the OPI (κ = 0.744), whereas fair agreement was obtained for both other sequences (IPI: κ = 0.375; T2WI: 0.348). For both raters, the identification rate of RAVs was higher with OPI (36/60; 60.0%) than with other sequences (IPI: 16/60, 26.7%; T2WI: 9/60, 15.0%; p < 0.05, each). Conclusions: OPI may play a screening role in the identification of RAVs preceding AVS, which could reduce the required radiation exposure and doses of contrast agent.

COVID-19 Vaccination reduced pneumonia severity.

Purpose: To investigate the effect of vaccinations and boosters on the severity of COVID-19 pneumonia on CT scans during the period of Delta and Omicron variants. Methods: Retrospectively studied were 303 patients diagnosed with COVID-19 between July 2021 and February 2022, who had obtained at least one CT scan within 6 weeks around the COVID-19 diagnosis (-2 to +4 weeks). The severity of pneumonia was evaluated with a 6-point scale Pneumonia Score. The association between demographic and clinical data and vaccination status (booster/additional vaccination, complete vaccination and un-vaccination) and the difference between Pneumonia Scores by vaccination status were investigated. Results: Of 303 patients (59.4 ± 16.3 years; 178 females), 62 (20 %) were in the booster/additional vaccination group, 117 (39 %) in the complete vaccination group, and 124 (41 %) in the unvaccinated group. Interobserver agreement of the Pneumonia Score was high (weighted kappa score = 0.875). Patients in the booster/additionally vaccinated group tended to be older (P = 0.0085) and have more underlying comorbidities (P < 0.0001), and the Pneumonia Scores were lower in the booster/additionally vaccinated [median 2 (IQR 0-4)] and completely vaccinated groups [median 3 (IQR 1-4)] than those in the unvaccinated group [median 4 (IQR 2-4)], respectively (P < 0.0001 and P < 0.0001, respectively). A multivariable linear analysis adjusted for confounding factors confirmed the difference. Conclusion: Vaccinated patients, with or without booster/additional vaccination, had milder COVID-19 pneumonia on CT scans than unvaccinated patients during the period of Delta and Omicron variants. This study supports the efficacy of the vaccine against COVID-19 from a radiological perspective.

A novel fast kilovoltage switching dual-energy computed tomography technique with deep learning: Utility for non-invasive assessments of liver fibrosis.

PURPOSE: To investigate whether the iodine density of liver parenchyma in the equilibrium phase and extracellular volume fraction (ECV) measured by deep learning-based spectral computed tomography (CT) can enable noninvasive liver fibrosis staging. METHOD: We retrospectively analyzed 63 patients who underwent dynamic CT using deep learning-based spectral CT before a hepatectomy or liver transplantation. The iodine densities of the liver parenchyma (I-liver) and abdominal aorta (I-aorta) were independently measured by two radiologists using iodine density images at the equilibrium phase. The iodine-density ratio (I-ratio: I-liver/I-aorta) and CT-ECV were calculated. Spearman's rank correlation analysis was used to evaluate the relationship between the I-ratio or CT-ECV and liver fibrosis stage, and receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic performances of the I-ratio and CT-ECV. RESULTS: The I-ratio and CT-ECV showed significant positive correlations with liver fibrosis stage (ρ = 0.648, p < 0.0001 and ρ = 0.723, p < 0.0001, respectively). The areas under the ROC curve for the CT-ECV were 0.882 (F0 vs ≥ F1), 0.873 (≤F1 vs ≥ F2), 0.848 (≤F2 vs ≥ F3), and 0.891 (≤F3 vs F4). CONCLUSIONS: Deep learning-based spectral CT may be useful for noninvasive assessments of liver fibrosis.

Right entorhinal cortical thickness is associated with Mini-Mental State Examination scores from multi-country datasets using MRI.

PURPOSE: To discover common biomarkers correlating with the Mini-Mental State Examination (MMSE) scores from multi-country MRI datasets. METHODS: The first dataset comprised 112 subjects (49 men, 63 women; range, 46-94 years) at the National Hospital Organization Kyushu Medical Center. A second dataset comprised 300 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database (177 men, 123 women; range, 57-91 years). Three-dimensional T1-weighted MR images were collected from both datasets. In total, 14 deep gray matter volumes and 70 cortical thicknesses were obtained from MR images using FreeSurfer software. Total hippocampal volume and the ratio of hippocampus to cerebral volume were also calculated. Correlations between each variable and MMSE scores were assessed using Pearson's correlation coefficient. Parameters with moderate correlation coefficients (r > 0.3) from each dataset were determined as independent variables and evaluated using general linear model (GLM) analyses. RESULTS: In Pearson's correlation coefficient, total and bilateral hippocampal volumes, right amygdala volume, and right entorhinal cortex (ERC) thickness showed moderate correlation coefficients (r > 0.3) with MMSE scores from the first dataset. The ADNI dataset showed moderate correlations with MMSE scores in more variables, including bilateral ERC thickness and hippocampal volume. GLM analysis revealed that right ERC thickness correlated significantly with MMSE score in both datasets. Cortical thicknesses of the left parahippocampal gyrus, left inferior parietal lobe, and right fusiform gyrus also significantly correlated with MMSE score in the ADNI dataset (p < 0.05). CONCLUSION: A positive correlation between right ERC thickness and MMSE score was identified from multi-country datasets.

Identification of predictors for mini-mental state examination and revised Hasegawa's Dementia Scale scores using MR-based brain morphometry.

PURPOSE: The early detection of cognitive function decline is crucial to help manage or slow the progression of symptoms. The Mini-Mental State Examination (MMSE) and revised Hasegawa's Dementia Scale (HDS-R) are widely used in screening for cognitive impairment. The purpose of this study was to explore common predictors of the two different cognitive testing systems using MR-based brain morphometry. MATERIALS AND METHODS: This retrospective study included 200 subjects with clinical suspicion of cognitive impairment who underwent 3D T1-weighted MRI at our institution between February 2019 and August 2020. Variables related to the volume of deep gray matter and 70 cortical thicknesses were obtained from the MR images using voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) and FreeSurfer software. The correlation between each variable including age and MMSE/HDS-R scores was evaluated using uni- and multi-variate logistic regression analyses. RESULTS: In univariate analysis, parameters include hippocampal volume and bilateral entorhinal cortex (ERC) thickness showed moderate correlation coefficients with both MMSE and HDS-R scores. Multivariate analysis demonstrated the right ERC thickness was the common parameter which significantly correlates with both MMSE and HDS-R scores (p < 0.05). CONCLUSION: Right ERC thickness appears to offer a useful predictive biomarker for both MMSE and HDS-R scores.

A practical system that enables physicians to respond expeditiously to significant unexpected findings (SUFs) in radiological reports.

PURPOSE: To demonstrate effectiveness of our present radiological report check flowchart enabling physicians to respond to significant unexpected findings (SUFs), by comparing the response periods from the examination date to the action date on untreated SUFs between the previous and present versions of our flowchart. METHODS: In the flowchart's previous version used February-October 2019, SUFs, which were notified by email, were audited every month. The physician received a phone call and was asked to act on the untreated SUF. In the flowchart's present version used from November 2019 to May 2020, SUFs were audited every 2 weeks. The physician and his/her chief were asked to return a written response to the untreated SUF. We evaluated the difference in the response periods between the previous and present versions of the flowchart. RESULTS: With the previous flowchart's use, untreated SUFs were 43 of 229 SUFs (18.8%) with the present flowchart untreated SUFs were 22 of 130 SUFs (16.9%). All SUFs in both periods were eventually responded. The present flowchart (median/range, 25/11-70 days) significantly had shorter response periods than the previous flowchart (70/16-290 days) (p < 0.0001). CONCLUSION: The present flowchart employing a shortened primary audit interval, a written response, and the department chief's intervention, helped reduce the response periods.

Supraduodenal and Right Gastric Arteries Originating from A Common Trunk: A Rare Anatomical Variant.

Knowledge of the anatomic variations of the supraduodenal artery (SDA) and right gastric artery (RGA) is necessary to reduce the procedure time and radiation exposure dose, as well as to avoid unexpected complications of catheter placement before hepatic arterial infusion chemotherapy. The SDA and RGA most commonly arise from the gastroduodenal artery (GDA) and the proper hepatic artery, respectively; however, they can branch from the left hepatic artery (LHA). In addition, the SDA frequently anastomoses with the RGA and occasionally with the GDA. We observed a rare anatomic variant of SDA and RGA originating from the LHA as a common trunk. The patient also had a variant of SDA communicating with the GDA. It is important for interventional radiologists to be aware of these variations.

Endovascular repair of a Clostridium perfringens infected pseudoaneurysm presenting as an intramural air pocket.

An infected aneurysm (IA) is a relatively rare but complex and life-threatening disease. We report a 78-year-old man with an IA in the common iliac artery (CIA) due to Clostridium perfringens. An initial computed tomography (CT) revealed an air pocket in the left CIA, and a pseudoaneurysm was seen on the CT taken the next day, in the area where the air pocket was initially observed. Due to the patient's high surgical risk, emergent endovascular aneurysm repair (EVAR) was performed. No indolent infection was found 1.5 years after the surgery. Because of its high risk of expansion and rupture, accurate diagnosis and immediate treatment is required for managing IAs. The case emphasizes that air density in an arterial wall could be an early radiologic feature of an IA, and EVAR could be a treatment option for IA.

The Japanese Breast Cancer Society clinical practice guidelines for surgical treatment of breast cancer, 2018 edition.

We have prepared the Japanese Breast Cancer Society clinical practice guidelines (CPGs) for surgical treatment of breast cancer, 2018 update after a systematic review (SR) of the literature based upon the Medical Information Network Distribution Service (Minds) procedure. The CPG committee for surgical treatment of breast cancer, composed of breast surgeons and plastic surgeons treating breast cancer, has developed the CPGs. Eight clinical questions (CQs) were selected and divided roughly into the following five categories: (1) breast surgery in initial therapy (CQs 1-3); (2) axillary surgery in initial therapy (CQs 4-5); (3) breast reconstruction in initial therapy (CQ 6); (4) surgical treatment for recurrent and metastatic breast cancer (CQs 7-8); and (5) others. Recommendations for these CQs were decided by the GRADE grid method. In addition, 4 outlines, 14 background questions (BQs), and 12 future research questions (FQs) were also selected. Statements for these BQs and FQs are provided. We developed the updated CPGs for surgical treatment of breast cancer, 2018, which include 8 CQs and recommendations. As a decision-making tool for the understanding and treatment of breast cancer, these guidelines will help surgical oncologists dealing with breast cancer, medical staff, and patients, along with their family members.

Successful treatment of esophagopleural fistula following pulmonary resection for primary lung cancer: a case report.

BACKGROUND: We report a rare case of esophagopleural fistula (EPF) developing during the postoperative period after pulmonary resection for primary lung cancer. CASE PRESENTATION: A 71-year-old male who underwent video-assisted thoracoscopic right lower lobectomy with lymph node dissection for primary lung cancer developed severe stabbing pain in his right shoulder and high fever 3 days after the operation. The fever persisted, the cough became more productive, and a plain chest X-ray showed slight a few infiltrative opacities in the right lung field. Intravenous antibiotic therapy was initiated. The patient developed a right pneumothorax 5 days after the operation, and contaminated discharge from the right chest tube was noted. A chest computed tomography showed right-sided empyema, while bronchoscopic examination revealed no evidence of a bronchopleural fistula. Open-window thoracostomy (OWT) was performed. Finally, 2 days after the OWT, the patient was diagnosed as having an EPF, because the right chest cavity was found to be contaminated with food materials. Ample purification of the right chest cavity was achieved by repeated dressing changes, and the EPF was finally closed by omentopexy. The post-surgical course was uneventful. Five weeks after the omentopexy, an esophagogram revealed no leakage of the contrast medium from the esophageal wall. The patient was discharged 13 weeks after the omentopexy. CONCLUSION: While EPF following pulmonary resection is a rare complication, it can lead to critical situations and the diagnosis is difficult. Prompt OWT and omentopexy were found to be effective treatment procedures for EPF following lung surgery.

Imaging of Metastatic Cancer Cells in Sentinel Lymph Nodes using Affibody Probes and Possibility of a Theranostic Approach.

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach for developing a more efficient SLN biopsy procedure, we reported a two-stage imaging method combining lymphoscintigraphy and near-infrared (NIR) fluorescence imaging to depict metastatic cancer cells in SLNs in vivo. Furthermore, the theranostic potential of the combined procedure was examined by cell culture and xenograft mouse model. Anti-HER2 and anti-epidermal growth factor receptor (EGFR) affibody probes were used for NIR fluorescence imaging. Strong NIR fluorescence signal intensity of the anti-EGFR affibody probe was observed in SAS cells (EGFR positive). Radioactivity in the SLNs was clearly observed in the in vivo studies. High anti-EGFR affibody NIR fluorescence intensity was observed in the metastatic lymph nodes in mice. The addition of the IR700-conjugated anti-EGFR affibody to the culture medium decreased the proliferation of SAS cells. Decreased proliferation was shown in Ki-67 immunohistochemistry in xenograft tumors. Our data suggest that a two-stage combined imaging method using lymphoscintigraphy and affibody probes may offer the direct visualization of metastatic lymph nodes as an easily applied technique in SLN biopsy. Although further animal studies are required to assess the effect of treating lymphatic metastasis in this approach, our study results provide a foundation for the further development of this promising imaging and treatment strategy for earlier lymph node metastasis detection and treatment.