Diagnostic value of one-stop CT energy spectrum and perfusion for angiogenesis in colon and rectum cancer.

OBJECTIVE: Evaluation of the predictive value of one-stop energy spectrum and perfusion CT parameters for microvessel density (MVD) in colorectal cancer cancer foci. METHODS: Clinical and CT data of 82 patients with colorectal cancer confirmed by preoperative colonoscopy or surgical pathology in our hospital from September 2019 to November 2022 were collected and analyzed retrospectively. Energy spectrum CT images were measured using the Protocols general module of the GSI Viewer software of the GE AW 4.7 post-processing workstation to measure the CT values of the arterial and venous phase lesions and the neighboring normal intestinal wall in a single energy range of 40 kev∼140 kev, and the slopes of the energy spectrum curves (λ) were calculated between 40 kev-90 kev; Iodine concentration (IC), Water concentration (WC), Effective-Z (Eff-Z) and Normalized iodine concentration (NIC) were measured by placing a region of interest (ROI) on the iodine concentration map and water concentration map at the lesion and adjacent to the normal intestinal wall.Perfusion CT images were scanned continuously and dynamically using GSI Perfusion software and analyzed by applying CT Perfusion 4.0 software.Blood volume (BV), blood flow (BF), surface permeability (PS), time to peak (TTP), and mean transit time (MTT) were measured respectively in the lesion and adjacent normal colorectal wall. Based on the pathological findings, the tumors were divided into a low MVD group (MVD < 35/field of view, n = 52 cases) and a high MVD group (MVD ≥ 35/field of view, n = 30 cases) using a median of 35/field of view as the MVD grouping criterion. The collected data were statistically analyzed, the subjects' operating characteristic curve (ROC) was plotted, and the area under curve (AUC), sensitivity, specificity, and Yoden index were calculated for the predicted efficacy of each parameter of the energy spectrum and perfusion CT and the combined parameters. RESULTS: The CT values, IC, NIC, λ, Eff-Z of 40kev∼140kev single energy in the arterial and venous phase of colorectal cancer in the high MVD group were higher than those in the low MVD group, and the differences were all statistically significant (p < 0.05). The AUC of each single-energy CT value in the arterial phase from 40 kev to 120 kev for determining the high or low MVD of colorectal cancer was greater than 0.8, indicating that arterial stage has a good predictive value for high or low MVD in colorectal cancer; AUC for arterial IC, NIC and IC + NIC were all greater than 0.9, indicating that in arterial colorectal cancer, both single and combined parameters of spectral CT are highly effective in predicting the level of MVD. The AUC of 40 kev to 90 kev single-energy CT values in the intravenous phase was greater than 0.9, and its diagnostic efficacy was more representative; The AUC of IC and NIC in venous stage were greater than 0.8, which indicating that the IC and NIC energy spectrum parameters in venous stage colorectal cancer have a very good predictive value for the difference between high and low MVDs, with the greatest diagnostic efficacy in IC.The values of BV and BF in the high MVD group were higher than those in the low MVD group, and the differences were statistically significant (P < 0.05), and the AUC of BF, BV, and BV + BF were 0.991, 0.733, and 0.997, respectively, with the highest diagnostic efficacy for determining the level of MVD in colorectal cancer by BV + BF. CONCLUSION: One-stop CT energy spectrum and perfusion imaging technology can accurately reflect the MVD in living tumor tissues, which in turn reflects the tumor angiogenesis, and to a certain extent helps to determine the malignancy, invasion and metastasis of living colorectal cancer tumor tissues based on CT energy spectrum and perfusion parameters.

Laparoscopic D3 lymph node dissection with left colic artery and first sigmoid artery preservation in rectal cancer.

BACKGROUND: D3 lymph node dissection with left colic artery (LCA) preservation in rectal cancer surgery seems to have little effect on reducing postoperative anastomotic leakage. So we first propose D3 lymph node dissection with LCA and first sigmoid artery (SA) preservation. This novel procedure deserves further study. METHODS: Rectal cancer patients who underwent laparoscopic D3 lymph node dissection with LCA preservation or with LCA and first SA preservation between January 2017 and January 2020 were retrospectively assessed. The patients were categorized into two groups: the preservation of the LCA group and the preservation of the LCA and first SA group. A 1:1 propensity score-matched analysis was performed to decrease confounding. RESULTS: Propensity score matching yielded 56 patients in each group from the eligible patients. The rate of postoperative anastomotic leakage in the preservation of the LCA and first SA group was significantly lower than that in the LCA preservation group (7.1% vs. 0%, P=0.040). No significant differences were observed in operation time, length of hospital stay, estimated blood loss, length of distal margin, lymph node retrieval, apical lymph node retrieval, and complications. A survival analysis showed patients' 3-year disease-free survival (DFS) rates of group 1 and group 2 were 81.8% and 83.5% (P=0.595), respectively. CONCLUSION: D3 lymph node dissection with LCA and first SA preservation for rectal cancer may help reduce the incidence of anastomotic leakage without compromising oncological outcomes compare with D3 lymph node dissection with LCA preservation alone.

Verification of blood flow path reconstruction mechanism in distal sigmoid colon and rectal cancer after high IMA ligation through preoperative and postoperative comparison by manual subtraction CTA.

INTRODUCTION: We aimed to investigate manual subtraction computed tomography angiography (MS-CTA) to further confirm the distribution and classification of LCA (left colic artery) ascending/descending branches, then observe the postoperative blood flow path to illustrate how the above branches evolved to postoperative blood path. MATERIAL AND METHODS: 89 patients with distal sigmoid and rectal cancer were referred in our observation and underwent MS-CTA between June 2020 and March 2022. We classified the distribution of LCA and confirmed whether there exists AMCA (accessory middle colic artery). Then we planned blood flow path based on the classification of LCA branches before operation. High ligation was applied in regular radical surgery. During operation, we carefully protect the bifurcation of ascending and descending LCA. Then we compared the planned blood flow path with the actual postoperative blood flow path to verify the mechanism we proposed previously. RESULTS: Of 89 patients, 82 cases met our criteria, we summarized 6 distribution pattens of LCA ascending and descending branches. These preoperative pattens are consistent with the inspection during operation. The postoperative blood flow path of 6 pattens is evolved from the above adjacent anastomotic branches and is consistent with the planned blood flow path. We also found 2 cases with IMA stenosis and 1 case with SMA stenosis under pathological condition, and their compensatory blood flow path is in accordance with our theory. The rate of the anastomotic leakage in our study group is relatively low (7.3%). CONCLUSION: MS-CTA could confirm the distribution of LCA and AMCA, display accurate postoperative blood reconstruction path after IMA high ligation, and it further verified the mechanism we proposed previously, which is the proximal anastomotic branches forming new blood flow path from high-pressure area to the low-pressure area. This mechanism might be helpful for performing accurate laparoscopic sigmoid and rectal cancer surgery.

Extramural venous invasion (EMVI) revisited: a detailed analysis of various characteristics of EMVI and their role as a predictive imaging biomarker in the neoadjuvant treatment response in rectal cancer.

PURPOSE: To assess whether size, diameter, and large vein involvement of MR-detected extramural venous invasion (MR-EMVI) have an impact on neoadjuvant therapy response in rectal adenocarcinoma. METHODS: 57 patients with locally advanced rectal adenocarcinoma scanned with MRI before and after neoadjuvant therapy were included. Two abdominal radiologists evaluated the images with special emphasis on EMVI, on initial staging and after neoadjuvant treatment. The sensitivity and specificity of MRI for detection of rest EMVI were determined. The association of various MR-EMVI characteristics including number, size, and main vein involvement with treatment response was investigated. In subjects with discordance of radiology and pathology, elastin stain was performed, and images and slides were re-evaluated on site with a multidisciplinary approach. RESULTS: At initial evaluation, 17 patients were MR-EMVI negative (29.8%) and 40 were MR-EMVI positive (70.2%). Complete/near-complete responders had less number (mean 1.45) and smaller diameter of MR-EMVI (mean 1.8 mm), when compared with partial responders (2.54 and 3.3 mm; p < 0.005). The sensitivity of MRI for rest EMVI detection was high, specificity was moderate, and in one patient elastin stain changed the final decision. In five patients with rest MR-EMVI positivity, carcinoma histopathologically had a distinctive serpiginous perivascular spread, growing along the track of vascular bundle, although it did not appear in intravascular spaces. CONCLUSION: This study demonstrates that not only the presence, but also size and number of EMVI that may be significant clinically and thus these parameters also ought to be incorporated to the MRI evaluation and prognostication of treatment response. From pathology perspective, tumors growing alongside major vessels may also reflect EMVI even if they are not demonstrably "intravascular."

[Elucidation for Intratumor Localization of a DDS-based Anticancer Drug and Enhancement of Its Therapeutic Effects via Improvement of the Tumor Microenvironment].

In the development of drug delivery system (DDS)-based anticancer drugs, the techniques for the intratumor mapping and quantification of active pharmaceutical ingredients (API) in pharmaceuticals must be pivotal for predicting pharmacological effects and adverse events. X-ray fluorescence spectrometry (XRF) is a potent analytical tool for mapping/quantifying platinum pharmaceutics such as oxaliplatin (l-OHP) and its liposomal formulation. In recent studies, we employed XRF to visualize the intratumor micro-distribution of l-OHP in a tumor-bearing model mouse intravenously injected with either free l-OHP or l-OHP liposomes. The intratumor distribution of l-OHP within tumor sections could be determined by XRF to detect platinum atoms. After treatment with the liposomal formulation, the l-OHP was localized near the tumor vessels and, via repeated injections, increasingly accumulated in tumors by a much greater degree than treatment with free l-OHP. The repeated injections of l-OHP liposomes improved the vascular permeability via inducing the apoptosis of tumor cells near the tumor vessels, which should improve the tumor microenvironment and enhance the intratumor accumulation of repeated doses of l-OHP liposomes. The proposed process was also used to visualize the intratumor distribution of l-OHP in rectal cancer specimens resected from a patient who had received l-OHP-based preoperative chemotherapy. We further revealed that neutralization of an acidic tumor microenvironment via oral administration with NaHCO3 could improve the therapeutic efficacy of weakly basic anticancer agent-encapsulating liposomes. Collectively, mapping/quantifying the intratumor API in DDS drugs and/or improving the tumor microenvironment would be an effective means to accelerate the clinical development of DDS-based anticancer drugs.

Comparison of Diagnostic Performance between Perfusion-Related Intravoxel Incoherent Motion DWI and Dynamic Contrast-Enhanced MRI in Rectal Cancer.

This study was aimed to determine the diagnostic performance of perfusion-related parameters derived from intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI) by comparing them with quantitative parameters from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) based on differentiation grades of rectal cancer. We retrospectively analyzed 98 patients with rectal cancer. Perfusion-related IVIM parameters (D ∗, f, and f·D ∗) and quantitative DCE parameters (K trans, K ep, V e , and V p ) were obtained by plotting the volume-of-interest on in-house software. Furthermore, we compared the difference and diagnostic performance of all well-moderately and poorly differentiated rectal cancer parameters. Finally, we analyzed the correlation between those DCE and IVIM parameters and pathological differentiation grade. The values of f, K trans, and K ep significantly differentiated poor and well-moderate rectal cancers. K trans achieved the highest area under the curve (AUC) value compared to perfusion-related IVIM and DCE parameters. Furthermore, K trans showed a better correlation with pathological differentiation grade than f. The diagnostic efficiency of DCE-MRI was greater than perfusion-related IVIM parameters. The f value derived from perfusion-related IVIM offered a diagnostic performance similar to DCE-MRI for patients with renal insufficiency.

Associations between initiating antihypertensive regimens on stage I-III colorectal cancer outcomes: A Medicare SEER cohort analysis.

PURPOSE: Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes. PATIENTS AND METHODS: This study was a non-interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The association between AH drug utilization on AJCC stage I-III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models. RESULTS: The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer-specific mortality (HR: 0.79, 95% CI: 0.75-0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.87), beta-blockers (HR: 0.87, 95% CI: 0.84-0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80-0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer-specific mortality (HR: 0.94, 95% CI: 0.90-0.98). CONCLUSION: Further research needs to be performed, but AH medications may present a promising, low-cost pathway to supporting CRC treatment for stage I-III cancers.

MRI-detected extramural vascular invasion potentiates the risk for pathological metastasis to the lateral lymph nodes in rectal cancer.

PURPOSE: Multidisciplinary treatment for locally advanced rectal cancer requires an accurate assessment of the risk of metastasis to the lateral lymph nodes (LNs). We herein aimed to stratify the risk of pathological metastasis to lateral LNs based on the preoperatively detected malignant features. METHODS: All patients with rectal cancer who underwent surgery from January 2016 to July 2020 were identified. We recorded the TNM factors; perirectal and lateral LN sizes; and MRI findings, including mesorectal fascia involvement, extramural vascular invasion (EMVI), tumor site, and tumor distance from the anal verge. RESULTS: 101 patients underwent rectal resection with lateral lymph node dissection, of whom 16 (15.8%) exhibited pathological metastases to the lateral LNs. Univariate analyses demonstrated that lateral LN metastasis was significantly correlated with mrEMVI positivity (p = 0.0023) and a baseline lateral LN short-axis length of ≥ 5 mm (p < 0.0001). These significant associations were confirmed by a multivariate analysis (p = 0.0254 and 0.0027, respectively). The lateral LN metastasis rate was as high as 44% in cases bearing both risk factors, compared to 0% in cases lacking both risk factors. CONCLUSION: The results elucidated in this study may contribute to risk stratification, which can be used when determining the indications for lateral lymph node dissection.

Laparoscopic fluorescence navigation for left-sided colon and rectal cancer: Blood flow evaluation, vessel and ureteral navigation, clip marking and trans-anal tube insertion.

BACKGROUND: Recently, the indocyanine green (ICG) fluorescence navigation method has attracted much attention as a means of intraoperative navigation, especially during laparoscopic surgery. The newly developed near-infrared (NIR) fluorescent resin also emits NIR fluorescence, as does ICG. Presently, new devices made with this resin are being developed. The purpose of this study was to present our fluorescence navigation techniques for left-sided colon and rectal cancer. METHOD: Fifty-nine patients with left-sided colon and rectal cancer underwent laparoscopic surgery with fluorescence navigation between July 2019 and April 2020. The surgeries included 54 intestinal blood flow (IBF) evaluations using ICG, 16 preoperative fluorescence clip marking (FCM) procedures, 7 fluorescence ureteral navigation procedures, 4 fluorescence vessel navigation (FVN) procedures during lateral lymph node dissection, and 3 fluorescence-guided trans-anal tube insertion procedures. Laparoscopic surgery and fluorescence observation were performed using a VISERA ELITE 2. In FCM, the Zeoclip FS device was used. In ureteral navigation and trans-anal tube insertion, the Near-Infrared Ray Catheter (NIRC™) fluorescent ureteral catheter (NIRFUC) was used. RESULTS: No complications related to the fluorescence navigation techniques, including those involving ICG, the Zeoclip FS and the NIRFUC, occurred. In 5 cases, the surgical plan was changed according to the IBF evaluation with ICG, and no anastomotic leakage occurred in those cases. These fluorescence navigation techniques provide previously unavailable visual information regarding the IBF, vessel and ureter routes and accurate endoscopic clip and drainage tube locations in the intestinal tract. CONCLUSIONS: Technology to visualize blood flow dynamics and structures using fluorescence can be considered innovative, especially when applied in laparoscopic surgery, which relies on vision. The popularity of fluorescence navigation has also appeared to increase the safety of colorectal surgery. CLINICAL TRIAL REGISTRATION: Examination of fluorescence navigation for laparoscopic colorectal cancer surgery. Research Ethics Committee of the Kawaguchi Municipal Medical Center (Saitama, Japan) approval number: 2020-3. https://kawaguchi-mmc.org/wp-content/uploads/clinicalresearch-r02.pdf.

[Controversy and consideration of high and low ligation of inferior mesenteric artery in radical resection of rectal cancer].

Radical resection is one of the most important treatment for rectal cancer, which requires not only removal of adequate bowel and mesorectum around the tumor, but also thorough lymphadenectomy. Besides, postoperative complications are surgeons' concerns as well. According to different ways to manage inferior mesenteric artery, procedures could be divided into two groups: inferior mesenteric artery (IMA) high ligation and low ligation, which lead to various outcomes of the extent of lymph nodes dissection, survival, preservation of intestinal blood supply, incidence of anastomotic leakage, and postoperative functions including defecation function, urinary function and sexual function. Author believes that for those patients with clinical stage T1, low ligation and D2 lymph nodes dissection could be considered. However, for patients with locally advanced carcinomas (clinical stage T2+or N+), especially suspicious metastasis of lymph nodes around IMA root, high ligation and D3 lymph node dissection is suggested to ensure en bloc resection. As for those patients with high risks for compromised intestinal blood supply, preservation of left colic artery plus D3 lymph nodes dissection might be a feasible way. Intraoperative indocyanine green fluorescent imaging might play a role in quality control of lymphadenectomy.

Role of dynamic perfusion magnetic resonance imaging in patients with local advanced rectal cancer.

BACKGROUND: The management of rectal cancer patients is mainly based on the use of the magnetic resonance imaging (MRI) technique as a diagnostic tool for both staging and restaging. After treatment, to date, the evaluation of complete response is based on the histopathology assessment by using different tumor regression grade (TRG) features (e.g., Dworak or Mandard classifications). While from the radiological point of view, the main attention for the prediction of a complete response after chemotherapy treatment focuses on MRI and the potential role of diffusion-weighted images and perfusion imaging represented by dynamic-contrast enhanced MRI. The main aim is to find a reliable tool to predict tumor response in comparison to histopathologic findings. AIM: To investigate the value of dynamic contrast-enhanced perfusion-MRI parameters in the evaluation of the healthy rectal wall and tumor response to chemo-radiation therapy in patients with local advanced rectal cancer with histopathologic correlation. METHODS: Twenty-eight patients with biopsy-proven rectal adenocarcinoma who underwent a dynamic contrast-enhanced MR study performed on a 1.5T MRI system (Achieva, Philips), before (MR1) and after chemoradiation therapy (MR2), were enrolled in this study. The protocol included T1 gadolinium enhanced THRIVE sequences acquired on axial planes. A dedicated workstation was used to generate color permeability maps. Region of interest was manually drawn on tumor tissue and normal rectal wall, hence the following parameters were calculated and statistically analyzed: Relative arterial enhancement (RAE), relative venous enhancement (RVE), relative late enhancement (RLE), maximum enhancement (ME), time to peak and area under the curve (AUC). Perfusion parameters were related to pathologic TRG (Mandard's criteria; TRG1 = complete regression, TRG5 = no regression). RESULTS: Ten tumors (36%) showed complete or subtotal regression (TRG1-2) at histology and classified as responders; 18 tumors (64%) were classified as non-responders (TRG3-5). Perfusion MRI parameters were significantly higher in the tumor tissue than in the healthy tissue in MR1 (P < 0.05). At baseline (MR1), no significant difference in perfusion parameters was found between responders and non-responders. After chemo-radiation therapy, at MR2, responders showed significantly (P < 0.05) lower perfusion values [RAE (%) 54 ± 20; RVE (%) 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to non-responders [RAE (%): 129 ± 45; RVE (%): 154 ± 39; RLE (%): 164 ± 35; ME (%): 1714 ± 427]. Moreover, in responders group perfusion values decreased significantly at MR2 [RAE (%): 54 ± 20; RVE (%): 73 ± 24; RLE (%): 82 ± 29; ME (%): 904 ± 429] compared to the corresponding perfusion values at MR1 [RAE (%): 115 ± 21; RVE (%): 119 ± 21; RLE (%): 111 ± 74; ME (%): 1060 ± 325]; (P < 0.05). Concerning the time-intensity curves, the AUC at MR2 showed significant difference (P = 0.03) between responders and non-responders [AUC (mm2 × 10-3) 121 ± 50 vs 258 ± 86], with lower AUC values of the tumor tissue in responders compared to non-responders. In non-responders, there were no significant differences between perfusion values at MR1 and MR2. CONCLUSION: Dynamic contrast perfusion-MRI analysis represents a complementary diagnostic tool for identifying vascularity characteristics of tumor tissue in local advanced rectal cancer, useful in the assessment of treatment response.

PSMA Expression in the Neovasculature Associated With Rectal Adenocarcinoma: A Potential Stromal Target for Nuclear Theranostics.

We report the case of a 63-year-old man who underwent MRI and Ga-PSMA-11 PET/CT for biochemical recurrence localization after radical prostatectomy (serum PSA, 0.25 ng/mL) and describe the incidental discovery of a rectal adenocarcinoma. Immunohistochemical analysis showed PSMA staining in the tumor-associated neovasculature, but not in normal vasculature, or tumor cells. After surgical removal, he was treated with salvage radiotherapy to the postoperative prostate bed. This case example has several implications: the findings confirm the expression of PSMA in the tumor-associated neovasculature of a rectal cancer, nonprostate cancers' stroma may represent a potentially relevant target for nuclear theranostics.

Pathways of spread in rectal cancer: a reappraisal of the true routes to distant metastatic disease.

Rectal cancer can spread in a number of ways which have been previously recognised and validated as prognostic markers. These routes of spread are not adequately recognised in the stage grouping of the tumour-node-metastasis system, which focuses predominantly on the depth of invasion and nodal status, thus limiting its prognostic accuracy. Tumour spread involving veins occurs in 40% of patients. Venous channels have greater direct access to distant sites by means of a vascular 'anatomical highway'. This rapid spread of tumour cells to distant metastatic sites by veins cannot occur by means of lymph node pathways. Thus, lymph nodes have been overestimated in their importance. Distinction between local tumour spread (lymph node metastases, perineural and lymphatic invasion) and tumour spread mediated by a direct vascular pathway to distant dissemination (extramural venous invasion and tumour deposits) must be made as the implications for prognosis and choice of treatment are not likely to be equal. Improved precision of radiological and pathological assessment is needed to scrutinise and carefully document each route of tumour spread. Only with this accurate information will it be possible to correctly weight each feature and develop a more prognostically accurate staging method that would allow separation of true high- and low-risk groups and subsequent improvements in patient care.

Novel nomogram with microvascular density in the surgical margins can accurately predict the risk for anastomotic leakage after anterior resection for rectal cancer.

BACKGROUND: Anastomotic leakage (AL) is a serious complication after anterior resection. The purpose of this study was to determine the role of microvascular density (MVD) in AL and to develop a nomogram to accurately predict AL. METHODS: This study retrospectively enrolled 477 consecutive patients who underwent anterior resection for rectal cancer from January 2011 to January 2019. Tissue samples of the resection margins were assessed for MVD. Univariate and multivariate regression analyses were used to identify the risk factors for AL. RESULTS: The incidence of clinical AL was 6.7%. MVD in the distal margin was associated with AL (P < .001). Univariate and multivariate regression analysis identified the following variables as independent risk factors for AL: preoperative albumin ≤35 g/L (odds ratio [OR] = 2.511), neoadjuvant treatment (OR = 3.560), location of tumor ≤7 cm (OR = 3.381), blood loss ≥100 mL (OR = 2.717), and MVD in the distal margin ≤20 (OR = 4.265). Then, a nomogram including these predictors was developed. The nomogram showed good discrimination (AUC = 0.816) and calibration (concordance index = 0.816). The decision curve analysis demonstrated that the nomogram was clinically useful. CONCLUSIONS: MVD in the distal margin is closely associated with AL. The nomogram can be used for individualized prediction of AL after anterior resection for patients with rectal cancer.

MRI evaluation of extramural vascular invasion by inexperienced radiologists.

OBJECTIVE: We proposed to determine whether the performance of inexperienced radiologists in determining extramural vascular invasion (EMVI) in rectal cancer on MRI can be promoted by means of targeted training. METHODS: 230 rectal cancer patients who underwent pre-operative chemoradiotherapy were included. Pre-therapy and post-therapy MR images and pathology EMVI evaluation were available for cases. 230 cases were randomly divided into 150 training cases and 80 testing cases, including 40 testing case A and 40 testing case B. Four radiologists were included for MRI EMVI evaluation, who were divided into targeted training group and non-targeted training group. The two groups evaluated testing case A at baseline, 3 month and 6 month, evaluated testing case B at 6 month. The main outcome was agreement with expert-reference for pre-therapy and post-therapy evaluation, the other outcome was accuracy with pathology for post-therapy evaluation. RESULTS: After 6 months of training, targeted training group showed statistically higher agreement with expert-reference than non-targeted training group for both pre-therapy and post-therapy MRI EMVI evaluation of testing case A and testing case B, all p < 0.05. Targeted training group also showed significantly higher accuracy with pathology than non-targeted training group for post-therapy evaluation of testing case A and testing case B after 6 months of training, all p < 0.05. CONCLUSION: The diagnostic performance for MRI EMVI evaluation could be promoted by targeted training for inexperienced radiologist. ADVANCES IN KNOWLEDGE: This study provided the first evidence that after 6 month targeted training, inexperienced radiologists demonstrated improved diagnostic performance, with a 20% increase in agreement with expert-reference for both pre-therapy and post-therapy MRI EMVI evaluation and also a 20% increase in or accuracy with pathology for post-therapy evaluation, while inexperienced radiologists could not gain obvious improvement in MRI EMVI evaluation through the same period of regular clinical practice. It indicated that targeted training may be necessary for helping inexperienced radiologist to acquire adequate experience for the MRI EMVI evaluation of rectal cancer, especially for radiologist who works in a medical unit where MRI EMVI diagnosis is uncommon.

Low doses of ionizing radiation activate endothelial cells and induce angiogenesis in peritumoral tissues.

PURPOSE: During radiotherapy the peritumoral tissues are daily exposed to subtherapeutic doses of ionizing radiation. Herein, the biological and molecular effects of doses lower than 0.8 Gy per fraction (LDIR), previously described as angiogenesis inducers, were assessed in human peritumoral tissues. MATERIAL AND METHODS: Paired biopsies of preperitoneal adipose tissue were surgically collected from 16 patients diagnosed with locally advanced rectal cancer who underwent neo-adjuvant radiotherapy. One of the biopsies is located in the vicinity of the region where the tumor received the prescribed dose of radiation, and thus exposed to LDIR; the other specimen, outside all beam apertures, was used as an internal calibrator (IC). Microvessel density (MDV) was quantified by immunohistochemistry and the expression of several pro-angiogenic genes was assessed by quantitative RT-PCR using exclusively endothelial cells (ECs) isolated by laser capture microdissection microscopy. RESULTS: LDIR activated peritumoral ECs by significantly up-regulating the expression of several pro-angiogenic genes such as VEGFR1, VEGFR2, ANGPT2, TGFB2, VWF, FGF2, HGF and PDGFC. Accordingly, the MVD was significantly increased in peritumoral tissues exposed to LDIR, compared to the IC. The patients that yielded a larger pro-angiogenic response, also showed the highest MVD. CONCLUSIONS: LDIR activate ECs in peritumoral tissues that are associated with increased MVD. Although the technological advances in radiotherapy have contributed to reduce the damage to healthy tissues over the past years, the anatomical regions receiving LDIR should be taken into account in the treatment plan report for patient follow-up and in future studies to correlate these doses with tumor dissemination.

Size and lipid modification determine liposomal Indocyanine green performance for tumor imaging in a model of rectal cancer.

Localization of rectal tumors is a challenge in minimally invasive surgery due to the lack of tactile sensation. We had developed liposomal indocyanine green (Lip-ICG) for localization of rectal tumor. In this study we evaluated the effects of liposome size and lipid PEGylation on imaging. We used an endoscopically-guided orthotopic experimental rectal cancer model in which tumor fluorescence was determined at different time points after intravenous (i.v.) administration of Lip-ICG and PEGylated liposomes (PEG-Lip-ICG). Signal intensity was measured by tumor-to-background ratio (TBR), or normalized TBR (compared to TBR of free ICG). Fluorescence microscopy of tumor tissue was performed to determine fluorescence localization within the tissue and blood vessels. Liposomes of 60 nm showed an increased TBR compared with free ICG at 12 hours after i.v. injection: normalized TBR (nTBR) = 3.11 vs. 1, respectively (p = 0.006). Larger liposomes (100 nm and 140 nm) had comparable signal to free ICG (nTBR = 0.98 ± 0.02 and 0.78 ± 0.08, respectively), even when additional time points were examined (0.5, 3 and 24 hours). PEG-Lip- ICG were more efficient than Lip-ICG (TBR = 4.2 ± 0.18 vs. 2.5 ± 0.12, p < 0.01) presumably because of reduced uptake by the reticulo-endothelial system. ICG was found outside the capillaries in tumor margins. We conclude that size and lipid modification impact imaging intensity.

Localization of mesenteric lymph node metastases in relation to the level of arterial ligation in rectal cancer surgery.

INTRODUCTION: For oncological reasons, central arterial ligation of the inferior mesenteric artery (IMA) is suggested in rectal cancer surgery although no conclusive evidence support this. We have therefore investigated the localization of lymph node metastases and compared central ligation of the IMA versus peripheral arterial ligation, in rectal cancer specimens. METHODS: This was a cross-sectional population-based study of consecutive recruited patients who underwent resection for rectal cancer in 2012-2015. Multiple linear regression analysis was used to explore the relationship between lymph node count and age, sex, body mass index, preoperative oncological treatment, type of surgery, tumour stage, and vessel and specimen length. RESULTS: 151 patients (54 women) were included, with median (range) age 70 (45-87) years. The median (range) number of lymph nodes retrieved was 25 (3-70), which was associated with body mass index, type of surgery and vessel length. Vessel length, median (range) 9.6 (5-14) and 9.2 (5-15) cm for reported central and peripheral arterial ligation, respectively, was associated with body mass index. In 39 of 42 samples, metastatic lymph nodes were located in the mesorectum, and 13 of 42 samples also had metastatic lymph nodes in the sigmoid mesentery. None were found around the ligated artery. CONCLUSION: To recruit all metastatic lymph nodes in rectal cancer surgery, it is important to include the sigmoid mesentery in the specimen, but not to perform a central ligation of the IMA compared with ligation of the SRA close to the left colic artery (LCA).

Added value of diffusion-weighted imaging for evaluation of extramural venous invasion in patients with primary rectal cancer.

OBJECTIVE:: To evaluate the added value of diffusion-weighted imaging (DWI) to T 2 weighted imaging (T 2WI) for detection of extramural venous invasion (EMVI) in patients with primary rectal cancer. METHODS:: 79 patients (50 men, 29 females, mean age 67.4 years, range 37-87 years) who had undergone rectal MRI and subsequently received surgical resection were included. The rectal MRI consisted of T 2WI in three planes and axial DWI (b-values, 0, 1000 s mm-2). Two radiologists blinded to the pathologic results independently reviewed the T 2WI first, and then the combined T 2WI and DWI 4 weeks later. They recorded their confidence scores for EMVI on a 5-point scale (0: definitely negative and 4: definitely positive). The diagnostic performance of each reading session for each reader was compared by pairwise comparison of receiver operating characteristic curves. The area under the ROC curve (AUC) was considered as the diagnostic performance. The result of a histopathological examination served as the reference standard for EMVI. RESULTS:: For both readers, the diagnostic performance was not significantly different between the two image sets (for reader 1, AUC, 0.828 and 0.825, p = 0.9426 and for reader 2, AUC, 0.723 and 0.726, p = 0.9244, respectively). CONCLUSION:: There was no added value of DWI to T2WI for detection of EMVI in patients with primary rectal cancer. ADVANCES IN KNOWLEDGE:: High-resolution T2WI alone is sufficient to assess EMVI and a supplementary DWI has no added value in patients with primary rectal cancer.