Small arteriole sign: an imaging feature for staging T4a colon cancer.

OBJECTIVES: By analyzing the distribution of existing and newly proposed staging imaging features in pT1-3 and pT4a tumors, we searched for a salient feature and validated its diagnostic performance. METHODS: Preoperative multiphase contrast-enhanced CT images of the training cohort were retrospectively collected at three centers from January 2016 to December 2017. We used the chi-square test to analyze the distribution of several stage-related imaging features in pT1-3 and pT4a tumors, including small arteriole sign (SAS), outer edge of the intestine, tumor invasion range, and peritumoral adipose tissue. Preoperative multiphase contrast-enhanced CT images of the validation cohort were retrospectively collected at Beijing Cancer Hospital from January 2018 to December 2018. The diagnostic performance of the selected imaging feature, including accuracy, sensitivity, and specificity, was validated and compared with the conventional clinical tumor stage (cT) by the McNemar test. RESULTS: In the training cohort, a total of 268 patients were enrolled, and only SAS was significantly different between pT1-3 and pT4a tumors. The accuracy, sensitivity, and specificity of the SAS and conventional cT in differentiating T1-3 and T4a tumors were 94.4%, 81.6%, and 97.3% and 53.7%, 32.7%, and 58.4%, respectively (all p < 0.001). In the validation cohort, a total of 135 patients were collected. The accuracy, sensitivity, and specificity of the SAS and the conventional cT were 93.3%, 76.2%, and 96.5% and 62.2%, 38.1%, and 66.7%, respectively (p < 0.001, p = 0.021, p < 0.001). CONCLUSION: Small arteriole sign positivity, an indirect imaging feature of serosa invasion, may improve the accuracy of identifying T4a colon cancer. CLINICAL RELEVANCE STATEMENT: Small arteriole sign helps to distinguish T1-3 and T4a colon cancer and further improves the accuracy of preoperative CT staging of colon cancer. KEY POINTS: • The accuracy of preoperative CT staging of colon cancer is not ideal, especially for T4a tumors. • Small arteriole sign (SAS) is a newly defined imaging feature that shows the appearance of tumor-supplying arterioles at the site where they penetrate the intestine wall. • SAS is an indirect imaging marker of tumor invasion into the serosa with a great value in distinguishing between T1-3 and T4a colon cancer.

Intentional Watch and Wait or Organ Preservation Surgery Following Neoadjuvant Chemoradiotherapy Plus Consolidation CAPEOX for MRI-defined Low-risk Rectal Cancer: Findings From a Prospective Phase 2 Trial (PKUCH-R01 Trial, NCT02860234).

OBJECTIVE: To assess the efficacy and safety of intentional watch and wait (W&W) and organ preservation surgery following neoadjuvant chemoradiotherapy plus consolidation CAPEOX in magnetic resonance imaging (MRI)-defined low-risk rectal cancer. BACKGROUND: Clinical T2/early T3 rectal cancers can achieve high yield pathological complete response (ypCR) rates after chemoradiotherapy; thus, an intentional W&W or organ preservation strategy for good clinical responders in these subgroups can be further tested. METHODS: This prospective, single-arm, phase 2 trial enrolled patients with low-risk MRI prestaged rectal cancers, who concurrently received chemoradiation, followed by four 3-weekly cycles of CAPEOX regimen. Following reassessment, clinical complete response (cCR) or near-cCR patients underwent W&W/organ preservation surgery; the primary endpoint was a 3-year organ preservation rate. RESULTS: Of the 64 participants, 58 completed treatment, with 6.4% and 33.9% grade 3 to 4 toxicities in the radiotherapy and consolidation CAPEOX phases, respectively, during a median 39.5-month follow-up. Initial cCR, and non-cCR occurred in 33, 13, and 18 patients, respectively. Of the 31 cCR and 7 near-cCR cases managed by W&W, local regrowth occurred in 7; of these, 6 received salvage surgery. The estimated 2-year local regrowth rates were 12.9% [95% confidence interval (CI): 1.1%-24.7%] in cCR and 42.9% (95% CI: 6.2%-79.6%) in near-cCR cases, respectively. Eight patients received local excision, including 2 with regrowth salvage. Lung metastases occurred in 3 patients and multiple metastasis occurred in 1 patient; no local recurrence occurred. The estimated 3-year organ preservation rate was 67.2% (95% CI: 55.6%-78.8%). The estimated 3-year cancer-specific survival, non-regrowth disease-free survival, and stoma-free survival were 96.6% (95% CI: 92.1%-100%), 92.2% (95% CI: 85.5%-98.9%), and 82.7% (95% CI: 73.5%-91.9%), respectively. CONCLUSIONS: Chemoradiotherapy plus consolidation CAPEOX for MRI-defined low-risk rectal cancer can lead to high rates of organ preservation through intentional W&W or local excision. The oncologic safety of this strategy should be further tested.

Discrimination of Liver Metastases of Digestive System Neuroendocrine Tumors From Neuroendocrine Carcinoma by Computed Tomography-Based Radiomics Analysis.

OBJECTIVE: The aim of the study is to investigate the value of computed tomography (CT) radiomics features to discriminate the liver metastases (LMs) of digestive system neuroendocrine tumors (NETs) from neuroendocrine carcinoma (NECs). METHODS: Ninety-nine patients with LMs of digestive system neuroendocrine neoplasms from 2 institutions were included. Radiomics features were extracted from the portal venous phase CT images by the Pyradiomics and then selected by using the t test, Pearson correlation analysis, and least absolute shrinkage and selection operator method. The radiomics score (Rad score) for each patient was constructed by linear combination of the selected radiomics features. The radiological model was constructed by radiological features using the multivariable logistic regression. Then, the combined model was constructed by combining Rad score and the radiological model into logistic regression. The performance of all models was evaluated by the receiver operating characteristic curves with the area under curve (AUC). RESULTS: In the radiological model, only the enhancement degree (odds ratio, 8.299; 95% confidence interval, 2.070-32.703; P = 0.003) was an independent predictor for discriminating the LMs of digestive system NETs from those of NECs. The combined model constructed by the Rad score in combination with the enhancement degree showed good discrimination performance, with AUCs of 0.893, 0.841, and 0.740 in the training, testing, and external validation groups, respectively. In addition, it performed better than radiological model in the training and testing groups (AUC, 0.893 vs 0.726; AUC, 0.841 vs 0.621). CONCLUSIONS: The CT radiomics might be useful for discrimination LMs of digestive system NECs from NETs.

Preoperative assessment of retroperitoneal Liposarcoma using volume-based 18F-FDG PET/CT: implications for surgical strategy and prognosis.

PURPOSE: Retroperitoneal liposarcoma (RLPS) poses a challenging scenario for surgeons due to its unpredictable biological behavior. Surgery remains the primary curative option for RLPS; however, the need for additional information to guide surgical strategies persists. Volume-based 18F-FDG PET/CT may solve this issue. METHODS: We analyzed data from 89 RLPS patients, measuring metabolic tumor volume (MTV), total lesion glycolysis (TLG), and maximum standardized uptake value (SUVmax) and explored their associations with clinical, prognostic, and pathological factors. RESULTS: MTV, TLG of multifocal and recurrent RLPS were significantly higher than unifocal and primary ones (P < 0.001, P < 0.001, P = 0.003 and P = 0.002, respectively). SUVmax correlated with FNCLCC histological grade, mitotic count and Ki-67 index (P for G1/G2 = 0.005, P for G2/G3 = 0.017, and P for G1/G3 = 0.001, P < 0.001 and P = 0.024, respectively). MTG, TLG and SUVmax of WDLPS were significantly lower than DDLPS and PLPS (P for MTV were 0.009 and 0.022, P for TLG were 0.028 and 0.048, and P for SUVmax were 0.027 and < 0.001, respectively). Multivariable Cox analysis showed that MTV > 457.65 (P = 0.025), pathological subtype (P = 0.049) and FNCLCC histological grade (P = 0.033) were related to overall survival (OS). CONCLUSIONS: Our findings indicate that MTV is an independent prognostic factor for RLPS, while MTV, TLG, and SUVmax can preoperatively predict multifocal lesions, histological grade, and pathological subtype. Volume-based 18F-FDG PET/CT offers valuable information to aid in the decision-making process for RLPS surgical strategies.

Analysis of enhanced CT imaging signs and clinicopathological prognostic factors in hepatoid adenocarcinoma of stomach patients with radical surgery: a retrospective study.

BACKGROUND: To investigate the association between CT signs and clinicopathological features and disease recurrence in patients with hepatoid adenocarcinoma of stomach (HAS). METHODS: Forty nine HAS patients undergoing radical surgery were retrospectively collected. Association between CT and clinicopathological features and disease recurrence was analyzed. Multivariate logistic model was constructed and evaluated for predicting recurrence by using receiver operating characteristic (ROC) curve. Survival curves between model-defined risk groups was compared using Kaplan-Meier method. RESULTS: 24(49.0%) patients developed disease recurrence. Multivariate logistic analysis results showed elevated serum CEA level, peritumoral fatty space invasion and positive pathological vascular tumor thrombus were independent factors for disease recurrence. Odds ratios were 10.87 (95%CI, 1.14-103.66), 6.83 (95%CI, 1.08-43.08) and 42.67 (95%CI, 3.66-496.85), respectively. The constructed model showed an area under ROC of 0.912 (95%CI,0.825-0.999). The model-defined high-risk group showed poorer overall survival and recurrence-free survival than the low-risk group (both P < 0.001). CONCLUSIONS: Preoperative CT appearance of peritumoral fatty space invasion, elevated serum CEA level, and pathological vascular tumor thrombus indicated poor prognosis of HAS patients.

Treatment algorithm and surgical outcome for primary and recurrent retroperitoneal sarcomas: A long-term single-center experience of 242 cases.

BACKGROUND AND OBJECTIVES: Retroperitoneal sarcomas (RPSs) are difficult to manage, rare malignant tumors. This single-center, retrospective study aimed to analyze the treatment algorithm and outcomes of aggressive surgical treatment in patients with primary and recurrent RPS. METHODS: Data of 242 consecutive patients with RPS who underwent surgical treatment at the Peking University Cancer Hospital Sarcoma Center between January 2010 and February 2021 were collected and analyzed. Indications for surgery were based on the treatment algorithm. RESULTS: A total of 145 patients with primary RPS and 97 with recurrent RPS were included. The recurrent cohort comprised more patients with multifocal tumors than the primary cohort (64.9% vs. 15.2%). R0/R1 resection was achieved in 94.5% and 81.4% of the primary and recurrent RPS cases, respectively. Major complication rates in the primary and recurrent cohorts were 17.9% and 30.9%, respectively. During a median follow-up of 51 months, the estimated 5-year overall survival, local recurrence, and distant metastasis rates for patients with primary and recurrent RPS were 61.0% versus 37.1%, 47.4% versus 71.3%, and 18.4% versus 17.6%, respectively. CONCLUSIONS: Aggressive surgical treatment achieved good local control and long-term survival in patients with primary RPS, whereas the prognosis in patients with recurrence were significantly worse.

MRI measurements predict major low anterior resection syndrome in rectal cancer patients.

PURPOSE: Current low anterior resection syndrome (LARS) score is lagging behind and only based on clinical symptoms patient described. Preoperative imaging indicators which can be used to predict LARS is unknown. We proposed preoperative MRI parameters for identifying major LARS. METHODS: Patients receiving curative restorative anterior resection from Sept. 2007 to Sept. 2015 were collected to complete LARS score (median 75.7 months since surgery). MRI measurements associated with LARS were tested, and a multivariate logistic model was conducted for predicting LARS. Receiver operating characteristic curve was used to evaluate the model. RESULTS: Two hundred fifty-five patients undergoing neoadjuvant chemoradiotherapy and 72 patients undergoing direct surgery were enrolled. The incidence of major LARS in NCRT group was significantly higher (53.3% vs.34.7%, P = 0.005). In patients with neoadjuvant chemoradiotherapy, the thickness of ARJ (TARJ), the distance between the tumor's lower edge and anal rectal joint (DTA), and sex were independent factors for predicting major LARS; ORs were 0.382 (95% CI, 0.198-0.740), 0.653 (95% CI, 0.565-0.756), and 0.935 (95% CI, 0.915-0.955). The AUC of the multivariable model was 0.842 (95% CI, 0.794-0.890). In patients with direct surgery, only DTA was the independent factor for predicting major LARS; OR was 0.958 (95% CI, 0.930-0.988). The AUC was 0.777 (95% CI: 0.630-0.925). CONCLUSIONS: Baseline MRI measurements have the potential to predict major LARS in rectal cancer, which will benefit the decision-making and improve patients' life quality.

Predicting Rectal Cancer Response to Neoadjuvant Chemoradiotherapy Using Deep Learning of Diffusion Kurtosis MRI.

Background Preoperative response evaluation with neoadjuvant chemoradiotherapy remains a challenge in the setting of locally advanced rectal cancer. Recently, deep learning (DL) has been widely used in tumor diagnosis and treatment and has produced exciting results. Purpose To develop and validate a DL method to predict response of rectal cancer to neoadjuvant therapy based on diffusion kurtosis and T2-weighted MRI. Materials and Methods In this prospective study, participants with locally advanced rectal adenocarcinoma (≥cT3 or N+) proved at histopathology and baseline MRI who were scheduled to undergo preoperative chemoradiotherapy were enrolled from October 2015 to December 2017 and were chronologically divided into 308 training samples and 104 test samples. DL models were constructed primarily to predict pathologic complete response (pCR) and secondarily to assess tumor regression grade (TRG) (TRG0 and TRG1 vs TRG2 and TRG3) and T downstaging. Other analysis included comparisons of diffusion kurtosis MRI parameters and subjective evaluation by radiologists. Results A total of 383 participants (mean age, 57 years ± 10 [standard deviation]; 229 men) were evaluated (290 in the training cohort, 93 in the test cohort). The area under the receiver operating characteristic curve (AUC) was 0.99 for the pCR model in the test cohort, which was higher than the AUC for raters 1 and 2 (0.66 and 0.72, respectively; P < .001 for both). AUC for the DL model was 0.70 for TRG and 0.79 for T downstaging. AUC for pCR with the DL model was better than AUC for the best-performing diffusion kurtosis MRI parameters alone (diffusion coefficient in normal diffusion after correcting the non-Gaussian effect [Dapp value] before neoadjuvant therapy, AUC = 0.76). Subjective evaluation by radiologists yielded a higher error rate (1 - accuracy) (25 of 93 [26.9%] and 23 of 93 [24.8%] for raters 1 and 2, respectively) in predicting pCR than did evaluation with the DL model (two of 93 [2.2%]); the radiologists achieved a lower error rate (12 of 93 [12.9%] and 13 of 93 [14.0%] for raters 1 and 2, respectively) when assisted by the DL model. Conclusion A deep learning model based on diffusion kurtosis MRI showed good performance for predicting pathologic complete response and aided the radiologist in assessing response of locally advanced rectal cancer after neoadjuvant chemoradiotherapy. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Koh in this issue.

Efficacy and safety of neoadjuvant intensity-modulated radiotherapy with concurrent capecitabine for locally advanced rectal cancer.

BACKGROUND: We previously conducted a prospective phase II clinical trial studying a unique 22-fraction neoadjuvant intensity-modulated radiotherapy with concurrent capecitabine treatment followed by total mesorectal excision for locally advanced rectal cancer. OBJECTIVE: The objective of this study was to retrospectively review the efficacy, toxicity, and surgical complications following intensity-modulated radiotherapy in patients who have rectal cancer. DESIGN: This was a retrospective study. SETTING: Data were gathered from a surgical database. PATIENTS: This study included patients who underwent intensity-modulated radiotherapy with gross tumor volume/clinical target volume of 50.6/41.8 Gy in 22 fractions with concurrent capecitabine treatment over a period of 30 days, after which the patients underwent surgery for rectal cancer in Peking University Cancer Hospital (2007-2013). MAIN OUTCOME MEASURES: The primary end points were acute toxicity, postoperative complications, and complete response rate. RESULTS: A total of 260 patients were included in our analysis. The median age was 55 years (range, 21-87 years), and 68.5% of the patients were male. The yield complete response rate was 18.5% (48/260). There were no grade 4 toxicity and perioperative mortality. The grade 3 toxicity rate was 5.8%, which included diarrhea (4.2%), neutropenia (1.2%), and radiation dermatitis (0.4%). The 30-day postoperative and severe complication (≥grade 3) rates were 23.1% and 2.7%. The anastomotic leakage rate was 3.3% (5/152). Perineal wound complications (29.2%, 28/96) represented the most common problem following abdominoperineal resection. The estimated 3-year local recurrence-free survival, cancer-specific survival, and disease-free survival rates were 94.2% (95% CI, 90.1%-98.3%), 92.2% (95% CI, 87.5%-97.0%), and 81.4% (95% CI, 75.4%-87.4%). LIMITATION: The retrospective nature and the single-arm design was the limitation of the study. CONCLUSION: The 22-fraction neoadjuvant intensity-modulated radiotherapy regimen used to treat rectal cancer in this study has a high efficacy rate and a low toxicity rate. Further studies are needed to better define the role of intensity-modulated radiotherapy for rectal cancer treatment in a neoadjuvant setting.

Prognostic value of CD45RO(+) tumor-infiltrating lymphocytes for locally advanced rectal cancer following 30 Gy/10f neoadjuvant radiotherapy.

AIM: This study aims to evaluate the prognostic value of CD45RO(+) tumor-infiltrating lymphocytes (TILs) in locally advanced rectal cancer treated with 30 Gy/10 fraction (10 f) neoadjuvant radiotherapy. METHODS: This retrospective study involved 185 patients with locally advanced rectal cancer who underwent 30 Gy/10 f nRT (biologic equivalent dose, 30 Gy) followed by total mesorectal excision (TME) between August 2003 and October 2009. The density of CD45RO(+) TILs was assessed by immunohistochemistry using an image-analysis system and tissue microarray and was evaluated for its association with histopathologic features along with disease-free survival (DFS). RESULTS: Following neoadjuvant radiotherapy, the median density of CD45RO(+) TILs is 654/mm(2). High density of CD45RO(+) TILs was significantly associated with increased T and N downstaging effect (p = 0.006; p = 0.014), lesser-advanced T stage (p = 0.003) and TNM stage (p = 0.022). Prolonged DFS (89.0 vs. 68.1%) was also observed in CD45RO(+Hi) cases. On multivariate regression model, CD45RO(+) TILs (p = 0.026; odds ratio (OR), 0.436 (95% confidence interval (CI), 0.209-0.907)), tumor differentiation (p = 0.057; OR, 1.878 (95% CI, 0.982-3.593)), ypT stage (p = 0.066; OR, 2.383 (95% CI, 0.943-6.025)), and ypN stage (p = 0.009; OR, 2.612 (95% CI, 1.266-5.388)) were independent factors for DFS. CONCLUSION: The density of CD45RO(+) TILs cannot only predict tumor downstaging and ypTNM stage for rectal cancer following 30 Gy/10 f nRT but also promisingly predict long-term outcomes. These findings may be used to stratify patients and make alternative strategy of adjuvant treatment.

[Application of endoscopic submucosal dissection in treatment of early gastric cancer].

OBJECTIVE: To evaluate the clinical outcomes of endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) in a single center in China. METHODS: We performed a retrospective analysis of the patients with single EGC lesion who received ESD in Peking University Cancer Hospital from January 2011 to December 2013.Their clinicopathologic data, resectability, curability, complications and follow-up data were assessed. RESULTS: A total of 116 patients were enrolled in the study. The patients included 88 men and 28 women, with a median age of 63 years (range: 25-80 years).The post-operative histology of the lesions included 28 (24.1%) high grade intraepithelial neoplasia, 35 (30.2%) well differentiated adenocarcinoma, 35 (30.2%) moderated differentiated adenocarcinoma and 18 (15.5%) poorly differentiated adenocarcinoma. Of all the lesions, 75.0% (87/116) were confined into mucosa, 15.5% (18/116) invaded SM1 (<500 µm from the muscularis mucosae) and 9.5% (11/116) invaded SM2 (≥ 500 µm from the muscularis mucosae). The mean tumor size was (1.49 ± 0.96) cm, and the rate of ulceration was 14.7% (17/116). The en bloc resection rates were 96.7% (111/116), complete resection rates were 93.1% (108/116) and curative resection rates were 77.6% (90/116). According to the curability, 62 (53.4%) cases were classified into the standard curative resection (sCR) group, 28 (24.2%) into the expanded curative resection (eCR) group and 26 (22.4%) into the non-curative resection (nCR) group. The mean tumor size of the sCR group was smaller than that of the eCR and nCR group (t=-4.121, P<0.001 and t=-3.420, P=0.001). In the nCR group, the portion of type 0-III lesion and ulceration were significantly higher (χ² = 10.287, P=0.006 and χ² = 17.737, P<0.001). In multivariate analysis, EGC with ulceration and submucosal invasion were the risk factors for non-curative resection (OR=6.634, P=0.006 and OR=12.735, P<0.001). The ESD-related complications included 4 (3.4%) post-operative bleeding, 3 (2.6%) intra-operative perforation, 2 (1.7%) cardiac stenosis and 1 (0.9%) heart failure. In the study, 106 of the 116 patients received periodic follow-up, during a median follow-up of 22 months (12-47 months). Local tumor recurrence developed in 1 patient of the eCR group 8 months post the ESD. CONCLUSION: ESD is a safe and feasible option for EGC in China, ulceration and submucosal invasion are associated with non-curative resection, and post-operative bleeding and intra-operative perforation should be concerned as the main complications.

[Correlation between tumor cell proliferation and prognosis of primary cutaneous malignant melanoma in 127 patients].

OBJECTIVE: To investigate the correlations among Ki-67 expression, mitosis and other clinicopathological parameters of primary cutaneous malignant melanoma, and search for prognostic factors of malignant melanoma. METHODS: Totally 127 cases of primary cutaneous malignant melanoma were collected from Beijing Cancer Hospital. Immunohistochemical study for Ki-67 was performed, and the mitosis was calculated referring to "hot spot" method recommended by the seventh edition of the American Joint Committee on Cancer (AJCC) melanoma staging system. The correlations of Ki-67 expression, mitosis and other clinicopathological parameters were analyzed, and the survival analysis of all these risk factors including TNM and Clark level was conducted based on follow up data. RESULTS: The expression level of Ki-67 was associated with necrosis and Breslow thickness (P < 0.05). Mitosis was correlated with Clark level and Ki-67 expression (P < 0.05). Univariate analysis indicated Ki-67 expression level (P = 0.043), mitosis (P = 0.030) and TNM stage (P < 0.001) might influence the survival of patients. However, multivariate analysis showed that the TNM staging was the only independent prognostic factor affecting survival. CONCLUSIONS: The prognosis of patients with primary cutaneous malignant melanoma was closely related to the TNM staging at the fist examination. Ki-67 expression and mitosis are two important clinicopathological parameters of primary cutaneous malignant melanoma.

[Expression and prognostic significance of galectin-1 and galectin-3 in benign nevi and melanomas].

OBJECTIVE: To study the expression and prognostic significance of galectin-1 and galectin-3 in different melanocytic lesions. METHODS: The expression of galectin-1 and galectin-3 in 39 cases of benign nevus, 58 cases of primary cutaneous melanoma, 24 cases of primary mucosal melanoma, 69 cases of melanoma with lymph node metastasis and 8 cases of melanoma with distant metastasis were studied by immunohistochemistry and tissue microarray. RESULTS: The expression of galectin-1 and galectin-3 was higher in benign nevi than in melanomas (P < 0.01). The nuclear expression of galectin-3 was higher in primary cutaneous melanomas than in primary mucosal melanomas or melanomas with metastases (P < 0.01, respectively). The expression correlated with age of patients (P < 0.05), necrosis (P < 0.05) and survival time (P < 0.01). Clark's level also correlated with survival time in patients with cutaneous melanomas (P = 0.037). TNM staging was the only independent prognostic factor for melanomas (P < 0.01). CONCLUSIONS: The expression of galectin-1 and galectin-3 is decreased in melanomas. The decrease in nuclear expression of galectin-3 may represent a poor prognostic factor for melanomas. TNM staging is an independent prognostic factor which influences the survival time.

Efficacy and safety of preoperative immunotherapy in patients with mismatch repair-deficient or microsatellite instability-high gastrointestinal malignancies.

BACKGROUND: Programmed death protein (PD)-1 blockade immunotherapy significantly prolongs survival in patients with metastatic mismatch repair-deficient (dMMR)/microsatellite instability-high (MSI-H) gastrointestinal malignancies such gastric and colorectal cancer. However, the data on preoperative immunotherapy are limited. AIM: To evaluate the short-term efficacy and toxicity of preoperative PD-1 blockade immunotherapy. METHODS: In this retrospective study, we enrolled 36 patients with dMMR/MSI-H gastrointestinal malignancies. All the patients received PD-1 blockade with or without chemotherapy of CapOx regime preoperatively. PD1 blockade 200 mg was given intravenously over 30 min on day 1 of each 21-d cycle. RESULTS: Three patients with locally advanced gastric cancer achieved pathological complete response (pCR). Three patients with locally advanced duodenal carcinoma achieved clinical complete response (cCR), followed by watch and wait. Eight of 16 patients with locally advanced colon cancer achieved pCR. All four patients with liver metastasis from colon cancer reached CR, including three with pCR and one with cCR. pCR was achieved in two of five patients with non-liver metastatic colorectal cancer. CR was achieved in four of five patients with low rectal cancer, including three with cCR and one with pCR. cCR was achieved in seven of 36 cases, among which, six were selected for watch and wait strategy. No cCR was observed in gastric or colon cancer. CONCLUSION: Preoperative PD-1 blockade immunotherapy in dMMR/MSI-H gastrointestinal malignancies can achieve a high CR, especially in patients with duodenal or low rectal cancer, and can achieve high organ function protection.

Usefulness of attenuation value on computed tomography plain scan for diagnosing enlarged mediastinal lymph nodes metastases.

Background: To evaluate the diagnostic value of computed tomography (CT) attenuation in mediastinal lymph node metastases of malignant tumors. Methods: A retrospective review was conducted of a Chinese institutional database of consecutive patients with a history of malignant tumors. Those who had enlarged, necrotic, or hypermetabolic lymph nodes detected in the mediastinum during routine CT examination or positron emission tomography (PET)/CT imaging from January 2019 to December 2021 were collected for investigation. All patients underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and were followed up for at least 6 months to diagnose lymph node metastases. One-to-one correlation was attempted between the CT images of the lymph nodes and EBUS-TBNA area of the same lymph node groups and similar size. Radiologists measured size, as well as plain CT and contrast-enhanced CT (CECT) attenuation values of mediastinal lymph nodes, and evaluated the effectiveness of these variables in diagnosing lymph node metastasis. Results: A total of 135 lymph nodes of 114 patients were included in the study. In the univariate analysis, the long-axis diameter, short-axis diameter, short-axis/long-axis ratio, and plain CT attenuation values of lymph nodes were found to be statistically significantly different between the metastatic and non-metastatic lymph nodes. The areas under receiver operator characteristic (ROC) curves (AUCs) of long-axis diameter, short-axis diameter, short-axis/long-axis ratio, and plain CT attenuation value for diagnosing metastases were 0.711, 0.788, 0.671, and 0.827, respectively. The best value of the AUC for diagnosing lymph node metastases was 0.827 [95% confidence interval (CI): 0.749-0.890] using plain CT attenuation value ≤45 Hounsfield units (HU). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 92.8%, 69.2%, 86.5%, and 81.8%, respectively. Similar results were obtained from the 68 cases of lung cancer. Plain CT attenuation values reached the best AUC (0.860) for diagnosing lymph node metastases. Conclusions: Plain CT attenuation of lymph nodes is an effective method for diagnosing enlarged mediastinal lymph nodes with a history of multiple malignancies or lung cancer. Plain CT could be used as an additional test where there is no PET/CT available in cases of diagnostic dilemma.

KRAS, NRAS, BRAF signatures, and MMR status in colorectal cancer patients in North China.

We assessed the clinicopathological features and prognostic values of KRAS, NRAS, BRAF, and DNA mismatch repair status in colorectal cancer (CRC) to provide real-world data in developing countries. We enrolled 369 CRC patients and analyzed the correlation between RAS/BRAF mutation, mismatch repair status with clinicopathological features, and their prognostic roles. The mutation frequencies of KRAS, NRAS, and BRAF were 41.7%, 1.6%, and 3.8%, respectively. KRAS mutations and deficient mismatch repair (dMMR) status were associated with right-sided tumors, aggressive biological behaviors, and poor differentiation. BRAF (V600E) mutations are associated with well-differentiated and lymphovascular invasion. The dMMR status predominated in young and middle-aged patients and tumor node metastasis stage II patients. dMMR status predicted longer overall survival in all CRC patients. KRAS mutations indicated inferior overall survival in patients with CRC stage IV. Our study showed that KRAS mutations and dMMR status could be applied to CRC patients with different clinicopathological features.

Total neoadjuvant treatment for MRI-stratified high-risk rectal cancer: a single-center, single-arm, prospective Phase II trial (PKUCH-R02).

Background: Induction chemotherapy combined with neoadjuvant chemoradiotherapy has been recommended for patients with high-risk, locally advanced rectal cancer. However, the benefit of more intensive total neoadjuvant treatment (TNT) is unknown. This study aimed to assess the safety and efficacy of induction chemotherapy combined with chemoradiotherapy and consolidation chemotherapy for magnetic resonance imaging-stratified high-risk rectal cancer. Methods: This was a single-center, single-arm, prospective Phase II trial in Peking University Cancer Hospital (Beijing, China). Patients received three cycles of induction oxaliplatin and capecitabine (CapeOX) followed by chemoradiotherapy and two cycles of consolidation CapeOX. The primary end point was adverse event rate and the second primary end points were 3-year disease-free survival rate, completion of TNT, and pathological downstaging rate. Results: Between August 2017 and August 2018, 68 rectal cancer patients with at least one high risk factor (cT3c/3d/T4a/T4b, cN2, mesorectal fascia involvement, or extramural venous invasion involvement) were enrolled. The overall compliance of receiving the entire treatment was 88.2% (60/68). All 68 patients received induction chemotherapy, 65 received chemoradiotherapy, and 61 received consolidation chemotherapy. The Grade 3-4 adverse event rate was 30.8% (21/68). Nine patients achieved clinical complete response and then watch and wait. Five patients (7.4%) developed distant metastasis during TNT and received palliative chemotherapy. Fifty patients underwent surgical resection. The complete response rate was 27.9%. After a median follow-up of 49.2 months, the overall 3-year disease-free survival rate was 69.7%. Conclusions: For patients with high-risk rectal cancer, this TNT regimen can achieve favorable survival and complete response rates but with high toxicity. However, it is necessary to pay attention to the possibility of distant metastasis during the long treatment period.

Deep learning-derived spatial organization features on histology images predicts prognosis in colorectal liver metastasis patients after hepatectomy.

Histopathological images of colorectal liver metastases (CRLM) contain rich morphometric information that may predict patients' outcomes. However, to our knowledge, no study has reported any practical deep learning framework based on the histology images of CRLM, and their direct association with prognosis remains largely unknown. In this study, we developed a deep learning-based framework for fully automated tissue classification and quantification of clinically relevant spatial organization features (SOFs) in H&E-stained images of CRLM. The SOFs based risk-scoring system demonstrated a strong and robust prognostic value that is independent of the current clinical risk score (CRS) system in independent clinical cohorts. Our framework enables fully automated tissue classification of H&E images of CRLM, which could significantly reduce assessment subjectivity and the workload of pathologists. The risk-scoring system provides a time- and cost-efficient tool to assist clinical decision-making for patients with CRLM, which could potentially be implemented in clinical practice.

[ICAM-1 469K/E gene polymorphisms increase the risk of gastric dysplasia].

OBJECTIVE: To investigate the influence of ICAM-1 469K/E gene polymorphisms on the risk of atrophic gastritis and dysplasia. METHODS: The ICAM-1 469K/E gene polymorphisms in a total of 372 subjects were detected by polymerase chain reaction-direct sequencing. All of the subjects were from Linqu County, a high risk area of gastric cancer in Shandong Province of northern China. All cases were initially diagnosed as normal or superficial gastritis at the beginning of this study. After a 5-year follow-up, the cases were subdivided into no progression group (no histological progression, n=137), progression group I (progressed to severe chronic atrophic gastritis, n=194) and progression group II (progressed to low-grade dysplasia, n=41). RESULTS: In all 372 subjects, the frequencies of KK, KE or EE genotype of ICAM-1 K469E were 50.5%, 39.2% and 10.2%, respectively. No significant differences were observed in the ICAM-1 469K/E genotype frequencies between the progression group I and no progression group (P>0.05). The frequencies of KK genotype (68.3%) were significantly higher in the progression group II than in the no progression group (49.6%, P=0.035), and also than in the progression group I (47.4%, P=0.015). An increased risk of the progressing to dysplasia from normal or superficial gastritis was found in the individuals with ICAM-1 469KK genotype [odds ratio (OR)=2.21, 95%CI, 1.10-4.42]. CONCLUSION: ICAM-1 469K/E gene polymorphisms are significantly associated with the risk of gastric low-grade dysplasia, but not related with severe chronic atrophic gastritis in a population with high risk of gastric cancer in Linqu County, Shandong Province, China.

[Characteristics and Sources of DOM in Lake Sediments Under Different Inundation Environments].

The characteristics and sources of DOM in sediments are significantly affected by fluctuations in lake water levels. However, the impact of spatial differences on water levels remain unclear. Here, 36 sediment samples were collected from the flood passage and coastal beach of East Dongting Lake. The differences in the composition and source of DOM in sediments under perennial inundation and seasonal inundation were studied using UV-visible absorbance (UV-Vis) and fluorescent excitation-emission matrix (EEM)-parallel factor analysis (PARAFAC). Three fluorescent components of DOM in the sediment were identified. The relative abundance of protein-like components was as high as (72.95±8.94)%, including tryptophan (C2) and tyrosine (C3). However, the humic-like component (C1) abundance was (27.05±8.94)%. Compared with that in perennial inundation, DOM in seasonal inundation had a higher and lower relative abundance of protein-like components and humic-like components, respectively. Further, the aromatic and hydrophobic components were higher in perennial inundation, showing a spatial pattern of the middle>entrance>outlet of the lake, which was more conducive to the migration of pollutants. The high FI (1.93) and BIX (0.91) and low HIX (1.57) indicated that the DOM in sediments had the mixed characteristics of being mainly endogenic and relatively weakly terrigenous. This was mainly influenced by human input and sediment characteristics. The direct effect of sewage discharge was intensified by sediment exposure in the seasonal inundation zone. Additionally, the contents of clay and total nitrogen (TN) were significantly positively correlated with FI, indicating that high nutrients and clay in sediments enhanced the endogenous input of DOM (FI>1.9). The perennial inundation zone was influenced by external runoff input. At the same time, the pH and C/N were significantly positively correlated with HIX and C1, indicating that DOM in the sediments had higher terrigenic characteristics (HIX=1.38±0.57) than those in the seasonal inundation zone owing to the alkaline environment (pH>7.5) and runoff input. The results above revealed the relevant theories of the response of DOM in sediment to water quality and pollution in the process of hydrology and human activities and provide a scientific basis for the prevention and control of sediment pollution in lakes.