Laparoscopic Radical Antegrade Modular Pancreatosplenectomy via Dorsal-Caudal Artery Approach for Pancreatic Neck-Body Cancer.

Laparoscopic radical resection of the pancreatic neck is one of the most complicated radical operations for pancreatic cancer, especially for patients who have had neoadjuvant chemotherapy. Here, we present a technique to perform laparoscopic radical antegrade modular pancreatosplenectomy (L-RAMPS) using the dorsal-caudal artery approach by making full use of the high-definition vision and operation modes of the laparoscope. The innovation and optimization of this operation are provided in the protocol. Priority should be given to the dorsal resection plane, including the dorsal side of the superior mesenteric artery (SMA), the dorsal side of the pancreatic head, the root of the celiac artery (CeA), the ventral side of the left renal vessels, and the renal hilum. On the condition that the operation for pancreatic neck-body cancer is feasible and safe, the second step is to perform tumor resection en bloc surrounding the SMA and CeA from the caudal to the cephalic side to increase the rate of R0 (radical zero) resection and further prognosis.

Laparoscopic central hepatectomy using a parenchymal-first approach: how we do it.

BACKGROUND: Laparoscopic central hepatectomy (LCH) is a difficult and challenging procedure. This study aimed to describe our experience with LCH using a parenchymal-first approach. METHODS: Between July 2017 and June 2021, 19 consecutive patients underwent LCH using a parenchymal-first approach at our institution. Herein, the details of this procedural strategy are described, and the demographic and clinical data of the included patients were retrospectively analyzed. RESULTS: There were 1 female and 18 male patients, all with hepatocellular carcinoma without major vascular invasion. The mean age was 57 ± 10 years. No patients underwent conversion to open surgery, and no blood transfusions were needed intraoperatively. The average operative duration and the average Pringle maneuver duration were 223 ± 65 min and 58 ± 11 min. respectively. The median blood loss was 200 ml (range: 100-800 ml). Postoperative morbidities occurred in 3 patients (15.8%), including 2 cases of bile leakage and 1 case of acquired pulmonary infection; there were no postoperative complications happened such as bleeding, hepatic failure, or mortality. The average postoperative hospital stay was 10 ± 3 days. CONCLUSION: The optimized procedure of LCH using a parenchymal-first approach is not only feasible but also expected to provide an advantage in laparoscopic anatomical hepatectomy.

Association of the collagen signature with pathological complete response in rectal cancer patients.

Collagen in the tumor microenvironment is recognized as a potential biomarker for predicting treatment response. This study investigated whether the collagen features are associated with pathological complete response (pCR) in locally advanced rectal cancer (LARC) patients receiving neoadjuvant chemoradiotherapy (nCRT) and develop and validate a prediction model for individualized prediction of pCR. The prediction model was developed in a primary cohort (353 consecutive patients). In total, 142 collagen features were extracted from the multiphoton image of pretreatment biopsy, and the least absolute shrinkage and selection operator (Lasso) regression was applied for feature selection and collagen signature building. A nomogram was developed using multivariable analysis. The performance of the nomogram was assessed with respect to its discrimination, calibration, and clinical utility. An independent cohort (163 consecutive patients) was used to validate the model. The collagen signature comprised four collagen features significantly associated with pCR both in the primary and validation cohorts (p < 0.001). Predictors in the individualized prediction nomogram included the collagen signature and clinicopathological predictors. The nomogram showed good discrimination with area under the ROC curve (AUC) of 0.891 in the primary cohort and good calibration. Application of the nomogram in the validation cohort still gave good discrimination (AUC = 0.908) and good calibration. Decision curve analysis demonstrated that the nomogram was clinically useful. In conclusion, the collagen signature in the tumor microenvironment of pretreatment biopsy is significantly associated with pCR. The nomogram based on the collagen signature and clinicopathological predictors could be used for individualized prediction of pCR in LARC patients before nCRT.

A Nomogram Based on a Collagen Feature Support Vector Machine for Predicting the Treatment Response to Neoadjuvant Chemoradiotherapy in Rectal Cancer Patients.

BACKGROUND: The relationship between collagen features (CFs) in the tumor microenvironment and the treatment response to neoadjuvant chemoradiotherapy (nCRT) is still unknown. This study aimed to develop and validate a perdition model based on the CFs and clinicopathological characteristics to predict the treatment response to nCRT among locally advanced rectal cancer (LARC) patients. METHODS: In this multicenter, retrospective analysis, 428 patients were included and randomly divided into a training cohort (299 patients) and validation cohort (129 patients) [7:3 ratio]. A total of 11 CFs were extracted from a multiphoton image of pretreatment biopsy, and a support vector machine (SVM) was then used to construct a CFs-SVM classifier. A prediction model was developed and presented with a nomogram using multivariable analysis. Further validation of the nomogram was performed in the validation cohort. RESULTS: The CFs-SVM classifier, which integrated collagen area, straightness, and crosslink density, was significantly associated with treatment response. Predictors contained in the nomogram included the CFs-SVM classifier and clinicopathological characteristics by multivariable analysis. The CFs nomogram demonstrated good discrimination, with area under the receiver operating characteristic curves (AUROCs) of 0.834 in the training cohort and 0.854 in the validation cohort. Decision curve analysis indicated that the CFs nomogram was clinically useful. Moreover, compared with the traditional clinicopathological model, the CFs nomogram showed more powerful discrimination in determining the response to nCRT. CONCLUSIONS: The CFs-SVM classifier based on CFs in the tumor microenvironment is associated with treatment response, and the CFs nomogram integrating the CFs-SVM classifier and clinicopathological characteristics is useful for individualized prediction of the treatment response to nCRT among LARC patients.

Predicting postoperative peritoneal metastasis in gastric cancer with serosal invasion using a collagen nomogram.

Accurate prediction of peritoneal metastasis for gastric cancer (GC) with serosal invasion is crucial in clinic. The presence of collagen in the tumour microenvironment affects the metastasis of cancer cells. Herein, we propose a collagen signature, which is composed of multiple collagen features in the tumour microenvironment of the serosa derived from multiphoton imaging, to describe the extent of collagen alterations. We find that a high collagen signature is significantly associated with a high risk of peritoneal metastasis (P < 0.001). A competing-risk nomogram including the collagen signature, tumour size, tumour differentiation status and lymph node metastasis is constructed. The nomogram demonstrates satisfactory discrimination and calibration. Thus, the collagen signature in the tumour microenvironment of the gastric serosa is associated with peritoneal metastasis in GC with serosal invasion, and the nomogram can be conveniently used to individually predict the risk of peritoneal metastasis in GC with serosal invasion after radical surgery.

Association of the Collagen Signature in the Tumor Microenvironment With Lymph Node Metastasis in Early Gastric Cancer.

Importance: Lymph node status is the primary determinant in treatment decision making in early gastric cancer (EGC). Current evaluation methods are not adequate for estimating lymph node metastasis (LNM) in EGC. Objective: To develop and validate a prediction model based on a fully quantitative collagen signature in the tumor microenvironment to estimate the individual risk of LNM in EGC. Design, Setting, and Participants: This retrospective study was conducted from August 1, 2016, to May 10, 2018, at 2 medical centers in China (Nanfang Hospital and Fujian Provincial Hospital). Participants included a primary cohort (n = 232) of consecutive patients with histologically confirmed gastric cancer who underwent radical gastrectomy and received a T1 gastric cancer diagnosis from January 1, 2008, to December 31, 2012. Patients with neoadjuvant radiotherapy, chemotherapy, or chemoradiotherapy were excluded. An additional consecutive cohort (n = 143) who received the same diagnosis from January 1, 2011, to December 31, 2013, was enrolled to provide validation. Baseline clinicopathologic data of each patient were collected. Collagen features were extracted in specimens using multiphoton imaging, and the collagen signature was constructed. An LNM prediction model based on the collagen signature was developed and was internally and externally validated. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) of the prediction model and decision curve were analyzed for estimating LNM. Results: In total, 375 patients were included. The primary cohort comprised 232 consecutive patients, in whom the LNM rate was 16.4% (n = 38; 25 men [65.8%] with a mean [SD] age of 57.82 [10.17] years). The validation cohort consisted of 143 consecutive patients, in whom the LNM rate was 20.9% (n = 30; 20 men [66.7%] with a mean [SD] age of 54.10 [13.19] years). The collagen signature was statistically significantly associated with LNM (odds ratio, 5.470; 95% CI, 3.315-9.026; P < .001). Multivariate analysis revealed that the depth of tumor invasion, tumor differentiation, and the collagen signature were independent predictors of LNM. These 3 predictors were incorporated into the new prediction model, and a nomogram was established. The model showed good discrimination in the primary cohort (AUROC, 0.955; 95% CI, 0.919-0.991) and validation cohort (AUROC, 0.938; 95% CI, 0.897-0.981). An optimal cutoff value was selected in the primary cohort, which had a sensitivity of 86.8%, a specificity of 93.3%, an accuracy of 92.2%, a positive predictive value of 71.7%, and a negative predictive value of 97.3%. The validation cohort had a sensitivity of 90.0%, a specificity of 90.3%, an accuracy of 90.2%, a positive predictive value of 71.1%, and a negative predictive value of 97.1%. Among the 375 patients, a sensitivity of 87.3%, a specificity of 92.1%, an accuracy of 91.2%, a positive predictive value of 72.1%, and a negative predictive value of 96.9% were found. Conclusions and Relevance: This study's findings suggest that the collagen signature in the tumor microenvironment is an independent indicator of LNM in EGC, and the prediction model based on this collagen signature may be useful in treatment decision making for patients with EGC.

A case-control study of using carbon nanoparticles to trace decision-making lymph nodes around inferior mesenteric artery in rectal cancer.

BACKGROUND: Accurate identification of lymph nodes localized around inferior mesenteric artery (IMA), with or without metastasis, is of crucial importance for surgeons when dissecting D2 or D3 lymph nodes in patients with rectal cancer (RC). The following study evaluates whether carbon nanoparticles can be used for detection of decision-making lymph nodes (DLNs) in station 253 lymph nodes found around IMA during RC surgery. METHODS: A total of 66 patients with rectal adenocarcinomas were recruited between January 2014 and August 2017. Patients were divided into carbon nanoparticle (CN) group and control (CL) group; for the CN group, 1 ml nanoparticles were endoscopically injected into submucosal layer of primary tumor 1 day before surgery. DLNs were defined as black-dyed nodes in CN group or macroscopic lymph nodes in CL group localized along the IMA, proximal to the origin of the left colic artery. D3 lymph nodes were dissected using laparoscopic radical resection, and then examined using pathological approach. Intra-operative and post-operative data were compared between the two groups. RESULTS: In CN group, black-dyed DLNs were easily found under laparoscopy; the median number of DLNs was 3 (range 1-9). In CL group, the median number of DLNs was 0 (range 0-3). Consistency between intra-operative DLNs and post-operative station 253 nodes were confirmed by pathological examination. Significant higher number of DLNs in station 253 nodes (2.91 ± 2.47 vs 0.58 ± 0.75, p < 0.001), number of station 251 nodes (12.85 ± 8.99 vs 8.09 ± 5.85, p = 0.014), number of station 253 nodes (5.21 ± 5.26 vs 3.15 ± 2.32, p = 0.045), and the number of total lymph nodes (24.06 ± 13.20 vs 16.21 ± 9.09, p = 0.007) were found in the CN group compared to CL group. CONCLUSIONS: Carbon nanoparticles are useful for identifying DLNs in station 253 LNs around IMA in RC. It is not necessary to perform D3 lymph node dissection if there are no intra-operative DLNs metastases in RC.

Real-time in vivo optical biopsy using confocal laser endomicroscopy to evaluate distal margin in situ and determine surgical procedure in low rectal cancer.

BACKGROUND: In low rectal cancer, a negative distal margin (DM) is necessary for R0 radical resection, and therefore, the choice of surgical procedure is dependent on whether the planned transection rectum has residual cancer or not. Currently, surgeons choose surgical procedures according to intraoperative in vitro DM frozen sections. This study aimed to investigate the feasibility of real-time in vivo optical biopsy using confocal laser endomicroscopy (CLE) to evaluate DM in situ and determine the surgical procedure in low rectal cancer. METHODS: Optical biopsy using CLE was performed when the rectum was dissected at the levator ani plane and rectum transection was ready. For negative DM, the surgical procedure of low anterior resection (LAR) was chosen. For positive DM, the surgical procedure of abdominoperineal resection (APR) was chosen. The specimen at the site of the planned transection rectum underwent intraoperative frozen section and routine pathological procedures. RESULTS: Eighteen patients underwent real-time in vivo optical biopsy using CLE in surgery. Eleven patients' CLE images of DM showed a regular, round crypt, and round luminal opening covered by a simple layer of columnar epithelial cells and goblet cells. LAR was then performed. Pathology revealed that the 11 DMs were negative, and the median length of the DMs was 2.0 cm. The remaining seven patients' CLE images of the planned transection rectum showed the loss of crypt architecture and irregular epithelial layer with loss of goblet cells. APR was then performed. Pathology confirmed cancer invasion, and the median distance from tumor to dentate line was 1.0 cm. The sensitivity, specificity, and accuracy of CLE optical biopsy of DM were 85.71%, 100%, and 94.44%, respectively. CONCLUSIONS: It is feasible to perform real-time in vivo optical biopsy using CLE to evaluate DM in situ and determine the surgical procedure in low rectal cancer.

Multiphoton imaging provides a superior optical biopsy to that of confocal laser endomicroscopy imaging for colorectal lesions.

BACKGROUND: Confocal laser endomicroscopy (CLE) requires fluorescence agents, the use of which leads to blurred images and low diagnostic accuracy owing to fluorescein leakage. We aimed to explore whether multiphoton imaging (MPI) could serve as a better method of optical biopsy. METHODS: First, a pilot study was performed to set up the optical diagnostic criteria of MPI for benign or malignant colorectal lesions in 30 patients. Then, a blinded study was conducted to compare the sensitivity, specificity, and accuracy of MPI versus CLE imaging in 79 patients. RESULTS : In the pilot study, MPI revealed regular tissue architecture and cell morphology in the normal tissue, and irregular tubular structures, and cellular and nuclear pleomorphism in the abnormal tissue. In the blinded study, compared with CLE imaging, MPI significantly improved the diagnostic sensitivity, specificity, and accuracy of the optical biopsy (89.74 % vs. 61.54 %, P = 0.008; 92.5 % vs. 67.5 %, P = 0.009; and 91.14 % vs. 64.56 %, P = 0.001, respectively). CONCLUSIONS : MPI can provide a superior optical biopsy to that of CLE imaging for colorectal lesions.

Real-time optical diagnosis of gastric cancer with serosal invasion using multiphoton imaging.

A real-time optical biopsy, which could determine tissue histopathology, would be of extraordinary benefit to staging laparoscopy for gastric cancer with serosal invasion (T4) that requires downstage treatment. We investigated the feasibility of using multiphoton imaging to perform a real-time optical diagnosis of gastric cancer with or without serosal invasion. First, a pilot study was performed to establish the optical diagnostic features of gastric cancer with or without serosal invasion using multiphoton imaging compared with hematoxylin-eosin staining and Masson's trichrome staining. Second, a blinded study was performed to compare the diagnostic sensitivity, specificity, and accuracy of multiphoton imaging and endoscopic ultrasonography (EUS) for T4 gastric cancer. In the pilot study, multiphoton imaging revealed collagen loss and degradation and cellular and nuclear pleomorphism in gastric cancer with serosal invasion. The collagen content in gastric cancer with or without serosal invasion was 0.36 ± 0.18 and 0.79 ± 0.16 (p < 0.001), respectively. In the blinded study, the sensitivity, specificity, and accuracy of EUS and multiphoton imaging for T4 gastric cancer were 70% and 90% (p = 0.029), 66.67% and 96.67% (p = 0.003), and 68.33% and 93.33% (p = 0.001), respectively. It is feasible to use multiphoton imaging to make a real-time optical diagnosis of gastric cancer with or without serosal invasion.

A multicenter study of using carbon nanoparticles to show sentinel lymph nodes in early gastric cancer.

BACKGROUND: Lymph node metastasis occurs in approximately 10% of early gastric cancer. Preoperative or intra-operative identification of lymph node metastasis in early gastric cancer is crucial for surgical planning. The purpose of this study was to evaluate the feasibility of using carbon nanoparticles to show sentinel lymph nodes (SLNs) in early gastric cancer. METHODS: A multicenter study was performed between July 2012 and November 2014. Ninety-one patients with early gastric cancer identified by preoperative endoscopic ultrasonography were recruited. One milliliter carbon nanoparticles suspension, which is approved by Chinese Food and Drug Administration, was endoscopically injected into the submucosal layer at four points around the site of the primary tumor 6-12 h before surgery. Laparoscopic radical resection with D2 lymphadenectomy was performed. SLNs were defined as nodes that were black-dyed by carbon nanoparticles in greater omentum and lesser omentum near gastric cancer. Lymph node status and SLNs accuracy were confirmed by pathological analysis. RESULTS: All patients had black-dyed SLNs lying in greater omentum and/or lesser omentum. SLNs were easily found under laparoscopy. The mean number of SLNs was 4 (range 1-9). Carbon nanoparticles were around cancer in specimen. After pathological analysis, 10 patients (10.99%) had lymph node metastasis in 91 patients with early gastric cancer. SLNs were positive in 9 cases and negative in 82 cases. In pathology, carbon nanoparticles were seen in lymphatic vessels, lymphoid sinus, and macrophages in SLNs. When SLNs were positive, cancer cells were seen in lymph nodes. The sensitivity, specificity, and accuracy of black-dyed SLNs in early gastric cancers were 90, 100, and 98.9 %, respectively. No patient had any side effects of carbon nanoparticles in this study. CONCLUSIONS: It is feasible to use carbon nanoparticles to show SLNs in early gastric cancer. Carbon nanoparticles suspension is safe for submucosal injection.