A Deep Neural Network-Based Decision Support Tool for the Detection of Lymph Node Metastases in Colorectal Cancer Specimens.

The identification of lymph node metastases in colorectal cancer (CRC) specimens is crucial for the planning of postoperative treatment and can be a time-consuming task for pathologists. In this study, we developed a deep neural network (DNN) algorithm for the detection of metastatic CRC in digitized histologic sections of lymph nodes and evaluated its performance as a diagnostic support tool. First, the DNN algorithm was trained using pixel-level annotations of cancerous areas on 758 whole slide images (360 with cancerous areas). The algorithm's performance was evaluated on 74 whole slide images (43 with cancerous areas). Second, the algorithm was evaluated as a decision support tool on 288 whole slide images covering 1517 lymph node sections, randomized in 16 batches. Two senior pathologists (C.K. and C.O.) assessed each batch with and without the help of the algorithm in a 2 × 2 crossover design, with a washout period of 1 month in between. The time needed for the evaluation of each node section was recorded. The DNN algorithm achieved a median pixel-level accuracy of 0.952 on slides with cancerous areas and 0.996 on slides with benign samples. N+ disease (metastases, micrometastases, or tumor deposits) was present in 103 of the 1517 sections. The algorithm highlighted cancerous areas in 102 of these sections, with a sensitivity of 0.990. Assisted by the algorithm, the median time needed for evaluation was significantly shortened for both pathologists (median time for pathologist 1, 26 vs 14 seconds; P < .001; 95% CI, 11.0-12.0; median time for pathologist 2, 25 vs 23 seconds; P < .001; 95% CI, 2.0-4.0). Our DNN showed high accuracy for detecting metastatic CRC in digitized histologic sections of lymph nodes. This decision support tool has the potential to improve the diagnostic workflow by shortening the time needed for the evaluation of lymph nodes in CRC specimens without impairing diagnostic accuracy.

Importance of Arterial Vessel Length for Metastatic Lymph Node Retrieval and Survival in Standardized Left- and Right-Sided Colon Cancer Surgery.

BACKGROUND: We investigated the localization of lymph node metastases, and the role of arterial vessel and specimen lengths in left- and right-sided colon cancer surgery, for survival. METHODS: This was a prospective cross-sectional population-based study of specimens from patients who underwent standardized surgical resection for colon cancer in 2012-2015. The mesocolon of the specimens was divided into four sections for pathological analysis of lymph nodes. Multiple linear regression analysis was used to explore the relationship between lymph node counts and patient- and surgery-related factors. For survival analysis, a multivariable Cox regression method was used. RESULTS: A total of 317 patients (160 females) were included. Median (range) age was 74 (30-95) years. Median number of lymph node retrieval was 32 (8-198) and was associated with increased specimen length but not to arterial vessel length. One hundred and thirty-three (42%) patients had lymph node metastases. All patients had these located < 5 cm from the tumour. Ten, two, and three specimens had lymph node metastases around the central and peripheral ligation of the ileocolic artery and at the central ligation of the inferior mesenteric artery, respectively. The tumour stages in these specimens were T3-4N2M0-1. No statistically significant survival benefit was associated with longer arterial vessel length (p = 0.429). CONCLUSIONS: Neither retrieval of lymph nodes nor statistically significant survival was affected by vessel length in standardized left- and right-sided colon cancer surgery.

A comparative study of the pathological outcomes of robot-assisted versus open surgery for rectal cancer.

Purpose: The use of robot-assisted surgery for rectal cancer is increasing, but the pathological outcomes have not been fully clarified. We compared the surgical and pathological outcomes between robot-assisted and open surgery in specimens from patients operated on for rectal cancer. Methods: All patients who underwent resection for rectal cancer from 2016 to 2018 were included. Specimens were divided into 3 sections to analyze the pathology of the lymph nodes (LNs) (n=137). Results: The total specimen lengths were shorter in the robot-assisted group than in the open surgery group (mean± standard deviation: 29.1±8.6 cm vs. 33.8±9.9 cm, P=0.004) because of a shorter proximal resection margin (21.7±8.7 vs. 26.4±10.6 cm, P=0.006). The number of recruited LNs (35.8±21.8 vs. 39.6±16.5, P=0.604) and arterial vessel length (8.84±2.6 cm vs. 8.78±2.4 cm, P=0.891) did not differ significantly between the 2 surgical approaches. LN metastases were found in 33 of 137 samples (24.1%), but the numbers did not differ significantly between the procedures. Among these 33 cases, metastatic LNs were located in the mesorectum (75.8%), in the sigmoid colon mesentery (33.3%), and at the arterial ligation site of the inferior mesenteric artery (12.1%). The circumferential resection margin and the proportion of complete mesorectal fascia were comparable between the groups. Conclusion: There were no significant differences between the 2 surgical approaches regarding arterial vessel length, recruitment of LN metastases, and resection margins.

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).

Blood pressure targeting by partial REBOA is possible in severe hemorrhagic shock in pigs and produces less circulatory, metabolic and inflammatory sequelae than total REBOA.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is an effective adjunct in exsanguinating torso hemorrhage, but causes ischemic injury to distal organs. The aim was to investigate whether blood pressure targeting by partial REBOA (pREBOA) is possible in porcine severe hemorrhagic shock and to compare pREBOA and total REBOA (tREBOA) regarding hemodynamic, metabolic and inflammatory effects. METHODS: Eighteen anesthetized pigs were exposed to induced controlled hemorrhage to a systolic blood pressure (SBP) of 50 mmHg and randomized into three groups of thoracic REBOA: 30 min of pREBOA (target SBP 80-100 mmHg), tREBOA, and control. They were then resuscitated by autologous transfusion and monitored for 3 h. Hemodynamics, blood gases, mesenteric blood flow, intraperitoneal metabolites, organ damage markers, histopathology from the small bowel, and inflammatory markers were analyzed. RESULTS: Severe hemorrhagic shock was induced in all groups. In pREBOA the targeted blood pressure was reached. The mesenteric blood flow was sustained in pREBOA, while it was completely obstructed in tREBOA. Arterial pH was lower, and lactate and troponin levels were significantly higher in tREBOA than in pREBOA and controls during the reperfusion period. Intraperitoneal metabolites, the cytokine response and histological analyses from the small bowel were most affected in the tREBOA compared to the pREBOA and control groups. CONCLUSION: Partial REBOA allows blood pressure titration while maintaining perfusion to distal organs, and reduces the ischemic burden in a state of severe hemorrhagic shock. Partial REBOA may lower the risks of post-resuscitation metabolic and inflammatory impacts, and organ dysfunction.

Computed Tomography Follow-Up Assessment of Patients with Low-Grade Appendiceal Mucinous Neoplasms: Evaluation of Risk for Pseudomyxoma Peritonei.

BACKGROUND: Low-grade appendiceal mucinous neoplasms are rare. Both classification and management vary. This study aimed to follow up on patients with a diagnosis of LAMN after primary surgery with computer tomography (CT) scans to examine the risk for the development of pseudomyxoma peritonei (PMP). METHODS: This population-based prospective study investigated patients who underwent appendectomy between 2007 and 2013 and had histology results demonstrating the presence of LAMN. The patients were followed up with a CT scan every 6 months for 2 years, until December 2015. RESULTS: The study investigated 41 patients (20 females) with a median age of 65 years (range 20-87 years). The entire appendix was processed and examined, with results showing that 12 were perforated, and 3 had a positive margin. Extra-appendiceal mucin on the surface of the appendix was found in ten cases, and in two cases, extra-mucinous epithelial cells were detected. During a median follow-up period of 5.1 years (range 2-8.6 years), none of the patients experienced the development of PMP. CONCLUSIONS: These data suggest that for patients with LAMN confined to the appendix, involvement of the appendectomy margin or perforation with mucin locally, even with epithelial cells, did not predict the development of PMP, and a conservative approach seems justified. No reoperation was needed, and regular follow-up evaluation with CT scans was sufficient.

Detection of Free Cancer Cells in Pelvic Lavage with Double Immunocytochemistry at Rectal Cancer Surgery.

BACKGROUND/AIM: The aim of the present study was to describe a double immunocytochemical staining method for detecting free cancer cells after rectal cancer surgery and to evaluate their extent and prognostic role. MATERIALS AND METHODS: Immunocytochemistry was performed using antibodies against cytokeratin 20/caudal-typehomeobox transcription factor 2 (CDX2) and mucin glycoprotein-2 (MUC2)/p53 protein. The study included 29 patients with infraperitoneal rectal cancer who underwent bowel resection and four controls. The pelvic lavage was retrieved at the start of laparotomy, after total mesorectal excision and after abdominal lavage with sterile water. RESULTS: Free cancer cells were detected with the double immunocytochemical method in the two controls with carcinomatosis and one control with sigmoidal cancer. None of the patients with rectal tumours had presence of free cancer cells. CONCLUSION: Immunocytochemical analysis of peritoneal lavage was feasible and negative in patients with infraperitoneal rectal cancer. Further studies are encouraged to investigate the clinical relevance in cases with free cancer cells after incomplete total mesorectal excision.

Lymphovascular and perineural invasion in stage II rectal cancer: a report from the Swedish colorectal cancer registry.

BACKGROUND: Adjuvant chemotherapy for stage II and III rectal cancer patients is a matter of discussion. The aim of the present study was to evaluate the prognostic value of lymphovascular (LVI) and perineural (PNI) invasion in stage II rectal cancer on a national level. MATERIALS AND METHODS: Clinico-pathological factors associated with disease-free survival (DFS) and time to recurrence in stage II rectal cancer patients were analyzed from patient data registered in the Swedish Colorectal Cancer Registry between 2006 and 2012. RESULTS: Of 2649 patients with TNM stage II disease, 1395 (53%) received preoperative radiotherapy and 456 (17%) preoperative chemoradiotherapy. LVI and PNI were detected in 387 (15%) and 269 (10%) patients, respectively. Adjuvant chemotherapy was planned in 14%, but more often if LVI or PNI was detected (25% and 31%, respectively, p < .001 for both). The three-year DFS and time to recurrence were 78% and 17%, respectively. Both LVI and PNI indicated worse outcome. In patients not receiving postoperative chemotherapy, the risks of recurrence after three years were 20% if LVI was seen and 22% if PNI was detected (p < .001 for both). In the absence of LVI and PNI, it was 13% and 12%, respectively. In a multivariate Cox regression analysis, patients with LVI (hazard ratio 1.44, 95% CI 1.09-1.90; p = .011) and PNI (hazard ratio 1.80, 95% CI 1.34-2.43, p < .001) had significantly increased risks of recurrence. CONCLUSIONS: Stage II rectal cancer patients with LVI and PNI have an increased risk of recurrence which emphasizes the need to properly evaluate the role of adjuvant chemotherapy particularly in these subgroups.

Circumferential resection margin as a prognostic marker in the modern multidisciplinary management of rectal cancer.

BACKGROUND: A positive circumferential resection margin has been associated with a high risk of local recurrence and a decrease in survival in patients who have rectal cancer. OBJECTIVE: The purpose of this study was to analyze the involvement of circumferential resection margin in local recurrence and survival in a multidisciplinary population-based setting by using tailored oncological therapy and surgery with total mesorectal excision. DESIGN: Data were collected in a prospective database and retrospectively analyzed. Between 1996 and 2009, 448 patients with rectal cancer underwent a curative bowel resection. SETTINGS: Population-based data were collected at a single institution in the county of Västmanland, Sweden. RESULTS: Preoperative radiotherapy was delivered to 334 patients (74%); it was delivered to 35 patients (8%) concomitantly with preoperative chemotherapy. In 70 patients (16%), en bloc resections of the prostate and vagina were performed. Intraoperative perforations were seen in 7 patients (1.6%). The mesorectal fascia was assessed as complete in 117/118 cases. In 32 cases (7%), the circumferential resection margin was 1 mm or less. After a median follow-up of 68 months, 5 (1.1%) patients developed a local recurrence; one of them had circumferential resection margin involvement. The 5-year overall survival was 77%. In the multivariate analysis, the circumferential resection margin was not an independent factor for disease-free survival. LIMITATIONS: Mesorectal fascia was not assessed before 2007. The findings might be explained by a type II error but, from a clinical perspective, enough patients were included to motivate the conclusion of the study. CONCLUSIONS: Circumferential resection margin is an important measurement in rectal cancer pathology, but the correlation to local recurrence is much less than previously stated, probably because of oncological treatment and surgery that respects the mesorectal fascia and, when required, en bloc resections. Circumferential resection margin should not be used as a prognostic marker in the modern multidisciplinary management of rectal cancer.