Long-term quality of life after hybrid robot-assisted and open Ivor Lewis esophagectomy for esophageal cancer in a single center: a comparative analysis.

PURPOSE: Due to improved survival of esophageal cancer patients, long-term quality of life (QoL) is increasingly gaining importance. The aim of this study is to compare QoL outcomes between open Ivor Lewis esophagectomy (Open-E) and a hybrid approach including laparotomy and a robot-assisted thoracic phase (hRob-E). Additionally, a standard group of healthy individuals serves as reference. METHODS: With a median follow-up of 36 months after hRob-E (n = 28) and 40 months after Open-E (n = 43), patients' QoL was assessed using the European Organization for Research and Treatment of Cancer (EORTC) QoL Questionnaire Core 30 (QLQ-C30) and the EORTC Esophagus specific QoL questionnaire 18 (QLQ-OES18). RESULTS: Patients showed similar clinical-pathological characteristics, but hRob-E patients had significantly higher ASA scores at surgery (p < 0.001). Patients and healthy controls reported similar global health status and emotional and cognitive functions. However, physical functioning of Open-E patients was significantly reduced compared to healthy controls (p = 0.019). Operated patients reported reduced role and social functioning, fatigue, nausea and vomiting, dyspnea, and diarrhea. A trend towards a better pain score after hRob-E compared to Open-E emerged (p = 0.063). Regarding QLQ-OES18, hRob-E- and Open-E-treated patients similarly reported eating problems, reflux, and troubles swallowing saliva. CONCLUSIONS: The global health status is not impaired after esophagectomy. Despite higher ASA scores, QoL of hRob-E patients is similar to that of patients operated with Open-E. Moreover, patients after hRob-E appear to have a better score regarding physical functioning and a better pain profile than patients after Open-E, indicating a benefit of minimally invasive surgery.

Assessment of resectability of pancreatic cancer using novel immersive high-performance virtual reality rendering of abdominal computed tomography and magnetic resonance imaging.

PURPOSE: Virtual reality (VR) allows for an immersive and interactive analysis of imaging data such as computed tomography (CT) and magnetic resonance imaging (MRI). The aim of this study is to assess the comprehensibility of VR anatomy and its value in assessing resectability of pancreatic ductal adenocarcinoma (PDAC). METHODS: This study assesses exposure to VR anatomy and evaluates the potential role of VR in assessing resectability of PDAC. Firstly, volumetric abdominal CT and MRI data were displayed in an immersive VR environment. Volunteering physicians were asked to identify anatomical landmarks in VR. In the second stage, experienced clinicians were asked to identify vascular involvement in a total of 12 CT and MRI scans displaying PDAC (2 resectable, 2 borderline resectable, and 2 locally advanced tumours per modality). Results were compared to 2D standard PACS viewing. RESULTS: In VR visualisation of CT and MRI, the abdominal anatomical landmarks were recognised by all participants except the pancreas (30/34) in VR CT and the splenic (31/34) and common hepatic artery (18/34) in VR MRI, respectively. In VR CT, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 22/24, 20/24 and 19/24 scans, respectively. Whereas, in VR MRI, resectable, borderline resectable, and locally advanced PDAC were correctly identified in 19/24, 19/24 and 21/24 scans, respectively. Interobserver agreement as measured by Fleiss κ was 0.7 for CT and 0.4 for MRI, respectively (p < 0.001). Scans were significantly assessed more accurately in VR CT than standard 2D PACS CT, with a median of 5.5 (IQR 4.75-6) and a median of 3 (IQR 2-3) correctly assessed out of 6 scans (p < 0.001). CONCLUSION: VR enhanced visualisation of abdominal CT and MRI scan data provides intuitive handling and understanding of anatomy and might allow for more accurate staging of PDAC and could thus become a valuable adjunct in PDAC resectability assessment in the future.

Omission of perioperative morphine reduces postoperative pain in proctological interventions: a single-center analysis.

There is an increase in outpatient procedures and this trend will continue in the future. For hemorrhoidectomy, it is the standard of treatment in many health care systems. Perioperative management including adequate pain control is of paramount importance to ensure successful ambulatory surgery. This study investigates the role and effect of morphine compared to short-acting opiates applied before, during, or after proctological interventions and with focus on hemorrhoidectomy. A retrospective analysis of a prospective database was conducted comparing two populations. The control cohort received morphine (Yes-Mô) intra- and postoperatively, while the intervention group did not receive morphine (No-Mô) between January 2018 and January 2020. Both cohorts were balanced by propensity score matching. The outcomes were postoperative pain measured by numeric ratings scale (NRS) one hour postoperatively, pain 24 h postoperatively, success rate of outpatient management, and complication rate including postoperative nausea and vomiting as well as urinary retention. The intervention population comprised 54 patients and the control group contained 79 patients. One hour after surgery, patients in No-Mô reported lower NRS (1.44 ± 1.41) compared to Yes-Mô (2.48 ± 2.30) (p = 0.029). However, there was no difference in NRS 24 h postoperatively (No-Mô: 1.61 ± 1.41 vs Yes-Mô: 1.63 ± 1.72; p = 0.738). 100% of No-Mô was managed as outpatients while only 50% of Yes-Mô was dismissed on the day of the operation (p = < 0.001). There was no difference in postoperative complications (including postoperative nausea and vomiting (PONV) and urinary retention) between the two groups (PONV No-Mô 7.4% vs Yes-Mô 5.6%, p = 1.0 and urinary retention No-Mô 3.7% vs Yes-Mô 7.4%, p = 0.679). No-Mô received an oral morphine equivalent of 227.25 ± 140.35 mg intraoperatively and 11.02 ± 18.02 mg postoperatively. Yes-Mô received 263.17 ± 153.60 mg intraoperatively and 15.97 ± 14.17 mg postoperatively. The difference in received morphine equivalent between the groups was not significant after matching for the intraoperative (p = 0.212) and postoperative (p = 0.119) received equivalent. Omission of perioperative morphine is a viable but yet not understood method for reducing postoperative pain. Omission of morphine leads to a lower use of total morphine equivalent to attain satisfactory analgesia. The reduction of the overall opiate load and using opiates with a very short half-life potentially leads to a reduction of side effects like sedation. This in turn promotes discharge of the patient on the day of surgery. Omission of morphine is safe and does not increase postoperative complications.

The short- and long-term outcome after the surgical management of common bile duct stones in a tertiary referral hospital.

BACKGROUND: The removal of common bile duct stones by endoscopic retrograde cholangiopancreatography (ERCP) shows excellent results with low complication rates and is therefore considered a gold standard. However, in case of stones non-removable by ERCP, surgical extraction is needed. The surgical approach is still controversial and clinical guidelines are missing. This study aims to analyze the outcomes of patients treated with choledochotomy or hepaticojejunostomy for common bile duct stones. METHODS: All patients who underwent choledochotomy or hepaticojejunostomy for common bile duct stones at a tertiary referral hospital over 11 years were included. The analyzed data contains basic demographics, diagnostics, surgical parameters, length of hospitalization, and morbidity and mortality. RESULTS: Over the study period, 4375 patients underwent cholecystectomy, and 655 received an ERCP with stone extraction, with 48 of these patients receiving subsequent surgical treatment. ERCP was attempted in 23/30 (77%) of the choledochotomy patients pre/intraoperatively and 11/18 (56%) in hepaticojejunostomy patients. The 30-day major complication rate (Clavien-Dindo > II) was 1/30 (3%) in the choledochotomy group and 2/18 (11%) in the hepaticojejunostomy group. Complications after 30 days occurred in 3/30 (10%) patients and 2/18 (11%), respectively, and no mortality occurred. CONCLUSION: ERCP should still be considered the gold standard, although due to low short- and long-term morbidity rates, choledochotomy and hepaticojejunostomy represent effective surgical solutions for common bile duct stones.

Comprehensive Treatment Algorithms of the Swiss Peritoneal Cancer Group for Peritoneal Cancer of Gastrointestinal Origin.

Peritoneal cancer (PC) is a dire finding, yet in selected patients, long-term survival is possible. Complete cytoreductive surgery (CRS) together with combination immunochemotherapy is essential to achieve cure. Hyperthermic intraperitoneal chemotherapy (HIPEC) and pressurized intraperitoneal aerosol chemotherapy (PIPAC) are increasingly added to the multimodal treatment. The Swiss Peritoneal Cancer Group (SPCG) is an interdisciplinary group of expert clinicians. It has developed comprehensive treatment algorithms for patients with PC from pseudomyxoma peritonei, peritoneal mesothelioma, gastric, and colorectal origin. They include multimodal neoadjuvant treatment, surgical resection, and palliative care. The indication for and results of CRS HIPEC and PIPAC are discussed in light of the current literature. Institutional volume and clinical expertise required to achieve best outcomes are underlined, while inclusion of patients considered for CRS HIPEC and PIPAC in a clinical registry is strongly advised. The present recommendations are in line with current international guidelines and provide the first comprehensive treatment proposal for patients with PC including intraperitoneal chemotherapy. The SPCG comprehensive treatment algorithms provide evidence-based guidance for the multimodal care of patients with PC of gastrointestinal origin that were endorsed by all Swiss clinicians routinely involved in the multimodal care of these challenging patients.

Magnetic resonance cholangiopancreatography enhanced by virtual reality as a novel tool to improve the understanding of biliary anatomy and the teaching of surgical trainees.

Objective: The novel picture archiving and communication system (PACS), compatible with virtual reality (VR) software, displays cross-sectional images in VR. VR magnetic resonance cholangiopancreatography (MRCP) was tested to improve the anatomical understanding and intraoperative performance of minimally invasive cholecystectomy (CHE) in surgical trainees. Design: We used an immersive VR environment to display volumetric MRCP data (Specto VRTM). First, we evaluated the tolerability and comprehensibility of anatomy with a validated simulator sickness questionnaire (SSQ) and examined anatomical landmarks. Second, we compared conventional MRCP and VR MRCP by matching three-dimensional (3D) printed models and identifying and measuring common bile duct stones (CBDS) using VR MRCP. Third, surgical trainees prepared for CHE with either conventional MRCP or VR MRCP, and we measured perioperative parameters and surgical performance (validated GOALS score). Setting: The study was conducted out at Clarunis, University Center for Gastrointestinal and Liver Disease, Basel, Switzerland. Participants: For the first and second study step, doctors from all specialties and years of experience could participate. In the third study step, exclusively surgical trainees were included. Of 74 participating clinicians, 34, 27, and 13 contributed data to the first, second, and third study phases, respectively. Results: All participants determined the relevant biliary structures with VR MRCP. The median SSQ score was 0.75 (IQR: 0, 3.5), indicating good tolerability. Participants selected the corresponding 3D printed model faster and more reliably when previously studying VR MRCP compared to conventional MRCP: We obtained a median of 90 s (IQR: 55, 150) and 72.7% correct answers with VR MRCP versus 150 s (IQR: 100, 208) and 49.6% correct answers with conventional MRCP, respectively (p < 0.001). CBDS was correctly identified in 90.5% of VR MRCP cases. The median GOALS score was higher after preparation with VR MRCP than with conventional MRCP for CHE: 16 (IQR: 13, 22) and 11 (IQR: 11, 18), respectively (p = 0.27). Conclusions: VR MRCP allows for a faster, more accurate understanding of displayed anatomy than conventional MRCP and potentially leads to improved surgical performance in CHE in surgical trainees.

Modern Machine Learning Practices in Colorectal Surgery: A Scoping Review.

OBJECTIVE: The use of machine learning (ML) has revolutionized every domain of medicine. Surgeons are now using ML models for disease detection and outcome prediction with high precision. ML-guided colorectal surgeries are more efficient than conventional surgical procedures. The primary aim of this paper is to provide an overview of the latest research on "ML in colorectal surgery", with its viable applications. METHODS: PubMed, Google Scholar, Medline, and Cochrane library were searched. RESULTS: After screening, 27 articles out of 172 were eventually included. Among all of the reviewed articles, those found to fit the criteria for inclusion had exclusively focused on ML in colorectal surgery, with justified applications. We identified existing applications of ML in colorectal surgery. Additionally, we discuss the benefits, risks, and safety issues. CONCLUSIONS: A better, more sustainable, and more efficient method, with useful applications, for ML in surgery is possible if we and data scientists work together to address the drawbacks of the current approach. Potential problems related to patients' perspectives also need to be resolved. The development of accurate technologies alone will not solve the problem of perceived unreliability from the patients' end. Confidence can only be developed within society if more research with precise results is carried out.

Identification of TPM2 and CNN1 as Novel Prognostic Markers in Functionally Characterized Human Colon Cancer-Associated Stromal Cells.

Stromal infiltration is associated with poor prognosis in human colon cancers. However, the high heterogeneity of human tumor-associated stromal cells (TASCs) hampers a clear identification of specific markers of prognostic relevance. To address these issues, we established short-term cultures of TASCs and matched healthy mucosa-associated stromal cells (MASCs) from human primary colon cancers and, upon characterization of their phenotypic and functional profiles in vitro and in vivo, we identified differentially expressed markers by proteomic analysis and evaluated their prognostic significance. TASCs were characterized by higher proliferation and differentiation potential, and enhanced expression of mesenchymal stem cell markers, as compared to MASCs. TASC triggered epithelial-mesenchymal transition (EMT) in tumor cells in vitro and promoted their metastatic spread in vivo, as assessed in an orthotopic mouse model. Proteomic analysis of matched TASCs and MASCs identified a panel of markers preferentially expressed in TASCs. The expression of genes encoding two of them, calponin 1 (CNN1) and tropomyosin beta chain isoform 2 (TPM2), was significantly associated with poor outcome in independent databases and outperformed the prognostic significance of currently proposed TASC markers. The newly identified markers may improve prognostication of primary colon cancers and identification of patients at risk.

From open Ivor Lewis esophagectomy to a hybrid robotic-assisted thoracoscopic approach: a single-center experience over two decades.

PURPOSE: Robotic-assisted procedures are increasingly used in esophageal cancer surgery. We compared postoperative complications and early oncological outcomes following hybrid robotic-assisted thoracoscopic esophagectomy (Rob-E) and open Ivor Lewis esophagectomy (Open-E), performed in a single mid-volume center, in the context of evolving preoperative patient and tumor characteristics over two decades. METHODS: We evaluated prospectively collected data from a single center from 1999 to 2020 including 321 patients that underwent Ivor Lewis esophagectomy, 76 underwent Rob-E, and 245 Open-E. To compare perioperative outcomes, a 1:1 case-matched analysis was performed. Endpoints included postoperative morbidity and 30-day mortality. RESULTS: Preoperative characteristics revealed increased rates of adenocarcinomas and wider use of neoadjuvant treatment over time. A larger number of patients with higher ASA grades were operated with Rob-E. In case-matched cohorts, there were no differences in the overall morbidity (69.7% in Rob-E, 60.5% in Open-E, p value 0.307), highest Clavien-Dindo grade per patient (43.4% vs. 38.2% grade I or II, p value 0.321), comprehensive complication index (median 20.9 in both groups, p value 0.401), and 30-day mortality (2.6% in Rob-E, 3.9% in Open-E, p value 1.000). Similar median numbers of lymph nodes were harvested (24.5 in Rob-E, 23 in Open-E, p value 0.204), and comparable rates of R0-status (96.1% vs. 93.4%, p value 0.463) and distribution of postoperative UICC stages (overall p value 0.616) were observed. CONCLUSIONS: Our study demonstrates similar postoperative complications and early oncological outcomes after Rob-E and Open-E. However, the selection criteria for Rob-E appeared to be less restrictive than those of Open-E surgery.

Therapeutic Potential of the Cyclin-Dependent Kinase Inhibitor Flavopiridol on c-Myc Overexpressing Esophageal Cancer.

Tumors with elevated c-Myc expression often exhibit a highly aggressive phenotype, and c-Myc amplification has been shown to be frequent in esophageal cancer. Emerging data suggests that synthetic lethal interactions between c-Myc pathway activation and small molecules inhibition involved in cell cycle signaling can be therapeutically exploited to preferentially kill tumor cells. We therefore investigated whether exploiting elevated c-Myc expression is effective in treating esophageal cancer with the CDK inhibitor flavopiridol. We found frequent overexpression of c-Myc in human esophageal cancer cell lines and tissues. c-Myc overexpression correlated with accelerated esophageal cancer subcutaneous xenograft tumor growth. Esophageal cancer cells with elevated c-Myc expression were found preferentially more sensitive to induction of apoptosis by the CDK inhibition flavopiridol compared to esophageal cancer cells with lower c-Myc expression. In addition, we observed that flavopiridol alone or in combination with the chemotherapeutic agent nanoparticle albumin-bound paclitaxel (NPT) or in combinations with the targeted agent BMS-754807 significantly inhibited esophageal cancer cell proliferation and subcutaneous xenograft tumor growth while significantly enhancing overall mice survival. These results indicate that aggressive esophageal cancer cells with elevated c-Myc expression are sensitive to the CDK inhibitor flavopiridol, and that flavopiridol alone or in combination can be a potential therapy for c-Myc overexpressing esophageal cancer.

Pathology reporting of pelvic exenteration specimens for locally recurrent rectal cancer.

INTRODUCTION: Reporting of pelvic exenteration specimens for locally recurrent rectal cancer (LRRC) can be challenging for structured pathological analysis and currently, there is a lack of specific guidelines. The aim of this study was to assess the quality of pathology reporting in a cohort of patients who underwent pelvic exenteration for LRRC in a high-volume tertiary unit. MATERIALS AND METHODS: In a retrospective analysis of histopathology reports of consecutive patients who underwent pelvic exenteration for LRRC from 1996 to 2018, the quality of pathology reporting was assessed using the Structure Reporting Protocol for Colorectal Cancer. The primary endpoint was the completeness of pathology reporting, secondary endpoints were the association between the reporting style (narrative versus synoptic), reporting period (the first half versus the second half), as well as the activity of the pathologists with the completeness of pathology reporting. RESULTS: 221 patients who underwent pelvic exenteration for LRRC were included into the study. There was a high variability in completeness of pathology reporting within the cohort, ranging from 9.5% to 100%. Notably, microscopic clearance was reported in only 92.4% of the reports. Overall, a significantly higher rate of completeness was observed in synoptic reports when compared to narrative reports and in more recent compared to earlier reports. There was no significant association between the activity of pathologists and the completeness of reporting. CONCLUSIONS: This study shows a significant variability in the quality of reporting in pelvic exenteration for LRRC. The use of synoptic reporting clearly resulted in more complete reports.

Dynamic Serosal Perfusion Assessment during Colorectal Resection Using Visible Light Spectroscopy.

INTRODUCTION: Anastomotic leakage (AL) in colorectal surgery occurs with an incidence of up to 20%. Bowel perfusion is deemed to be one of the most important factors for anastomotic healing. However, not much is known about its variability during colorectal surgery and its impact on the outcome. Therefore, this study aims to evaluate serosal oxygen saturation patterns during colorectal resections with visible light spectroscopy (VLS). MATERIALS AND METHODS: Bowel perfusion in patients undergoing left-sided colorectal resections was assessed at different timepoints during surgery using VLS on the colonic serosa. The primary outcome parameter was serosal oxygen saturation (StO2) at the anastomosis during different timepoints of surgery. RESULTS: We included 50 patients who underwent colorectal resection for bowel cancer (58%) and diverticular disease (34%). StO2 at the proximal site of the anastomosis increased significantly throughout the surgery (mean difference 3.61%; 95% CI -6.22 to -1.00; p = 0.008). However, aberrancy from this identified perfusion pattern had no impact on the postoperative outcome. CONCLUSION: During colorectal resections, we could demonstrate an increase of the colonic StO2 throughout surgery. Appearance of AL was not associated with lower StO2, underlining the multifactorial genesis of developing AL.

Nestin and CD34 expression in colorectal cancer predicts improved overall survival.

BACKGROUND: Nestin, a class VI intermediate filament protein of the cytoskeleton, and CD34, a transmembrane phosphoglycoprotein, are markers of progenitor cells. This study aimed to evaluate their expression and clinical significance in colorectal cancer. METHODS: A clinically annotated tissue microarray, including 599 patients with colorectal cancer, was analyzed by immunohistochemistry. Furthermore, nestin and CD34 correlations with HIF-1a and a panel of cytokines and chemokines were assessed using quantitative reverse transcription PCR and The Cancer Genome Atlas dataset. RESULTS: Expression of nestin and CD34 was observed only in the tumor stroma. Patients displaying high expression of nestin and CD34 demonstrated higher rates of T1 and T2 tumors (p = .020), lower vascular invasion (p < .001) and improved 5-year overall survival (65%; 95% CI = 55-73 vs 45%; 95% CI = 37-53) after adjusting for clinicopathological characteristics (HR: 0.67; 95% CI = 0.46-0.96). A moderate to strong correlation (r = 0.37-0.78, p < .03) of nestin and CD34 was demonstrated for the following markers; HIF-1α, CD4, CD8, FOXP3, IRF1, GATA3, CCL2, CCL3, CXCL12 and CCL21. CONCLUSIONS: Combined expression of nestin and CD34 expression is associated with better overall survival possibly by modulating a favorable immune response.

Infiltration by IL22-Producing T Cells Promotes Neutrophil Recruitment and Predicts Favorable Clinical Outcome in Human Colorectal Cancer.

Immune cell infiltration in colorectal cancer effectively predicts clinical outcome. IL22, produced by immune cells, plays an important role in inflammatory bowel disease, but its relevance in colorectal cancer remains unclear. Here, we addressed the prognostic significance of IL22+ cell infiltration in colorectal cancer and its effects on the composition of tumor microenvironment. Tissue microarrays (TMA) were stained with an IL22-specific mAb, and positive immune cells were counted by expert pathologists. Results were correlated with clinicopathologic data and overall survival (OS). Phenotypes of IL22-producing cells were assessed by flow cytometry on cell suspensions from digested specimens. Chemokine production was evaluated in vitro upon colorectal cancer cell exposure to IL22, and culture supernatants were used to assess neutrophil migration in vitro Evaluation of a testing (n = 425) and a validation TMA (n = 89) revealed that high numbers of IL22 tumor-infiltrating immune cells were associated with improved OS in colorectal cancer. Ex vivo analysis indicated that IL22 was produced by CD4+ and CD8+ polyfunctional T cells, which also produced IL17 and IFNγ. Exposure of colorectal cancer cells to IL22 promoted the release of the neutrophil-recruiting chemokines CXCL1, CXCL2, and CXCL3 and enhanced neutrophil migration in vitro Combined survival analysis revealed that the favorable prognostic significance of IL22 in colorectal cancer relied on the presence of neutrophils and was enhanced by T-cell infiltration. Altogether, colorectal cancer-infiltrating IL22-producing T cells promoted a favorable clinical outcome by recruiting beneficial neutrophils capable of enhancing T-cell responses.

Low Expression of Programmed Death 1 (PD-1), PD-1 Ligand 1 (PD-L1), and Low CD8+ T Lymphocyte Infiltration Identify a Subgroup of Patients With Gastric and Esophageal Adenocarcinoma With Severe Prognosis.

Prognosis of gastric and esophageal cancer is poor and treatment improvements are needed. Programmed cell death 1 receptor (PD-1) interaction with its ligand PD-L1 in tumor micro-environment promotes immune tolerance and blocking monoclonal antibodies have entered clinical practice. However, clinical significance of PD-1 and PD-L1 expression in gastric and esophageal adenocarcinomas, particularly in non-Asian patients, is still unclear. Three tissue microarrays including 190 clinically annotated esophageal (n = 31) and gastric (n = 159) adenocarcinomas and 58 paired mucosa specimens, were stained with PD-1, PD-L1, and CD8-specific reagents in indirect immunohistochemistry assays. PD-L1 expression was detectable in 23.2% of cancer specimens. High PD-1 expression was detectable in 37.3% of cases and high CD8+ infiltration in 76%. PD-L1 and high PD1 expression significantly correlated with each other (r s = 0.404, P < 0.0001) and both significantly correlated with CD8+ infiltration (r s = 0.435, P = 0.0003, and r s = 0.444; P = 0.0004, respectively). CD8+ lymphocyte infiltration correlated with improved survival in univariate (P = 0.009), but not multivariate analysis. Most interestingly, multivariate analysis and Kaplan-Meier curves indicate that combined low PD-1/PD-L1 expression and low CD8+ lymphocyte infiltration significantly correlate with poor prognosis. Our data document the clinical significance of a microenvironmental signature including PD-1/PD-L1 expression and CD8+ lymphocyte infiltration in gastric and esophageal adenocarcinomas and contribute to identify a patients' subset requiring more aggressive peri-operative treatments.

Tumor Infiltration by OX40+ Cells Enhances the Prognostic Significance of CD16+ Cell Infiltration in Colorectal Cancer.

OBJECTIVES: Analysis of tumor immune infiltration has been suggested to outperform tumor, node, metastasis staging in predicting clinical course of colorectal cancer (CRC). Infiltration by cells expressing OX40, a member of the tumor necrosis factor receptor family, or CD16, expressed by natural killer cells, monocytes, and dendritic cells, has been associated with favorable prognosis in patients with CRC. We hypothesized that assessment of CRC infiltration by both OX40+ and CD16+ cells might result in enhanced prognostic significance. METHODS: Colorectal cancer infiltration by OX40 and CD16 expressing cells was investigated in 441 primary CRCs using tissue microarrays and specific antibodies, by immunohistochemistry. Patients' survival was evaluated by Kaplan-Meier and log-rank tests. Multivariate Cox regression analysis, hazard ratios, and 95% confidence intervals were also used to evaluate prognostic significance of OX40+ and CD16+ cell infiltration. RESULTS: Colorectal cancer infiltration by OX40+ and CD16+ cells was subclassified into 4 groups with high or low infiltration levels in all possible combinations. High levels of infiltration by both OX40+ and CD16+ cells were associated with lower pT stage, absence of peritumoral lymphocytic (PTL) inflammation, and a positive prognostic impact. Patients bearing tumors with high infiltration by CD16+ and OX40+ cells were also characterized by significantly longer overall survival, as compared with the other groups. These results were confirmed by analyzing an independent validation cohort. CONCLUSIONS: Combined infiltration by OX40+ and CD16+ immune cells is an independent favorable prognostic marker in CRC. The prognostic value of CD16+ immune cell infiltration is significantly improved by the combined analysis with OX40+ cell infiltration.

High prevalence of asymptomatic internal hernias after laparoscopic anterior resection in a retrospective analysis of postoperative computed tomography.

PURPOSE: Internal hernia (IH) after laparoscopic left-sided colorectal resection (small bowel herniating underneath the neo-descending colon) can be a potentially devastating complication, resulting in acute small bowel obstruction or ischemia. IH has been described as a rare occurrence in a few retrospective case series; however, patients undergoing laparoscopic resection seem to be more prone to this complication. We assessed the prevalence of IH in a large cohort of patients who had undergone laparoscopic left-sided colorectal resection for colon or rectal cancer (CRC). METHODS: A database of consecutive patients at a single institution from 2012 to 2017 was reviewed. Postoperative abdominal computed tomography (CT) scans performed for routine cancer follow-up between 3 and 36 months after surgery were assessed retrospectively. RESULTS: During the study period, 276 patients had undergone anterior resection for CRC, with 206 (75%) having been performed laparoscopically. A total of 198 eligible patients were identified, and a follow-up CT scan was available in 105 (53%) of these patients (median time to CT 10 months, range 3-34). Only one of the 198 (0.5%) patients presented with an acute small bowel obstruction secondary to an IH during follow-up. However, the prevalence of asymptomatic IH was noted to be much higher in the postoperative CT scans occurring in 22 of 105 (21%) patients. CONCLUSION: Asymptomatic IH after laparoscopic left-sided colorectal resection is common. Given the potential risk of acute small bowel obstruction and ischemia, routine closure of the mesenteric defect should be considered.

Infiltration by myeloperoxidase-positive neutrophils is an independent prognostic factor in breast cancer.

PURPOSE: Myeloperoxidase (MPO) is an enzyme secreted by neutrophil granulocytes as a result of phagocytosis during inflammation. In colorectal cancer, tumour infiltration by MPO expressing cells has been shown to be independently associated with a favourable prognosis. In this study, we explored the role of MPO-positive cell infiltration and its prognostic significance in invasive breast cancer. METHODS: We performed immunohistochemical staining for MPO on multiple tissue microarrays comprising a total of 928 human breast cancer samples with detailed clinical-pathological annotation and outcome data. RESULTS: MPO-positive cell infiltration (≥ 5 cells/tissue punch) was found in 150 (16%) of the 928 evaluable breast cancer cases. In univariate survival analyses, infiltration by MPO-positive cells was associated with a significantly better overall survival (p < 0.001). In subset univariate analyses, the infiltration by MPO-positive cells was associated with significantly better overall survival in the Luminal B/HER2-negative subtype (p = 0.005), the HER2 enriched subtype (p = 0.011), and the Triple Negative subtype (p < 0.001). In multivariate analysis, MPO expression proved to be an independent prognostic factor for improved overall survival (p < 0.001). CONCLUSIONS: This is the first study to show that infiltration of MPO-positive cells is an independent prognostic biomarker for improved overall survival in human breast cancer.

Expression of RET is associated with Oestrogen receptor expression but lacks prognostic significance in breast cancer.

BACKGROUND: The Rearranged during Transfection (RET) protein is overexpressed in a subset of Estrogen Receptor (ER) positive breast cancer, with both signalling pathways functionally interacting. This cross-talk plays a pivotal role in the resistance of breast cancer cells to anti-endocrine therapies, and RET expression is assumed to correlate with poor prognosis based on findings in small patient cohorts. The aim of our study was to investigate the impact of RET expression on patient outcome in human breast cancer. METHODS: We performed an immunohistochemical analysis of RET protein expression on a tissue microarray encompassing 990 breast cancer patients and correlated its expression with clinicopathological parameters and survival data. RESULTS: Expression of RET was detected in 409 out of 990 cases (41.3%). RET and ER expression significantly correlated (p < 0.0001). The Luminal B HER2-positive subtype showed the highest expression rate (48.9%). In univariate and multivariate survival analyses, RET expression had no impact on overall survival. CONCLUSION: We confirmed the co-expression of RET and ER, but we did not find RET expression to be an independent prognostic factor in human breast cancer. Clinical trials with newly developed RET inhibitors are needed to evaluate if RET inhibition has a beneficial impact on patient survival in ER positive breast cancer.

Maintenance of Primary Human Colorectal Cancer Microenvironment Using a Perfusion Bioreactor-Based 3D Culture System.

Colorectal cancer (CRC) is a leading cause of cancer-related death. Conventional chemotherapeutic regimens have limited success rates, and a major challenge for the development of novel therapies is the lack of adequate in vitro models. Nonmalignant mesenchymal and immune cells of the tumor microenvironment (TME) are known to critically affect CRC progression and drug responsiveness. However, tumor drug sensitivity is still evaluated on systems, such as cell monolayers, spheroids, or tumor xenografts, which typically neglect the original TME. Here, it is investigated whether a bioreactor-based 3D culture system can preserve the main TME cellular components in primary CRC samples. Freshly excised CRC fragments are inserted between two collagen scaffolds in a "sandwich-like" format and cultured under static or perfused conditions up to 3 d. Perfused cultures maintain tumor tissue architecture and densities of proliferating tumor cells to significantly higher extents than static cultures. Stromal and immune cells are also preserved and fully viable, as indicated by their responsiveness to microenvironmental stimuli. Importantly, perfusion-based cultures prove suitable for testing the sensitivity of primary tumor cells to chemotherapies currently in use for CRC. Perfusion-based culture of primary CRC specimens recapitulates TME key features and may allow assessment of tumor drug response in a patient-specific context.