Cancer Resection Surgery Research Articles

Short- and long-term outcomes as well as anal function of transanal natural orifice specimen extraction surgery versus conventional laparoscopic surgery for sigmoid colon or rectal cancer resection: a retrospective study with over 5-year follow-up.

IntroductionTo date, long-term safety including functional outcomes of transanal natural orifice specimen extraction surgery (NOSES) for colorectal cancer resection has not been confirmed.AimTo explore the short- and long-term outcomes as well as anal function of transanal NOSES versus conventional laparoscopic surgery for sigmoid colon or rectal cancer resection.Material and methodsA retrospective review of data from a prospectively maintained database was performed to analyze the data of 69 patients who underwent transanal NOSES for sigmoid colon or rectal cancer resections and another 69 matched patients who underwent conventional laparoscopic (CL) surgery. Anal function of patients was evaluated using the Wexner fecal incontinence scale postoperatively.ResultsTransanal NOSES resulted in faster recovery of intestinal function, shorter postoperative length of stay, less incisional pain, fewer postoperative complications and shorter scars than CL surgery (p < 0.05). The two groups had similar overall survival (p = 0.863) and disease-free survival (p = 0.961). Wexner scores of the NOSES group at 1, 3 and 6 months after surgery were higher than in the CL group (p < 0.05), and there was no difference between the two groups at 12, 18 and 24 months after surgery.ConclusionsTransanal NOSES achieves similar survival outcomes to CL surgery. Transanal NOSES has the advantages of faster recovery, shorter postoperative hospital stay, less incisional pain, shorter scars, etc. However, transanal NOSES can indeed impair anal function, needing more attention.

Robotic-Assisted vs. Standard Laparoscopic Surgery for Rectal Cancer Resection: A Systematic Review and Meta-Analysis of 19,731 Patients.

Simple SummarySurgery remains a mainstay of combined modality treatment at patients with rectal cancer; however, there is a growing interest in using laparoscopic techniques (LG); including robotic-assisted techniques (RG). Therefore, we have prepared a meta-analysis of the literature regarding the safety and efficacy of robotic versus laparoscopic approaches in patients undergoing curative surgery for rectal cancer. The results indicate a number of advantages of RG in terms of both safety and efficacy. Operative time in the RG group was shorter and associated with a statistically significantly lower conversion of the procedure to open surgery. RG technique provided a shorter duration of hospital stay and lowered urinary risk retention. No differences were found between these techniques regarding TNM stage; N stage or lymph nodes harvested. Survival to hospital discharge or 30-day overall survival rate was 99.6% in RG vs. 98.8% for LG.Robotic-assisted surgery is expected to have advantages over standard laparoscopic approach in patients undergoing curative surgery for rectal cancer. PubMed, Cochrane Library, Web of Science, Scopus and Google Scholar were searched from database inception to 10 November 2021, for both RCTs and observational studies comparing robotic-assisted versus standard laparoscopic surgery for rectal cancer resection. Where possible, data were pooled using random effects meta-analysis. Forty-Two were considered eligible for the meta-analysis. Survival to hospital discharge or 30-day overall survival rate was 99.6% for RG and 98.8% for LG (OR = 2.10; 95% CI: 1.00 to 4.43; p = 0.05). Time to first flatus in the RG group was 2.5 ± 1.4 days and was statistically significantly shorter than in LG group (2.9 ± 2.0 days; MD = −0.34; 95%CI: −0.65 to 0.03; p = 0.03). In the case of time to a liquid diet, solid diet and bowel movement, the analysis showed no statistically significant differences (p > 0.05). Length of hospital stay in the RG vs. LG group varied and amounted to 8.0 ± 5.3 vs. 9.5 ± 10.0 days (MD = −2.01; 95%CI: −2.90 to −1.11; p < 0.001). Overall, 30-days complications in the RG and LG groups were 27.2% and 19.0% (OR = 1.11; 95%CI: 0.80 to 1.55; p = 0.53), respectively. In summary, robotic-assisted techniques provide several advantages over laparoscopic techniques in reducing operative time, significantly lowering conversion of the procedure to open surgery, shortening the duration of hospital stay, lowering the risk of urinary retention, improving survival to hospital discharge or 30-day overall survival rate.

Oral and Parenteral vs. Parenteral Antibiotic Prophylaxis for Patients Undergoing Laparoscopic Colorectal Resection: An Intervention Review with Meta-Analysis.

This study aims to systematically assess the efficacy of parenteral and oral antibiotic prophylaxis compared to parenteral-only prophylaxis for the prevention of surgical site infection (SSI) in patients undergoing laparoscopic surgery for colorectal cancer resection. Published and unpublished randomized clinical trials comparing the use of oral and parenteral prophylactic antibiotics vs. parenteral-only antibiotics in patients undergoing laparoscopic colorectal surgery were collected searching electronic databases (MEDLINE, CENTRAL, EMBASE, SCIENCE CITATION INDEX EXPANDED) without limits of date, language, or any other search filter. The outcomes included SSIs and other infectious and noninfectious postoperative complications. Risk of bias was assessed using the Cochrane revised tool for assessing risk of bias in randomized trials (RoB 2). A total of six studies involving 2252 patients were finally included, with 1126 cases in the oral and parenteral group and 1126 cases in the parenteral-only group. Meta-analysis results showed a statistically significant reduction of SSIs (OR 0.54, 95% CI 0.40 to 0.72; p < 0.0001) and anastomotic leakage (OR 0.55, 95% CI 0.33 to 0.91; p = 0.02) in the group of patients receiving oral antibiotics in addition to intravenous (IV) antibiotics compared to IV alone. Our meta-analysis shows that a combination of oral antibiotics and intravenous antibiotics significantly lowers the incidence of SSI compared with intravenous antibiotics alone.

O-OGC03 Real-time tracking and classification of tumour and non-tumour tissue in upper gastrointestinal cancer specimens using diffuse reflectance spectroscopy

Abstract Background Diffuse reflectance spectroscopy (DRS) is a technique that allows discrimination of normal and abnormal tissue based on spectral data. It is a promising technique for cancer margin assessment. However, application in a clinical setting is limited by the inability of DRS to mark the tissue that has been scanned and its lack of continuous real-time spectral measurements. This aim of this study was to develop a real-time tracking system to enable localisation of the tip of a handheld DRS probe to aid classification of tumour and non-tumour tissue. Methods A coloured marker was attached to the DRS fibre probe and was detected using colour segmentation. A Kalman filter was used to estimate the probe’s tip position during scanning of the tissue specimen. In this way, the system was robust to partial occlusion allowing real-time detection and tracking. Supervised classification algorithms were used for the discrimination between tumour and non-tumour tissue, and evaluated in terms of overall accuracy, sensitivity, specificity, and the area under the curve (AUC). A live augmented view with all the tracked and classified optical biopsy sites were presented, providing visual feedback to the surgeons. Results A green coloured marker was successfully used to track the DRS probe. The measured root mean square error of probe tip tracking was 1.18±0.58mm and 1.05±0.28mm for the X and Y directions, respectively, whilst the maximum measured error was 1.76mm. Overall, 47 distinct sets of tumour and non-tumour tissue data were recorded through real-time tracking of ex vivo oesophageal and gastric tissue. The overall diagnostic accuracy of the system to classify tumour and non-tumour tissue in real-time was 94% for stomach and 96% for the oesophagus. Conclusions We have been able to successfully develop a real-time tracking system for a DRS probe when used on stomach and oesophageal tissue for tumour detection, and the accuracy derived demonstrates the strength and clinical value of the technique. The method allows real-time tracking and classification with short data acquisition time to aid margin assessment in cancer resection surgery.

EP.TU.582Impact of enteral prophylactic antibiotic course on the trends of inflammatory markers following laparoscopic colorectal cancer surgery

Abstract Introduction The study aimed to assess the effect of oral prophylactic antibiotic (OAB) with mechanical bowel preparation (MBP) on the serial measurement of postoperative inflammatory markers and clinical outcomes of the patients undergoing laparoscopic colorectal cancer resection surgery. Methods A retrospective data collection was carried out from January 2019 to March 2020 for the patients undergoing laparoscopic colorectal cancer resection. Daily measurements of inflammatory markers were obtained upto 7 days following surgery. The measurements of inflammatory markers were compared between patients who received a 1 week course of OAB along with MBP to those who only received MBP. Results There were a total of 110 patients that were divided into 2 groups: patients who received OAB and MBP (n = 44, 40%) and those who had MBP only (n = 66, 60%). There was no significant difference between the patient characteristics and preoperative staging of the cancer between the 2 groups. The overall length of stay was significantly lower in the patients who received OAB (9.09 days [SD 7.94] vs. 6.63 days [SD 4.96], P 0.02). The patients with OAB and MAP had persistently and significantly low levels of white blood cell count, CRP, and neutrophil count throughout the postoperative period as compared to those who only had MBP. Conclusion The study demonstrated reduction in serial measurement of inflammatory markers throughout postoperative stay for the patients receiving preoperative OAB. The use of OAB helps in physiological recovery of the patient by reducing the inflammatory process postoperatively.

SP7.1.6 Using Diffuse Reflectance Spectroscopy (DRS) to Identify Tumour and Non-tumour Tissue in Upper Gastrointestinal Specimens

Abstract Aim Cancers of the upper gastrointestinal (GI) tract remain a major contributor to the global cancer risk. Surgery aims to completely resect tumour with clear margins, whilst preserving as much surrounding tissue. Diffuse reflectance spectroscopy (DRS) is a novel technique that presents a promising advancement in cancer diagnosis. We have developed a novel DRS system with tracking capability. Our aim is to classify tumour and non-tumour GI tissue in real-time using this device to aid intra-operative analysis of resection margins. Method An ex-vivo study was undertaken in which data was collected from consecutive patients undergoing upper GI cancer resection surgery between August 2020- January 2021. A hand-held DRS probe and tracking system was used on normal and cancerous tissue to obtain spectral information. After acquisition of all spectra, a classification system using histopathology results was created. A user interface was developed using Python 3.6 and Qt5. A support vector machine was used to classify the results. Results The data included 4974 normal spectra and 2108 tumour spectra. The overall accuracy of the DRS probe in differentiating normal versus tumour tissue was 88.08% for the stomach (sensitivity 84.8%, specificity 89.3%), and 91.42% for the oesophagus (sensitivity 76.3%, specificity 98.9%). Conclusion We have developed a successful DRS system with tracking capability, able to process thousands of spectra in a small timeframe, which can be used in real-time to distinguish tumour and non-tumour tissue. This can be used for intra-operative decision-making during upper GI cancer surgery to help select the best resection plane.

Risk factors associated with postoperative complications after liver cancer resection surgery in western China

ObjectivesPostoperative complications increase the workload of nursing staff as well as the financial and mental distress suffered by patients. The objective of this study is to identify clinical factors associated with postoperative complications after liver cancer resection surgery.MethodsData from liver cancer resections occurring between January 1st, 2019 to December 31st, 2019 was collected from the Department of Liver Surgery in West China Hospital of Sichuan University. The Kruskal–Wallis test and logistic regression were used to perform single-factor analysis. Stepwise logistic regression was used for multivariate analysis. Models were established using R 4.0.2 software.ResultsBased on data collected from 593 cases, the single-factor analysis determined that there were statistically significant differences in BMI, incision type, incision length, duration, incision range, and bleeding between cases that experienced complications within 30 days after surgery and those did not. Stepwise logistic regression models based on Kruskal–Wallis test and single-factor logistic regression determined that BMI, incision length, and duration were the primary factors causing complications after liver resection. The adjust OR of overweight patients and patients with obesity (stage 1) compared to low weight patients were 0.12 (95% CI:0.02–0.72) with p = 0.043 and 0.18 (95% CI:0.03–1.00) with p = 0.04, respectively. An increase of 1 cm in incision length increased the relative risk by 13%, while an increase of 10 min in surgical duration increased the relative risk by 15%.ConclusionsThe risk of postoperative complications after liver resection can be significantly reduced by controlling factors such as bleeding, incision length, and duration of the surgery.

Minimally Invasive Surgical Approach for Esophageal Adenocarcinoma in a Patient with Previous Belsey Mark IV Fundoplication: A Case Report

Background: Historically, the management for recurrent or persistent Gastro-esophageal reflux disease included selective vagotomy and fundoplication. Despite these surgical interventions, the risk of Barrett’s esophagus (BE) and subsequent malignant transformation remains, requiring cancer resection surgery. We present a case of a patient with a gastro-esophageal junction (GEJ) adenocarcinoma, who underwent a pediatric thoracotomy and Belsey Mark IV fundoplication, and was successfully treated by Laparoscopic Ivor-Lewis Esophagectomy (LILE). Case Presentation: This 64-year-old gentleman with BE and GEJ adenocarcinoma was previously deemed unsuitable for curative surgery due to clinical staging indicating a tumor length of 10cm and suspected invasion of the left pleura. Further staging by Endoscopic ultrasound indicated no evidence of pleural invasion with the distal esophageal thickening in keeping with his previous Belsey Mark IV fundoplication. He underwent neo-adjuvant chemotherapy and a subsequent LILE with complete laparoscopic reversion of the gastric fundoplication without injury to the gastroepiploic artery or fundus. There was sufficient preservation of conduit length to enable a tension free hand-sewn anastomosis with an uneventful post-operative recovery. Final histopathology confirmed ypT1 ypN0 moderately differentiated adenocarcinoma with R0 resection margins. The patient has completed 24 months of cancer recurrence free surveillance. Conclusion: We describe the successful management of a patient by LILE on a background of previous hiatal fundoplication surgery, previously refused curative surgery. We highlight the importance of EUS as a staging modality for such cases showing invasive disease to increase the final clinical staging accuracy. We suggest a minimally invasive approach may be utilized for successful re-do hiatal dissection as an alternative to a conventional open surgery.

Machine-Learning Assisted Discrimination of Precancerous and Cancerous from Healthy Oral Tissue Based on Multispectral Autofluorescence Lifetime Imaging Endoscopy.

Simple SummaryComplete resection of dysplastic and malignant tissue improves overall survival and delays cancer recurrence in oral cancer patients; however, intraoperative surgical margin assessment is limited to visual inspection and palpation, making it difficult to achieve total resection. There is currently no tool capable of providing real-time, accurate, and continuous margin-assessment guidance during oral cancer resection surgery. Multispectral autofluorescence lifetime imaging (maFLIM) is a label-free imaging modality that enables quantifying a plurality of metabolic and compositional autofluorescence biomarkers of oral dysplasia and cancer. We have developed and validated a machine-learning assisted computer aided detection (CAD) system for automated discrimination of dysplastic and cancerous from healthy oral tissue based on in vivo widefield maFLIM endoscopy data. This CAD system can be potentially embedded into maFLIM endoscopes to enable continuous in situ detection of positive margins during oral cancer resection surgery, thus facilitating maximal tumor resection and improving surgical outcomes for oral cancer patients.Multispectral autofluorescence lifetime imaging (maFLIM) can be used to clinically image a plurality of metabolic and biochemical autofluorescence biomarkers of oral epithelial dysplasia and cancer. This study tested the hypothesis that maFLIM-derived autofluorescence biomarkers can be used in machine-learning (ML) models to discriminate dysplastic and cancerous from healthy oral tissue. Clinical widefield maFLIM endoscopy imaging of cancerous and dysplastic oral lesions was performed at two clinical centers. Endoscopic maFLIM images from 34 patients acquired at one of the clinical centers were used to optimize ML models for automated discrimination of dysplastic and cancerous from healthy oral tissue. A computer-aided detection system was developed and applied to a set of endoscopic maFLIM images from 23 patients acquired at the other clinical center, and its performance was quantified in terms of the area under the receiver operating characteristic curve (ROC-AUC). Discrimination of dysplastic and cancerous from healthy oral tissue was achieved with an ROC-AUC of 0.81. This study demonstrates the capabilities of widefield maFLIM endoscopy to clinically image autofluorescence biomarkers that can be used in ML models to discriminate dysplastic and cancerous from healthy oral tissue. Widefield maFLIM endoscopy thus holds potential for automated in situ detection of oral dysplasia and cancer.

Journal-related Activities and Other Special Activities at the 2021 American Society of Anesthesiologists Meeting

Journal-related Activities and Other Special Activities at the 2021 American Society of Anesthesiologists Meeting

Outcomes after pulmonary lobectomy in patients with history of head and neck carcinoma

BackgroundWe aimed to determine whether video assisted thoracic surgery (VATS) was associated with better short-term outcomes compared to open approach and to determine factors affecting long term survival after lobectomy in patients with history of head and neck carcinoma (HNC). MethodsWe performed a retrospective monocentric analysis of consecutive standard lobectomies performed for lung cancer in patients with history of HNC between 2010 and 2017. Patients’ characteristics, surgical approach, lung tumor histology, in-hospital and 90-days morbi-mortality and long term survival were analyzed; VATS and open lobectomy groups were compared. ResultsAmong 85 patients, 52 underwent an open lobectomy and 33 a VATS lobectomy. There was no significant difference between the two groups regarding age, preoperative characteristics, pathology and stage of lung cancer (All p = NS). In the VATS group, there was a significant decrease in proportion of in-hospital postoperative life-threatening complications requiring hospitalization in intensive care unit (12/52 vs. 1/33, p = 0.01). The 90-days postoperative comprehensive complication index was significantly increased in the open thoracotomy group (median (interquartile range):33.5 (0-53.5) vs. 8.7 (0-34.1), p = 0.018). Long term survival was not significantly different between the 2 groups - Log-rank test comparison, p = NS). Patients with squamous cell histology presented a significantly poorer survival (both Log-rank test comparison, p < 0.01). ConclusionsMinimally invasive approach improved in-hospital and 90-days outcomes compared to open surgery for lung cancer resection in patients with history of HNC. The poor long-term results in patients with squamous cell carcinoma highlight the need to improve therapeutic strategies for this subset of patients.

Impact of enteral prophylactic antibiotics on the trends of inflammatory markers following laparoscopic colorectal cancer surgery: A retrospective and prospective Cohort Study

BackgroundThe study aimed to assess the effect of oral prophylactic antibiotics (OAB) with mechanical bowel preparation (MBP) on the serial measurement of postoperative inflammatory markers and clinical outcomes of the patients undergoing laparoscopic colorectal cancer resection surgery. MethodsA retrospective and prospective data collection was carried out from January 2019 to March 2020 for the patients undergoing laparoscopic colorectal cancer resection. Daily measurements of inflammatory markers were obtained up to 7 days following surgery. The measurements of inflammatory markers were compared between patients who received a 1 week course of OAB along with MBP to those who only received MBP. ResultsThere were a total of 110 patients that were divided into 2 groups: patients who received OAB and MBP (n = 44, 40%) and those who had MBP only (n = 66, 60%). There was no significant difference between the patient characteristics and preoperative staging of the cancer between the 2 groups. The overall length of stay was significantly lower in the patients who received OAB (9.09 days [SD 7.94] vs. 6.63 days [SD 4.96], P 0.02). The patients with OAB and MAP had persistently and significantly low levels of white blood cell count, CRP, and neutrophil count throughout the postoperative period as compared to those who only had MBP. ConclusionThe study demonstrated reduction in serial measurement of inflammatory markers throughout postoperative stay for the patients receiving preoperative OAB. The use of OAB helps in physiological recovery of the patient by reducing the inflammatory process postoperatively.

The NEAT Study (Novel ElectroAcupuncture) - Electroacupuncture After Laparoscopic Colon Cancer Resection: Thinking Outside The Box. Study Protocol.

Introduction: Colorectal cancer is the second leading cause of cancer-related death in the US; complete surgical resection is the only curative treatment for non-metastatic colorectal cancer (NMCC). Postoperative ileus (POI) frequently increases patient morbidity and healthcare costs. Enhanced recovery after surgery (ERAS) protocol is the standard of care in most institutions and has been shown to reduce postoperative complications, but there is no a completely effective treatment for this condition. Studies suggest that electroacupuncture (EA) can improve gastrointestinal tract function after surgery. Objective: We aim to determine if including EA in the standard treatment of POI decreases the time to the first defecation, enhancing the return of normal bowel function after colon resection for NMCC. Methods: We propose a phase II, single-center, randomized, triple-blinded, sham-controlled trial with two parallel arms and a 1:1 allocation ratio. Patients 40-80 years of age diagnosed with NMCC scheduled to undergo laparoscopic surgery for colon cancer resection will be included. The arms will be EA + standard treatment and sham EA + standard treatment. The standard treatment will follow the ERAS protocol. Discussion: This will be the first randomized clinical trial to evaluate the impact of using EA along with the ERAS protocol for POI. This intervention may reduce patient morbidity and improve healthcare costs associated with the disease.

Perineal eventration after abdominoperineal resection for rectal cancer: anatomical, surgical and clinico-pathological landmarks.

Perineal eventration (PE) is a rare complication after the lower rectal cancer resection surgery, affecting the quality of life of the patient. In 5.5 years of evolution, out of 620 patients with rectal cancer treated by curative surgery, 176 patients with lower ampullary rectal cancer treated by abdominoperineal resection (APR) with the closure of the defect by direct suture of the perineal floor were selected. Ten (5.6%) of them were diagnosed with PE. This paper shows the results of a retrospective study, which compares the clinico-pathological and therapeutic aspects of a subgroup of 166 patients (subgroup I) with APR without PE and a subgroup of 10 patients (subgroup II) with PE. Starting from the question of whether aspects can influence the evolution of PE, we aimed to investigate the similarities and differences between these two groups, from the histological, clinical and therapeutic points of view. Regarding the tumor, node, metastasis (TNM) staging, we encountered the following aspects: for the subgroup II with PE, pT3 predominated, stages N0 and N1 were equal (50%) and the absence of metastases (M0) was found in all cases; in subgroup I, pT3 and N0 also predominated, followed by N1 and N2, and for stage M, M0 is predominant, followed by M1. For the clinical profile of the PE group, the symptoms were characteristic, with the presence of the usual triggering factors [hysterectomy, radiochemotherapy and wide resection surgery – extralevatorial APR]. The therapeutic approach revealed various aspects, including plastic surgery procedures (direct closure, meshes, flaps) used in pelvic reconstruction. The accurate surgical technique applied in order to achieve oncological safety allowed for a longer survival, which favored the appearance of PE in addition to the other favoring factors. Our results underlined the clinico-pathological profile of the two subgroups, without being able to establish a correlation with the appearance and evolution of PE. However, the clinico-pathological risk factors for this condition are not yet fully defined. Therefore, reports based on the experience in the diagnosis and treatment of PE should bring valuable data, aiming to create the knowledge framework for prevention.

An &lt;em&gt;In Vivo&lt;/em&gt; Mouse Model of Total Intravenous Anesthesia During Cancer Resection Surgery

This paper describes a method for modeling total intravenous anesthesia (TIVA) during cancer resection surgery in mice. The goal is to replicate key features of anesthesia delivery to patients with cancer. The method allows investigation of how anesthetic technique affects cancer recurrence after resection surgery.

An In Vivo Mouse Model of Total Intravenous Anesthesia during Cancer Resection Surgery.

Anesthesia is a routine component of cancer care that is used for diagnostic and therapeutic procedures. The anesthetic technique has recently been implicated in impacting long-term cancer outcomes, possibly through modulation of adrenergic-inflammatory responses that impact cancer cell behavior and immune cell function. Emerging evidence suggests that propofol-based total intravenous anesthesia (TIVA) may be beneficial for long-term cancer outcomes when compared to inhaled volatile anesthesia. However, the available clinical findings are inconsistent. Preclinical studies that identify the underlying mechanisms involved are critically needed to guide the design of clinical studies that will expedite insight. Most preclinical models of anesthesia have been extrapolated from the use of anesthesia in in vivo research and are not optimally designed to study the impact of anesthesia itself as the primary endpoint. This paper describes a method for delivering propofol-TIVA anesthesia in a mouse model of breast cancer resection that replicates key aspects of clinical delivery in cancer patients. The model can be used to study mechanisms of action of anesthesia on cancer outcomes in diverse cancer types and can be extrapolated to other non-cancer areas of preclinical anesthesia research.

O65: C-MET PROTEIN AS A COLORECTAL CANCER BIOMARKER FOR FLUORESCENCE IMAGE-GUIDED SURGERY

Abstract Introduction The c-Met transmembrane protein is vital for cell differentiation and migration and is overexpressed in many gastrointestinal cancers. This study aimed to investigate a novel c-Met targeted peptide coupled to a fluorophore (EMI-137, Edinburgh Molecular Imaging Ltd.) for use in fluorescence image-guided colorectal cancer (CRC) surgery. Method A high c-Met expressing cell-line, HT29, was identified with temporary RNA suppression and used to develop a mouse xenograph CRC model. Tumours were allowed to grow to 10mm. EMI-137 was injected into the tail vein and biodistribution analysed using the IVIS system. Nine patients undergoing elective surgery for colon cancer received a single IV dose EMI-137 1-3 hours before surgery. Tumour and LN fluorescence was assessed with a prototype Karl Storz laparoscope. Intraoperative fluorescence was correlated with radiological and pathological TNM stage and tissue c-Met expression using immunohistochemistry. Result The HT29 xenograph CRC model demonstrated selective EMI-137 uptake and fluorescence 1- 6 hours post administration. Nine participants aged 67-77 years received EMI-137 106 minutes (S.D±17) before surgery. Marked background fluorescence was observed in all patients. 4/9 (44%) patients showed mild increase in tumour fluorescence over background. 5/9 patients had histological LN disease, but no fluorescent nodes were detected intraoperatively. There was no correlation with T-stage. At histopathological assessment 8/9 participants showed moderate or high tumour c-Met expression. 8/8 malignant LNs demonstrated high c-Met expression. Conclusion EMI-137 is specific for human c-Met in 2D and xenograph CRC models. EMI-137 is safe for human use but its utility is limited by insufficient tumour-to-background ratios. Take-home message This first-in-man study of a novel fluorescent peptide targeted to the c-Met receptor, found EMI-137 lacked the sensitivity and specificity to accurately map the tumour margins and lymph node burden in laparoscopic colonic cancer resection surgery.

Clinically relevant dual probe difference specimen imaging (DDSI) protocol for freshly resected breast cancer specimen staining

BackgroundRe-excision rates following breast conserving surgery (BCS) remain as high as ~ 35%, with positive margins detected during follow-up histopathology. Additional breast cancer resection surgery is not only taxing on the patient and health care system, but also delays adjuvant therapies, increasing morbidity and reducing the likelihood of a positive outcome. The ability to precisely resect and visualize tumor margins in real time within the surgical theater would greatly benefit patients, surgeons and the health care system. Current tumor margin assessment technologies utilized during BCS involve relatively lengthy and labor-intensive protocols, which impede the surgical work flow.MethodsIn previous work, we have developed and validated a fluorescence imaging method termed dual probe difference specimen imaging (DDSI) to accurately detect benign and malignant tissue with direct correlation to the targeted biomarker expression levels intraoperatively. The DDSI method is currently on par with touch prep cytology in execution time (~ 15-min). In this study, the main goal was to shorten the DDSI protocol by decreasing tissue blocking and washing times to optimize the DDSI protocol to < 10-min whilst maintaining robust benign and malignant tissue differentiation.ResultsWe evaluated the utility of the shortened DDSI staining methodology using xenografts grown from cell lines with varied epidermal growth factor receptor (EGFR) expression levels, comparing accuracy through receiver operator characteristic (ROC) curve analyses across varied tissue blocking and washing times. An optimized 8-min DDSI methodology was developed for future clinical translation.ConclusionsSuccessful completion of this work resulted in substantial shortening of the DDSI methodology for use in the operating room, that provided robust, highly receptor specific, sensitive diagnostic capabilities between benign and malignant tissues.

A Novel Fluorescent c-Met Targeted Imaging Agent for Intra-Operative Colonic Tumour Mapping: Translation from the Laboratory into a Clinical Trial

Background: Curative resection of colon cancer requires accurate intraoperative identification of tumour margins and lymph node (LN) burden. The c-Met protein is important for cell differentiation and migration and is overexpressed in many gastrointestinal cancers. We explored EMI-137, a novel c-Met targeting fluorescent probe, for application in fluorescence-guided colon surgery, in HT-29 colorectal cancer (CRC) cell line and an in vivo murine model. This informed a first-in-man clinical trial of EMI-137. Methods: HT-29 cells were used as a representative CRC model. SiRNA was used to demonstrate the specificity of EMI-137 for c-Met. A HT-29 CRC xenograft model was developed in female BALB/c mice. Tumours were cultured for 14 days to 10mm diameter. EMI-137 (0.18mg/kg) was injected into tail veins and biodistribution analysed through in vivo fluorescent imaging. Nine patients, aged 67-77 years, received a single intravenous dose of EMI-137 (0.13mg/kg), 1-3 hours before laparoscopic-assisted colon cancer resection surgery (NCT03360461). Tumour and LN fluorescence was assessed with a modified Karl Storz® laparoscope. Immunohistochemistry with a monoclonal antibody analysed c-Met expression in eight resected samples. Findings: c-Met expression in HT-29 cells was effectively silenced and imaged with EMI-137. Strong EMI-137 uptake in tumour xenografts was observed for up to 6 hours post-administration. At clinical trial, no serious adverse events related to EMI-137 were reported. Marked background fluorescence was observed in all trial participants, 4/9 showed an increase in tumour fluorescence over background; 5/9 had histological LN metastases; no fluorescent LN were detected intraoperatively. All primary tumours (8/8) and malignant LN (15/15) exhibited moderate to high c-Met protein expression. Interpretation: EMI-137, binds specifically to the human c-Met transmembrane protein, is safe in patients and with further refinement, shows potential for long-term application in fluorescence-guided colon surgery. Trial Registration: The trial was registered with ClinicalTrials.gov identifier NCT03360461. Funding: Research was supported by internal University of Leeds funding. Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Ethical approval was granted by the Yorkshire and Humber Leeds West Research and Ethics Committee (Ref 17/YH/0263), on 19th October 2017 and Regulatory approval was granted by the Medicines and Healthcare products Regulatory Agency (MHRA), under The Medicines for Human Use (Clinical Trials) regulations on 29th August 2017.

Morbidity and mortality of lung resection candidates defined by the American College of Chest Physicians as 'moderate risk': an analysis from the European Society of Thoracic Surgeons database.

The American College of Chest Physicians functional guidelines classify patients with predicted postoperative forced expiratory volume in 1 s or predicted postoperative carbon monoxide lung diffusion capacity <60% and with maximal oxygen consumption (VO2max) between 10 and 20 ml/kg/min in a heterogeneous category broadly defined as 'moderate risk' with variable morbidity and mortality. Data to support this statement are lacking. Using the European Society of Thoracic Surgeons database, our goal was to test this definition by evaluating the morbidity and mortality of those patients falling into this class. All patients who had anatomical lung resection for lung cancer (2007-2019) and were deemed of moderate risk were identified in the European Society of Thoracic Surgeons database. Cardiopulmonary morbidity and 30-day mortality of these patients were assessed by the type of operation. A total 2016 patients were identified. The incidence of cardiopulmonary complications in this group was 21% after lobectomy (294/1435), 29% after bilobectomy (33/112), 22% after pneumonectomy (72/333) and 16% after segmentectomy (22/136) (analysis of variance P = 0.07). The 30-day mortality was 3.4% after lobectomy (49/1435), 8.9% after bilobectomy (10/112), 7.8% after pneumonectomy (26/333) and 3.7% after segmentectomy (5/136) (analysis of variance P = 0.0005). The 30-day mortality rate was 1.6-fold higher in patients with a VO2max between 10 and 15 ml/kg/min compared to those with a higher VO2max [49/861 (5.7%) vs 41/1155 (3.5%); P = 0.022]. For operations that were less extensive than a pneumonectomy and were performed by minimally invasive surgery, there was no difference in mortality between patients with a VO2max between 10 and 15 ml/kg/min and those with a higher VO2max [7/181 (3.8%) vs 11/272 (4.0%); P = 0.92]. On the other hand, after open surgery, the mortality of patients with a lower VO2max (10-15 ml/kg/min) was higher than that of those with a higher VO2max [26/501 (5.1%) vs 20/721 (2.8%); P = 0.034]. Linear regression adjusting for the extent and access of the operation confirmed that within the moderate-risk group a VO2max <15 ml/kg/min was associated with higher mortality (P = 0.028; odds ratio 1.61; 95% confidence interval 1.1-2.5). Morbidity and mortality rates found in this study are not negligible and reinforce the recommendation to ensure careful patient discussion and informed decision-making prior to lung cancer resection surgery.