C-Reactive Protein-Lymphocyte Ratio Identifies Patients at Low Risk for Major Morbidity after Oesophagogastric Resection for Cancer.

INTRODUCTION: Complications following oesophagogastric surgery have significant implications for patient recovery. OBJECTIVE: identify cost-effective biomarkers which can predict morbidity. METHODS: Analysis of all upper gastrointestinal resections in Galway University Hospital from 2014 to 2018 was performed. The ability of C-reactive protein (CRP), neutrophil-lymphocyte ratio (NLR), and CRP-lymphocyte ratio (CLR) to predict morbidity, including anastomotic leak (AL), was assessed and compared. RESULTS: Seventy-one oesophagectomies and 77 gastrectomies were performed. There were 2 (1%) 30-day mortalities and 83 (56%) morbidities of which 30 (20%) were of Clavien-Dindo grade 3 or higher. The rate of major morbidity within the oesophagectomy cohort was 27% and was 14% in the gastrectomy cohort. There were 11 (7%) ALs, 7 in the oesophagectomy cohort, and 4 in the gastrectomy cohort. From post-operative day (POD) 2 onwards, CRP could predict AL (POD2 AUC = 0.705, p = 0.025; POD3 AUC = 0.757, p = 0.005, POD4 AUC = 0.811, p = 0.001; and POD5 AUC = 0.824, p = 0.001). CLR predicted AL on POD2 onwards (POD2 AUC = 0.722, p = 0.005; POD3 AUC = 0.736, p = 0.01; POD4 AUC = 0.775, p = 0.003; and POD5 AUC = 0.817, p = 0.001). CRP level of 218 mg/dL and CLR level of 301 at POD 2 generated negative predictive values of 97 and 98%, respectively, for AL. Post-operative NLR did not display sufficient discriminatory ability for the outcomes. CONCLUSION: CRP and CLR are reliable negative predictors of major morbidity, including AL, after oesophagogastric resection. Their use can inform patient intervention and recovery.

The effect of a pre- and post-operative exercise programme versus standard care on physical fitness of patients with oesophageal and gastric cancer undergoing neoadjuvant treatment prior to surgery (The PERIOP-OG Trial): Study protocol for a randomised controlled trial.

BACKGROUND: Advances in peri-operative oncological treatment, surgery and peri-operative care have improved survival for patients with oesophagogastric cancers. Neoadjuvant cancer treatment (NCT) reduces physical fitness, which may reduce both compliance and tolerance of NCT as well as compromising post-operative outcomes. This is particularly detrimental in a patient group where malnutrition is common and surgery is demanding. The aim of this trial is to assess the effect on physical fitness and clinical outcomes of a comprehensive exercise training programme in patients undergoing NCT and surgical resection for oesophagogastric malignancies. METHODS: The PERIOP-OG trial is a pragmatic, multi-centre, randomised controlled trial comparing a peri-operative exercise programme with standard care in patients with oesophagogastric cancers treated with NCT and surgery. The intervention group undergo a formal exercise training programme and the usual care group receive standard clinical care (no formal exercise advice). The training programme is initiated at cancer diagnosis, continued during NCT, between NCT and surgery, and resumes after surgery. All participants undergo assessments at baseline, post-NCT, pre-surgery and at 4 and 10 weeks after surgery. The primary endpoint is cardiorespiratory fitness measured by demonstration of a 15% difference in the 6-min walk test assessed at the pre-surgery timepoint. Secondary endpoints include measures of physical health (upper and lower body strength tests), body mass index, frailty, activity behaviour, psychological and health-related quality of life outcomes. Exploratory endpoints include a health economics analysis, assessment of clinical health by post-operative morbidity scores, hospital length of stay, nutritional status, immune and inflammatory markers, and response to NCT. Rates of NCT toxicity, tolerance and compliance will also be assessed. DISCUSSION: The PERIOP-OG trial will determine whether, when compared to usual care, exercise training initiated at diagnosis and continued during NCT, between NCT and surgery and then during recovery, can maintain or improve cardiorespiratory fitness and other physical, psychological and clinical health outcomes. This trial will inform both the prescription of exercise regimes as well as the design of a larger prehabilitation and rehabilitation trial to investigate whether exercise in combination with nutritional and psychological interventions elicit greater benefits. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03807518 . Registered on 1 January 2019.

Serial CRP levels following oesophagectomy: a marker for anastomotic dehiscence.

BACKGROUND: Following oesophagectomy, the most concerning complication is that of anastomotic leak (AL). Prompt diagnosis and intervention are crucial to facilitate an optimal outcome. Other complications, particularly respiratory, are not infrequent. Early identification of AL versus other sources of the inflammatory response can be problematic. AIMS: To evaluate the role of serial CRP as a prognosticator for oesophagogastric AL. METHODS: All oesophagectomies carried out at our institution from 2010 to 2017 were included. Serial C-reactive protein (CRP) and white cell count (WCC) were recorded pre-operatively and on each consecutive day up to day 10 post-op. All complications were recorded and the timing of diagnosis compared with serial CRP and WCC measurements to determine any correlation. RESULTS: One hundred and two patients underwent oesophagectomy (84 male, 18 female) with a mean age of 62.5 years (± 9.8). Forty-seven patients developed post-operative complications, with pulmonary (n = 28) the most common. There were 5 cases of AL. Patients in the AL group (n = 5) had a significantly higher mean CRP compared to those who did not develop AL (n = 97) pre-operatively (50 vs. 14, p = 0.046), on post-op day 3 (300 vs. 218, p = 0.02) and on post-op day 4 (279 vs. 184, p = 0.009). There was no significant difference in mean daily CRP between patients with pulmonary complications (PC, n = 29) and those who did not develop complications (NC, n = 54). CONCLUSIONS: Elevated CRP may be a useful marker in facilitating the prompt diagnosis of AL following oesophagectomy. Serial CRP may not contribute to identifying lower respiratory tract infections, partly as a result of the pro-inflammatory response following surgery.

National early warning score (NEWS) - evaluation in surgery.

PURPOSE: The purpose of this paper is to evaluate staff opinion on the impact of the National Early Warning Score (NEWS) system on surgical wards. In 2012, the NEWS system was introduced to Irish hospitals on a phased basis as part of a national clinical programme in acute care. DESIGN/METHODOLOGY/APPROACH: A modified established questionnaire was given to surgical nursing staff, surgical registrars, surgical senior house officers and surgical interns for completion six months following the introduction of the NEWS system into an Irish university hospital. FINDINGS: Amongst the registrars, 89 per cent were unsure if the NEWS system would improve patient care. Less than half of staff felt consultants and surgical registrars supported the NEWS system. Staff felt the NEWS did not correlate well clinically with patients within the first 24 hours (Day zero) post-operatively. Furthermore, 78-85 per cent of nurses and registrars felt a rapid response team should be part of the escalation protocol. RESEARCH LIMITATIONS/IMPLICATIONS: Senior medical staff were not convinced that the NEWS system may improve patient care. Appropriate audit proving a beneficial impact of the NEWS system on patient outcome may be essential in gaining support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward. ORIGINALITY/VALUE: Appropriate audit of the impact of the NEWS system on patient outcome may be pertinent to obtain the support from senior doctors. Deficiencies with the system were also observed including the absence of a rapid response team as part of the escalation protocol and a lack of concordance of the NEWS in patients Day zero post-operatively. These issues should be addressed moving forward.

Early post-operative removal of urethral catheter in patients undergoing colorectal surgery with epidural analgesia ­ a prospective pilot clinical study.

BACKGROUND: Urethral catheter (UC) removal is often delayed following colorectal resection due to the perceived increased risk of post-operative urinary retention (POUR) in patients with post-operative epidural analgesia (POEA). We aimed to determine if UC removal at 48 h, irrespective of ongoing POEA use, altered the risk of POUR and other morbidities associated with urethral catheterisation and immobility. METHODS: We performed a prospective randomised controlled pilot clinical study. Eligible patients were randomised to an experimental arm, SG1 (UC removal 48 h post-operatively), or a control arm, SG2 (UC removed following cessation of POEA). Rates of POUR, urinary tract infection (UTI), pulmonary complications and surgical site infection (SSI) were recorded. Forty-four patients were recruited (SG1: n = 22; SG2: n = 22). RESULTS: No females developed POUR, while it occurred in three males (20%) in SG1 and 2 males (22.2%) in SG2. All patients who developed POUR had undergone rectal resection. Males in SG1 were not at significantly increased risk of POUR compared to those in SG2 (R.R 0.875, p = 1). No patient developed UTI post-operatively. The rate of pulmonary complications (SG1: n = 2; SG2: n = 3, p = 0.229) and SSI (SG1: n = 5; SG2: n = 2, p = 0.146) were similar between both study arms. DISCUSSION: Males undergoing rectal surgery appear to be at increased risk of developing POUR in the presence of epidural analgesia, independent of the timing of UC removal. CONCLUSIONS: All female patients undergoing colorectal resection and male patients undergoing colonic resection may have their urethral catheter removed at 48 h irrespective of use of POEA. CLINICAL TRIALS REGISTRATION NUMBER: NCT01508767 (http://www.clinicaltrials.gov).

Aerosolized intraperitoneal local anesthetic for laparoscopic surgery: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Postoperative pain remains a significant challenge following laparoscopy. Aerosolized intraperitoneal local anesthetic (AILA) is a novel method to deliver local anesthetic. The aim was to evaluate aerosolized ropivacaine in pain management following laparoscopic Nissen fundoplication (LNF) and cholecystectomy (LC). METHODS: This prospective randomized double-blinded placebo-controlled trial enrolled consecutive patients undergoing LNF and LC. The treatment group (TG) received intraperitoneal ropivacaine (5 mL 1 % Naropin(®)) at CO2 insufflation via the AeroSurge(®) aerosolizer device through the camera port. The control group (CG) received 5 mL of saline in the same manner. Postoperative shoulder tip pain at rest 6 h postoperatively was the primary study endpoint, with secondary endpoints of shoulder and abdominal pain within the first 24 h, recovery room stay, hospital stay, and postoperative analgesia use. Pain scores were collected using the Verbal Rating Score. RESULTS: Eighty-seven patients were included in the final analysis (TG n = 40, CG n = 47). There was no significant difference between CG and TG at the primary endpoint. In the LC group, AILA significantly reduced shoulder tip pain at rest at 10 (p = 0.030) and 30 min (p = 0.040) and shoulder tip pain on movement at 10 (p = 0.030) and 30 min (p = 0.037). In the LNF group, AILA significantly reduced postoperative abdominal pain at rest at 6 h (p = 0.009). AILA reduced overall incidence of shoulder tip pain in the LC group (11.8 vs. 57.9 %, p = 0.004). CONCLUSION: This study did not demonstrate a significant difference between TG and CG in the primary endpoint, pain at 6 h postoperatively.

Awareness and uptake of family screening in patients diagnosed with colorectal cancer at a young age.

Background. One-fifth of people who develop colorectal cancer (CRC) have a first-degree relative (FDR) also affected. There is a large disparity in guidelines for screening of relatives of patients with CRC. Herein we address awareness and uptake of family screening amongst patients diagnosed with CRC under age 60 and compare guidelines for screening. Study Design. Patients under age 60 who received surgical management for CRC between June 2009 and May 2012 were identified using pathology records and theatre logbooks. A telephone questionnaire was carried out to investigate family history and screening uptake among FDRs. Results. Of 317 patients surgically managed for CRC over the study period, 65 were under age 60 at diagnosis (8 deceased). The mean age was 51 (30-59). 66% had node positive disease. 25% had a family history of colorectal cancer in a FDR. While American and Canadian guidelines identified 100% of these patients as requiring screening, British guidelines advocated screening for only 40%. Of 324 FDRs, only 40.9% had been screened as a result of patient's diagnosis. Conclusions. Uptake of screening in FDRs of young patients with CRC is low. Increased education and uniformity of guidelines may improve screening uptake in this high-risk population.

Total systemic ropivacaine concentrations following aerosolized intraperitoneal delivery using the AeroSurge.

STUDY OBJECTIVE: To evaluate intraperitoneal ropivacaine delivery with the AeroSurge device in the clinical setting and to evaluate the total systemic ropivacaine levels achieved following delivery of 50 mg of aerosolized ropivacaine. DESIGN: Preliminary, prospective, nonrandomized study. SETTING: Operating room of a university hospital. PATIENTS: 5 consecutive ASA physical status 1 and 2 patients undergoing elective laparoscopic Nissen fundoplication or cholecystectomy. INTERVENTION: Five mL of 1% ropivacaine was delivered through the 10 mm port using the AeroSurge device at peritoneal insufflation. MEASUREMENTS: Venous blood samples were collected and total ropivacaine concentration was determined using liquid chromatography-mass spectrometry. MAIN RESULTS: The AeroSurge device delivered ropivacaine, visible as mist within the peritoneal cavity. Peak concentration (Cmax) was attained between 10 and 30 minutes following the end of aerosolized ropivacaine delivery. At no stage did any level approach toxic levels. CONCLUSIONS: This preliminary study confirms that aerosolized intraperitoneal local anesthetic is feasible, with ropivacaine concentrations remaining within safe levels.

Acta from the EndoFLIP® Symposium.

Laparoscopic fundoplication (LF) is a surgical treatment for gastroesophageal reflux disease (GERD) that has been performed for more than 20 years. High-volume centers of excellence report long-term success rates greater than 90% with LF. On the other hand, general population-based outcomes are reported to be markedly worse, leading to a nihilistic perception of the procedure on the part of the medical referral population. The lack of standardization of the technique and the lack of tools to calibrate objectively the repairs are probably among the causes of variability in the outcomes and may explain the decline in the number of LF procedures in recent years. The functional lumen imaging probe (EndoFLIP(®)) device is essentially a "smart bougie" in the form of a balloon catheter that measures shape and compliance of the gastroesophageal junction (GEJ) during surgery using impedance planimetry. With approximately 3 years of international experience gained with this tool, a symposium was convened in October 2012 in Strasbourg, France, with the aim of determining if intraoperative EndoFLIP use could provide standardization of surgical treatment of GERD through the understanding of physiological changes occurring to the GEJ during fundoplication. This article provides a brief history of the EndoFLIP system and reviews data previously published on the use of EndoFLIP to characterize the GEJ in normal subjects. It then summarizes the data from the 5 high-volume international sites with expert surgeons performing LF presented in Strasbourg to objectively profile the characteristics of a normal postoperative GEJ.

Solid pseudopapillary neoplasm of the pancreas.

Solid pseudopapillary neoplasms (SPNs) are rare entities accounting for between 0.13 and 2.7 per cent of pancreatic tumours. This neoplasm has a predilection for females under the age of 35. The authors report this case of a SPN incidentally discovered when a 59-year-old female underwent a chest x-ray to investigate a wheeze. A subsequent CT abdomen revealed a 10 cm well-circumscribed mass adjacent to the tail of the pancreas. This mass was successfully resected. Immunohistochemical markers established the diagnosis of a SPN. The wheeze associated with the presentation of this case was unrelated to the tumour which was an incidental finding. These neoplasms are largely asymptomatic and indolent reaching a large size before detection. Diagnosis is confirmed on histology and in this case surgical resection was curative and there was no metastasis at presentation.

Increased use of multidisciplinary treatment modalities adds little to the outcome of rectal cancer treated by optimal total mesorectal excision.

PURPOSE: Total mesorectal excision (TME) is the standard surgical treatment for rectal cancer. The roles of chemotherapy and radiotherapy have become more defined, accompanied by improvements in preoperative staging and histopathological assessment. We analyse our ongoing results in the light of changing patterns of treatment over consecutive time periods. METHODS: In total, 151 consecutive patients underwent potentially curative rectal excision for cancer in a single institution. Management and outcomes were compared between 1993-1999 and 2000-2007 which corresponded with the restructuring of the regional oncological services. RESULTS: We found an increase in patients treated with neoadjuvant chemoradiotherapy after 1999 (20/89 vs 1/62, p < 0.001). There was an increase in the mean number of lymph nodes examined (11.9 vs 9.4, p = 0.037). The locoregional recurrence rate was 5.3%. The rates were not significantly different between the two study periods [4/89 (4.5%) 1999-2007 vs 4/62 (6.5%) 1993-1999, p = 0.597]. There was no statistical difference in overall or disease-free survival in the time periods examined. CONCLUSIONS: Increasing use of neoadjuvant therapy and concomitant improvement in lymph node assessment did not translate into a concurrent reduction in the local recurrence, disease-free and overall survival rates. Our results demonstrate the enduring benefit of specialist training in TME in the outcome of rectal cancer surgery. This observational study suggests that low local recurrence rates are surrogate markers for improved overall and disease-free survival. Multidisciplinary team practice should be examined and made cost effective according to the individual unit's local recurrence rate in the light of this and other reports.

MicroRNA signature analysis in colorectal cancer: identification of expression profiles in stage II tumors associated with aggressive disease.

PURPOSE: Colorectal cancer (CRC) is a clinically diverse disease whose molecular etiology remains poorly understood. The purpose of this study was to identify miRNA expression patterns predictive of CRC tumor status and to investigate associations between microRNA (miRNA) expression and clinicopathological parameters. METHODS: Expression profiling of 380 miRNAs was performed on 20 paired stage II tumor and normal tissues. Artificial neural network (ANN) analysis was applied to identify miRNAs predictive of tumor status. The validation of specific miRNAs was performed on 102 tissue specimens of varying stages. RESULTS: Thirty-three miRNAs were identified as differentially expressed in tumor versus normal tissues. ANN analysis identified three miRNAs (miR-139-5p, miR-31, and miR-17-92 cluster) predictive of tumor status in stage II disease. Elevated expression of miR-31 (p = 0.004) and miR-139-5p (p < 0.001) and reduced expression of miR-143 (p = 0.016) were associated with aggressive mucinous phenotype. Increased expression of miR-10b was also associated with mucinous tumors (p = 0.004). Furthermore, progressively increasing levels of miR-10b expression were observed from T1 to T4 lesions and from stage I to IV disease. CONCLUSION: Association of specific miRNAs with clinicopathological features indicates their biological relevance and highlights the power of ANN to reliably predict clinically relevant miRNA biomarkers, which it is hoped will better stratify patients to guide adjuvant therapy.

Primary splenic lymphoma presenting with ascites.

An 84 year-old gentleman presented with abdominal distension, anorexia and occasional epigastric pain over a four-week period. Blood parameters revealed a hypochromic microcytic anaemia. Both CT and US scan identified ascites and a mass in the left upper quadrant. An ascitic tap was performed identifying bloody ascites and the presence of reactive mesothelial cells on cytology. A subsequent laparotomy and splenectomy was performed. Histology of the resected spleen revealed a Grade 2 follicular lymphoma (Figure 2). The patient had an uneventful postoperative recovery and was well at 6 months follow up. The spleen is an organ with an important immunological function. Primary splenic involvement occurs in less than 1% of non-hodgkin's lymphoma. Symptoms of primary splenic lymphoma (PSL) include pyrexia, weight-loss, night sweats, generalised weakness and left upper quadrant pain secondary to spleno - megaly. Ascites is a rare presenting feature of PSL. This report illustrates a case of primary splenic lymphoma which poses diagnostic challenges for the pathologist and clinician and ultimately requires definitive splenectomy to confirm a diagnosis.Figure 2Photograph of histology slide displaying the lymphoma at 10× magnification.

Laparoscopic mesh repair of a diaphragmatic hernia of Bochdalek.

The advent of minimally invasive surgery has facilitated the laparoscopic repair of diaphragmatic hernias. One of the difficulties associated with long-standing Bochdalek or Morgagni hernias is that the herniated contents are often quite adherent to the diaphragmatic defect and require considerable dissection before the reduction of herniated organs. Ultrasonic dissection using a harmonic coagulation shears allowed safe, bloodless division of the long-standing adhesions, which is essential for atraumatic reduction of herniated thoracic contents. We herein report the successful laparoscopic mesh repair of a Bochdalek hernia in a 67-year-old man.

Factors contributing to failure of laparoscopic Nissen fundoplication and the predictive value of preoperative assessment.

BACKGROUND: Laparoscopic Nissen fundoplication (LNF) has established itself as the procedure of choice in the surgical management of the majority of patients suffering from gastroesophageal reflux disease (GERD). There are, however, few available data on the assessment of long-term failures after LNF. METHODS: We sought to clarify the mechanisms of failure among a group of patients who reported suboptimal results after LNF. In addition, we attempted to identify specific elements in the preoperative evaluation of GERD patients that might herald a predisposition to anatomical or physiological failure. RESULTS: One hundred and thirty-one consecutive patients who underwent LNF by a single surgeon were analyzed to identify reasons for surgical failure. Fourteen patients (10.6%) comprised the failure group. Detailed independent statistical analysis identified a hiatus hernia greater than 3 cm at operation (P = 0.003), abnormal preoperative pH analysis in the upright position (P = 0.039), failure to respond to proton pump inhibition preoperatively (P = 0.015), and a preoperative psychiatric history (P = 0.0012) as predictors of subsequent failure. CONCLUSIONS: In patients who do not respond to proton pump inhibition preoperatively, the evaluating surgeon should be circumspect in advocating antireflux surgery. A detailed assessment of underlying psychiatric or psychological symptoms must also be made. If a large (>3 cm approximately) hiatus hernia is identified or there is abnormal pH analysis in the upright position preoperatively, the surgeon should be guarded about the long-term outcome, and patients should be advised accordingly.