Emergency Abdominal Surgery in the Elderly: Can We Predict Mortality?

BACKGROUND: The United Kingdom population is ageing. Half of patients requiring an emergency laparotomy are aged over 70, 20 % die within 30 days, and less than half receive good care. Frailty and delay in management are associated with poor surgical outcomes. P-POSSUM risk scoring is widely accepted, but its validity in patients aged over 70 undergoing emergency laparotomy is unclear. AIMS: To assess if P-POSSUM risk stratification reliably predicts inpatient mortality in this group and establish whether those who died within 30 days received delayed care. METHODS: Observational study of consecutive patients aged 70 and over fulfilling the National Emergency Laparotomy Audit criteria from a tertiary hospital. The predictive value of pre-operative P-POSSUM, ASA, lactate and other routine variables was assessed. Surgical review, decision to operate, consultant surgical review, antibiotic prescription, laparotomy and discharge or death time points were assessed by 30-day survival. RESULTS: One hundred and ninety-three patients were included. This represented 46.28 % of those undergoing an emergency laparotomy in our centre. Pre-operative P-POSSUM scoring, ASA grade and lactate were moderate predictors of mortality (AUC 0.784 and 0.771, respectively, lactate AUC 0.705, all p ≤ 0.001). No correlation existed between pre-operative P-POSSUM and days to death (p = 0.209), nor were there delays in key management timings in those who died in 30 days. CONCLUSIONS: P-POSSUM scoring may predict inpatient mortality with moderate discrimination. Addition of frailty scoring in this high-risk group might better identify those with a high risk of mortality after emergency laparotomy and would be a fertile area for further research.

Tumour infiltrating lymphocytes correlate with improved survival in patients with oesophageal adenocarcinoma.

BACKGROUND: Oesophageal adenocarcinoma (OAC) is increasingly common in the west, and survival remains poor at 10-15 % at 5 years. Immune responses are increasingly implicated as a determining factor of tumour progression. The ability of lymphocytes to recognise tumour antigens provides a mechanism for a host immune attack against cancer providing a potential treatment strategy. MATERIALS AND METHODS: Tumour infiltrating lymphocytes (TILs: CD3+, CD4+, CD8+ and FOXp3+) were assessed by immunohistochemistry using tissue microarrays in a contemporary and homogeneous cohort of OAC patients (n = 128) undergoing curative treatment. RESULTS: Multivariate analysis identified three independent prognostic factors for improved cancer-specific survival (CSS): increased CD8+ TILs (p = 0.003), completeness of resection (p < 0.0001) and lower pathological N stage (p < 0.0001). Independent prognostic factors for favourable disease-free survival included surgery-only treatment (p = 0.015), completeness of resection (p = 0.001), increased CD8+ TILs (p < 0.0001) and reduced pathological N stage (p < 0.0001). Higher levels of TILs in the pathological specimen were associated with significant pathological response to neoadjuvant chemotherapy (NAC). On multivariate analysis increased levels of CD4+ (p = 0.017) and CD8+ TILs (p = 0.005) were associated with significant local tumour regression and lymph node downstaging, respectively. DISCUSSION: Our results establish an association of TILs and survival in OAC, as seen in other solid tumours, and identify particular TIL subsets that are present at higher levels in patients who responded to NAC compared to non-responders. These findings highlight potential therapeutic strategies in EAC based on utilising the host immunological response and highlight the immune responses biomarker potential.

The relevance of the Siewert classification in the era of multimodal therapy for adenocarcinoma of the gastro-oesophageal junction.

INTRODUCTION: The Siewert classification has been used to plan treatment for tumours of the gastro-oesophageal junction since its proposal in the 1980s. The purpose of this study was to assess its continued relevance by evaluating whether there were differences in the biology and clinical characteristics of adenocarcinomas by Siewert type, in a contemporary cohort of patients, in whom the majority had received neoadjuvant chemotherapy. METHODS: A prospective database was reviewed for all patients who underwent resection from 2005 to 2011 and analysed with regard to Siewert classification determined from the pathological specimen, treatment and clinicopathological outcomes. RESULTS: Two hundred and sixteen patients underwent oesophagogastric resection: 133 for type I, 51 for type II and 33 for type III tumours. 135 Patients (62.5%) received neoadjuvant chemotherapy with no difference between groups. There were no significant differences in age, sex, pT stage, pN stage, pM stage, ASA, or inpatient complications between patients with adenocarcinoma based on their Siewert classification. There was a significant increase in maximum tumour diameter (P = 0.023), perineural invasion (P = 0.021) and vascular invasion (P = 0.020), associated with more distal tumours (Type III > Type II > Type I). Median overall survival was significantly shorter for more distal tumours (Type I: 4.96 years vs. Type II: 3.3 years vs. Type III: 2.64 years; P = 0.04). The surgical approach did not influence survival. CONCLUSION: In the era of multi-modal treatment pathological Siewert tumour type is of prognostic value, as patients with Type III disease are likely to have larger and more aggressive tumours that lead to worse outcomes.

The role of systemic inflammatory and nutritional blood-borne markers in predicting response to neoadjuvant chemotherapy and survival in oesophagogastric cancer.

The aim of this study was to interrogate whether blood-borne inflammatory and nutritional markers predict long-term survival and response to neoadjuvant chemotherapy in radically treated oesophagogastric cancer patients. This retrospective study included 246 patients who underwent oesophageal resection for high-grade dysplasia or carcinoma between 2005 and 2010. The predictive value of routine preoperative immunonutritional blood tests was assessed for their association with survival and response to chemotherapy. On multivariate analysis, higher neutrophil-lymphocyte ratio (NLR) (p < 0.0001), N stage (p < 0.0001) and perineural invasion (p < 0.0001) were associated with poor overall survival. Regarding disease-free survival, multivariate analysis showed reduced serum albumin (p = 0.034), N stage (p < 0.0001), M stage (p = 0.037), vascular invasion (p < 0.0001) and presence of R1 resection (p = 0.003) to correlate with earlier recurrence. In those who received neoadjuvant chemotherapy, analysis of prechemotherapy characteristics showed only serum albumin (p = 0.037) to predict pathological response to chemotherapy. Preoperative immunonutritional markers, NLR and albumin, were independent prognostic markers for overall survival and disease-free survival, respectively, after oesophageal cancer resection. Prospective studies evaluating the role of immunonutritional modulation to improve response to chemotherapy and long-term outcome are required.

Refining pathological evaluation of neoadjuvant therapy for adenocarcinoma of the esophagus.

AIM: To assess tumour regression grade (TRG) and lymph node downstaging to help define patients who benefit from neoadjuvant chemotherapy. METHODS: Two hundred and eighteen consecutive patients with adenocarcinoma of the esophagus or gastro-esophageal junction treated with surgery alone or neoadjuvant chemotherapy and surgery between 2005 and 2011 at a single institution were reviewed. Triplet neoadjuvant chemotherapy consisting of platinum, fluoropyrimidine and anthracycline was considered for operable patients (World Health Organization performance status ≤ 2) with clinical stage T2-4 N0-1. Response to neoadjuvant chemotherapy (NAC) was assessed using TRG, as described by Mandard et al. In addition lymph node downstaging was also assessed. Lymph node downstaging was defined by cN1 at diagnosis: assessed radiologically (computed tomography, positron emission tomography, endoscopic ultrasonography), then pathologically recorded as N0 after surgery; ypN0 if NAC given prior to surgery, or pN0 if surgery alone. Patients were followed up for 5 years post surgery. Recurrence was defined radiologically, with or without pathological confirmation. An association was examined between t TRG and lymph node downstaging with disease free survival (DFS) and a comprehensive range of clinicopathological characteristics. RESULTS: Two hundred and eighteen patients underwent esophageal resection during the study interval with a mean follow up of 3 years (median follow up: 2.552, 95%CI: 2.022-3.081). There was a 1.8% (n = 4) inpatient mortality rate. One hundred and thirty-six (62.4%) patients received NAC, with 74.3% (n = 101) of patients demonstrating some signs of pathological tumour regression (TRG 1-4) and 5.9% (n = 8) having a complete pathological response. Forty four point one percent (n = 60) had downstaging of their nodal disease (cN1 to ypN0), compared to only 15.9% (n = 13) that underwent surgery alone (pre-operatively overstaged: cN1 to pN0), (P < 0.0001). Response to NAC was associated with significantly increased DFS (mean DFS; TRG 1-2: 5.1 years, 95%CI: 4.6-5.6 vs TRG 3-5: 2.8 years, 95%CI: 2.2-3.3, P < 0.0001). Nodal down-staging conferred a significant DFS advantage for those patients with a poor primary tumour response to NAC (median DFS; TRG 3-5 and nodal down-staging: 5.533 years, 95%CI: 3.558-7.531 vs TRG 3-5 and no nodal down-staging: 1.114 years, 95%CI: 0.961-1.267, P < 0.0001). CONCLUSION: Response to NAC in the primary tumour and in the lymph nodes are both independently associated with improved DFS.

Risk assessment using a novel score to predict anastomotic leak and major complications after oesophageal resection.

BACKGROUND: Oesophagectomy is associated with significant morbidity and mortality. A simple score to define a patient's risk of developing major complications would be beneficial. METHODS: Patients who underwent upper gastrointestinal resections with an oesophageal anastomosis between 2005 and 2010 were reviewed and formed the development dataset with resections performed in 2011 forming a prospective validation dataset. The association between post-operative C-reactive protein (CRP), white cell count (WCC) and albumin levels with anastomotic leak (AL) or major complication including death using the Clavien-Dindo (CD) classification were analysed by receiver operating characteristic curves. After multivariate analysis, from the development dataset, these factors were combined to create a novel score which was subsequently tested on the validation dataset. RESULTS: Two hundred fifty-eight patients were assessed to develop the score. Sixty-three patients (25%) developed a major complication, and there were seven (2.7%) in-patient deaths. Twenty-six (10%) patients were diagnosed with AL at median post-operative day 7 (range: 5-15). CRP (p = 0.002), WCC (p < 0.0001) and albumin (p = 0.001) were predictors of AL. Combining these markers improved prediction of AL (NUn score > 10: sensitivity 95%, specificity 49%, diagnostic accuracy 0.801 (95% confidence interval: 0.692-0.909, p < 0.0001)). The validation dataset confirmed these findings (NUn score > 10: sensitivity 100%, specificity 57%, diagnostic accuracy 0.879 (95% CI 0.763-0.994, p = 0.014)) and a major complication or death (NUn > 10: sensitivity 89%, specificity 63%, diagnostic accuracy 0.856 (95% CI 0.709-1, p = 0.001)). CONCLUSIONS: Blood-borne markers of the systemic inflammatory response are predictors of AL and major complications after oesophageal resection. When combined they may categorise a patient's risk of developing a serious complication with higher sensitivity and specificity.

Laparoscopic cholecystectomy in a patient with erythropoietic protoporphyria.

Erythropoietic protoporphyria (EPP) is an inherited defect in haem synthesis causing dangerous phototoxic reactions following exposure to wavelengths of light around 400nm. It can cause catastrophic post-operative complications following open surgery, in which environment various safety measures are now routinely employed. The dangers at laparoscopy have never been discussed in the literature, and nor have any specific precautions been recommended. We describe a 35 year old woman with gallstones undergoing prophylactic laparoscopic cholecystectomy to prevent future cholestasis precipitating porphyric liver failure. A pre-operative trial of the cutaneous effects of the laparoscopic light source was performed to assess the potential risk of use within the peritoneal cavity. The procedure was uneventful and the patient suffered no adverse reaction. We suggest that a trial of the effects of the laparoscopic light source on the skin of EPP patients provides valid reassurance regarding the safety of the laparoscopy for short surgical procedures.