Cachexia index for prognostication in surgical patients with locally advanced oesophageal or gastric cancer: multicentre cohort study.

BACKGROUND: Features of cancer cachexia adversely influence patient outcomes, yet few currently inform clinical decision-making. This study assessed the value of the cachexia index (CXI), a novel prognostic marker, in patients for whom neoadjuvant chemotherapy and surgery for oesophagogastric cancer is planned. METHODS: Consecutive patients newly diagnosed with locally advanced (T3-4 or at least N1) oesophagogastric cancer between 1 January 2010 and 31 December 2015 were identified through the West of Scotland and South-East Scotland Cancer Networks. CXI was calculated as (L3 skeletal muscle index) × (serum albumin)/(neutrophil lymphocyte ratio). Sex-stratified cut-off values were determined based on the area under the curve (AUC), and patients were divided into groups with low or normal CXI. Primary outcomes were disease progression during neoadjuvant chemotherapy and overall survival (at least 5 years of follow-up). RESULTS: Overall, 385 patients (72% men, median age 66 years) were treated with neoadjuvant chemotherapy for oesophageal (274) or gastric (111) cancer across the study interval. Although patients with a low CXI (men: CXI below 52 (AUC 0.707); women: CXI below 41 (AUC 0.759)) were older with more co-morbidity, disease characteristics were comparable to those in patients with a normal CXI. Rates of disease progression during neoadjuvant chemotherapy, leading to inoperability, were higher in patients with a low CXI (28 versus 12%; adjusted OR 3.07, 95% c.i. 1.67 to 5.64; P < 0.001). Low CXI was associated with worsened postoperative mortality (P = 0.019) and decreased overall survival (median 14.9 versus 56.9 months; adjusted HR 1.85, 1.42 to 2.42; P < 0.001). CONCLUSION: CXI is associated with disease progression, worse postoperative mortality, and overall survival, and could improve prognostication and decision-making in patients with locally advanced oesophagogastric cancer.

Evaluating temporal trends and the impact of surgical subspecialisation on patient outcomes following adhesional small bowel obstruction: a multicentre cohort study.

PURPOSE: Small bowel obstruction (SBO) is the most common indication for laparotomy in the UK. While general surgeons have become increasingly subspecialised in their elective practice, emergency admissions commonly remain undifferentiated. This study aimed to assess temporal trends in the management of adhesional SBO and explore the influence of subspecialisation on patient outcomes. METHODS: Data was collected for patients admitted acutely with adhesional SBO across acute NHS trusts in Northern England between 01/01/02 and 31/12/16, including demographics, co-morbidities and procedures performed. Patients were excluded if a potentially non-adhesional cause was identified and were grouped by the responsible consultant's subspecialty. The primary outcome of interest was 30-day inpatient mortality. RESULTS: Overall, 2818 patients were admitted with adhesional SBO during a 15-year period. There was a consistent female preponderance, but age and comorbidity increased significantly over time (both p < 0.001). In recent years, more patients were managed operatively with a trend away from delayed surgery also evident (2002-2006: 65.7% vs. 2012-2016: 42.7%, p < 0.001). Delayed surgery was associated with an increased mortality risk on multivariable regression analysis (OR: 2.46 (1.46-4.23, p = 0.001)). CT scanning was not associated with management strategy or timing of surgery (p = 0.369). There was an increased propensity for patients to be managed by gastrointestinal (colorectal and upper gastrointestinal) subspecialists over time. Length of stay (p < 0.001) and 30-day mortality (p < 0.001) both improved in recent years, with the best outcomes seen in colorectal (2.6%) and vascular subspecialists (2.4%). However, following adjustment for confounding variables, consultant subspecialty was not a predictor of mortality. CONCLUSION: Outcomes for patients presenting with adhesional SBO have improved despite the increasing burden of age and co-morbidity. While gastrointestinal subspecialists are increasingly responsible for their care, mortality is not influenced by consultant subspecialty.

Staging the Tumor and Staging the Host: Pretreatment Combined Neutrophil Lymphocyte Ratio and Modified Glasgow Prognostic Score Is Associated with Overall Survival in Patients with Esophagogastric Cancers Undergoing Treatment with Curative Intent.

BACKGROUND: This study examined whether an innate systemic inflammatory response (SIR) measured by combination neutrophil to lymphocyte ratio (NLR) and modified Glasgow Prognostic Score (mGPS) was associated with overall survival (OS) in patients with esophagogastric cancer (EC) undergoing neoadjuvant chemotherapy (NAC) followed by surgery. METHODS: Patients diagnosed with EC, managed with NAC prior to surgery at a regional referral center, between January 2010 and December 2015, were included. The mGPS and NLR were calculated within 12 weeks before NAC. Patients were grouped by combined NLR/mGPS score into three groups of increasing SIR: NLR ≤ 3 (n = 152), NLR > 3 + mGPS = 0 (n = 55), and NLR > 3 + mGPS > 0 (n = 32). Univariable and multivariable Cox regression was used to analyse OS. RESULTS: Overall, 337 NAC patients were included, with 301 (89%) proceeding to surgery and 215 (64%) having R0 resection. There were 203 deaths, with a median follow-up of those alive at censor of 69 months (range 44-114). Higher combined NLR/mGPS score (n = 239) was associated with poorer OS independent of clinical stage and performance status (hazard ratio 1.28, 95% confidence interval 1.02-1.61; p = 0.032), higher rate of progression on NAC (7% vs. 7% vs. 19%; p = 0.003), and lower proportion of eventual resection (80% vs. 84% vs. 53%; p = 0.003). CONCLUSIONS: The combined NLR/mGPS score was associated with OS and initial treatment outcomes in patients undergoing NAC prior to surgery for EC, stratifying survival in addition to clinical staging and performance status. The host SIR may be a useful adjunct to multidisciplinary decision making.

Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer.

BACKGROUND: There is increasing evidence that the patient-related systemic inflammatory response is a powerful prognostic factor. The aim of the present study was to compare the prognostic value of selected markers of the systemic inflammatory response in patients undergoing resection of gastric cancer. METHODS: One hundred twenty patients undergoing resection of gastric cancer, had measurements of various systemic inflammatory markers in addition to tumor-related factors. From these, the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and metastatic lymph node ratio were calculated. RESULTS: On multivariate analysis, only the ratio of positive to total lymph nodes (hazard ratio, 2.29%; 95% confidence interval, 1.57%-3.33%; P < .001) and the mGPS (hazard ratio, 2.23%; 95% confidence interval, 1.40%-3.54%; P = .001) were independently associated with cancer-specific survival in patients with gastric cancer. An increase in the mGPS was associated with a higher neutrophil/lymphocyte ratio (P < .05) and poorer survival (P < .001). CONCLUSIONS: The present study indicates that the mGPS, an acute-phase, protein-based prognostic score, is a superior predictor of cancer survival compared with the cellular components of the systemic inflammatory response in patients undergoing resection of gastric cancer.

Comparison of the prognostic value of tumour- and patient-related factors in patients undergoing potentially curative resection of oesophageal cancer.

BACKGROUND: Evidence is increasing that elevated systemic inflammation is associated with poor survival in patients with oesophageal carcinoma. However, it is not yet established if any specific component of systemic inflammatory response is a better predictor of cancer survival. The aim of the present study was to compare the predictive value of selected markers of systemic inflammation in patients who undergo surgical resection of oesophageal cancer. METHODS: One hundred twelve patients who underwent potentially curative resection for oesophageal carcinoma, including type I and type II tumours of the gastro-oesophageal junction (Siewert and Stein in Dis Esophagus 9:173-182, 1996), between 1996 and 2008 were included in the study. Patients had laboratory measurement of white cells, neutrophils, lymphocytes, platelet counts, albumin, and C-reactive protein. Glasgow Prognostic Score (mGPS), neutrophil lymphocyte ratio (NLR), platelet lymphocyte ratio (PLR), and metastatic lymph node ratio (LNR) were calculated. RESULTS: On multivariate analysis, only the LNR (HR 2.87, 95% CI 1.99-4.15, p < 0.001) and the mGPS (HR 4.31, 95% CI 2.20-8.45, p < 0.001) were independently associated with cancer-specific survival in oesophageal cancer. An elevated mGPS was associated with high white cell count (p < 0.05) and poorer survival (p = 0.001). CONCLUSION: The present study indicates that the mGPS, an acute-phase protein-based prognostic score, better predicts cancer survival compared with the cellular components of systemic inflammation in patients with oesophageal carcinoma.

Interrelationships between tumor proliferative activity, leucocyte and macrophage infiltration, systemic inflammatory response, and survival in patients selected for potentially curative resection for gastroesophageal cancer.

BACKGROUND: A number of accepted criteria, including pathological tumor, node, metastasis system stage, lymph node metastasis, and tumor differentiation, predict survival in patients undergoing surgery for gastroesophageal cancer. We examined the interrelationships between standard clinicopathological factors, systemic and local inflammatory responses, tumor proliferative activity, and survival. METHODS: The interrelationships between the systemic inflammatory response (Glasgow prognostic score, mGPS), standard clinicopathological factors, local inflammatory response (Klintrup criteria, macrophage infiltration), and tumor proliferative activity (Ki-67) were examined by immunohistochemistry in 100 patients (44 esophageal [19 squamous, 25 adenocarcinoma], 19 junctional, and 37 gastric cancers) selected for potentially curative resection. RESULTS: The minimum follow-up was 59 months. On multivariate survival analysis, lymph node ratio (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.11-2.40, P < 0.05), tumor differentiation (HR 2.63, 95% CI 1.45-4.77, P = 0.001), mGPS (HR 3.91, 95% CI 1.96-8.11, P < 0.001), Klintrup score (HR 3.47, 95% CI 1.14-10.55, P < 0.05), and Ki-67 (HR 0.67, 95% CI 0.47-0.96, P < 0.05) were independently associated with cancer-specific survival. A higher lymph node ratio was associated with poor tumor differentiation (P < 0.05), low-grade Klintrup criteria (P < 0.005), and low tumor proliferative activity (P < 0.05). CONCLUSION: Tumor proliferation rate and local and systemic inflammatory responses are important predictors of survival, albeit in a heterogeneous cohort of patients including esophageal, junctional, and gastric cancers. These scores may be combined with accepted tumor-based factors to improve prediction of outcome.

Endoscopic mucosal resection for gastroesophageal cancer in a U.K. population. Long-term follow-up of a consecutive series.

BACKGROUND: Endoscopic mucosal resection (EMR) of early gastric and esophageal tumors is effective and avoids the morbidity and mortality of surgery. We report the long-term results of a consecutive series of 93 endoscopic resections, during a 7-year period, in a U.K. population. METHODS: Eighty-eight patients with 93 lesions were included. EMR was performed for 64 and 29 malignant and benign lesions, respectively. Patients with malignant disease were subgrouped into "high risk" or "low risk" for recurrence. RESULTS: Of the 35 lesions in the low-risk group, local control was achieved in 31; 29 after 1 EMR session. Two had residual invasive carcinoma, one had treatment ceased due to pancreatic cancer, and one patient did not attend follow-up. Of the 29 lesions in the high-risk group, local control was achieved in 15; 13 after 1 EMR session. Median follow-up was 53 months. Cancer specific survival for the 45 invasive cancers (T1m and T1sm) was 93%; three patients died from their disease. CONCLUSIONS: This study has shown for the first time in a U.K. population that EMR is effective in controlling disease in patients with local high grade dysplasia (HGD) and early invasive carcinoma, with no mortality and low morbidity.

Is hypoalbuminemia an independent prognostic factor in patients with gastric cancer?

BACKGROUND: Studies have indicated that hypoalbuminemia is associated with decreased survival of patients with gastric cancer. However, the prognostic value of albumin may be secondary to an ongoing systemic inflammatory response. The aim of the study was to assess the relation between hypoalbuminemia, the systemic inflammatory response, and survival in patients with gastric cancer. METHODS: Patients diagnosed with gastric carcinoma attending the upper gastrointestinal surgical unit in the Royal Infirmary, Glasgow between April 1997 and December 2005 and who had a pretreatment measurement of albumin and C-reactive protein (CRP) were studied. RESULTS: Most of the patients had stage III/IV disease and received palliative treatment. The minimum follow-up was 15 months. During follow-up, 157 (72%) patients died of their cancer. On univariate analysis, stage (p < 0.001), treatment (p < 0.001), albumin level (p < 0.001), and CRP level (p < 0.001) were significant predictors of survival. On multivariate analysis, stage (p < 0.001), treatment (p < 0.001), and CRP level (p < 0.001) remained significant predictors of survival. Albumin was no longer an independent predictor of survival. CONCLUSIONS: Low albumin concentrations are associated with poorer survival in patients with gastric cancer. However, the strength of this relation with survival is dependent on the presence of a systemic inflammatory response, as evidenced by an elevated CRP level. Therefore, it appears that the relation between hypoalbuminemia and poor survival is secondary to that of the systemic inflammatory response.

Comparison of pre-treatment clinical prognostic factors in patients with gastro-oesophageal cancer and proposal of a new staging system.

BACKGROUND: Clinical staging in patients with gastro-oesophageal cancer, is of crucial importance in determining the likely benefit of treatment. Despite recent advances in clinical staging, overall survival remains poor. The aim of the present study was to examine the relationship between pre-treatment clinical prognostic factors and cancer-specific survival. METHODS: Two hundred and seventeen patients, undergoing staging investigations including host factors (Edinburgh Clinical Risk Score (ECRS)) and the systemic inflammatory response (Glasgow Prognostic score (mGPS)), in the upper GI surgical unit at Glasgow Royal Infirmary, were studied. RESULTS: During the follow-up period, 188 (87%) patients died; 178 of these patients died from the disease. The minimum follow-up was 46 months, and the median follow-up of the survivors was 65 months. On multivariate survival analysis of the significant factors, only cTNM stage (HR 1.84, 95% CI 1.56-2.17, p < 0.001), mGPS (HR 1.67, 95% CI 1.35-2.07, p < 0.001) and treatment (HR 2.12, 95% CI 1.73-2.60, p < 0.001) were independently associated with survival. An elevated mGPS was associated with advanced cTNM stage, poor performance status, an elevated ECRS and more conservative treatment. CONCLUSIONS: Pre-treatment mGPS improves clinical staging in patients with gastro-oesophageal cancer. Therefore, it is likely to aid clinical decision making for these difficult to treat patients.

Comparison of an inflammation-based prognostic score (GPS) with performance status (ECOG-ps) in patients receiving palliative chemotherapy for gastroesophageal cancer.

AIM: The aim of the present study was to compare an inflammation-based prognostic score (Glasgow Prognostic Score, GPS) with performance status (ECOG-ps) in patients receiving platinum-based chemotherapy for palliation of gastroesophageal cancer. METHODS: Sixty-five patients presenting with gastroesophageal carcinoma to the Royal Infirmary, Glasgow between January 1999 and December 2005 and who received palliative chemotherapy or chemo-radiotherapy were studied. ECOG-ps, C-reactive protein, and albumin were recorded at diagnosis. Patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a GPS of 2. Patients in whom only one of these biochemical abnormalities was present were allocated a GPS of 1 and patients with a normal C-reactive protein and albumin were allocated a score of 0. Toxicity was recorded using the Common Toxicity Criteria. RESULTS: The minimum follow up was 14 months. During the follow-up period, 59 (91%) of the patients died. On univariate and multivariate survival analysis, only the GPS (hazard ratios 1.65, 95% CI 1.10-2.47, P < 0.05) was a significant independent predictor of cancer survival. In addition, in comparison with patients with GPS of 0, those patients with a GPS of 1 or 2 required more frequent chemotherapy dose reduction (P < 0.05), were less likely to exhibit a clinical response to treatment (P < 0.05), and had shorter survival (P < 0.05). CONCLUSION: The presence of a systemic inflammatory response, as evidenced by the GPS, appears to be superior to the subjective assessment of performance status (ECOG-ps) in predicting the response to platinum-based chemotherapy in patients with advanced gastroesophageal cancer.