Disease recurrence after right hemicolectomy in Scotland: Is there rationale to adopt complete mesocolic excision (CME)?

AIMS: Complete mesocolic excision (CME) has been proposed as a way to improve the oncological outcomes in patients with colon cancer. To investigate whether there is rationale for adopting the technique in Scotland, our aim was to define the incidence of disease recurrence following standard right hemicolectomy and to compare this with published CME outcomes. METHODS: Data was collected on consecutive patients undergoing right or extended right hemicolectomy for colonic adenocarcinoma (2012-2017) at three hospitals in Scotland (Raigmore Hospital, Aberdeen Royal Infirmary and Glasgow Royal Infirmary). Emergency or palliative surgery was excluded. Patients were followed up with CT scans and colonoscopy for a minimum of 3 years. RESULTS: 689 patients (M 340, F 349) were included. 30-day mortality was 1.6%. Final pathological stage was Stage I (14%), Stage II (49.8%) and Stage III (36.1%). During follow-up, 10.5% developed loco-regional recurrence and 12.2% developed distant metastases. The 1, 3 and 5-year disease-free survival (DFS) was 94%, 84% and 82% respectively. Primary determinants of recurrence were T stage (p < 0.001), N stage (p < 0.001), apical node involvement (p < 0.001) and EMVI (p < 0.001). When compared to the literature, 30-day mortality was lower than many published series and DFS rates were similar to the largest CME study to date (4 year DFS 85.8% versus 83%). CONCLUSION: The outcomes of patients undergoing right hemicolectomy in Scotland compare favourably with many published CME studies. The technique demands further evaluation before it can be recommended for adoption into routine surgical practice.

Prognostic Value of Computed Tomography: Measured Parameters of Body Composition in Primary Operable Gastrointestinal Cancers.

BACKGROUND: Previous reports suggest that body composition parameters can be used to predict outcomes for patients with gastrointestinal (GI) cancers. However, evidence for an association with long-term survival is conflicting, with much of the data derived from patients with advanced disease. This study examined the effect of body composition on survival in primary operable GI cancer. METHODS: Patients with resectable adenocarcinoma of the GI tract (esophagus, stomach, colon, rectum) between 2006 and 2014 were identified from a prospective database. Computed tomography (CT) scans were analyzed using a transverse section at L3 to calculate sex-specific body composition indices for skeletal muscle, visceral fat, and subcutaneous fat. Kaplan-Meier and log-rank analysis were used to compare unadjusted survival. Multivariate survival analyses were performed using a proportional hazards model. RESULTS: The study enrolled 447 patients (191 woman and 256 men) with esophagogastric (OG) (n = 108) and colorectal (CR) (n = 339) cancer. Body composition did not predict survival for the OG cancer patients. Among the CR cancer patients, survival was shorter for those with sarcopenia (p = 0.017) or low levels of subcutaneous fat (p = 0.005). Older age (p = 0.046) and neutrophilia (p = 0.013) were associated with sarcopenia in patients with CR. Tumor stage (p = 0.033), neutrophil count (p = 0.011), and hypoalbuminemia (p = 0.023) were associated with sarcopenia in OG cancer patients. In the multivariate analysis, no single measure of body composition was an independent predictor of reduced survival. CONCLUSION: Sarcopenia and reduced subcutaneous adiposity are associated with reduced survival for patients with primary operable CR cancer. However, in this study, no parameter of body composition was an independent prognostic marker when considered with age, tumor stage, and systemic inflammation.

National multicentre audit of pregnancy status in general surgery admissions in Scotland.

BACKGROUND: Documentation of pregnancy status (PS) is an integral component of the assessment of women of reproductive age when admitted to hospital. Our aim was to determine how accurately PS was documented in a multicentre audit of female admissions to general surgery. METHODS: A prospective multicentre audit of elective and emergency admissions was performed in 18 Scottish centres between 08:00 on 11 May 2015 and 07:59 on 25 May 2015. The lower age limit was the minimum age for admission to the adult surgical ward and the upper age limit was 55 years. RESULTS: There were 2743 admissions, with 612 (22.3%) women of reproductive age. After 82 exclusions, the final total was 530: 169 (31.9%) elective and 361 (68.1%) emergency. Documentation of PS was achieved in 274 (51.7%) cases: 52 (30.8%) elective and 222 (61.5%) emergency. In 318 (88.1%) of the emergency admissions, the patient had abdominal pain. Of these, 211 (65.1%) had a documented PS. The possibility of pregnancy was established in 237 (44.7%) cases. DISCUSSION: Establishing the possibility of pregnancy before surgery is poor, particularly in the elective setting. Objective documentation of PS in the emergency setting in those with abdominal pain is also poor. Our study highlights an important safety issue in the management of female patients. We advocate electronic storage of pregnancy test results and new guidelines to cover both elective and emergency surgery. PS should form part of the pre-theatre safety brief and checklist.

The clinical utility of the combination of T stage and venous invasion to predict survival in patients undergoing surgery for colorectal cancer.

OBJECTIVE: To examine the clinical utility of improved detection of venous invasion (VI) in patients undergoing potentially curative resection of colorectal cancer. BACKGROUND: VI is a feature of colorectal cancer (CRC) progression. Elastica staining can be used to improve detection of VI and correspondingly its prediction of patient survival. METHODS: A single-center, observational study of pathology variables, including detection of VI by staining for elastica, using 631 stage I to III CRC specimens, collected from 1997 to 2009 (176 analyzed retrospectively and 455 analyzed prospectively), was performed. RESULTS: VI was detected in 56% of patients with CRC. Over a median follow-up period of 73 months, 238 patients died (134 from cancer). On multivariate analysis, VI by elastica staining was associated with a shorter survival duration, independent of other pathology features, in all cases [hazard ratio (HR) = 3.94, 95% confidence interval (CI): 2.33-6.65, P < 0.001] and in node-negative cases (HR = 3.55, 95% CI: 1.81-6.97; P < 0.001). In the absence of elastica-detected VI, with the exception of T stage, no other pathology features were associated with survival time. Therefore, the combination of T stage and VI (TVI) on survival was examined. Five-year cancer mortality could be stratified between 100% and 54% for patients with node-negative tumors and between 100% and 33% for patients with node-positive tumors. In all cases, the TVI had similar predictive value as that of T stage and node status (TNM). In node-negative disease, TVI had superior predictive value. CONCLUSIONS: The results of the present study have prompted the development of a novel tumor staging system based on TVI. The TVI has clinical utility, especially in node-negative disease, in predicting outcome following curative resection for CRC.

The impact of perioperative risk, tumor pathology and surgical complications on disease recurrence following potentially curative resection of colorectal cancer.

OBJECTIVE: The objective of the study was to identify determinants of disease recurrence after potentially curative resection of colorectal cancer. SUMMARY BACKGROUND DATA: The identification of patients at increased risk of disease recurrence is currently based on pathological factors. Recently, there has been considerable interest in the potential impact of perioperative factors on long-term colorectal cancer outcome. Few studies have examined pre-, intra-, and postoperative variables in a single cohort. METHODS: Four hundred and twenty-three patients with histologically confirmed colorectal cancer who underwent surgery with curative intent between 1997 and 2007 were included. Pre-, intra-, and postoperative variables were recorded. Logistic and Cox regression analyses were performed to identify predictors of surgical complications and disease recurrence, respectively. RESULTS: The postoperative mortality rate was 4% and the morbidity rate 34%. The most important predictors of complications were smoking (odd ratio [OR] 1.32), ASA grade (OR 1.90) and POSSUM operative score (OR 1.32). During follow up (median 80 months), 35% of patients developed disease recurrence. Predictors of recurrence, independent of tumor stage, were POSSUM physiology score (hazard ratio [HR] 1.31) and systemic inflammatory response (HR 1.31). CONCLUSIONS: Preoperative risk factors, but not postoperative complications, are associated with early disease recurrence after potentially curative resection of colorectal cancer.

The revised ACPGBI model is a simple and accurate predictor of operative mortality after potentially curative resection of colorectal cancer.

BACKGROUND: The Association of Coloproctology of Great Britain and Ireland (ACPGBI) risk-adjustment model for colorectal cancer surgery has been recently revised. The aim of the present study was to compare the performance of the revised ACPGBI model, the original ACPGBI model, P-POSSUM, and CR-POSSUM, in the prediction of operative mortality after resection of colorectal cancer. METHODS: A total of 423 patients who underwent potentially curative resection of colorectal cancer at a single institution (1997-2007) were included. Data used in the construction of the ACPGBI model was collected prospectively. The models were compared by examining observed to expected (O:E) ratios, the Hosmer-Lemeshow (H-L) goodness-of-fit test, and area under the receiver operator characteristic curve (AUC) analysis. RESULTS: The 30-day mortality rate was 4%. The performance of the models was as follows: revised ACPGBI model (O:E ratio = 1.05, AUC = 0.73, H-L = 11.02), original ACPGBI model (O:E ratio = 0.58, AUC = 0.76, H-L = 14.23), P-POSSUM (O:E ratio = 0.87, AUC = 0.79, H-L = 10.63), and CR-POSSUM (O:E ratio = 0.63, AUC = 0.84, H-L = 15.84). In subgroup analysis, the revised ACPGBI model performed well in both elective cases (O:E ratio = 1.06) and emergency cases (O:E ratio = 0.91). CONCLUSIONS: The revised ACPGBI model is simple to construct and accurately predicts operative mortality after potentially curative resection of colorectal cancer.

The prognostic value of histological tumor necrosis in solid organ malignant disease: a systematic review.

BACKGROUND: Tumor necrosis has been proposed as a marker of poor prognosis in a variety of solid organ malignant tumor types. Despite this, its assessment has yet to be adopted into routine clinical practice and the mechanisms underpinning the relationships with cancer outcome are undetermined. AIMS: To examine the prognostic value of tumor necrosis in solid organ malignant disease and to summarize the known clinical, pathological and inflammatory associations. METHODS: A systematic review of data published from 1966-2011 was undertaken by two reviewers according to a predefined protocol. A total of 57 independent studies relating to renal (n = 23), breast (n = 13), lung (n = 7), colorectal (n = 5) and other solid tumors (n = 9) were included in the final review. CONCLUSION: There is now a substantial body of evidence confirming the prognostic value of tumor necrosis in solid organ malignant disease. There are consistent associations between necrosis and the presence of other high-risk tumor characteristics but the survival impact appears to be independent of pathological stage. We propose that relationships with the host inflammatory response, both local and systemic, may explain the influence of tumor necrosis on cancer outcome.

Revising the definition of vertical margin involvement following endoscopic polypectomy may reduce unnecessary surgery in patients with malignant colorectal polyps.

BACKGROUND AND STUDY AIMS: Endoscopically resected malignant colorectal polyps (MCPs) present a dilemma regarding whether the risk of residual disease justifies a major bowel resection. Overtreatment is common, and the vast majority of patients who undergo resection have no residual tumor. The aim of this study was to investigate whether revising the definition of vertical margin involvement following MCP polypectomy could reduce unnecessary surgery. PATIENTS AND METHODS: This was a cohort study of consecutive patients with MCPs treated at a tertiary hospital between 2004 and 2018. Data on demographics, index colonoscopy, polyp pathology, and any subsequent surgical resection were analyzed. Polypectomy resection margins were reviewed and measured to the nearest decimal place. The ability of existing guidelines (requiring a margin clearance of ≥ 1 mm) to predict residual disease was compared to a revised version requiring a margin clearance of ≥ 0.1 mm. RESULTS: A total of 129 patients with an MCP were included. Of these 129 patients, 77 (60%) underwent surgical resection, of which 62 (81%) had no residual tumor. Existing guidelines, requiring a margin clearance of ≥ 1 mm, classified 28 patients as being at "low risk" for residual disease. Of these, four underwent surgery, but none had residual tumor (P = 0.031). Revised guidelines, requiring a margin clearance of ≥ 0.1 mm, classified 44 patients as "low risk." Of these, in the 13 that had surgery, no residual tumor was found (P = 0.003). CONCLUSIONS: Revising the definition of vertical margin involvement leads to more patients being correctly classified as being at low risk of residual disease. This has the potential to reduce unnecessary surgery in patients with MCPs.

Results of a national multicenter audit assessment of gynecologic history in surgical patients.

OBJECTIVE: To determine the adequacy of assessing gynecologic history for females of reproductive age (FRA) admitted to a general surgery department. METHODS: The present prospective multicenter audit included FRA who were admitted for elective or emergency procedures to general surgery departments in Scotland between May 11 and May 25, 2015. Data were compared between patients who were admitted for elective and emergency treatment. RESULTS: There were 530 FRA included from 18 centers, including 169 (31.9%) and 361 (68.1%) elective and emergency admissions, respectively. The date of last menstrual period was document for 203 (38.3%) patients, use of contraception for 149 (28.1%), sexual activity for 83 (15.7%), pregnancy status for 274 (51.7%), and the possibility of pregnancy for 237 (44.7%). A higher incidence of documented date of last menstrual period (P=0.002) and pregnancy status (P<0.001) were identified among emergency admissions, and the possibility of pregnancy was documented more commonly among elective admissions (P<0.001). CONCLUSIONS: Key factors required for gynecologic assessment were often not documented for FRA admitted to general surgery both as elective and emergency admissions. Surgical teams and medical undergraduates require educating regarding the importance of obtaining gynecologic history for all FRA.

Developments in contact lens measurement: A comparative study of industry standard geometric inspection and optical coherence tomography.

PURPOSE: The aim of this study was to compare a developmental optical coherence tomography (OCT) based contact lens inspection instrument to a widely used geometric inspection instrument (Optimec JCF), to establish the capability of a market focused OCT system. METHODS: Measurements of 27 soft spherical contact lenses were made using the Optimec JCF and a new OCT based instrument, the Optimec is830. Twelve of the lenses analysed were specially commissioned from a traditional hydrogel (Contamac GM Advance 49%) and 12 from a silicone hydrogel (Contamac Definitive 65), each set with a range of back optic zone radius (BOZR) and centre thickness (CT) values. Three commercial lenses were also measured; CooperVision MyDay (Stenfilcon A) in -10D, -3D and +6D powers. Two measurements of BOZR, CT and total diameter were made for each lens in temperature controlled saline on both instruments. RESULTS: The results showed that the is830 and JCF measurements were comparable, but that the is830 had a better repeatability coefficient for BOZR (0.065mm compared to 0.151mm) and CT (0.008mm compared to 0.027mm). Both instruments had similar results for total diameter (0.041mm compared to 0.044mm). CONCLUSIONS: The OCT based instrument assessed in this study is able to match and improve on the JCF instrument for the measurement of total diameter, back optic zone radius and centre thickness for soft contact lenses in temperature controlled saline.

Evaluation of a tumor microenvironment-based prognostic score in primary operable colorectal cancer.

PURPOSE: The tumor microenvironment is recognized as an important determinant of progression and outcome in colorectal cancer. The aim of the present study was to evaluate a novel tumor microenvironment-based prognostic score, based on histopathologic assessment of the tumor inflammatory cell infiltrate and tumor stroma, in patients with primary operable colorectal cancer. EXPERIMENTAL DESIGN: Using routine pathologic sections, the tumor inflammatory cell infiltrate and stroma were assessed using Klintrup-Mäkinen (KM) grade and tumor stroma percentage (TSP), respectively, in 307 patients who had undergone elective resection for stage I-III colorectal cancer. The clinical utility of a cumulative score based on these characteristics was examined. RESULTS: On univariate analysis, both weak KM grade and high TSP were associated with reduced survival (HR, 2.42; P = 0.001 and HR, 2.05; P = 0.001, respectively). A cumulative score based on these characteristics, the Glasgow Microenvironment Score (GMS), was associated with survival (HR, 1.93; 95% confidence interval, 1.36-2.73; P < 0.001), independent of TNM stage and venous invasion (both P < 0.05). GMS stratified patients in to three prognostic groups: strong KM (GMS = 0), weak KM/low TSP (GMS = 1), and weak KM/high TSP (GMS = 2), with 5-year survival of 89%, 75%, and 51%, respectively (P < 0.001). Furthermore, GMS in combination with node involvement, venous invasion, and mismatch repair status further stratified 5-year survival (92% to 37%, 93% to 27%, and 100% to 37%, respectively). CONCLUSIONS: The present study further confirms the clinical utility of assessment of the tumor microenvironment in colorectal cancer and introduces a simple, routinely available prognostic score for the risk stratification of patients with primary operable colorectal cancer.

The clinical utility of the local inflammatory response in colorectal cancer.

BACKGROUND: The host immune response is important in the prevention of tumour progression in solid organ cancers. The aim was to evaluate the clinical utility of the local inflammatory response in patients with colorectal cancer. METHODS: Three hundred and sixty-five patients with primary operable colorectal cancer were included. The local inflammatory response was assessed using three different methods; (1) individual T-cell subtypes (CD3, CD8, CD45R0, FOXP3), (2) an immunohistochemistry-based immune score (Galon Immune Score) and (3) a histopathological assessment (Klintrup-Makinen grade). Relationships with tumour and host characteristics were established and the prognostic value of each method compared. RESULTS: A strong infiltration of tumour infiltrating lymphoctyes (TIL's) was associated with improved cancer-specific survival. When individual T-cell subtypes were considered, CD3-positive cells were the strongest predictor of survival at the invasive margin (CD3(+) IM) while CD8-positive cells were the strongest predictor in the cancer cell nests (CD8(+) CCN). Infiltration of T-cells was related to early tumour stage, expanding growth pattern and lower levels of venous invasion but was not influenced by host characteristics or degree of systemic inflammation. In summary, CD3(+) IM, CD8(+) CCN, The Galon Immune Score and the Klintrup-Makinen grade all exhibited similar survival relationships in both node-positive and node-negative colorectal cancer. CONCLUSION: A coordinated adaptive immune response is an important factor in predicting outcome in patients with primary operable colorectal cancer. By comparing different methodologies we have provided a foundation on which to develop a standardised approach for assessing the local inflammatory response in these patients.

The relationships between body composition and the systemic inflammatory response in patients with primary operable colorectal cancer.

BACKGROUND: Weight loss is recognised as a marker of poor prognosis in patients with cancer but the aetiology of cancer cachexia remains unclear. The aim of the present study was to examine the relationships between CT measured parameters of body composition and the systemic inflammatory response in patients with primary operable colorectal cancer. PATIENT AND METHODS: 174 patients with primary operable colorectal cancer who underwent resection with curative intent (2003-2010). Image analysis of CT scans was used to measure total fat index (cm(2)/m(2)), subcutaneous fat index (cm(2)/m(2)), visceral fat index (cm(2)/m(2)) and skeletal muscle index (cm(2)/m(2)). Systemic inflammatory response was measured by serum white cell count (WCC), neutrophil:lymphocyte ratio (NLR) and the Glasgow Prognostic Score (mGPS). RESULTS: There were no relationships between any parameter of body composition and serum WCC or NLR. There was a significant relationship between low skeletal muscle index and an elevated systemic inflammatory response, as measured by the mGPS (p = 0.001). This was confirmed by linear relationships between skeletal muscle index and both C-reactive protein (r = -0.21, p = 0.005) and albumin (r = 0.31, p<0.001). There was no association between skeletal muscle index and tumour stage. CONCLUSIONS: The present study highlights a direct relationship between low levels of skeletal muscle and the presence of a systemic inflammatory response in patients with primary operable colorectal cancer.

A systematic review of POSSUM and its related models as predictors of post-operative mortality and morbidity in patients undergoing surgery for colorectal cancer.

INTRODUCTION: The Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) model and its Portsmouth (P-POSSUM) and colorectal (CR-POSSUM) modifications are used extensively to predict and audit post-operative mortality and morbidity. This aim of this systematic review was to assess the predictive value of the POSSUM models in colorectal cancer surgery. METHODS: Major electronic databases, including Medline, Embase, Cochrane Library and Pubmed were searched for original studies published between 1991 and 2010. Two independent reviewers assessed each study against inclusion and exclusion criteria. All data was specific to colorectal cancer surgery. Predictive value was assessed by calculating observed to expected (O/E) ratios. RESULTS: Nineteen studies were included in final review. The mortality analysis included ten studies (4,799 patients) on POSSUM, 17 studies (6,576 patients) on P-POSSUM and 14 studies (5,230 patients) on CR-POSSUM. Weighted O/E ratios for mortality were 0.31 (CI 0.31-0.32) for POSSUM, 0.90 (CI 0.88-0.92) for P-POSSUM and 0.64 (CI 0.63-0.65) for CR-POSSUM. The morbidity analysis included four studies (768 patients) on POSSUM with a weighted O/E ratio of 0.96 (CI 0.94-0.98). CONCLUSIONS: P-POSSUM was the most accurate model for predicting post-operative mortality after colorectal cancer surgery. The original POSSUM model was accurate in predicting post-operative complications.

Randomised trial of thyroxine to prevent postnatal depression in thyroid-antibody-positive women.

BACKGROUND: Women who are positive for thyroid antibodies in early gestation are prone to post-partum depression, apparently independent of thyroid dysfunction, as measured by serum levels of free thyroxine, free triodothyroxine and thyroid-stimulating hormone. This finding may be due to infrequent monitoring of thyroid function, because hyperthyroidism, hypothyroidism and combinations of both may occur post-partum. AIMS: To test the hypothesis that stabilising thyroid function post-partum by administering daily thyroxine reduces the rate of occurrence and severity of associated depression. METHOD: In a randomised double-blind placebo-controlled trial, 100 microg of thyroxine or placebo was given daily to 446 thyroid-antibody-positive women (342 of whom were compliant) from 6 weeks to 6 months post-partum, assessing their psychiatric and thyroid status at 4-weekly intervals. RESULTS: There was no evidence that thyroxine had any effect on the occurrence of depression. The 6-month period prevalence of depression was similar to that reported previously. CONCLUSIONS: The excess of depression in thyroid-antibody-positive women in the post-partum period is not corrected by daily administration of thyroxine.