Peroral endoscopic myotomy compared to laparoscopic Heller myotomy and pneumatic dilation in the treatment of achalasia: a systematic review.

Peroral endoscopic myotomy (POEM) is an intervention for the treatment of achalasia which has gained popularity over the last decade. It's efficacy and invasiveness are comparable to laparoscopic Heller myotomy (LHM). The purpose of this systematic review is to compare POEM to existing therapies. The systematic review was performed following the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. MEDLINE, EMBASE, Web of Science and Cochrane Libraries were searched using keywords: esophageal achalasia, POEM, LHM, pneumatic dilation (PD), and related terms. The studied outcomes were Eckardt score, clinical success, hospital stay, cost-utility analysis, complications, and post-treatment gastro-esophageal reflux disease. Articles were reviewed by one researcher and uncertainty was resolved by a second researcher. The search strategy retrieved 1948 citations. After removing duplicates and applying the exclusion criteria, 91 studies were selected for full-text review of which a total of 31 studies were considered eligible for further analysis, including two studies which were found through manual searching. POEM has improved efficacy compared to PD with similar cost-effectiveness. POEM results showed comparable patient outcomes when compared with laparoscopic myotomy. Overall, POEM is a feasible first-line treatment for achalasia.

Early outcomes following EndoFLIP-tailored peroral endoscopic myotomy (POEM): the establishment of POEM services in two UK centers.

Peroral endoscopic myotomy (POEM) is a safe and effective minimally invasive treatment for achalasia. Postoperative reflux rates remain high. The functional luminal imaging probe (FLIP) allows intraoperative measurement of lower esophageal distensibility during POEM. In theory, this enables a tailoring of myotomies to ensure adequate distensibility while minimizing postoperative reflux risk. Two prospectively collected POEM databases were analyzed from two UK tertiary upper GI centers. The operators in each center used FLIP measurements to ensure adequate myotomy. Outcome measures included Eckardt score (where <3 indicated clinical success) and proton-pump inhibitor use (PPI), collected at the first postoperative appointment. Length of stay was recorded as were complications. In all, 142 patients underwent POEM between 2015 and 2019. Overall, 90% (128/142) had postoperative Eckardt scores of <3 at 6 weeks. Clinical success improved to 93% (66/71) in the latter half of each series with a significantly higher rate of complete symptom resolution (53 versus 26%, P = 0.003). In all, 79% of the poor responders had previous interventions compared with 55% of responders (P = 0.09). Median post-myotomy distensibility index was 4.0 mm2/mmHg in responders and 2.9 in nonresponders (P = 0.16). Myotomy length of <7 cm was associated with 93% clinical success and 40% post op PPI use compared with 60% PPI use with longer myotomies. There were two type IIIa, two type IIIb, and one IV Clavien-Dindo complications. This is the largest series of endoluminal functional lumen imaging probe (EndoFLIP)-tailored POEM in the UK to date. The shorter myotomies, allowed through EndoFLIP tailoring, remained clinically effective at 6 weeks. Complete symptom response rates improved in the latter half of each series. More data will be needed from high-volume collaborations to decipher optimal myotomy profiles based on EndoFLIP parameters.

Comparison of Outcomes with Semi-mechanical and Circular Stapled Intrathoracic Esophagogastric Anastomosis following Esophagectomy.

BACKGROUND: Several techniques have been described for esophagogastric anastomosis following esophagectomy. This study compared the outcomes of circular stapled anastomoses with semi-mechanical technique using a linear stapler. METHODS: Perioperative data were extracted from a contemporaneously collected database of all consecutive esophagectomies for cancer with intrathoracic anastomoses performed in the Trent Oesophago-Gastric Unit between January 2015 and April 2018. Anastomotic techniques: circular stapled versus semi-mechanical, were evaluated and outcomes were compared. The primary outcome was anastomotic leak rate. Secondary outcomes included anastomotic stricture, overall complication rates, length of stay (LOS) and 30 day all-cause mortality. RESULTS: One hundred and fifty-nine consecutive esophagectomies with intrathoracic anastomosis were performed during the study period. There were no significant differences between the two groups in terms of age, American Society of Anaesthesiologists score, Charlson comorbidity index and neoadjuvant therapies received. Circular stapled anastomoses were performed in 85 patients, while 74 patients received a semi-mechanical anastomosis. Clavien-Dindo complications II or more were higher in the circular stapled group (p = 0.02). There were 16 (10%) anastomotic leaks overall, three (4%) in semi-mechanical group versus 13 (15%) in the circular stapled group (p < 0.019). There was no statistically significant difference between the two groups in terms of LOS, 30-day mortality or the need for endoscopic dilatation of the anastomosis at 3 months follow-up. CONCLUSION: The move from a circular stapled to a semi-mechanical intrathoracic anastomosis has been associated with a reduced postoperative anastomotic leak rate following esophagectomy for esophageal cancer.

Postoperative inflammation and insulin resistance in relation to body composition, adiposity and carbohydrate treatment: A randomised controlled study.

BACKGROUND & AIMS: The aims of this study were to identify whether differences in distribution of adipose tissue and skeletal muscle in obese and non-obese individuals contribute to the magnitude of the postoperative inflammatory response and insulin resistance, with and without preoperative treatment with carbohydrate drinks. METHODS: Thirty-two adults (16 obese/16 non-obese) undergoing elective major open abdominal surgery participated in this 2 × 2 factorial, randomised, double-blind, placebo-controlled study. Participants received Nutricia preOp® or placebo (800 ml on the night before surgery/400 ml 2-3 h preoperatively) after stratifying for obesity. Insulin sensitivity was measured using the hyperinsulinaemic-euglycaemic clamp preoperatively and on the 1st postoperative day. Vastus lateralis, omental and subcutaneous fat biopsies were taken pre- and postoperatively and analysed after RNA extraction. The primary endpoint was within subject differences in insulin sensitivity. RESULTS: Major abdominal surgery was associated with a 42% reduction in insulin sensitivity from mean(SD) M value of 37.3(11.8) µmol kg-1 fat free mass (FFM) to 21.7(7.4) µmol kg-1 FFM, but this was not influenced by obesity or preoperative carbohydrate treatment. Activation of the triggering receptor expressed on myeloid cells (TREM1) pathway was seen in response to surgery in omental fat samples. In postoperative muscle samples, gene expression differences indicated activation of the peroxisome proliferator-activated receptor (PPAR-α)/retinoid X-receptor (RXR-α) pathway in obese but not in non-obese participants. There were no significant changes in gene expression pathways associated with carbohydrate treatment. CONCLUSION: The reduction in insulin sensitivity associated with major abdominal surgery was confirmed but there were no differences associated with preoperative carbohydrates or obesity.

A comparison of three methods to assess body composition.

OBJECTIVE: The aim of this study was to compare the accuracy of measurements of body composition made using dual x-ray absorptiometry (DXA), analysis of computed tomography (CT) scans at the L3 vertebral level, and bioelectrical impedance analysis (BIA). METHODS: DXA, CT, and BIA were performed in 47 patients recruited from two clinical trials investigating metabolic changes associated with major abdominal surgery or neoadjuvant chemotherapy for esophagogastric cancer. DXA was performed the week before surgery and before and after commencement of neoadjuvant chemotherapy. BIA was performed at the same time points and used with standard equations to calculate fat-free mass (FFM). Analysis of CT scans performed within 3 mo of the study was used to estimate FFM and fat mass (FM). RESULTS: There was good correlation between FM on DXA and CT (r2 = 0.6632; P < 0.0001) and FFM on DXA and CT (r2 = 0.7634; P < 0.0001), as well as FFM on DXA and BIA (r2 = 0.6275; P < 0.0001). Correlation between FFM on CT and BIA also was significant (r2 = 0.2742; P < 0.0001). On Bland-Altman analysis, average bias for FM on DXA and CT was 0.2564 with 95% limits of agreement (LOA) of -9.451 to 9.964. For FFM on DXA and CT, average bias was -0.1477, with LOA of -8.621 to 8.325. For FFM on DXA and BIA, average bias was -3.792, with LOA of -15.52 to 7.936. For FFM on CT and BIA, average bias was -2.661, with LOA of -22.71 to 17.39. CONCLUSION: Although a systematic error underestimating FFM was demonstrated with BIA, it may be a useful modality to quantify body composition in the clinical situation.

The impact of sarcopenia and myosteatosis on outcomes of unresectable pancreatic cancer or distal cholangiocarcinoma.

BACKGROUND & AIMS: Patients with pancreatic cancer have a poor prognosis, are often cachectic, and frequently demonstrate features of systemic inflammation, which may contribute to the phenomenon of myosteatosis. Analysis of body composition from CT scans has been used to study sarcopenia and its association with prognosis in a number of types of cancer, particular in combination with obesity. It has also been suggested that myosteatosis, defined as attenuated mean skeletal muscle Hounsfield units (HU), is associated with reduced survival in cancer. This study aimed to assess the association between body composition (sarcopenia and myosteatosis) and outcome in patients with unresectable pancreatic cancer. METHODS: All patients diagnosed with unresectable pancreatic cancer at Nottingham University Hospitals NHS Trust between 2006 and 2013 were considered for the study. A total of 228 patients were included retrospectively. Body composition was assessed using cross-sectional CT analysis to calculate a skeletal muscle index (SMI) for sarcopenia and use mean skeletal muscle HU for myosteatosis. RESULTS: The prevalence of sarcopenia in the whole patient group at baseline was 60.5% (138/228). Overall, patients who were sarcopenic had no significant difference in overall survival versus those who were not (p = 0.779). However, patients who were overweight/obese and sarcopenic had a significantly lower survival (p = 0.013). Of the 58 patients who were overweight or obese and sarcopenic, 32 were also myosteatotic. The prevalence of myosteatosis overall at baseline was 55.3% (126/228) and this was associated with significant reduction in overall survival (p = 0.049). Univariate Cox regression revealed myosteatosis but not sarcopenia to be predictive of reduced survival, however this relationship was lost on multivariate testing. Myosteatosis was associated with significantly greater levels of systemic inflammation (white cell count, neutrophil-lymphocyte ratio and C-reactive protein), anaemia and worsening of baseline blood urea. This relationship was not seen with sarcopenia. CONCLUSIONS: This is the largest study on the association between body composition and survival in patients with unresectable pancreatic cancer and has shown that although sarcopenia alone did not have a bearing on survival, the presence of myosteatosis was associated significantly with the presence of systemic inflammation and reduced survival.

Mixed periampullary adenocarcinoma and somatostatinoma with small bowel gastrointestinal stromal tumour in neurofibromatosis type 1.

CONTEXT: Gastrointestinal (GI) involvement is present in about one quarter of cases of neurofibromatosis type 1 (NF1). Adenocarcinomas have been reported in several organs. Gastrointestinal stromal tumors are the most common GI lesion seen in NFI. GISTs in combination with ampullary neuroendocrine tumors in NF-1 have been reported rarely. CASE REPORT: We present the case of a 44-year-old man who presented with a history of obstructive jaundice and weight loss. Investigations revealed a pancreatic tumor associated with a common bile duct (CBD) stricture. At operation, an ampullary adenocarcinoma that infiltrated into the head of pancreas with an adjacent somatostatinoma was found. In addition, a small bowel GIST was present. CONCLUSIONS: Mixed periampullary adenocarcinoma and somatostatinoma in a patient with NF1 has only been previously reported once. The current case highlights the spectrum of associated tumor types which can be seen in association with NF1. Patients with NF1 who present with jaundice and weight loss should be investigated in the usual manner with increased suspicion for duodenal and ampullary tumors.

Lymphoepithelial cyst of the pancreas and elevated cyst fluid carcinoembryonic antigen: a diagnostic challenge.

CONTEXT: Pancreatic lymphoepithelial cysts are rare, benign cysts which can present diagnostic difficulties. Non-invasive imaging alone is unreliable in distinguishing between benign and malignant cysts. Endoscopic ultrasound (EUS) and fine needle aspiration (FNA) with analysis of cyst fluid is more reliable, but invasive. In addition, tumor markers such as carcinoembryonic antigen (CEA) can be grossly elevated in cyst fluid of benign cysts. CASE REPORT: We present the case of a 67 year old man with an incidental finding of a pancreatic cyst. EUS and FNA-guided aspiration of cyst fluid was performed. Fluid CEA was grossly elevated and resectional surgery was performed. On histological examination the diagnosis was confirmed as lymphoepithelial cyst of the pancreas. CONCLUSION: Tumor markers such as CEA can be elevated in the cyst fluid of benign pancreatic conditions such as lymphoepithelial cyst. Although the diagnosis is challenging preoperatively, if a systematic algorithm is followed, these conditions can be managed safely and efficiently.

The presence of tumour-associated lymphocytes confers a good prognosis in pancreatic ductal adenocarcinoma: an immunohistochemical study of tissue microarrays.

BACKGROUND: Tumour-associated lymphocytes (TALs) have been linked with good prognosis in several solid tumours. This study aimed to evaluate the prognostic significance of CD3, CD8 and CD20 positive lymphocytes in pancreatic ductal adenocarcinoma. METHODS: After histological re-evaluation of the tumours of 81 patients who underwent surgical resection for exclusively pancreatic ductal adenocarcinoma, tissue micro-arrays (TMA) were constructed and immunohistochemistry was performed for CD3, CD8 and CD20. The number of lymphocytes within specific tumour compartments (i.e. stromal and intratumoural) was quantified. X-tile software (Yale School of Medicine, CT, USA) was used to stratify patients into 'high' and 'low' for each of the lymphocytes stained and their association with survival. Receiver operating curves (ROC) were constructed to evaluate the association between the TALs, alone and in combination, with clinicopathological features. RESULTS: CD3 and CD8 positive lymphocytes were associated with grade of tumour differentiation. The presence of intratumoural CD3 positive cells was associated with improved survival (p = 0.028), and intratumoural and stromal CD3 in combination also correlated with improved survival (p = 0.043). When CD20 positive lymphocyte levels were high, survival improved (p = 0.029) and similar results were seen for CD20 in combination with intratumoural CD3 (p = 0.001) and stromal CD8 (p = 0.013). CONCLUSIONS: This study has shown a correlation between the presence of TALs and survival in pancreatic ductal adenocarcinoma.

Three cases of concomitant intraductal papillary mucinous neoplasm and pancreatic neuroendocrine tumour.

CONTEXT: Intraductal papillary mucinous neoplasms (IPMNs) are uncommon tumours which can be associated with pancreatic and extrapancreatic malignancies. The association of IPMN and neuroendocrine tumours of the pancreas has been reported previously but is exceedingly rare. CASE REPORT: We report three cases of IPMN treated with total pancreatectomy/extended distal pancreatectomy. Histopathological analysis of the resected specimens revealed concomitant IPMN and neuroendocrine tumour. Two patients had adenocarcinoma as well. CONCLUSIONS: The presence of an IPMN may place the entire pancreas at risk of developing other tumour types and vigilance during all stages of management is necessary to ensure optimal treatment.

Regulation of food intake after surgery and the gut brain axis.

PURPOSE OF REVIEW: To highlight recent developments relating control of food intake after surgery and the gut-brain axis by reviewing clinically relevant English language articles mainly from January 2011 to March 2013. RECENT FINDINGS: The gut-brain axis involves a number of complex interactions between hypothalamic nuclei and the gastrointestinal tract. In the postoperative period, release of cytokines and neuromodulators are involved in the control of food intake. Analogues of neuromodulators have been developed and tested in animal studies. The emerging field of metabolic surgery has allowed study of these mechanisms in greater detail. SUMMARY: The current epidemic of worldwide obesity demands further research into the mechanisms underlying control of food intake.

The utilisation of the MUST nutritional screening tool on vascular surgical wards.

Whilst malnutrition is prevalent in approximately 40% of general surgical patients, the prevalence of malnutrition and nutritional screening practices amongst vascular patients remain unknown. The Malnutrition Universal Screening Tool (MUST) is recommended for risk screening and provides 3 scores for risk classification: 0=low risk, 1=intermediate risk, 2=high risk. The aim of this preliminary study was to evaluate the use of MUST on vascular wards. This prospective study was undertaken in a tertiary referral vascular unit in the UK. Patient demographics, utilisation of MUST by nursing staff (N-MUST) and referral to nutritional support teams (NST) were studied. When MUST was not completed by nursing staff, the study team (S-MUST) performed it. Fifty-three patients, median (interquartile range, IQR) age 67 (59-75) years were initially studied. For N-MUST: Overall MUST score was recorded in 18/25 (72%) patients, of whom 1 (4%) scored 2, whilst the remainder scored 0. For S-MUST: Overall MUST scores were recorded in 28 patients, MUST=0 in 75% and ≥2 in 21%. An educational session on use of MUST was delivered to nursing staff, as well as a Trust-wide educational initiative to improve assessment of nutritional status and, after a 2-month period, the study was repeated. The second cohort comprised forty-two patients, median (IQR) age 72 (64-79) years. For N-MUST: Overall MUST score was recorded in 37/40 (93%) patients, of whom 3 (8%) scored ≥2. For S-MUST: Overall MUST scores were recorded in 2 patients, MUST = 0 in 67% and ≥2 in 33%. Despite the ease of use of MUST, it was under-utilised on vascular wards. However, following provision of a dedicated educational programme to ward nursing staff, utilisation of MUST for risk scoring patients on admission increased to over 90%.

Nutritional status affects long term survival after lobectomy for lung cancer.

STUDY OBJECTIVES: Nutritional status has been reported as a predictor of complications following surgery for lung cancer. However, the impact of impaired nutrition in the long term has not been extensively studied. We have analysed our own experience after lobectomy for non-small cell lung cancer (NSCLC). PATIENTS: Six hundred and forty-two consecutive patients undergoing lobectomy for primary lung cancer in a single centre between October 1991 and April 2004 were included in the study. STUDY DESIGN: Impaired nutritional status was defined as any of low pre-operative albumin level (less than 30g/L), recent history of weight loss or low body mass index (BMI)--less than 18.5kg/m(2). There were 400 males and 242 females, median age 66 (range 32-89 years). Outcomes studied were hospital mortality and complications, and long term survival. RESULTS: A high proportion of patients (185 of 642, 28%) were classed as having poor nutritional status. There were 12 hospital deaths (1.9%). Nutritional depletion had no significant impact on hospital mortality (1.3% versus 2.7%), cardiac (14.4% versus 16.8%), or respiratory (17.5% versus 18.9%) complications. The overall median survival was 48+/-6 months (standard error). On Cox multivariate analysis, impaired nutritional status, tumour stage and need for en bloc chest wall excision were all independent predictors of survival. CONCLUSIONS: Nutritional status does not appear to significantly influence immediate outcomes following lobectomy for lung cancer. However, it is a predictor of survival in the long term independently of tumour extension and staging.