Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis.

The aim of this study was to evaluate the effect of intraoperative botulinum toxin (BT) injection on delayed gastric emptying (DGE) and need for endoscopic pyloric intervention (NEPI) following esophagectomy. In compliance with Preferred Reporting Items for Systematic reviews and Meta-Analyses statement standards, a systematic review of studies reporting the outcomes of intraoperative BT injection in patients undergoing esophagectomy for esophageal cancer was conducted. Proportion meta-analysis model was constructed to quantify the risk of the outcomes and direct comparison meta-analysis model was constructed to compare the outcomes between BT injection and no BT injection or surgical pyloroplasty. Meta-regression was modeled to evaluate the effect of variations in different covariates among the individual studies on overall summary proportions. Nine studies enrolling 1070 patients were included. Pooled analyses showed that the risks of DGE and NEPI following intraoperative BT injection were 13.3% (95% confidence interval [CI]: 7.9-18.6%) and 15.2% (95% CI: 7.9-22.5%), respectively. There was no difference between BT injection and no BT injection in terms of DGE (odds ratio [OR]: 0.57, 95% CI: 0.20-1.61, P = 0.29) and NEPI (OR: 1.73, 95% CI: 0.42-7.12, P = 0.45). Moreover, BT injection was comparable to pyloroplasty in terms of DGE (OR: 0.85, 95% CI: 0.35-2.08, P = 0.73) and NEPI (OR: 8.20, 95% CI: 0.63-105.90, P = 0.11). Meta-regression suggested that male gender was negatively associated with the risk of DGE (coefficient: -0.007, P = 0.003). In conclusion, level 2 evidence suggests that intraoperative BT injection may not improve the risk of DGE and NEPI in patients undergoing esophagectomy. The risk of DGE seems to be higher in females and in early postoperative period. High quality randomized controlled trials with robust statistical power are required for definite conclusions. The results of the current study can be used for hypothesis synthesis and power analysis in future prospective trials.

Colonic Interposition After Adult Oesophagectomy: Systematic Review and Meta-analysis of Conduit Choice and Outcome.

BACKGROUND: Colonic interposition is a second-line option after oesophagectomy when a gastric neo-oesophagus is not viable. There is no consensus on the optimum anatomical colonic conduit (right or left), or route of placement (posterior mediastinal, retrosternal or subcutaneous). The aim of this review was to determine the optimum site and route of neo-oesophageal conduit after adult oesophagectomy. METHODS: PubMed, MEDLINE, and the Cochrane Library (January 1985 to January 2017) were systematically searched for studies which reported outcomes following colonic interposition in adults. The outcome measures were overall morbidity and mortality. RESULTS: Twenty-seven observational studies involving 1849 patients [1177 males; median age (range) 60.5 (18-84) years] undergoing colonic interposition for malignant (n = 697) and benign (n = 1152) pathology were analysed. Overall pooled morbidity of left vs. right colonic conduit was 15.7% [95% CI (11.93-19.46), p < 0.001] and 18.7% [95% CI (15.58-21.82), p < 0.001] respectively. Overall pooled mortality of left vs. right colonic conduit was 6.5% [95% CI (4.55-8.51), p < 0.001] and 10.1% [95% CI (7.35-12.82), p < 0.001] respectively. Retrosternal route placement was associated with the lowest overall pooled morbidity and mortality of 9.2% [95% CI (6.48-11.99), p < 0.001] and 4.8% [95% CI (3.74-5.89), p < 0.001] respectively. CONCLUSION: Left colonic conduits placed retrosternally were safest.

Systematic Review and Meta-analysis of SurgicalTreatment of Non-Zenker's Oesophageal Diverticula.

BACKGROUND: Oesophageal diverticula are rare outpouchings of the oesophagus which may be classified anatomically as pharyngeal (Zenker's), mid-oesophageal and epiphrenic. While surgery is indicated for symptomatic patients, no consensus exists regarding the optimum technique for non-Zenker's oesophageal diverticula. The aim of this study was to determine the outcome of surgery in patients with non-Zenker's oesophageal diverticula. METHODS: PubMed, MEDLINE and the Cochrane Library (January 1990 to January 2016) were searched for studies which reported outcomes of surgery in patients with non-Zenker's oesophageal diverticula. Primary outcome measure was the rate of staple line leakage. RESULTS: Twenty-five observational studies involving 511 patients (259 male, median age 62 years) with mid-oesophageal (n = 53) and epiphrenic oesophageal (n = 458) diverticula who had undergone surgery [thoracotomy (n = 252), laparoscopy (n = 204), thoracoscopy (n = 42), laparotomy (n = 5), combined laparoscopy and thoracoscopy (n = 8)] were analysed. Myotomy was performed in 437 patients (85.5%), and anti-reflux procedures were performed in 342 patients (69.5%). Overall pooled staple line leak rates were reported in 13.3% [95% c.i. (11.0-15.7), p < 0.001] and were less common after myotomy (12.4%) compared with no myotomy (26.1%, p = 0.002). CONCLUSIONS: No consensus exists regarding the surgical treatment of non-Zenker's oesophageal diverticula, but staple line leakage is common and is reduced significantly by myotomy.

A rare complication with a single dose of alendronate.

The authors present a case of an 84-year-old patient who presented to the emergency department with sudden onset abdominal pain radiating to the neck. The patient's medication included warfarin, and alendronate, which was started by the general practitioner 2 days prior to presentation. Initial systemic examination and investigations, including chest x-ray, were unremarkable. Within 24 h of presentation the patient developed bilateral pneumonia with effusions. Due to continued clinical deterioration over the next 48 h, a CT thorax was performed that showed evidence of large oesophageal perforation with mediastinitis and gas in the mediastinum. The patient was treated with an expandable metal stent, bilateral chest drains, broad spectrum antibiotics, antifungals and total parenteral nutrition. Over a period of 8 weeks the patient made an excellent recovery. This rare case illustrates the importance of vigilance for the life-threatening complication of oesophageal perforation with alendronate treatment.

Prognostic significance of endoscopic ultrasound-defined pleural, pericardial or peritoneal fluid in oesophageal cancer.

BACKGROUND: Endoscopic ultrasound (EUS) is known to detect smaller effusion volumes than computerised tomography (CT), yet the outcomes for patients diagnosed with oesophageal carcinoma and EUS-defined pleural, pericardial or ascitic fluid effusions (EDFE) are unknown. The aim of this study was to determine the outcome of multidisciplinary stage directed treatment for such patients. METHODS: Forty-nine (9.2%) out of a consecutive 527 patients diagnosed with oesophageal cancer from a single regional upper gastrointestinal (GI) cancer network were found to have evidence of EDFE undetected by CT. Thirty-nine (79.6%) patients had pleural effusions, eight (16.3%) pericardial effusions, and two (4.1%) ascites. RESULTS: Twelve (24.4%) underwent surgery, 3 (6.1%) received neoadjuvant chemotherapy without subsequent surgery, 12 (24.5%) received definitive chemoradiotherapy (dCRT), and 22 (44.9%) received palliative treatment. Survival in patients with EDFE was significantly shorter (median and 2-year survival 15.6 months and 24%, respectively) when compared with patients without EDFE (26.7 months and 40%, respectively, p = 0.001), and was unrelated to EDFE type (p = 0.192). Two-year survival after oesophagectomy with or without neoadjuvant therapy was 45% in patients with EDFE compared with 42% in patients without EDFE (p = 0.668). CONCLUSIONS: EDFE was an important adverse prognostic indicator, but patients deemed to have operable tumours should still be treated with radical intent.

Prospective comparison of the perceived preoperative computed tomographic, endosonographic and histopathological stage of oesophageal cancer related to body mass indices.

Pre-morbid weight loss and low body mass index (BMI) have been reported to be associated with decreased odds of misclassification of the defined stage of oesophageal cancer by endoluminal ultrasound (EUS). The aim of this study was to assess the strengths of agreement between the perceived preoperative radiological T and N stage compared with the final histopathological stage related to four categories of BMI (low <20, normal 20-24.9, high 25-30, and obese >30 kg/m(2)). One hundred sixty-six patients with oesophageal carcinoma were studied. Strength of agreement between the CT and EUS stages and histopathological stage was determined by the weighted kappa statistic (Kw). Kw for EUS T stage related to increasing BMI category was 0.840 (P = 0.0001) to 0.620 (P = 0.001), compared with 0.415 (P = 0.018) to 0.260 (P = 0.011) for CT. Kw for EUS N stage related to increasing BMI category was 0.438 (P = 0.067) to 0.513 (P = 0.010), compared with 0.143 (P = 0.584) to 0.582 (P = 0.030) for CT. EUS was good at predicting tumour infiltration irrespective of BMI when compared with CT, while CT N staging accuracy improved with higher BMIs. Multidisciplinary teams should be aware of these limitations when planning treatment strategies.

Prognostic significance of gastrin expression in patients undergoing R0 gastrectomy for adenocarcinoma.

BACKGROUND: Gastrointestinal (GI) hormones regulate several GI functions, including the proliferation and repair of normal mucosa, and hormone receptors may therefore be implicated in the growth, invasion, and metastasis of cancers of the GI tract. The aim of this study was to determine the cellular distribution of gastrin in intestinal-type gastric cancers, and to determine its relationship to outcomes after R0 gastrectomy. METHODS: Eighty-six consecutive patients undergoing R0 gastrectomy for adenocarcinoma were studied. Normal gastric mucosa and tumor were stained for gastrin and their specific cellular distribution was determined. RESULTS: The duration of survival of patients whose tumors exhibited well-differentiated gastrin-positive tumor (GPT) cells (n = 12) was significantly poorer than that of patients whose tumors were GPT-negative (5-year survival, 30% vs 54%; P = 0.037). Patients with GPT-positive intestinal-type gastric cancer (5 of 47 patients) had the poorest survival of all (median, 14 months; 5-year survival, 0%; P = 0.006). In a multivariate analysis, only lymph node metastases (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.2 to 3.79; P = 0.01) and the presence of GPT cells (HR, 6.61; 95% CI, 1.74 to 25.09; P = 0.01) were independently and significantly associated with durations of survival in patients with intestinal-type gastric cancer. CONCLUSION: The presence of GPT cells in patients with gastric adenocarcinoma is a significant and independent prognostic indicator.

Relative value of repeat gastric ulcer surveillance gastroscopy in diagnosing gastric cancer.

BACKGROUND: Gastric cancer can present with the endoscopic appearances of a benign gastric ulcer (GU). Opinion remains divided on the need for follow-up of patients diagnosed with GU, and the aim of this study was to examine the long-term outcomes of patients whose GU proved malignant on follow-up gastroscopy. METHODS: Between October 1, 1995, and September 30, 2003, 25,579 gastroscopies were performed in one unit. These identified 544 patients with apparently benign GU, of whom 277 (51%) underwent 334 elective follow-up endoscopies. Twelve of these patients (4.3%) were shown to have a malignant ulcer; their outcomes were compared to those of the 296 other patients diagnosed with gastric cancers in this time frame. RESULTS: The patients in the GU cancer group had earlier stage disease (stage I, 33% vs 6.4%; chi2 = 11.2; DF1; P = 0.001), and were more likely to undergo R0 gastrectomy (50% vs 30%; chi2 = 2.064; DF1; P = 0.151) and to survive long term (46% vs 16%; log-rank chi2, 5.79; DF1; P = 0.0162) than patients in the comparison cohort. CONCLUSION: Gastroscopic follow-up of 50 patients with an apparently benign GU will identify 1 patient with a malignancy destined to survive for 5 years following R0 gastrectomy. This justifies the diagnostic effort of repeat gastroscopy to ensure complete healing of GU.

Influence of socio-economic deprivation on outcomes for patients diagnosed with gastric cancer.

OBJECTIVE: Socio-economic deprivation has an influence on the outcome for patients diagnosed with breast, colorectal and bronchial cancer, but there are few data on its association with gastric cancer. The aim of this study was to determine the influence of socio-economic deprivation on outcomes for patients with gastric cancer. MATERIAL AND METHODS: Three hundred and thirty consecutive patients with gastric adenocarcinoma presenting to a single hospital between 1 October 1995 and 30 June 2004 were studied prospectively and deprivation scores calculated using the National Assembly for Wales Indices of Multiple Deprivation. The patients were subdivided into quintiles for analysis. RESULTS: Inhabitants of the most deprived areas (quintile 5) were younger at presentation (median 70 years versus 74 years, p=0.007), and experienced longer delays in diagnosis (18 weeks versus 9 weeks, p=0.02) when compared with patients from the least deprived areas (quintile 1). Operative mortality was 3-fold higher for patients from the most deprived areas when compared with patients from less deprived areas (15% versus 5%, p=0.03). There was no correlation between stage of disease and socio-economic deprivation. For patients undergoing potentially curative surgery, the 5-year survival for patients from the most deprived areas was 32%, compared with 66% for patients from the least deprived areas (p=0.03). CONCLUSIONS: Socio-economic deprivation was associated with younger age at diagnosis, longer diagnostic delay, greater operative mortality and a shorter duration of survival following R0 gastrectomy. These poorer outcomes were not explained by the stage of disease at diagnosis.

Progressive CT system technology and experience improve the perceived preoperative stage of gastric cancer.

BACKGROUND: Our goals were to measure the accuracy of specialist helical computed tomography (CT) in the preoperative staging of gastric cancer, to determine the relative benefit of progressive CT system technology, and to determine the magnitude of any learning curve in radiological interpretation. METHODS: One hundred patients (median age, 70 years; range 27-86 years; 68 male) underwent a preoperative CT (73 helical [hCT], 27 multislice [mCT]), performed by a single specialist radiologist, followed by surgery within 3 weeks. The strength of the agreement between the perceived CT stage and the histopathological stage was determined for each CT system and also for four serial cohorts of 25 patients, by the weighted Kappa statistic (Kw). RESULTS: The Kw values for T, N, M1 liver, and M1 peritoneal stage were 0.40, 0.18, 0.36, and 0.09 for hCT, compared with 0.57, 0.67, 0.66 (all P < 0.001), and 0.24 (P = 0.06) for mCT. Serial Kw for T and N stages improved from 0.26 and -0.14 in the first quartile of patients to 0.61 and 0.73 (P < 0.001) in the last quartile of patients. CONCLUSION: The role of CT in the preoperative staging of gastric cancer is becoming stronger as CT technology improves.

Prospective evaluation of nutritional status related to body mass indices and outcomes after modified D2 gastrectomy for carcinoma.

AIMS: The aim of this study was to examine the perioperative nutritional status, body mass indices (BMI) and nutritional intakes of patients undergoing a modified D2 gastrectomy (preserving pancreas and spleen) for carcinoma to determine whether a relationship exists between the above and outcomes. METHODS: Fifty consecutive patients [median age 71 years, 38 male] with gastric adenocarcinoma were studied prospectively. RESULTS: Seven patients (14%) were obese (BMI > 30 kg/m2), 16 patients (32%) were overweight (BMI > 25 kg/m2), 21 patients (42%) were of normal weight (BMI 20-25 kg/m2), and six patients (12%) were underweight (BMI < 20 kg/m2). Operative morbidity was commoner in underweight patients (33%) when compared with overweight patients (17%, P = 0.391) and patients of normal weight (14%, P = 0.289). Fatal complications, however (two patients, 4%) were confined to overweight patients (P = 0.118). Preoperative serum albumin levels were significantly higher in overweight patients (43 g/dl) compared to underweight patients (34.5 g/dl; P = 0.003), though no correlation was found between patients' serum albumin levels and postoperative morbidity (r = -0.023, P = 0.877). Overweight patients were significantly less likely to achieve their protein requirements postoperatively than underweight patients (P = 0.037). Early enteral feeding contributed to 56% of the median energy requirements and 45% of the median protein requirements on the seventh postoperative day. CONCLUSION: BMI alone is a poor indicator of outcomes after modified D2 gastrectomy for carcinoma. The role of early enteral nutrition in patients undergoing gastrectomy for cancer deserves further evaluation.

Prognostic significance of acute presentation with emergency complications of gastric cancer.

BACKGROUND: Although acute complications necessitating emergency hospital admission are well documented in patients with carcinoma of the colon, comparable data for patients with gastric carcinoma is thin. The aim of this study, therefore, was to examine the outcomes of patients presenting to hospital as acute admissions with emergency complications of previously undiagnosed gastric cancer. METHODS: Three hundred consecutive patients with gastric adenocarcinoma were studied prospectively, and subdivided into two groups according to whether the patients were referred as acute emergencies ( n = 116) or as outpatients ( n = 184). RESULTS: The commonest emergency complications were: abdominal pain (57%), vomiting (41%), gastrointestinal bleeding (37%), dysphagia (26%), and a palpable mass (18%). Stages of disease were significantly more advanced in patients presenting acutely (I : II : III : IV = 7 : 11 : 27 : 71) compared with patients referred via outpatients (20 : 23 : 50 : 91, Chi(2) = 3.955; DF, 1; P = 0.047). R0 gastrectomy was significantly less likely after acute presentation (23 patients; 20%) compared with patients referred via outpatients (70 patients; 38%; Chi(2) = 11.037; DF, 1; P = 0.001). Cumulative 5-year survival for patients referred acutely was 9%, compared with 22% after outpatient referral (Chi(2) = 9.11; DF, 1; P = 0.0025). Multivariate analysis revealed two factors to be significantly and independently associated with durations of survival: stage of disease (hazard ratio [HR], 1.742; 95% confidence interval [CI], 1.493-2.034; P = 0.0001) and presentation with acute complications (HR, 1.561; 95% CI, 1.151-2.117; P = 0.004). CONCLUSION: Emergency complications of gastric cancer are a significant and independent prognostic marker of poor outcome.

Open-access gastroscopy is associated with improved outcomes in gastric cancer.

OBJECTIVE: To examine whether patients with gastric cancer diagnosed via open-access gastroscopy (OAG) differ in their outcomes compared with patients referred conventionally to outpatient clinics or as acute emergencies. DESIGN AND SETTING: Prospective observational study in the gastroenterology and surgical units of a large district general hospital. PARTICIPANTS: One hundred consecutive patients with gastric adenocarcinoma. MAIN OUTCOME MEASURES: Data were collected prospectively and subdivided into two groups according to whether the patients were referred via the open-access route or the conventional route. RESULTS: Diagnostic delay from onset of symptoms was shorter for patients referred via OAG compared with those referred conventionally. Stages of disease were significantly earlier in patients referred via OAG compared with patients referred conventionally. Potentially curative resection was significantly more likely following OAG than after conventional referral. Cumulative five-year survival for patients referred via OAG was 30% compared with 12% after conventional outpatient referral and 13% after acute referral. Multivariate analysis revealed three factors to be associated with survival: stage of disease, distant metastases and referral via the open-access route. CONCLUSIONS: Gastric cancers presenting at OAG were diagnosed at an earlier stage than cancers diagnosed after conventional referral. This led to a higher proportion of potentially curative resections and better five-year survival.

Western body mass indices need not compromise outcomes after modified D2 gastrectomy for carcinoma.

BACKGROUND: To determine the role of body mass index (BMI) in a Western population on outcomes after modified D2 gastrectomy (preserving pancreas and spleen where possible) for gastric cancer. METHODS: Eighty-four consecutive patients undergoing an R0 modified D2 gastrectomy for gastric cancer were studied prospectively. Male patients with a BMI of greater than 24.7 kgm(-2) and female patients with a BMI of greater than 22.6 kgm(-2) were classified as overweight and compared with control patients with BMIs below these reference values. RESULTS: Thirty-eight of the patients (45%) were classified as overweight. The median BMI of the overweight patients was 27.0 kgm(-2) (range, 22.7-34.7 kgm(-2); 27 males) compared with 21.2 kgm(-2) (range, 15.2-24.7 kgm(-2), 31 males) for control patients. Operative morbidity and mortality were 26% and 7.9% in overweight patients compared with 22% and 6.5% in control patients (morbidity, chi(2) = 0.240; df = 1; P = 0.624; mortality, chi(2) = 0.059; df = 1; P = 0.808). Cumulative survival at 5 years was 52% for overweight patients compared with 55% for control patients (chi(2) = 0.15; df = 1; P = 0.7002). In a multivariate analysis, the number of lymph node metastases (hazard ratio, 1.441; 95% confidence interval [CI], 1.159-1.723; P = 0.009) and splenectomy (hazard ratio, 12.111; 95% CI, 9.645-14.577; P = 0.043) were independently associated with the duration of survival. CONCLUSION: High BMIs were not associated with increased operative risk, and longterm outcomes were similar in the two groups after modified D2 gastrectomy.

Laparoscopy significantly improves the perceived preoperative stage of gastric cancer.

BACKGROUND: The aim of this study was to examine the accuracy of laparoscopy is staging patients with gastric cancer in comparison with preoperative computed tomography (CT) examination. METHODS: One hundred patients out of a consecutive series of 258 patients with gastric adenocarcinoma underwent a preoperative staging CT followed by a staging laparoscopy. The strengths of the agreement between the CT stage, the laparoscopic stage, and the final histopathological stage were determined by the weighted Kappa statistic (Kw). RESULTS: The strengths of agreement between the CT stage and the final histopathological stage were Kw = 0.336 (95% confidence interval [CI]; 0.172-0.5; P = 0.0001) for T stage and 0.378 (95% CI; 0.226-0.53; P = 0.0001) for M stage, compared with 0.455 (95% CI; 0.301-0.609; P = 0.0001) and 0.73 (95% CI; 0.596-0.864; P = 0.0001) for the laparoscopic T and M stages, respectively. Unsuspected metastases that were not detected by CT, were found in 21 patients at laparoscopy, all of whom had T3 or T4 locally advanced tumors evident on CT. CONCLUSIONS: Preoperative laparoscopic staging of gastric cancer is indicated for potential surgical candidates with locally advanced disease in the absence of metastases on CT. The aim of this study was to examine the accuracy of laparoscopy in staging patients with gastric cancer in comparison with preoperative computed tomography (CT) examination.