Prognostic significance of positive circumferential resection margin post neoadjuvant chemotherapy in patients with esophageal or gastro-esophageal junction adenocarcinoma.

BACKGROUND: The aim of the present study was to assess the prognosis of patients with esophageal or gastroesophageal junction (E/GEJ) adenocarcinoma extending beyond the muscularis propria layer (≥ypT3) and positive circumferential resection margin (CRM), post neoadjuvant chemotherapy. METHODS: 177 patients were retrospectively studied. The majority (94.9%) received ECX (epirubicin, cisplatin, capecitabine), and all had clear proximal/distal resection margins. CRM was defined as positive (CRM+) when it was directly infiltrated (infiltrated CRM) or when tumor cells were detected within 1 mm from CRM (close CRM) and as negative (CRM-) when tumor cells were found in a distance > 1 mm from CRM. RESULTS: CRM+ was found in 83 patients (46.9%). Of them, infiltrated CRM was recorded in 36 (20.3%) and close CRM in 47 (26.6%). Adjuvant chemotherapy was administered to 132 patients (74.6%). Lymphovascular invasion and primary site in the lower esophagus were independently associated with higher risk of CRM+. Patients with infiltrated CRM, compared to those with close CRM and those CRM-, had the shortest median time-to-relapse (11.4 vs. 15.6 vs. 22.1 months, respectively, p = 0.005) and overall survival (18.7 vs. 23.1 vs. 38.8 months, respectively, p = 0.001). However, CRM status was not an independent predictor of poor outcome. Symptomatic isolated locoregional recurrences were rare in both CRM+ and CRM-patients (4/56 [7.1%] vs. 5/52 [9.6%], p = 0.736), as well as in infiltrated vs. non-infiltrated CRM (CRM- and close CRM) (0/26 [0%] vs. 9/82 [11.0%], p = 0.110). CONCLUSION: Although CRM status is associated with poor outcome, it does not represent an independent prognostic factor. The status of CRM did not significantly influence the pattern of cancer relapse.

Achalasia with massive oesophageal dilation causing tracheomalacia and asthma symptoms.

Achalasia is an uncommon oesophageal motor disorder characterized by failure of relaxation of the lower oesophageal sphincter and muscle hypertrophy, resulting in a loss of peristalsis and a dilated oesophagus. Gastrointestinal symptoms are invariably present in all cases of achalasia observed in adults. We report a case of a 34 year-old female patient with long standing history of asthma-like symptoms, labelled as uncontrolled and steroid resistant asthma with no gastrointestinal manifestations. Thoracic CT scan revealed a massive oesophagus due to achalasia, which caused severe tracheomalacia as a result of tracheal compression. Her symptoms regressed completely after a laparoscopic Heller myotomy surgery intervention.

Patient-Reported Outcomes for Acute Gallstone Pathology.

BACKGROUND: A number of prominent surgical trials and clinical guidelines regard length of hospital stay and rates of daycase surgery as being of upmost importance following cholecystectomy. However, it is unclear whether these outcomes also matter to patients. This study aimed to identify the factors patients regard as most important when admitted with acute gallstone pathology. METHODS: A 41-item survey was produced by combining outcomes assessed in recent clinical trials with results from a preliminary patient questionnaire. This was then given out prospectively to patients presenting with acute gallstone pathology, prior to their cholecystectomy. Patients were asked to read an information sheet about laparoscopic cholecystectomy and then complete the survey, scoring each item out of 100 in terms of importance to them. RESULTS: Fifty-six patients completed the survey (43 females; median age 51 years). Diagnoses were: cholecystitis (28 patients), biliary colic (13), pancreatitis (10), common bile duct stones (3) and cholangitis (2). The top-scoring survey item was "long-term quality of life after surgery", with a median value of 97 out of 100. Other high-scoring items included "cleanliness of the ward environment" and "pain control after surgery" (both 96). The lowest-scoring item was "being treated as a daycase" (54). CONCLUSION: Patients with acute gallstone pathology view long-term quality of life after surgery as the most important factor and daycase surgery as the least important. These results should be considered when planning future surgical trials and clinical guidelines.

DiPALS: Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis - a randomised controlled trial.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease resulting in death, usually from respiratory failure, within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment that when given to patients in respiratory failure leads to improved survival and quality of life. Diaphragm pacing (DP), using the NeuRx/4(®) diaphragm pacing system (DPS)™ (Synapse Biomedical, Oberlin, OH, USA), is a new technique that may offer additional or alternative benefits to patients with ALS who are in respiratory failure. OBJECTIVE: The Diaphragm Pacing in patients with Amyotrophic Lateral Sclerosis (DiPALS) trial evaluated the effect of DP on survival over the study duration in patients with ALS with respiratory failure. DESIGN: The DiPALS trial was a multicentre, parallel-group, open-label, randomised controlled trial incorporating health economic analyses and a qualitative longitudinal substudy. PARTICIPANTS: Eligible participants had a diagnosis of ALS (ALS laboratory-supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria), had been stabilised on riluzole for 30 days, were aged ≥ 18 years and were in respiratory failure. We planned to recruit 108 patients from seven UK-based specialist ALS or respiratory centres. Allocation was performed using 1 : 1 non-deterministic minimisation. INTERVENTIONS: Participants were randomised to either standard care (NIV alone) or standard care (NIV) plus DP using the NeuRX/4 DPS. MAIN OUTCOME MEASURES: The primary outcome was overall survival, defined as the time from randomisation to death from any cause. Secondary outcomes were patient quality of life [assessed by European Quality of Life-5 Dimensions, three levels (EQ-5D-3L), Short Form questionnaire-36 items and Sleep Apnoea Quality of Life Index questionnaire]; carer quality of life (EQ-5D-3L and Caregiver Burden Inventory); cost-utility analysis and health-care resource use; tolerability and adverse events. Acceptability and attitudes to DP were assessed in a qualitative substudy. RESULTS: In total, 74 participants were randomised into the trial and analysed, 37 participants to NIV plus pacing and 37 to standard care, before the Data Monitoring and Ethics Committee advised initial suspension of recruitment (December 2013) and subsequent discontinuation of pacing (on safety grounds) in all patients (June 2014). Follow-up assessments continued until the planned end of the study in December 2014. The median survival (interquartile range) was 22.5 months (lower quartile 11.8 months; upper quartile not reached) in the NIV arm and 11.0 months (6.7 to 17.0 months) in the NIV plus pacing arm, with an adjusted hazard ratio of 2.27 (95% confidence interval 1.22 to 4.25; p = 0.01). CONCLUSIONS: Diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure. FUTURE WORK: It may be that certain population subgroups benefit from DP. We are unable to explain the mechanism behind the excess mortality in the pacing arm, something the small trial size cannot help address. Future research should investigate the mechanism by which harm or benefit occurs further. TRIAL REGISTRATION: Current Controlled Trials ISRCTN53817913. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 45. See the HTA programme website for further project information. Additional funding was provided by the Motor Neurone Disease Association of England, Wales and Northern Ireland.

Out of sight but kept in mind: complications and imitations of dropped gallstones.

OBJECTIVE: The purpose of this article is to describe the diagnostic pitfalls caused by dropped gallstones left in situ after laparoscopic cholecystectomy. CONCLUSION: Dropped gallstones may rarely become symptomatic, causing recurrent abscesses. Diagnosis is challenging due to unusual clinical presentations, myriad locations, and radiologically occult calculi. Even asymptomatic dropped gallstones may cause diagnostic confusion by masquerading as intraperitoneal neoplastic deposits. Radiologists should be aware of techniques for identifying and retrieving dropped gallstones and be wary of their complications and imitations in patients who have undergone laparoscopic cholecystectomy.

Protocol for diaphragm pacing in patients with respiratory muscle weakness due to motor neurone disease (DiPALS): a randomised controlled trial.

BACKGROUND: Motor neurone disease (MND) is a devastating illness which leads to muscle weakness and death, usually within 2-3 years of symptom onset. Respiratory insufficiency is a common cause of morbidity, particularly in later stages of MND and respiratory complications are the leading cause of mortality in MND patients. Non Invasive Ventilation (NIV) is the current standard therapy to manage respiratory insufficiency. Some MND patients however do not tolerate NIV due to a number of issues including mask interface problems and claustrophobia. In those that do tolerate NIV, eventually respiratory muscle weakness will progress to a point at which intermittent/overnight NIV is ineffective. The NeuRx RA/4 Diaphragm Pacing System was originally developed for patients with respiratory insufficiency and diaphragm paralysis secondary to stable high spinal cord injuries. The DiPALS study will assess the effect of diaphragm pacing (DP) when used to treat patients with MND and respiratory insufficiency. METHOD/DESIGN: 108 patients will be recruited to the study at 5 sites in the UK. Patients will be randomised to either receive NIV (current standard care) or receive DP in addition to NIV. Study participants will be required to complete outcome measures at 5 follow up time points (2, 3, 6, 9 and 12 months) plus an additional surgery and 1 week post operative visit for those in the DP group. 12 patients (and their carers) from the DP group will also be asked to complete 2 qualitative interviews. DISCUSSION: The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND with respiratory muscle weakness. The project is funded by the National Institute for Health Research, Health Technology Assessment (HTA) Programme (project number 09/55/33) and the Motor Neurone Disease Association and the Henry Smith Charity. TRIAL REGISTRATION: Current controlled trials ISRCTN53817913. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the HTA programme, NIHR, NHS or the Department of Health.

Acoustic cough-reflux associations in chronic cough: potential triggers and mechanisms.

BACKGROUND & AIMS: Central sensitization is thought to play a role in chronic cough and might explain the temporal association between cough and gastroesophageal reflux (GOR) in patients in whom non-GOR causes have been excluded. Using our novel simultaneous acoustic cough recording and impedance/pH monitoring technique, we aimed to explore this further by assessing such temporal associations and their relationship to the acidity, duration, and proximal extent of reflux and the presence of erosive disease and cough reflex sensitivity in unselected patients (ie, including non-GOR causes) with chronic cough. METHODS: Twenty-four hour ambulatory acoustic cough monitoring with simultaneous impedance/pH recording was carried out in 71 unselected patients with chronic cough, aged 51-64 years (47 female). In addition, all patients underwent cough reflex sensitivity testing to citric acid, and 66 patients underwent gastroscopy. Temporal associations between cough and reflux were expressed using the symptom association probability. RESULTS: Seventy percent of patients exhibited temporal associations, with 48% having a positive symptom association probability (SAP(R-C)) for cough preceded by reflux (mainly distal), 56% a positive symptom association probability (SAP(C-R (2 min))) for reflux preceded by cough, and 32% both. Moreover, SAP(R-C) positive patients had a more sensitive cough reflex (P = .03) but similar esophageal reflux exposure and erosive disease, together with similar prevalence of extraesophageal causes of cough compared with SAP(R-C) negative patients. Reflux immediately following cough was rare. CONCLUSIONS: Cough temporally associates with reflux irrespective of proposed diagnoses, may be self-perpetuating in some patients, and is likely to be driven by central processes.

Randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in severe acute pancreatitis.

BACKGROUND: Based on equivocal clinical data, intravenous antioxidant therapy has been used for the treatment of severe acute pancreatitis. To date there is no randomised comparison of this therapy in severe acute pancreatitis. METHODS: We conducted a randomised, double blind, placebo controlled trial of intravenous antioxidant (n-acetylcysteine, selenium, vitamin C) therapy in patients with predicted severe acute pancreatitis. Forty-three patients were enrolled from three hospitals in the Manchester (UK) area over the period June 2001 to November 2004. Randomisation stratified for APACHE-II score and hospital site, and delivered groups that were similar at baseline. RESULTS: Relative serum levels of antioxidants rose while markers of oxidative stress fell in the active treatment group during the course of the trial. However, at 7 days, there was no statistically significant difference in the primary end point, organ dysfunction (antioxidant vs placebo: 32% vs 17%, p = 0.33) or any secondary end point of organ dysfunction or patient outcome. CONCLUSIONS: This study provides no evidence to justify continued use of n-acetylcysteine, selenium, vitamin C based antioxidant therapy in severe acute pancreatitis. In the context of any future trial design, careful consideration must be given to the risks raised by the greater trend towards adverse outcome in patients in the treatment arm of this study.

Benign gastro-bronchial fistula - an uncommon complication of esophagectomy: case report.

BACKGROUND: Gastro-bronchial fistula (GBF) is a rare and devastating complication following esophagectomy. Making the correct diagnosis is difficult and there is no agreement on the treatment for this rare condition. CASE PRESENTATION: We report the case of a 56-year-old man who presented with features of repeated aspiration and chest infections six years following an esophagectomy for Barrett's esophagus. Despite extensive investigations the cause of symptoms was difficult to determine. The correct diagnosis of fistula from stomach to right main stem bronchus was made at bronchoscopy under general anesthesia. After ruling out local recurrence of cancer, a successful primary repair was carried out by resection of fistula and direct repair of gastric conduit and bronchus. He is well after 6 months of treatment. CONCLUSION: Late development of gastro-bronchial fistula is a rare complication of esophageal resection that may be difficult to diagnose. Surgical resection and direct closure is the treatment of choice, although the method of treatment should be tailored according to the anatomy of the fistula and the patient's condition.