Concurrent cisplatin/etoposide plus 3D-conformal radiotherapy followed by surgery for stage IIB (superior sulcus T3N0)/III non-small cell lung cancer yields a high rate of pathological complete response

Introduction: Optimal preoperative treatment of stage IIB (Pancoast)/III non-small cell lung cancer (NSCLC) remains undetermined and a subject of controversy. The goal of our study is to confirm feasibility and pathological response rates after induction chemoradiation (CRT) in our community-based treatment center. Patients and methods: Patients were selected according to functional and resectability criteria. Induction treatment comprised 3D conformal 4500 cGy radiotherapy delivered to the primary tumor and pathologic hilar and/or mediastinal lymph nodes on CT scan with an extra-margin of 1–1.5 cm. Concurrent chemotherapy regimen was cisplatinum 20 mg/m² d1–d5 and etoposide 50 mg/m² d1–d5, d1–5 d29–33. Within 3–4 weeks after CRT completion, operability was re-assessed accordingly. Surgery was performed 4–6 weeks after CRT completion in patients (pts) deemed resectable. Inoperable pts were referred for a 20–25 Gy boost ±1 extra-cycle of cisplatinum + etoposide. Results: From 1996 to 2005, 107 pts were initially selected for treatment and received induction chemoradiation (stage IIB-Pancoast 18, IIIA 58 and IIIB 31, squamous cell carcinoma 48%, adenocarcinoma 44%, large-cell undifferentiated carcinoma 14%). After preoperative evaluation, 72 pts (67%) had a thoracotomy (pneumonectomy 21, lobectomy 45, bilobectomy 5) and all but one (unresectable tumor) had a macroscopic complete resection. During the 3-month postoperative time, five patients (6.9%) died, four after pneumonectomy (right 3, left 1). The analysis of tumoral samples showed a pathological complete response rate or microscopic residual foci of 39.5%. Median follow-up time was 22.3 months (survivors: 36.8 months), 2-year and 3-year overall survival rates were 55% and 40%, respectively (median = 26.7 months) for all the intention-to-treat population (n = 107), 62% and 51% (median = 36.5 months) for 71 resected pts, 41% and 16% for 36 non-resected pts (median = 19.1 months). On multivariate analysis, surgical resection and tumoral necrosis >50% (or pathological complete response) were the most pertinent predictive factors of the risk of death (hazard ratio = 0.50 and 0.48, p = 0.006 and 0.038, respectively). Conclusion: Surgery was feasible after induction chemoradiation, particularly lobectomy in PS 0–1, stage IIB (Pancoast)/III NSCLC pts but pneumonectomy carries a high risk of postoperative death (particularly, right pneumonectomy). Pathological response to induction chemoradiation was complete in 39.5% of patients and was a significant predictive factor of overall survival.     

Ten-year follow up after laparoscopic Nissen fundoplication for gastroesophageal reflux disease

Laparoscopic Nissen fundoplication was first undertaken in the early 1990s. Appreciable numbers of patients with 10-year follow up are only now available. This study assesses long-term outcome and durability of outcome after laparoscopic Nissen fundoplication for treatment of gastro-esophageal reflux disease. Since 1991, 829 patients have undergone laparoscopic fundoplications and are prospectively followed. Two hundred thirty-nine patients, 44 per cent male, with a median age of 53 years (+/- 15 standard deviation) underwent laparoscopic Nissen fundoplications at least 10 years ago; 28 (12%) patients were "redo" fundoplications. Before and after fundoplication, among many symptoms, patients scored the frequency and severity of dysphagia, chest pain, vomiting, regurgitation, choking, and heartburn using a Likert scale (0 = never/not bothersome to 10 = always/very bothersome). Symptom scores before versus after fundoplication were compared using a Wilcoxon matched-pairs test. Data are reported as median, mean +/- standard deviation, when appropriate. After fundoplication, length of stay was 2 days, 3 days +/- 4.8. Intra-operative inadvertent events were uncommon and without sequela: 1 esophagotomy, 1 gastrotomy, 3 cardiac dysrhythmias, and 3 CO2 pneumothoraces. Complications after fundoplication included: 1 postpneumonic empyema, 3 urinary retentions, 2 superficial wound infections, 1 urinary tract infection, 1 ileus, and 1 intraabdominal abscess. There were two perioperative deaths; 88 per cent of the patients are still alive. After laparoscopic Nissen fundoplication, frequency and severity scores dramatically improved for all symptoms queried (P < 0.001), especially for heartburn frequency (8, 8 +/- 3.2 versus 2, 3 +/- 2.8, P < 0.001) and severity (10, 8 +/- 2.9 versus 1, 2 +/- 2.5, P < 0.001). Eighty per cent of patients rate their symptoms as almost completely resolved or greatly improved, and 85 per cent note they would again have the laparoscopic fundoplication as a result of analysis of our initial experience, thereby promoting superior outcomes in the future. Nonetheless, follow up at 10 years and beyond of our initial experience documents that laparoscopic fundoplication durably provides high patient satisfaction resulting from long-term amelioration of the frequency and severity of symptoms of gastroesophageal reflux disease. These results promote further application of laparoscopic Nissen fundoplication.     

Laparoscopic Heller myotomy with anterior fundoplication ameliorates symptoms of achalasia in pediatric patients

BACKGROUND: This study was undertaken to define outcomes after laparoscopic Heller myotomy with anterior fundoplication in pediatric patients and compare their outcomes with those in adults. STUDY DESIGN: A total of 337 patients have undergone laparoscopic Heller myotomy with anterior fundoplication since 1992, and were prospectively followed; 14 were pediatric patients of median age 17 years (range 11 to 19 years). Symptoms noted by pediatric patients before and after myotomy were compared with symptoms of 56 concurrently treated adults (4 treated adults for each pediatric patient) of median age 48 years. Among many symptoms, patients scored the severity and frequency of dysphagia, chest pain, regurgitation, choking, vomiting, and heartburn before and after myotomy using a Likert scale, ranging from 0 (never/not bothersome) to 10 (always/very bothersome). Followups were 38 months, 42 months+/-33.1. Data are reported as median, mean +/- SD. RESULTS: For pediatric patients, length of stay after myotomy was 2 days, 3 days+/-2.9 versus 2 days, 2+/-2.1 for adults. Before myotomy, symptom frequency and severity were similar between groups. After myotomy, symptom frequency and severity were similar between pediatric and adult patients, except for the frequency of chest pain. CONCLUSIONS: Achalasia can produce disabling symptoms, which were similar between pediatric and adult patients before myotomy. Laparoscopic Heller myotomy with anterior fundoplication ameliorated symptoms of achalasia in all patients, with postmyotomy symptoms similar between pediatric and adult patients. Laparoscopic Heller myotomy dramatically improved symptoms of achalasia in pediatric patients and its use is encouraged.     

Risk profile of myocardial infarction in young versus older adults

Background

In developing countries, the number of adults who develop myocardial infarction (MI) at a young age is high. The popularity of waterpipe smoking (WPS) has increased among the same age group. It is unknown if WPS contributes to the incidence of early-onset MI.

A Phase IIb Trial Assessing the Addition of Disulfiram to Chemotherapy for the Treatment of Metastatic Non‐Small Cell Lung Cancer

Background.

Disulfiram, an alcohol aversion agent, has been in use for >50 years. Numerous authors have reported an anticancer effect of this drug in vitro and in mouse models. More recently, several reports have claimed that disulfiram also possesses anti-stem cell activity. We set out to obtain initial data regarding the safety of combining this drug with chemotherapy and the possible effectiveness of disulfiram in a combination regimen in non-small cell lung cancer (NSCLC).

Methods.

This phase II, multicenter, randomized, double-blinded study assessed the safety and efficacy of adding of disulfiram to cisplatin and vinorelbine for six cycles. Newly diagnosed NSCLC patients were recruited. Patients with either stage IV or what was considered at the time “wet IIIb” (since 2009, these patients have been considered stage IV) were recruited. The patients were treated with only chemotherapy, and none were treated with either surgery or chemoradiation. Disulfiram was administered at a dose of 40 mg three times daily.

Results.

Forty patients were treated for more than two cycles, half with and half without disulfiram, which was well tolerated. An increase in survival was noted for the experimental group (10 vs. 7.1 months). Interestingly, there were only two long-term survivors, both in the disulfiram group.

Conclusion.

The addition of disulfiram to a combination regimen of cisplatin and vinorelbine was well tolerated and appeared to prolong survival in patients with newly diagnosed non-small cell lung cancer. The results from this small study seem encouraging enough for assessment in larger trials. Disulfiram is an inexpensive and safe drug; if its addition to chemotherapy could be shown to prolong survival, an effective regimen could be established and used widely, even in resource-poor countries.     

MR-IMPACT: comparison of perfusion-cardiac magnetic resonance with single-photon emission computed tomography for the detection of coronary artery disease in a multicentre, multivendor, randomized trial.

AIMS: To determine in a multicentre, multivendor trial the diagnostic performance for perfusion-cardiac magnetic resonance (perfusion-CMR) in comparison with coronary X-ray angiography (CXA) and single-photon emission computed tomography (SPECT). METHODS AND RESULTS: Of 241 eligible patients from 18 centres, 234 were randomly dosed with 0.01, 0.025, 0.05, 0.075, or 0.1 mmol/kg Gd-DTPA-BMA (Omniscantrade mark, GE-Healthcare) per stress (0.42 mg/kg adenosine) and rest perfusion study. Coronary artery disease (CAD) was defined as diameter stenosis > or =50% on quantitative CXA. Five CMR and eight SPECT studies (of 225 complete studies) were excluded from analyses due to inadequate quality (three blinded readers scored per modality). The comparison of CMR vs. SPECT was based on receiver operating characteristic (ROC) analysis. Perfusion-CMR at the optimal CM dose (0.1 mmol/kg) had similar performance as SPECT, if only the SPECT studies of the 42 patients with this dose were considered [area under ROC curve (AUC): 0.86 +/- 0.06 vs. 0.75 +/- 0.09 for SPECT, P = 0.12]; however, diagnostic performance of perfusion-CMR was better vs. the entire SPECT population (AUC: 0.67 +/- 0.05, n = 212, P = 0.013). CONCLUSIONS: In this multicentre, multivendor trial, ROC analyses suggest perfusion-CMR as a valuable alternative to SPECT for CAD detection showing equal performance in the head-to-head comparison. Comparing perfusion-CMR with the entire SPECT population suggests CMR superiority over SPECT, which warrants further evaluation in larger trials.     

Ileal pouch anal-anastomosis without protective ileostomy

AIM: Ileo-anal anastomosis (IAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP) is usually associated with a defunctioning ileostomy, which may in itself cause morbidity. We report the results of a series of patients undergoing IAA without ileostomy. METHODS: Between 1993 and 1998, 84 patients underwent IAA without ileostomy: 51 for FAP, 30 for UC, 2 for non familial colonic polyposis and 1 for indeterminate colitis. Patients taking > 30 mg steroids daily were excluded. The decision not to fashion an ileostomy was taken if there were no perioperative difficulties. RESULTS: One patient died from a pulmonary embolus. Early and late complications were seen in 25 (30%) and 23 patients (27%) respectively, necessitating reoperation in 13, including three temporary ileostomies and one pouch excision for Crohn's disease. Functional results were analysed in 81 patients. Median follow-up was 22 months, the mean number of stools per day was 3.8 +/- 1. Daytime and night time continence was normal in 77 (95%) and 73 patients (90%) respectively. In 66 patients (94%) there was no urgency and in 61 (75%) no need for constipating agents. CONCLUSIONS: For a selected group of patients undergoing an IAA, a defunctioning ileostomy may be avoided. Morbidity and functional results are equivalent to those obtained with a defunctioning ileostomy     

Effects of preoperative radiotherapy for primary resectable rectal adenocarcinoma on male sexual and urinary function

PURPOSE: The purpose of this study was to determine whether preoperative radiotherapy had an influence on the urinary and sexual function of patients having a sphincter-saving, nerve-preserving total mesorectal excision. METHODS: Urinary and sexual function of male patients undergoing sphincter-saving, nerve-preserving total mesorectal excision for primary resectable rectal carcinoma between January 1998 and December 1999 were evaluated retrospectively. Assessment was by standardized questionnaires. RESULTS: Fifty male patients met the inclusion criteria. Three patients had died (hepatic metastases), and five were living outside the European community and could not be contacted. Sixteen patients underwent preoperative radiotherapy (Group 1), and 26 patients were not treated preoperatively (Group 2). There was no perioperative mortality. Age, tumor stage, and localization of the tumor were comparable. Median follow-up was 20 months. Urinary function was not significantly different. One patient in Group 1 and 2 patients in Group 2 were impotent before surgery. All remaining patients in Group 2 (n = 24) and 11 of 15 remaining patients in Group 1 were sexually active (P = 0.016). All sexually active patients (n = 24) in Group 2 and 9 of the 11 sexually active patients in Group 1 have normal ejaculation (P = 0.09). CONCLUSION: Preoperative radiotherapy for primary resectable rectal carcinoma treated by total mesorectal excision with autonomic nerve preservation may impair male sexual function.     

The use of contrast echocardiography: a matter of clinical judgement.

In their editorial, Buck and Erbel¹ raise the important questionin which settings application of contrast agents to an echocardiographicexamination is appropriate. There is no doubt that the beautyof echocardiography relates to its ease of use. We should acknowledgethat highest accuracy in the determination of left ventricularfunction is