Current status of laparoscopic transhiatal esophagectomy for esophageal cancer patients: a systematic review of the literature.

Minimally invasive techniques in transhiatal esophagectomy (THE) were introduced to reduce morbidity and enhance postoperative recovery. Aim of this study was to systematically review the current status and possible beneficial effects of the minimally invasive approach in THE. A systematic search was performed in PubMed, the Cochrane Library, and Embase to identify English articles published on laparoscopic THE. Comparative cohort studies were included for critical appraisal. Data describing perioperative and oncological outcomes were analyzed. A total of four comparative cohort studies that compared laparoscopic THE (n = 122) with open THE (n = 144) and four noncomparative cohort studies reporting on laparoscopic THE (n = 212) were included in this review. Median blood loss was significantly lower in the laparoscopic group in all studies (100-500 vs. 526-900 mL). Length of hospital stay was also significantly shorter for the laparoscopic approach in all studies (9-13 vs. 12-16 days). One study reported less major postoperative complications after laparoscopic THE (12 vs. 23%), in the other studies no differences were found. Also no differences were found with regard to operating time, postoperative morbidity, radicality, and lymph node retrieval. Based on these pioneer studies, laparoscopic THE was demonstrated to be safe and feasible with evidence of reduced blood loss and shorter hospital stays. However, level 1 evidence is lacking and further research is warranted to confirm these findings and also to evaluate long-term oncologic outcomes.

The effect of perioperative chemotherapy for patients with an adenocarcinoma of the gastroesophageal junction: A propensity score matched analysis.

BACKGROUND: The optimal neoadjuvant approach for patients with adenocarcinomas of the gastroesophageal junction (GEJ) remains unclear. Aim of this study was to evaluate the usefulness of perioperative chemotherapy in these patients. METHOD: Consecutive patients with GEJ adenocarcinoma, treated with surgery alone or chemotherapy plus surgery, were included from a prospective database (2003-2013). Propensity score matching was used to build comparable groups. Response to chemotherapy was assessed according to standardized regression grading. RESULTS: After propensity score matching, 196 patients were included. Chemotherapy was administered in 124 patients (63%). There was no difference between the chemotherapy plus surgery and surgery-alone group regarding overall and disease-free survival (p = 0.351 and p = 0.529). Pathological good response (i.e. tumor regression grading [TRG] 1-3) was achieved in 32 patients (34%), whereas 81 (66%) had poor response (TRG 4). Good responders had lower ypT-stage (p < 0.001), lower ypN-stage (p < 0.001) and more R0-resections (100% vs. 78%, p = 0.016) compared to surgery-alone patients, which improved the 5-year survival from 35% to 67% (p = 0.002). They also developed less recurrences (35% vs. 57%, p = 0.048). In poor responders, histopathology did not differ compared to surgery-alone and more recurrences were found (73% vs. 57%, p = 0.037). Overall survival in poor responders was 21% compared to 35% in surgery-alone patients (p = 0.551). CONCLUSION: Perioperative chemotherapy for GEJ adenocarcinoma leads to increased survival in good responders (34%) as compared to surgery alone. Poor responders had no survival benefit and developed more recurrences, which underlines the importance of the search for predictive biological or radiological markers to predict or assess chemotherapy sensitivity.

Staging of adenocarcinoma of the gastroesophageal junction.

BACKGROUND: Clinical staging of adenocarcinoma of the gastroesophageal junction (GEJ) determines the curative treatment regimen containing either neoadjuvant chemotherapy or chemoradiotherapy followed by either gastrectomy or esophagectomy. The value of current diagnostic tools is a matter of debate. METHODS: A prospective database (2003-2013) was used to identify 266 consecutive patients with adenocarcinoma of the GEJ in order to evaluate the accuracy of endoscopic ultrasound (EUS) and computed tomography (CT) regarding tumor localization according to Siewert, nodal status and its consequences on treatment strategy. RESULTS: Overall accuracy in determining tumor localization was 73% for endoscopy/EUS and 61% for CT (p = 0.018). With endoscopy/EUS, the accuracy was 97%, 66% and 75% respectively for type I, II and III. With CT this was respectively 69%, 57% and 80%. The overall accuracy for determining N-status (N0/N+) per patient was 75% for EUS and 71% for CT. Accuracy for determining a positive nodal station in patients without neoadjuvant therapy was 77% for EUS and 71% for CT (p = 0.001). Accuracy for detecting positive upper mediastinal nodes was 80-92%, whereas for peritumoral and abdominal nodes this was 50-80% in both EUS and CT. In 8/266 patients (3%) the type of surgery changed due to intraoperative findings. A radical resection was performed in 233 patients (88%). CONCLUSIONS: Despite the suboptimal accuracy of determining tumor localization with EUS and CT, in only a small number of patients an intraoperative change of surgical treatment was needed. EUS is superior to CT in determining nodal status and tumor localization in GEJ tumors.

Esophageal and Gastric Cancer Pearl: a nationwide clinical biobanking project in the Netherlands.

Esophageal and gastric cancer is associated with a poor prognosis since many patients develop recurrent disease. Treatment requires specific expertise and a structured multidisciplinary approach. In the Netherlands, this type of expertise is mainly found at the University Medical Centers (UMCs) and a few specialized nonacademic centers. Aim of this study is to implement a national infrastructure for research to gain more insight in the etiology and prognosis of esophageal and gastric cancer and to evaluate and improve the response on (neoadjuvant) treatment. Clinical data are collected in a prospective database, which is linked to the patients' biomaterial. The collection and storage of biomaterial is performed according to standard operating procedures in all participating UMCs as established within the Parelsnoer Institute. The collected biomaterial consists of tumor biopsies, blood samples, samples of malignant and healthy tissue of the resected specimen and biopsies of recurrence. The collected material is stored in the local biobanks and is encoded to respect the privacy of the donors. After approval of the study was obtained from the Institutional Review Board, the first patient was included in October 2014. The target aim is to include 300 patients annually. In conclusion, the eight UMCs of the Netherlands collaborated to establish a nationwide database of clinical information and biomaterial of patients with esophageal and gastric cancer. Due to the national coverage, a high number of patients are expected to be included. This will provide opportunity for future studies to gain more insight in the etiology, treatment and prognosis of esophageal and gastric cancer.

Prognosis and Treatment After Diagnosis of Recurrent Esophageal Carcinoma Following Esophagectomy with Curative Intent.

BACKGROUND: Strategies for the treatment of recurrence after initial curative esophagectomy are increasingly being recognized. The aim of this study was to identify prognostic factors that affect survival in patients with recurrence and to evaluate treatment strategies. METHODS: A prospective database (2003-2013) was used to collect consecutive patients with esophageal carcinoma treated with initial curative esophagectomy. Locations, symptoms, and treatment of recurrence were registered. Post-recurrence survival was defined as the time between the first recurrence and death or last follow-up. RESULTS: Of the 335 selected patients, 171 (51 %) developed recurrence. Multivariable analysis identified distant recurrence as opposed to locoregional recurrence [hazard ratio (HR) 2.15, 95 % confidence interval (CI) 1.27-3.65; p = 0.005], more than three recurrent locations (HR 2.42, 95 % CI 1.34-4.34; p = 0.003), and treatment (HR 0.29, 95 % CI 0.20-0.44; p < 0.001) as independent prognostic factors associated with post-recurrence survival. Primary tumor characteristics, including neoadjuvant therapy, histological type, pTN stage, and radicality, did not independently influence post-recurrence survival. Treatment was initiated in 62 patients (37 %) and included chemotherapy, radiotherapy, and/or surgery. Median post-recurrence survival of all patients was 3.0 months (range 0-112). In total, six patients (4 %) were still disease-free following treatment, indicating cure. CONCLUSIONS: In patients treated for esophageal cancer at curative intent, distant recurrence and more than three recurrent locations were independent prognostic factors associated with worse post-recurrence survival, irrespective of primary tumor characteristics. Although survival after recurrence was poor, treatment can prolong survival and can even lead to cure in selected patients.

Surgical treatment of adenocarcinomas of the gastro-esophageal junction.

BACKGROUND: Patients with adenocarcinoma of the gastro-esophageal junction (GEJ) may undergo either esophagectomy or gastrectomy. The aim of this study was to evaluate the outcome of surgical therapy with regard to postoperative outcome and survival in patients with Siewert type II tumors. METHODS: A prospective database of 266 consecutive patients with surgically resectable GEJ adenocarcinomas from 2003 to 2013 was analyzed. The surgical approach was based on preoperative imaging and intraoperative findings. RESULTS: According to the histopathological analysis, 67 patients (25 %) had type I tumor, 176 patients (66 %) had type II tumor, and 16 patients (6 %) had type III tumor. In total, 86 % were treated with esophagectomy and 14 % with gastrectomy. Overall 5-year survival was 38 %. In type II patients, the type of operation did not significantly influence overall survival on multivariate analysis (p = 0.606). A positive circumferential resection margin (CRM) at the site of the esophagus was more common with gastrectomy (29 vs. 11 %; p = 0.025). No significant differences in mortality, morbidity, or disease recurrence were found. In patients with type II tumors, upper mediastinal nodal involvement (subcarinal, paratracheal, and aortapulmonary window) was found in 11 % of the patients. In 34 % of patients treated with esophagectomy, paraesophageal lymph nodes metastases were harvested compared with 5 % of patients treated with gastrectomy. CONCLUSIONS: In patients with a type II GEJ adenocarcinoma, a positive CRM was more common with gastrectomy. Esophagectomy provides for a more complete para-esophageal lymphadenectomy. Furthermore, the high prevalence of mediastinal nodal involvement indicates that a full lymphadenectomy of these stations should be considered.

Small simulators for teaching procedural skills in a difficult airway algorithm.

Difficulty with intubation, ventilation or both is a significant issue for anaesthetists. The American Society of Anesthesiologists' Guidelines for the Management of the Difficult Airway is an algorithm widely used when airway difficulties are encountered. Ideally, anaesthetic trainees should have access to simulators suitable for learning and practising how to manage airway difficulties, but most models have been designed primarily for resuscitation training. The aim of this study was to determine which small airway simulators could be used to practise steps in the Difficult Airway Algorithm (DAA). We identified the essential elements of the DAA relating to endotracheal intubation (laryngoscope, Trachlight and Fastrach), external laryngeal manipulation, dedicated airway devices (LMA, Combitube) and trans-tracheal ventilation using the Enk oxygen flow modulator (Cook). Each element was studied in adult airway models sold for airway management training. The DAA elements were studied in 16 different airway models. No single model achieved our criteria of "good/very realistic" for all elements. All elements of the DAA could be used in the Difficult Airway Trainer Deluxe (MPL) and Bill (VBM/Mallinckrodt) but it would be necessary to acquire at least two trainers to achieve "good/very realistic" in all techniques studied. Anaesthetic departments planning to acquire small simulators for airway management training should undertake a training-needs analysis and apply this to the performance characteristics of the simulators. Generally, at least two airway training models will be needed to teach all steps of the DAA effectively.

p53 and bcl-2 immunohistochemistry in preoperative biopsies as predictors of biochemical recurrence after radical prostatectomy.

OBJECTIVE: To evaluate p53 and bcl-2 immunohistochemistry in preoperative biopsies and radical prostatectomy specimens, as predictors of biochemical recurrence. PATIENTS AND METHODS: Preoperative biopsies from 73 men, and the radical prostatectomies from these men and from a further 47 men, were evaluated. The serum prostate specific antigen (PSA) level, Gleason score, pathological stage and margin involvement were recorded. The immunohistochemical expression of p53 and bcl-2 was studied on a representative area of tumour with the highest Gleason grade. The median follow-up was 53 months. RESULTS: During the follow-up 47 of the 120 patients had a biochemical recurrence. Capsular penetration was present in 63 (53%) and the surgical margins were positive in 47 (39%). The Gleason score was < 7 in 81 (68%) patients; p53 was positive in 40 (66%) of 61 biopsies and 84 (71%) of 118 prostatectomy specimens. Bcl-2 was positive in eight (13%) of 63 biopsies and 20 (17%) of 118 prostatectomies. On multivariate analysis the biopsy p53, Gleason score and serum PSA were significant predictors of recurrence. On multivariate analysis, capsular penetration, PSA and margin status at prostatectomy were significant predictors of recurrence. There was also a significant interaction between PSA and margin status. Although univariately significant, neither p53 nor bcl-2 featured in the final multivariate model. CONCLUSION: Biopsy p53 status significantly predicts recurrence after radical prostatectomy, but its low specificity and technical issues suggest that it will not be useful in the clinical setting. However, a patient with negative p53 on biopsy is likely to have a good prognosis on prolonged follow-up.

Radiographic associations for "primary" hip osteoarthrosis: a retrospective cohort study of 47 patients.

This radiographic retrospective cohort study aims to identify relations between the prearthrotic anatomy of the hip joint and the type of subsequent osteoarthrosis (OA). Radiographs of 64 hips in 47 patients were evaluated. Several anatomical indices were measured on radiographs obtained before the onset of OA. The location, type and grade of OA were recorded on subsequent radiographs. Due to the small number of hips available, only three potential risk factors could be considered for both OA location and OA type (weight-bearing surface angle, spherical sector and neck shaft angle for both outcomes). The only variable that was found to be a significant predictor of OA location was the degree of inclination of the acetabular sourcil. Patients with craniomedial sourcils were more likely to have medial OA. No predictors of OA type could be identified. Our results suggest that the anatomy of the hip joint is a factor determining the location of developing osteoarthrosis.

Randomised controlled trial of nurse practitioner versus general practitioner care for patients requesting "same day" consultations in primary care.

OBJECTIVE: To ascertain any differences between care from nurse practitioners and that from general practitioners for patients seeking "same day" consultations in primary care. DESIGN: Randomised controlled trial with patients allocated by one of two randomisation schemes (by day or within day). SETTING: 10 general practices in south Wales and south west England. SUBJECTS: 1368 patients requesting same day consultations. MAIN OUTCOME MEASURES: Patient satisfaction, resolution of symptoms and concerns, care provided (prescriptions, investigations, referrals, recall, and length of consultation), information provided to patients, and patients' intentions for seeking care in the future. RESULTS: Generally patients consulting nurse practitioners were significantly more satisfied with their care, although for adults this difference was not observed in all practices. For children, the mean difference between general and nurse practitioner in percentage satisfaction score was -4.8 (95% confidence interval -6.8 to -2.8), and for adults the differences ranged from -8.8 (-13.6 to -3.9) to 3.8 (-3.3 to 10.8) across the practices. Resolution of symptoms and concerns did not differ between the two groups (odds ratio 1.2 (95% confidence interval 0.8 to 1.8) for symptoms and 1.03 (0.8 to 1.4) for concerns). The number of prescriptions issued, investigations ordered, referrals to secondary care, and reattendances were similar between the two groups. However, patients managed by nurse practitioners reported receiving significantly more information about their illnesses and, in all but one practice, their consultations were significantly longer. CONCLUSION: This study supports the wider acceptance of the role of nurse practitioners in providing care to patients requesting same day consultations.

Distribution of GABA(B) binding sites in the thalamus and basal ganglia of the rhesus monkey (Macaca mulatta).

The regional distribution of GABA(B) receptor binding sites in the thalamus and basal ganglia of rhesus monkey has been determined by receptor autoradiography using the agonist ligand, [3H]-GABA. Whilst binding sites were evident throughout the thalamus, the internuclear differences in the Bmax were up to 10-fold. In the basal ganglia the binding density was on average lower than in the thalamus. The highest number of binding sites was in striatum followed closely by substantia nigra. In both the thalamus and basal ganglia, the binding density was higher than previously described in the rat. Although our results do not allow us to differentiate between presynaptic and postsynaptic locations of GABA(B) sites we conclude that with a few exceptions the distribution pattern of GABA(B) binding sites in the monkey thalamus appears to correlate with the known innervation from the NRT.

Pertussis toxin decreases absence seizures and GABA(B) receptor binding in thalamus of a genetically prone rat (GAERS).

Postsynaptic GABA(B) receptor-mediated events have previously been shown to be reduced by prior treatment with pertussis toxin in rat brain. In the present study genetic absence epilepsy rats from Strasbourg (GAERS) were given single bilateral injections of pertussis toxin (PTx 0.4 microg), denatured-PTx or vehicle saline into the relay nuclei of the thalamus under anaesthesia. After recovery the spike and wave discharge duration (SWD) was monitored for up to 6 days following which the brains were removed and GABA(B) or GABA(A) receptor autoradiography performed on 10 microm transverse sections. By 6 days the SWD of the rats treated with PTx was suppressed by 96% compared with vehicle-injected rats with a significant (62%) reduction even after 1 day. Denatured toxin had no effect at any time. After 6 days GABA(B), but not GABA(A), receptor binding was significantly reduced by 70-80% in the ventrolateral and ventral posteriolateral thalamic nuclei. No changes in other brain regions were detected and denatured toxin failed to alter GABA(A) or GABA(B) receptor binding in any brain region. These data implicate G-protein mechanisms in the generation of SWD in GAERS and support the role of GABA(B) receptors in their induction within the thalamus.

Cytogenetic analysis in peripheral lymphocytes of cancer patients treated with cytostatic drugs: results from an EC Collaborative Study.

Many of the cytostatic drugs commonly used in cancer chemotherapy treatments have been shown to be genotoxic in vivo and in vitro. We present a cytogenetic collaborative study on 13 cancer patients treated with different antitumor agents. For comparison we also carried out a cytogenetic analysis on 14 healthy untreated controls. The frequency of sister chromatid exchanges and structural chromosome aberrations in peripheral blood lymphocytes of the cancer patients was determined prior to the treatment, just after it and 3-7 weeks later. The results obtained show clear differences between the basal levels of cytogenetic alterations in cancer patients, even though the mean value is higher in this group than the basal levels of the group of healthy individuals. Treatment with cytostatics increases the frequency of both cytogenetic biomarkers analyzed, which declined to values similar to those initially observed several weeks after the treatment. Our data are in qualitative and quantitative agreement with other results previously found by other authors.

School problems in Tourette's syndrome.

BACKGROUND: A retrospective study of 138 children with Tourette's syndrome for associated school problems revealed that at the time of initial evaluation, 64 subjects (46%) experienced a school-related problem. OBJECTIVE: To survey a childhood population with Tourette's syndrome to explore the contributions of neurobehavioral concomitants to academic difficulties. RESULTS: A diagnosis of a specific learning disorder had previously been made in 30 (22%) of 138 children. Among the 108 without a diagnosis of learning disorder, 36 (33%) experienced school difficulties defined as grade retention (16 [15%]) and/or special education placement (41 [38%]). Regression analysis of subjects without a diagnosis of learning disability revealed that the presence of attention-deficit hyperactivity disorder served as a significant predictor of school problems. CONCLUSIONS: Tics represented the primary reason for referral, but did not emerge as a significant predictor of academic problems. Rather, school-related difficulties appeared to be strongly associated with comorbid attention-deficit hyperactivity disorder.

Empyema thoracis and lung abscess due to Gemella morbillorum.

A case of empyema and lung abscess in an elderly patient who presented with clinical features of congestive cardiac failure is described. Gemella morbillorum was cultured from pleural exudate found postmortem to be associated with a lung abscess. To our knowledge this is the first reported case of infection with this organism in this setting. We discuss the clinical spectrum and management of infection with this infrequently encountered organism.