Soft tissue sarcoma

No abstract.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/34351/1/1_ftp.pd

Free jejunal flap transfer containing multiple vascular pedicles for pharyngoesophageal reconstruction in conjunction with anterior mediastinal tracheostomy

BackgroundWhen pharyngoesophagectomy is performed in conjunction with anterior mediastinal tracheostomy, reconstructing both the trachea and alimentary tract is extremely difficult. We developed a novel 1‐stage reconstructive procedure using a single free jejunal flap containing multiple vascular pedicles to decrease postoperative morbidity and mortality. Free jejunal flap transfer with multiple vascular pedicles could offer a viable option for reducing associated life‐threatening complications.MethodsWe performed a retrospective review of 34 patients who underwent free jejunal flap transfer with multiple vascular pedicles in anterior mediastinal tracheostomy and pharyngoesophagectomy due to lesions involving both the airway and esophagus. In all cases, 1‐stage reconstruction of the digestive tract and trachea was performed. Technical details and outcomes were analyzed.ResultsAll 34 jejunal flaps (100%) survived. Major morbidity classified as Clavien–Dindo grades III and IV occurred in 10 (29.4%) and 0 (0%) patients, respectively during hospitalization. With regard to common complications, anastomotic leakage from transferred jejunal flaps and surgical site infections occurred in 0 (0%) and 7 (20.6%) patients, respectively. Five (14.7%) patients experienced tracheal stoma dehiscence. Donor site morbidity was observed in 2 (5.9%) patients. The overall in‐hospital mortality rate was 2.9%.ConclusionsOur 1‐stage reconstruction procedure achieved low morbidity and low mortality rates following anterior mediastinal tracheostomy and pharyngoesophagectomy. Only 1 jejunal flap transfer is needed to simultaneously reconstruct the trachea and alimentary tract in a safe and reliable manner with this procedure.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146618/1/micr30359_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146618/2/micr30359.pd

Interventions for the treatment of oral cavity and oropharyngeal cancer:chemotherapy

<b>Background:</b> Oral cavity and oropharyngeal cancers are frequently described as part of a group of oral cancers or head and neck cancer. Treatment of oral cavity cancer is generally surgery followed by radiotherapy, whereas oropharyngeal cancers, which are more likely to be advanced at the time of diagnosis, are managed with radiotherapy or chemoradiation. Surgery for oral cancers can be disfiguring and both surgery and radiotherapy have significant functional side effects, notably impaired ability to eat, drink and talk. The development of new chemotherapy agents, new combinations of agents and changes in the relative timing of surgery, radiotherapy, and chemotherapy treatments may potentially bring about increases in both survival and quality of life for this group of patients.<p></p> <b>Objectives:</b> To determine whether chemotherapy, in addition to radiotherapy and/or surgery for oral cavity and oropharyngeal cancer results in improved survival, disease free survival, progression free survival, locoregional control and reduced recurrence of disease. To determine which regimen and time of administration (induction, concomitant or adjuvant) is associated with better outcomes.<p></p> <b>Search strategy:</b> Electronic searches of the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE, EMBASE, AMED were undertaken on 28th July 2010. Reference lists of recent reviews and included studies were also searched to identify further trials.<p></p> <b>Selection criteria:</b> Randomised controlled trials where more than 50% of participants had primary tumours in the oral cavity or oropharynx, and which compared the addition of chemotherapy to other treatments such as radiotherapy and/or surgery, or compared two or more chemotherapy regimens or modes of administration, were included.<p></p> <b>Data collection and analysis:</b> Trials which met the inclusion criteria were assessed for risk of bias using six domains: sequence generation, allocation concealment, blinding, completeness of outcome data, selective reporting and other possible sources of bias. Data were extracted using a specially designed form and entered into the characteristics of included studies table and the analysis sections of the review. The proportion of participants in each trial with oral cavity and oropharyngeal cancers are recorded in Additional Table 1.<p></p> <b>Main results:</b> There was no statistically significant improvement in overall survival associated with induction chemotherapy compared to locoregional treatment alone in 25 trials (hazard ratio (HR) of mortality 0.92, 95% confidence interval (CI) 0.84 to 1.00). Post-surgery adjuvant chemotherapy was associated with improved overall survival compared to surgery +/- radiotherapy alone in 10 trials (HR of mortality 0.88, 95% CI 0.79 to 0.99), and there was an additional benefit of adjuvant concomitant chemoradiotherapy compared to radiotherapy in 4 of these trials (HR of mortality 0.84, 95% CI 0.72 to 0.98). Concomitant chemoradiotherapy resulted in improved survival compared to radiotherapy alone in patients whose tumours were considered unresectable in 25 trials (HR of mortality 0.79, 95% CI 0.74 to 0.84). However, the additional toxicity attributable to chemotherapy in the combined regimens remains unquantified.<p></p> <b>Authors' conclusions:</b> Chemotherapy, in addition to radiotherapy and surgery, is associated with improved overall survival in patients with oral cavity and oropharyngeal cancers. Induction chemotherapy is associated with a 9% increase in survival and adjuvant concomitant chemoradiotherapy is associated with a 16% increase in overall survival following surgery. In patients with unresectable tumours, concomitant chemoradiotherapy showed a 22% benefit in overall survival compared with radiotherapy alone.<p></p&gt

Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial.

BACKGROUND: Neoadjuvant chemotherapy before surgery improves survival compared with surgery alone for patients with oesophageal cancer. The OE05 trial assessed whether increasing the duration and intensity of neoadjuvant chemotherapy further improved survival compared with the current standard regimen. METHODS: OE05 was an open-label, phase 3, randomised clinical trial. Patients with surgically resectable oesophageal adenocarcinoma classified as stage cT1N1, cT2N1, cT3N0/N1, or cT4N0/N1 were recruited from 72 UK hospitals. Eligibility criteria included WHO performance status 0 or 1, adequate respiratory, cardiac, and liver function, white blood cell count at least 3 × 10(9) cells per L, platelet count at least 100 × 10(9) platelets per L, and a glomerular filtration rate at least 60 mL/min. Participants were randomly allocated (1:1) using a computerised minimisation program with a random element and stratified by centre and tumour stage, to receive two cycles of cisplatin and fluorouracil (CF; two 3-weekly cycles of cisplatin [80 mg/m(2) intravenously on day 1] and fluorouracil [1 g/m(2) per day intravenously on days 1-4]) or four cycles of epirubicin, cisplatin, and capecitabine (ECX; four 3-weekly cycles of epirubicin [50 mg/m(2)] and cisplatin [60 mg/m(2)] intravenously on day 1, and capecitabine [1250 mg/m(2)] daily throughout the four cycles) before surgery, stratified according to centre and clinical disease stage. Neither patients nor study staff were masked to treatment allocation. Two-phase oesophagectomy with two-field (abdomen and thorax) lymphadenectomy was done within 4-6 weeks of completion of chemotherapy. The primary outcome measure was overall survival, and primary and safety analyses were done in the intention-to-treat population. This trial is registered with the ISRCTN registry (number 01852072) and ClinicalTrials.gov (NCT00041262), and is completed. FINDINGS: Between Jan 13, 2005, and Oct 31, 2011, 897 patients were recruited and 451 were assigned to the CF group and 446 to the ECX group. By Nov 14, 2016, 327 (73%) of 451 patients in the CF group and 302 (68%) of 446 in the ECX group had died. Median survival was 23·4 months (95% CI 20·6-26·3) with CF and 26·1 months (22·5-29·7) with ECX (hazard ratio 0·90 (95% CI 0·77-1·05, p=0·19). No unexpected chemotherapy toxicity was seen, and neutropenia was the most commonly reported event (grade 3 or 4 neutropenia: 74 [17%] of 446 patients in the CF group vs 101 [23%] of 441 people in the ECX group). The proportions of patients with postoperative complications (224 [56%] of 398 people for whom data were available in the CF group and 233 [62%] of 374 in the ECX group; p=0·089) were similar between the two groups. One patient in the ECX group died of suspected treatment-related neutropenic sepsis. INTERPRETATION: Four cycles of neoadjuvant ECX compared with two cycles of CF did not increase survival, and cannot be considered standard of care. Our study involved a large number of centres and detailed protocol with comprehensive prospective assessment of health-related quality of life in a patient population confined to people with adenocarcinomas of the oesophagus and gastro-oesophageal junction (Siewert types 1 and 2). Alternative chemotherapy regimens and neoadjuvant chemoradiation are being investigated to improve outcomes for patients with oesophageal carcinoma. FUNDING: Cancer Research UK and Medical Research Council Clinical Trials Unit at University College London

Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis

BACKGROUND: Carcinoma of the esophagus is an aggressive malignancy with an increasing incidence. Its virulence, in terms of symptoms and mortality, justifies a continued search for optimal therapy. The large and growing number of patients affected, the high mortality rates, the worldwide geographic variation in practice, and the large body of good quality research warrants a systematic review with meta-analysis. METHODS: A systematic review and meta-analysis investigating the impact of neoadjuvant or adjuvant therapy on resectable thoracic esophageal cancer to inform evidence-based practice was produced. MEDLINE, CANCERLIT, Cochrane Library, EMBASE, and abstracts from the American Society of Clinical Oncology and the American Society for Therapeutic Radiology and Oncology were searched for trial reports. Included were randomized trials or meta-analyses of neoadjuvant or adjuvant treatments compared with surgery alone or other treatments in patients with resectable thoracic esophageal cancer. Outcomes of interest were survival, adverse effects, and quality of life. Either one- or three-year mortality data were pooled and reported as relative risk ratios. RESULTS: Thirty-four randomized controlled trials and six meta-analyses were obtained and grouped into 13 basic treatment approaches. Single randomized controlled trials detected no differences in mortality between treatments for the following comparisons: - Preoperative radiotherapy versus postoperative radiotherapy. - Preoperative and postoperative radiotherapy versus postoperative radiotherapy. Preoperative and postoperative radiotherapy was associated with a significantly higher mortality rate. - Postoperative chemotherapy versus postoperative radiotherapy. - Postoperative radiotherapy versus postoperative radiotherapy plus protein-bound polysaccharide versus chemoradiation versus chemoradiation plus protein-bound polysaccharide. Pooling one-year mortality detected no statistically significant differences in mortality between treatments for the following comparisons: - Preoperative radiotherapy compared with surgery alone (five randomized trials). - Postoperative radiotherapy compared with surgery alone (five randomized trials). - Preoperative chemotherapy versus surgery alone (six randomized trials). - Preoperative and postoperative chemotherapy versus surgery alone (two randomized trials). - Preoperative chemoradiation therapy versus surgery alone (six randomized trials). Single randomized controlled trials detected differences in mortality between treatments for the following comparison: - Preoperative hyperthermia and chemoradiotherapy versus preoperative chemoradiotherapy in favour of hyperthermia. Pooling three-year mortality detected no statistically significant difference in mortality between treatments for the following comparison: - Postoperative chemotherapy compared with surgery alone (two randomized trials). Pooling three-year mortality detected statistically significant differences between treatments for the following comparisons: - Preoperative chemoradiation therapy versus surgery alone (six randomized trials) in favour of preoperative chemoradiation with surgery. - Preoperative chemotherapy compared with preoperative radiotherapy (one randomized trial) in favour of preoperative radiotherapy. CONCLUSION: For adult patients with resectable thoracic esophageal cancer for whom surgery is considered appropriate, surgery alone (i.e., without neoadjuvant or adjuvant therapy) is recommended as the standard practice

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS)

textabstractBackground. A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial. Methods/design. The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm. The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up. Discussion. This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen. Trial registration. ISRCTN80832026

Erratum to: 36th International Symposium on Intensive Care and Emergency Medicine

[This corrects the article DOI: 10.1186/s13054-016-1208-6.]

Correlation of admission serum 25-hydroxyvitamin D levels and clinical outcomes in critically ill medical patients

Summary: Purpose: The aim of this study was to determine the incidence of hypovitaminosis D and the correlation of admission serum 25-hydroxyvitamin D (25-OHD) levels and clinical outcomes in critically ill medical patients. Methods: A prospective, observational study was conducted. All critically ill medical patients admitted to the medical ICU were recruited. Blood sampling for serum 25-OHD was taken within 24 h after ICU admission. The levels of 25-OHD were dichotomized into deficiency and sufficiency groups. A serum 25-OHD level <20 ng/dL was defined as a vitamin D deficiency. All demographic data as well as biochemical tests were recorded. The primary outcome was incidence of hypovitaminosis D and 28-day mortality. The secondary outcomes were ICU and hospital mortality, ICU and hospital length of stay, mechanical ventilator days, and ICU-acquired infection. Results: From 116 cases, the incidence of hypovitaminosis D was 64.66%. The median serum 25-OHD was 15.1 (3.0, 67.2) ng/dL. There was no difference in 28-day mortality between the vitamin D statuses (20% vs. 17.1%, p = 0.70). However, the ICU-acquired infection tended to be higher in the vitamin D deficiency group but this was not statistically significant (25.3% vs. 19.5%, p = 0.07). Other secondary outcomes were comparable between the groups. Vitamin D levels were significantly correlated to the severity of illness of critically ill medical patients (r = −0.258, p = 0.005.) Conclusions: The incidence of hypovitaminosis D in critically ill medical patients in our region was high. In this current finding, vitamin D deficiency in critically ill medical patients may not related to 28-day mortality, ICU and hospital mortality, ICU and hospital length of stay, mechanical ventilator days or ICU-acquired infection, but vitamin D levels were significantly correlated to the severity of the illness. However, the larger study is required to confirm this finding. Trial registration: The study protocol is retrospectively registered at the Thai Clinical Trial Registry (TCTR) with the identification number TCTR20180211004. Keywords: 25-hydroxyvitamin D, Hypovitaminosis D, Vitamin D deficiency, Critically ill patients, Mortalit

Diagnostic value of endoscopic ultrasonography for common bile duct dilatation without identifiable etiology detected from cross-sectional imaging

Background/aims: Endoscopic ultrasonography (EUS) is warranted when cross-sectional imaging demonstrates common bile duct (CBD) dilatation without identifiable causes. This study aimed to assess the diagnostic performance of EUS in CBD dilatation of unknown etiology. Methods: Retrospective review of patients with dilated CBD without definite causes undergoing EUS between 2012 and 2017. Results: A total of 131 patients were recruited. The mean age was 63.2±14.1 years. The most common manifestation was abnormal liver chemistry (85.5%). The mean CBD diameter was 12.2±4.1 mm. The area under the receiver operating characteristic curve (AUROC) of EUS-identified pathologies, including malignancy, choledocholithiasis, and benign biliary stricture (BBS), was 0.98 (95% confidence interval [CI], 0.95-1.00). The AUROC of EUS for detecting malignancy, choledocholithiasis, and BBS was 0.91 (95% CI, 0.85-0.97), 1.00 (95% CI, 1.00-1.00), and 0.93 (95% CI, 0.87-0.99), respectively. Male sex, alanine aminotransferase ≥3× the upper limit of normal (ULN), alkaline phosphatase ≥3× the ULN, and intrahepatic duct dilatation were predictors for pathological obstruction, with odds ratios of 5.46 (95%CI, 1.74-17.1), 5.02 (95% CI, 1.48-17.0), 4.63 (95% CI, 1.1-19.6), and 4.03 (95% CI, 1.37-11.8), respectively. Conclusion: EUS provides excellent diagnostic value in identifying the etiology of CBD dilatation detected by cross-sectional imaging