Summary Background Thalidomide plus dexamethasone (TD) is a standard induction therapy for myeloma. We aimed to assess the efficacy and safety of addition of bortezomib to TD (VTD) versus TD alone as ...induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma. Methods Patients (aged 18–65 years) with previously untreated symptomatic myeloma were enrolled from 73 sites in Italy between May, 2006, and April, 2008, and data collection continued until June 30, 2010. Patients were randomly allocated (1:1 ratio) by a web-based system to receive three 21-day cycles of thalidomide (100 mg daily for the first 14 days and 200 mg daily thereafter) plus dexamethasone (40 mg daily on 8 of the first 12 days, but not consecutively; total of 320 mg per cycle), either alone or with bortezomib (1·3 mg/m2 on days 1, 4, 8, and 11). The randomisation sequence was computer generated by the study coordinating team and was stratified by disease stage. After double autologous stem-cell transplantation, patients received two 35-day cycles of their assigned drug regimen, VTD or TD, as consolidation therapy. The primary endpoint was the rate of complete or near complete response to induction therapy. Analysis was by intention to treat. Patients and treating physicians were not masked to treatment allocation. This study is still underway but is not recruiting participants, and is registered with ClinicalTrials.gov , number NCT01134484 , and with EudraCT , number 2005-003723-39. Findings 480 patients were enrolled and randomly assigned to receive VTD (n=241 patients) or TD (n=239). Six patients withdrew consent before start of treatment, and 236 on VTD and 238 on TD were included in the intention-to-treat analysis. After induction therapy, complete or near complete response was achieved in 73 patients (31%, 95% CI 25·0–36·8) receiving VTD, and 27 (11%, 7·3–15·4) on TD (p<0·0001). Grade 3 or 4 adverse events were recorded in a significantly higher number of patients on VTD (n=132, 56%) than in those on TD (n=79, 33%; p<0·0001), with a higher occurrence of peripheral neuropathy in patients on VTD (n=23, 10%) than in those on TD (n=5, 2%; p=0·0004). Resolution or improvement of severe peripheral neuropathy was recorded in 18 of 23 patients on VTD, and in three of five patients on TD. Interpretation VTD induction therapy before double autologous stem-cell transplantation significantly improves rate of complete or near complete response, and represents a new standard of care for patients with multiple myeloma who are eligible for transplant. Funding Seràgnoli Institute of Haematology at the University of Bologna, Bologna, Italy.
Background Previous studies examining the effect of fellow participation on adenoma detection rate in colonoscopy have yielded conflicting results, and factors such as adenoma size and location have ...not been rigorously evaluated. Objective To examine whether fellow participation during screening, surveillance, or diagnostic colonoscopy affects overall, size-specific, or location-specific adenoma or polyp detection rate. Methods This was a retrospective study of 2430 colonoscopies performed in our ambulatory surgical center between September 2006 and December 2007, comparing adenoma and polyp detection rates of colonoscopies performed by fellows with supervising staff endoscopists (n = 318) with colonoscopies performed by staff endoscopists without fellow participation (n = 2112). Study participants included patients who underwent screening, surveillance, or diagnostic colonoscopies in our GI suite. Logistic regression analysis was used to evaluate the association of fellow participation with adenoma and polyp detection. Results There was evidence of a higher rate of small (<5 mm) adenoma detection in colonoscopies with a fellow present (25% vs 17%, P = .001). This remained significant after multiple-testing adjustment ( P ≤ .003 considered significant). Findings were similar, although not significant for small polyps (36% vs 29%, P = .007). There was a trend toward increased adenoma detection in colonoscopies with a fellow present compared with those without (30% vs 26%, P = .11). Multivariable adjustment for potentially confounding variables did not alter these associations. Limitations The study had a retrospective design, and information regarding bowel preparation was not available for 37% of patients. Conclusion Fellow involvement was associated with increased detection rates of small adenomas, providing evidence that the presence of a fellow during colonoscopy plays a role in enhancing the effectiveness of the examination.
Background and Aims Endoscopic therapy is the standard treatment for high-grade dysplasia and some cases of T1a esophageal adenocarcinoma (EAC), but it is not appropriate for deeply invasive disease. ...Data on the value of EUS for patient selection for endoscopic or surgical resection are conflicting. We investigated the outcome of esophageal EUS for the staging and treatment selection of patients with treatment-naive, premalignant Barrett’s esophagus (BE) and suspected superficial EAC. Methods We retrospectively reviewed consecutive patients who underwent EUS for staging of treatment-naive, suspected premalignant BE and superficial EAC from January 2006 to June 2014. All patients referred for endoscopic therapy routinely underwent EUS. Patients with esophageal masses, squamous cell cancers, previous neoadjuvant therapy, or unrelated pathologies were excluded. Each patient’s final diagnosis was verified by EMR, esophagectomy, or forceps biopsy sampling. Test characteristics of EUS were calculated. Results Three hundred thirty-five patients (mean age, 68 years; 86% male) with BE, a Prague C mean of 2.8 cm, and a Prague M mean of 4.5 cm were staged (pT0, 78% 6% nondysplastic, 24% low-grade dysplasia, 42% high-grade dysplasia; pT1a, 14%; pT1b, 7%; and pT2, 1%). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for patient selection to endoscopic (T1aN0 or less) or surgical therapy with EUS TN staging were 50%, 93%, 40%, 95%, and 90%, respectively. Comparable rates were achieved for patients with nodular BE. Overstaging occurred in 7% of patients, and EUS selected 11% for incorrect treatment modalities compared with pathologic staging. Conclusions This study confirms the limited value of EUS suggested in the latest American College of Gastroenterology guidelines for BE management.
Background Probe-based confocal laser scanning endomicroscopy enables in vivo real time histopathology of the mucosa layer. Recently, a prototype of a new confocal miniprobe has been developed that ...is small enough to be introduced through a 22-gauge puncture needle. Objective The aim of this study was to evaluate the feasibility of such needle-based confocal laser scanning endomicroscopy (nCLE) for in vivo histology of various organs in a porcine model. Design Feasibility study. Setting Nonsurvival animal experiments with the animals under general anesthesia at three academic centers. Interventions Ten pigs were examined while they were under general anesthesia. Either EUS-guided organ puncture or natural-orifice transluminal endoscopic surgery (NOTES) procedure was used. The confocal miniprobe was inserted through the 22-gauge needle, and puncture of various intra-abdominal structures and organs was performed (lymph nodes, diaphragm, ovaries, liver, spleen, and pancreas) after intravenous injection of fluorescein (5-10 mL 1% or 2 mL 10% solution). Real-time sequences were recorded. Biopsy specimens were taken for standard histopathology. Main Outcome Measurements and Results It was technically feasible to introduce the needle-based confocal miniprobe into various organs at the time of EUS or NOTES procedures. The device enabled real-time in vivo collection of images at histologic resolutions and of acceptable image quality from several intra-abdominal organs interrogated. Limitations Data were assessed in an experimental animal setting and on healthy organs only. Conclusions Needle-based confocal laser endomicroscopy (CLE) of intra-abdominal organs is feasible in a porcine model. This innovative, minimally invasive technique has the potential to facilitate in vivo histology during EUS punctures or NOTES peritoneoscopy.
Background Residual neoplasia after EMR of colorectal lesions is common. There is a critical need for imaging methods to accurately diagnose residual disease and to guide retreatment in real time. ...Objective The aim was to estimate and compare the accuracy of virtual chromoendoscopy (VCE) and probe-based confocal laser endomicroscopy (pCLE) for detection of residual neoplastic tissue at the site of prior EMR. Design Prospective, blind, pilot comparison of advanced endoscopic imaging (VCE and pCLE) by using matching histology as reference standard. Setting Three tertiary-care referral hospitals. Patients This study involved 92 participants who underwent follow-up colonoscopies for the evaluation of prior EMR sites within 1 year. Intervention The EMR scars were assessed during follow-up high-resolution colonoscopy by using VCE (narrow-band imaging/Fujinon Intelligent Color Enhancement FICE), and pCLE. Confocal videos of EMR scars were interpreted in real time and were also stored and reviewed offline, blinded to histopathology and endoscopic appearance. Tissue confirmation by biopsies or polypectomy/repeat EMR was performed in all cases. Main Outcome Measurements Sensitivity, specificity, and accuracy for VCE and pCLE alone and in combination against histopathology as the standard reference standard. Results Among 129 EMR scars, residual neoplasia was confirmed by histology in 29 sites (22%). For VCE, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 72%, 77%, 49%, 91%, and 77%, respectively, and were 97%, 77%, 55%, 99%, and 81% for pCLE ( P = .045 for sensitivity). When only EMR scars for which VCE and pCLE agreed on the diagnosis were analyzed (95/129 scars), the accuracy, sensitivity, specificity, PPV, and NPV of pCLE and VCE were 90%, 100%, 87%, 67%, and 100%, respectively. Limitations Small sample size, lack of power, involvement of highly experienced pCLE experts. Conclusion Confocal endomicroscopy significantly increases the sensitivity for detecting residual neoplasia after colorectal EMR compared with endoscopy alone. When confocal endomicroscopy is used in combination with VCE, the accuracy is extremely high, and sensitivity approaches that of histopathology. Together, they may reduce the need for histologic examination and allow a highly accurate on-table decision to treat again or not, thus avoiding unnecessary repeat procedures. (Clinical trial registration number: 00874263 .)
ABSTRACT Background In the past two decades, pancreas surgery (PS) has undergone significant advances in operative techniques and with a focus on multidisciplinary high-volume practices. Methods A ...review of patients undergoing PS from 3/1995-2/2015 was conducted; dividing patients into group A (1995-2005) and group B (2005-2015) for a detailed comparison. Effect of surgeon volume in group B was determined. Results A total of 1001 patients underwent PS (group A: 259; group B: 742). The mean age was 62.7 years and 52.8% were female. Group B patients were associated with a higher rate of pylorus preservation and minimally invasive resection and a lower rate of morbidity, pancreas fistula (PF), and delayed gastric emptying (DGE) than group A. High-volume surgeons (HVS) had lower operative blood loss (300 mL vs 600 mL), transfusion requirements, PF (14% vs 20%), DGE, surgical site infections, reoperations, and major morbidity rate (15.5 vs 39%) than low-volume surgeons. Conclusions This study demonstrates improved patient outcomes and hospital resource utilization over the past 20 years. Concentration of PS to HVS results in superior results.
Background There are few randomized studies examining efficacy of snares and agents in EMR. Objective To compare the use of a combined needle and snare unit with injectate versus a spiral wire and ...injectate (primary); saline solution versus hydroxypropyl methylcellulose (secondary). Design Prospective, randomized, factorial, single center. Setting Tertiary-care academic medical center. Patients A total of 140 patients with large (>15 mm), sessile, colorectal polyps. Interventions Polyps randomized to either 1 of 2 snare types and 1 of 2 injectates. Main Outcome Measurements Primary—the Sydney resection quotient (SRQ), defined as the size of the polyp divided by the number of pieces resected and the amount of tissue per snare attempt. Secondary—procedure time, adverse events, residual neoplasia at follow-up. Results The SRQ was higher with the combined unit (median 13.8 mm vs 7.1 mm; P = .019); additionally, procedure time was less (median 6 vs 11 minutes; P < .001). Resection was considered complete after the EMR in 62% (42/68) with the combined needle and snare unit versus 51% (37/72; P = .22) with the spiral wire. Rates of adverse events were similar. Residual neoplasia was found at follow-up in 22% (10/46) with the combined needle and snare unit versus 21% (10/48; P = .89) with the spiral wire. There was no evidence of differences in outcomes by lifting agent. Limitations The SRQ is only a surrogate marker. Conclusion This study provides evidence that the integrated needle-snare may be superior to the snare alone for the removal of large, flat polyps. Additionally, the type of injectate appears to have no impact on outcome.
Background The factors associated with maximizing the cytological adequacy of EUS-guided FNA (EUS-FNA) in pancreatic tumor evaluation are not well-known. Objective To examine associations of ...physician and procedural factors with the endpoint: the presence of an adequate cytological specimen found by using EUS-FNA in patients with pancreatic tumors and lymph nodes. Design Retrospective cohort study. Setting A U.S. tertiary care center. Patients Patients undergoing EUS-FNA of pancreatic masses and lymph nodes. Interventions Analysis of EUS-FNA procedures performed in our institution from 1997 to 2007. Main Outcome Measurements Associations were evaluated between the primary endpoint of cytological adequacy and factors including the endoscopist, needle gauge, the number of needle passes attempted, the pathologist, and the presence of an onsite cytotechnologist to confirm an adequate specimen. EUS-FNA adequacy was determined by a pathologist based on the presence of definite benign or malignant tissue. Results EUS-FNA was performed in 247 pancreatic masses and 276 lymph nodes. An adequate cytological sample was obtained in 240 (97%) pancreatic tumors (95% CI, 94%-99%) and 252 (91%) lymph nodes (95% CI, 87%-94%). For pancreatic tumors, there was no evidence of any associations between factors and cytological adequacy. For lymph nodes, cytological adequacy was improved when an onsite cytotechnologist was present (96% vs 84%, P = .002); no other factors showed statistically significant associations with cytological adequacy. Limitations Retrospective study, low power to detect associations. Conclusions The presence of an onsite cytotechnologist is an important factor in achieving successful EUS-FNA of suspicious lymph nodes in patients with pancreatic masses.
Background Cystic neoplastic lesions of the pancreas (CNLP) are increasingly detected and are associated with a potential for malignant transformation. Diagnostic assessment of these lesions is often ...limited by the cystic nature and focality of neoplastic progression of these lesions. EUS-guided FNA (EUS-FNA) of cyst fluid and exfoliated cells is one of the most accurate methods of diagnosis but still has limited sensitivity. A new, through-the-needle cytologic brush system has recently been approved for use during EUS evaluation of cystic lesions of the pancreas. Objective To evaluate the cytologic yield and safety profile of the new cytobrush compared with conventional FNA in evaluating CNLP. Design Ten consecutive patients with CNLP were included. All cysts were sampled by standard EUS-FNA (0.5 of cyst volume) followed by brush cytology, then by aspiration of the remaining fluid. Fluid samples were separately submitted (standard FNA and cytobrushings FNA) but were read by the same pathologist. Complications were assessed during the immediate postprocedure period (2-3 hours) and by a telephone call conducted approximately 30 days after the procedure to inquire about any new symptoms, including abdominal pain, melena, hematochezia, hematemesis, fever, nausea, and vomiting. Setting High-volume EUS referral center. Patients Ten consecutive patients with CNLP that measured at least 20 mm in maximal dimension were included. Main Outcome Measurements Cellularity and presence of diagnostic cells on the FNA. Results In 7 of 10 cases, the EchoBrush specimen was superior to FNA in terms of cellularity and detection of diagnostic cells. Two cases had complications: 1 major and 1 minor intracystic bleed. No infection or pancreatitis was observed. Limitations The interpreting pathologist for the case was not blinded to the results of either of the samples. In addition, this pilot study represents only a single-center experience. Conclusions This study suggests that brush cytology specimens obtained at the time of EUS are superior to conventional FNA because of the higher yield of epithelial cells. It is unclear whether bleeding is more common after EchoBrush sampling; however, caution should be taken in patients who require anticoagulation until further data are available.
Background According to the field effect theory, by detecting microvasculature changes such as early increase in blood supply (EIBS) in the surrounding tissue, neoplastic lesions can be identified ...from a distance. Objective To determine the feasibility and efficacy of a fiberoptic probe containing novel polarization gating spectroscopy technology to identify patients with pancreatic adenocarcinoma (PAC) by the field effect theory. Design Prospective cohort (pilot) study. Setting Outpatient tertiary care center. Patients Adult (≥18 years) patients undergoing EGD-EUS were screened. Patients with PAC were included in the “cancer” group and patients without PAC were included in the “control” group. We excluded patients with other known malignancies and gastroduodenal premalignant lesions. Interventions and Main Outcome Measures Spectroscopic measurements of EIBS variables, such as deoxyhemoglobin concentration (DHb) and mean blood vessel radius (BVR), were obtained from 5 periampullary locations. The Mann-Whitney rank sum test was used for the statistical analysis ( P ≤ .05). Results Fourteen patients (mean age 72 years, 79% male) in the cancer group and 15 patients (mean age 63 years, 60% male) in the control group were included in the final analysis. At the ampullary site, both DHb ( P = .001) and BVR ( P = .03) were higher in PAC patients than in the control subjects. The DHb alone (92% sensitivity, 86% specificity) or in combination with BVR (92% sensitivity, 79% specificity) can differentiate PAC from control subjects with high accuracy. Limitations Small sample size, unmatched control subjects. Conclusions Spectroscopic measurements of EIBS by fiberoptic probes are feasible. Preliminary evidence suggests that in vivo measurement of normal-appearing duodenal tissue can differentiate PAC patients from a distance with high accuracy.
PDF