The delivered dose assessment in pancreas SBRT with the target position determined using an in-house position monitoring system.

Purpose: This study assessed the delivered dose accuracy in pancreas SBRT by incorporating the real-time target position determined using an in-house position monitoring system. Methods and materials: An online image-based position monitoring system, SeedTracker, was developed to monitor radiopaque marker positions using monoscopic x-ray images, available from the Elekta XVI imaging system. This system was applied to patients receiving SBRT for pancreatic cancer on the MASTERPLAN Pilot trial (ACTRN 12617001642370). All patients were implanted pre-treatment with at least three peri-tumoral radiopaque markers for target localisation. During treatment delivery, marker positions were compared to expected positions delineated from the planning CT. The position tolerance of ±3mm from the expected position of the markers was set to trigger a gating event (GE) during treatment. The dosimetric impact of position deviations and actual dose delivered with position corrections was assessed by convolving the plan control point dose matrices with temporal target positions determined during treatment. Results: Eight patients were treated within this study. At least one GE was observed in 38% of the treatment fractions and more than one GE was observed in 10% of the fractions. The position deviations resulted in the mean(range) difference of -0.1(-1.1 - 0.4)Gy in minimum dose to tumour and 1.9(-0.1- 4.6)Gy increase to Dmax to duodenum compared to planned dose. In actual treatment delivery with the patient realignment, the mean difference of tumour min dose and duodenal Dmax was reduced to 0.1(-1.0 - 1.1)Gy and 1.1 (-0.7 - 3.3)Gy respectively compared to the planned dose. Conclusions: The in-house real-time position monitoring system improved the treatment accuracy of pancreatic SBRT in a general-purpose linac and enabled assessment of delivered dose by incorporating the temporal target position during delivery. The intrafraction motion impacts the dose to tumour even if target position is maintained within a 3mm position tolerance.

The first real-time intrafraction target position monitoring in pancreas SBRT on an Elekta linear accelerator.

To perform implanted fiducial based real-time target position monitoring in pancreas stereotactic body radiotherapy (SBRT) using the x-ray imaging system available in a Elekta linear accelerator. An in-house system was developed and clinically utilised for real-time target position monitoring of pancreas SBRT delivery. The developed system was used for the target position monitoring of a pancreas cancer patient treated in free breathing treatment within the study entitled 'Mfolfirinox And STEreotactic Radiotherapy for Patients with Locally Advanced paNcreas cancer (MASTERPLAN): a feasibility study' (ACTRN 12617001642370) consisting of five treatment fractions. The clinical efficacy of the system was studied by performing a retrospective cumulative dose assessment of delivered dose using observed position deviations. The developed system identified two events of baseline shifts in target position that exceeded the accepted tolerance level of ± 3 mm from reference planned position. The retrospective dose assessment study showed that if the position deviations were not detected and corrected for, the maximum dose to duodenum would have increased from 34.6 to 38.8 Gy. The first real-time position monitoring in pancreas SBRT on an Elekta linear accelerator was successfully performed. The developed system was shown to improve the safety and accuracy of SBRT delivery.

Barrett's esophagus with low-grade dysplasia: high rate of upstaging at Barrett's esophagus referral units suggests progression rates may be overestimated.

BACKGROUND AND AIMS: The reported progression rate from low-grade dysplasia (LGD) in Barrett's esophagus (BE) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) ranges from .4% to 13.4% per year. We hypothesize that some reported progression rates may be overestimated because of prevalent HGD or EAC that was not identified during endoscopic assessments performed in the community. Our aim is to determine the proportion of prevalent HGD or EAC detected by BE referral units (BERUs) in patients referred from the community with a recent diagnosis of LGD. METHODS: All patients referred from the community to 6 BERUs with a diagnosis of BE with LGD were identified. Patients with an assessment endoscopy performed at BERUs more than 6 months from their referral endoscopy in the community were excluded. Visible lesions and histology outcomes were compared between the community referral endoscopy and the assessment endoscopy performed at BERUs. RESULTS: The median time between BERU assessment and referral endoscopy was 79 days (interquartile range, 54-114). Of the 75 patients referred from the community with LGD, BERU assessment identified HGD or EAC in 20 patients (27%). BERU assessment identified more visible lesions than referral endoscopy performed in the community (39 [52%] vs 9 [12%], respectively; P = .029). CONCLUSIONS: BERU assessment endoscopy identified more visible lesions than community referral endoscopy and identified HGD or EAC in 27% of patients referred from the community with a recent diagnosis of LGD. Reported progression rates from LGD to HGD or EAC may be overestimated.

Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review.

The causal link between high-risk human papillomavirus (hr-HPV) infection and cervical, anogenital, and some oropharyngeal malignancies has been established by both molecular and epidemiological data. The association between HPV and esophageal squamous cell carcinoma (ESCC) remains controversial, as is the true prevalence of HPV infection in ESCC. The wide range in reported rates reflects variability in the primary literature, with some larger scale case-control studies suggesting the infection rates range from 0% to 78%. Interactions between HPV and the Barrett's metaplasia-dysplasia-carcinoma sequence have been explored, and these studies have shown some conflicting data. Overall, systematic reviews have reported the prevalence of HPV-positive DNA in esophageal adenocarcinoma patients of between 13% and 35%. Postulated reasons for discrepancies in HPV prevalence rates in esophageal cancer include variations in testing methodology and assay sensitivities; technical issues, including the lack of a gold-standard primer; types of specimens utilized (fresh-frozen versus formalin-fixed tissue); geographical variation; cross-contamination; and small sample sizes. Thus, efforts must be undertaken to (1) standardize HPV testing, ideally in a central laboratory and utilizing tests that detect viral transcriptional activity; (2) avoid cross-contamination; and (3) recruit large numbers of patients to accurately ascertain HPV rates in esophageal malignancy.

Antibodies against human papillomavirus proteins in Barrett's dysplasia and intramucosal esophageal adenocarcinoma.

High-risk human papillomavirus (HPV) types 16/18 have been associated with Barrett's dysplasia (BD)/esophageal adenocarcinoma (EAC). Nevertheless, no data exist in relation to serological analysis for HPV antibodies in BD/EAC with site-specific viral DNA status. We prospectively examined antibodies to multiple HPV types in 438 patients representing hospital/reflux controls and Barrett's metaplasia (BM)/BD/intramucosal EAC. Antibody responses to HPV6/11/16/18/31/33/45/52/58 were analyzed using multiplex serology, including antibodies to E6/E7/E1/E2 and L1 antigens. Seropositivity for individual HPV proteins was infrequent in both cases and controls and was ≤10.2%. There was no difference in the seroprevalence of antibodies to any HPV antigen/antibody combination between reclassified cases (BD/EAC) and controls (hospital/reflux/BM) or between HPV16 or HPV18 DNA cases and controls, respectively. Among HPV16 DNA-positive BD/EAC cases, antibodies to HPV16 E7 were significantly more prevalent (3/26, 11.5%) than in hospital and reflux controls plus BM (5/328, 1.5%) (adjusted OR = 10.12, 95% CI: 1.61-63.73, P = 0.014). Among HPV18 DNA-positive cases, antibodies to HPV18 E1 were present in 3/6 (50%) cases versus 5/328 (1.5%) controls (adjusted OR = 44.28, 95% CI: 6.10-321.47, P = 0.0002). Although antibodies against HPV were generally uncommon in cases and controls, immune responses against two early proteins of HPV16/18 were significantly more frequent in viral DNA-positive BD/intramucosal EAC.

Association of Biomarkers for Human Papillomavirus With Survival Among Adults With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma.

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status.

Survival Rates for Patients With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma With or Without Human Papillomavirus Infection.

Importance: High-risk human papillomavirus (HPV) has been associated with Barrett dysplasia and esophageal adenocarcinoma. Nevertheless, the prognostic significance of esophageal tumor HPV status is unknown. Objective: To determine the association between HPV infection and related biomarkers in high-grade dysplasia or esophageal adenocarcinoma and survival. Design, Setting, and Participants: Retrospective case-control study. The hypothesis was that HPV-associated esophageal tumors would show a favorable prognosis (as in viral-positive head and neck cancers). Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction, in situ hybridization for E6 and E7 messenger RNA (mRNA), and immunohistochemistry for the proteins p16INK4A and p53. Sequencing of TP53 was also undertaken. The study took place at secondary and tertiary referral centers, with 151 patients assessed for eligibility and 9 excluded. The study period was from December 1, 2002, to November 28, 2017. Main Outcomes and Measures: Disease-free survival (DFS) and overall survival (OS). Results: Among 142 patients with high-grade dysplasia or esophageal adenocarcinoma (126 [88.7%] male; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. Patients who were HPV positive mostly had high p16INK4A expression, low p53 expression, and wild-type TP53. There were more Tis, T1, and T2 tumors in HPV-positive patients compared with HPV-negative patients (75.7% vs 54.3%; difference, 21.4%; 95% CI, 4.6%-38.2%; P = .02). Mean DFS was superior in the HPV-positive group (40.3 vs 24.1 months; difference, 16.2 months; 95% CI, 5.7-26.8; P = .003) as was OS (43.7 vs 29.8 months; difference, 13.9 months; 95% CI, 3.6-24.3; P = .009). Recurrence or progression was reduced in the HPV-positive cohort (24.3% vs 58.1%; difference, -33.8%; 95% CI, -50.5% to -17.0%; P < .001) as was distant metastasis (8.1% vs 27.6%; difference, -19.5%; 95% CI, -31.8% to -7.2%; P = .02) and death from esophageal adenocarcinoma (13.5% vs 36.2%; difference, -22.7%; 95% CI, -37.0% to -8.3%; P = .01). Positive results for HPV and transcriptionally active virus were both associated with a superior DFS (hazard ratio [HR], 0.33; 95% CI, 0.16-0.67; P = .002 and HR, 0.44; 95% CI, 0.22-0.88; P = .02, respectively [log-rank test]). Positivity for E6 and E7 mRNA, high p16INK4A expression, and low p53 expression were not associated with improved DFS. On multivariate analysis, superior DFS was demonstrated for HPV (HR, 0.39; 95% CI, 0.18-0.85; P = .02), biologically active virus (HR, 0.36; 95% CI, 0.15-0.86; P = .02), E6 and E7 mRNA (HR, 0.36; 95% CI, 0.14-0.96; P = .04), and high p16 expression (HR, 0.49; 95% CI, 0.27-0.89; P = .02). Conclusions and Relevance: Barrett high-grade dysplasia and esophageal adenocarcinoma in patients who are positive for HPV are distinct biological entities with a favorable prognosis compared with viral-negative esophageal tumors. Confirmation of these findings in larger cohorts with more advanced disease could present an opportunity for treatment de-escalation in the hope of reducing toxic effects without deleteriously affecting survival.

Active human papillomavirus involvement in Barrett's dysplasia and oesophageal adenocarcinoma is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway.

We have previously demonstrated that transcriptionally active high-risk HPV (hr-HPV) is strongly incriminated in Barrett's dysplasia (BD) and oesophageal adenocarcinoma (OAC) using mainly fresh frozen tissue. This study aimed to identify biomarkers of active HPV infection in Barrett's metaplasia, (BM)/BD/OAC by immunohistochemical staining (IHC) of formalin-fixed paraffin embedded (FFPE) tissue for aberrations of p53 and the retinoblastoma (pRb) pathway, which are targets for the viral oncoproteins, E6/E7, respectively. Prospectively, BM (n = 81)/BD (n = 72)/OAC (n = 65) FFPE specimens were subjected to IHC staining for pRb, p16INK4A , cyclin D1 , p53 and RNA in-situ hybridization for E6/E7 transcripts. HPV DNA was determined via PCR in fresh frozen specimens. Viral load measurement (real-time PCR) and Next Generation Sequencing of TP53 was performed. Of 218 patients, 56 were HPV DNA positive [HPV16 (n = 42), 18 (n = 13), 6 (n = 1)]. Viral load was low. Transcriptionally active HPV (DNA+ /RNA+ ) was only found in the dysplastic and adenocarcinoma group (n = 21). The majority of HPV DNA+ /RNA+ BD/OAC were characterized by p 16highINK4A (14/21, 66.7%), pRblow (15/21, 71.4%) and p53low (20/21, 95%) and was significantly different to controls [combination of HPV DNA- /RNA- (n = 94) and HPV DNA+ /RNA- cohorts (n = 22)]. p53low had the strongest association with DNA+ /RNA+ oesophageal lesions (OR = 23.5, 95% CI = 2.94-187.8, p = 0.0029). Seventeen HPV DNA+ /RNA+ BD/OAC identified as p53low, were sequenced and all but one exhibited wild-type status. pRblow /p53low provided the best balance of strength of association (OR = 8.0, 95% CI = 2.6-25.0, p = 0.0003) and sensitivity (71.4%)/specificity (71.6%) for DNA+ /RNA+ BD/OAC. Active HPV involvement in BD/OAC is characterized by wild-type p53 and aberrations of the retinoblastoma protein pathway.

Australian clinical practice guidelines for the diagnosis and management of Barrett's esophagus and early esophageal adenocarcinoma.

Barrett's esophagus (BE), a common condition, is the only known precursor to esophageal adenocarcinoma (EAC). There is uncertainty about the best way to manage BE as most people with BE never develop EAC and most patients diagnosed with EAC have no preceding diagnosis of BE. Moreover, there have been recent advances in knowledge and practice about the management of BE and early EAC. To aid clinical decision making in this rapidly moving field, Cancer Council Australia convened an expert working party to identify pertinent clinical questions. The questions covered a wide range of topics including endoscopic and histological definitions of BE and early EAC; prevalence, incidence, natural history, and risk factors for BE; and methods for managing BE and early EAC. The latter considered modification of lifestyle factors; screening and surveillance strategies; and medical, endoscopic, and surgical interventions. To answer each question, the working party systematically reviewed the literature and developed a set of recommendations through consensus. Evidence underpinning each recommendation was rated according to quality and applicability.

Persistence of Human Papillomavirus, Overexpression of p53, and Outcomes of Patients After Endoscopic Ablation of Barrett's Esophagus.

We investigated the role of high-risk human papillomavirus (hr-HPV) in patients with Barrett's dysplasia and adenocarcinoma (EAC). Clearance vs persistence of HPV (DNA, E6 or E7 mRNA, and p16INK4A protein) and overexpression or mutation of p53 were determined for 40 patients who underwent endotherapy for Barrett's dysplasia or EAC. After ablation, dysplasia or neoplasia was eradicated in 34 subjects (24 squamous, 10 intestinal metaplasia). Six patients had detectable lesions after treatment; 2 were positive for transcriptionally active hr-HPV, and 4 had overexpression of p53. Before endotherapy, 15 patients had biologically active hr-HPV, 13 cleared the infection with treatment, and dysplasia or EAC was eliminated from 12 patients. One patient who cleared HPV after ablation acquired a p53 mutation, and their cancer progressed. Of 13 patients with overexpression of p53 before treatment, 10 cleared the p53 abnormality after ablation with eradication of dysplasia or neoplasia, whereas 3 of 13 had persistent p53 mutation-associated dysplasia after endotherapy (P = .004). Immunohistochemical and sequence analyses of p53 produced concordant results for 36 of 40 samples (90%). Detection of dysplasia or neoplasia after treatment was associated with HPV persistence or continued p53 overexpression.

Transcriptionally active human papillomavirus is strongly associated with Barrett's dysplasia and esophageal adenocarcinoma.

OBJECTIVES: The role of human papillomavirus (HPV) in Barrett's esophagus (BE) remains unclear. The few studies that have previously investigated HPV and esophageal adenocarcinoma (EAC) or BE have produced either negative data or positive results of doubtful clinical/etiological significance or have detected only low-risk HPV types. We therefore prospectively determined the prevalence of biologically active HPV in esophageal epithelium of patients representing the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. METHODS: HPV DNA was estimated by nested PCR and viral transcriptional activity detected by E6/7 oncogene mRNA expression and p16INK4A immunohistochemistry in fresh frozen and paraffin-embedded esophageal biopsies of patients with BE, Barrett's dysplasia (BD), and EAC, as well as controls. Biopsies were obtained from the transformation zone (squamocolumnar junction (SCJ)) and the lesion, or corresponding site in controls, i.e., 2 cm above the gastroesophageal junction (GEJ). RESULTS: Of the 261 patients, 81 were positive for HPV DNA. In controls and BE, the virus was mostly detected at the transformation zone. Compared with controls (18.0%), HPV positivity was significantly more common in BD (68.6%, incidence rate ratio (IRR) 2.94, 95% confidence interval (CI) 1.78-4.85, P<0.001) and EAC (66.7%, IRR 2.87, 95% CI 1.69-4.86, P<0.001), but not in BE (22.1%, IRR 1.06, 95% CI 0.60-1.85, P=0.85). Of the patients, 92.6% were high-risk (HR) HPV, i.e., types 16 and 18. Again, p16INK4A positivity was greatest in BD and EAC and much less in BE patients (44.1%, IRR 17.0 (95% CI 4.86-59.6, P<0.001), 44.4%, 17.0 (95% CI 4.87-59.4, P<0.001), and 10.6%, 3.93 (95% CI 1.01-15.3, P=0.048) respectively). In 66 HPV DNA-positive patients tested for E6/E7 mRNA, none of the control (n=16) or BE (n=13) individuals were positive, whereas 9/22 BD and 9/15 EAC patients demonstrated oncogene expression (P<0.001). When HPV DNA, p16INK4A, and E6/E7 mRNA were all positive, there was a very strong association with disease severity (SCJ: odds ratio (OR) 104, 95% CI 20.3-529, P<0.001; lesion: OR 62.2, 95% CI 12.4-311, P<0.001) than when all were negative. CONCLUSIONS: Transcriptionally active HR-HPV was strongly associated with BD and EAC, but was largely biologically irrelevant in BE and controls, suggesting a potential role in esophageal carcinogenesis. These data provide robust justification for further detailed longitudinal, interventional, and molecular studies.

Focal or diffuse "fullness" of the pancreas on CT. Usually benign, but EUS plus/minus FNA is warranted to identify malignancy.

CONTEXT: The role of EUS to evaluate subtle radiographic abnormalities of the pancreas is not well defined. OBJECTIVE: To assess the yield of EUS+/-FNA for focal or diffuse pancreatic enlargement/fullness seen on abdominal CT scan in the absence of discrete mass lesions. DESIGN: Retrospective database review. SETTING: Tertiary referral center. PATIENTS AND INTERVENTIONS: Six hundred and 91 pancreatic EUS exams were reviewed. Sixty-nine met inclusion criteria of having been performed for focal enlargement or fullness of the pancreas. Known chronic pancreatitis, pancreatic calcifications, acute pancreatitis, discrete mass on imaging, pancreatic duct dilation (greater than 4 mm) and obstructive jaundice were excluded. MAIN OUTCOME MEASUREMENT: Rate of malignancy found by EUS+/-FNA. RESULTS: FNA was performed in 19/69 (27.5%) with 4 new diagnoses of pancreatic adenocarcinoma, one metastatic renal cell carcinoma, one metastatic colon cancer, one chronic pancreatitis and 12 benign results. Eight patients had discrete mass lesions on EUS; two were cystic. All malignant diagnoses had a discrete solid mass on EUS. CONCLUSIONS: Pancreatic enlargement/fullness is often a benign finding related to anatomic variation, but was related to malignancy in 8.7% of our patients (6/69). EUS should be strongly considered as the next step in the evaluation of patients with focal enlargement of the pancreas when clinical suspicion of malignancy exists.

Circumferential ablation of Barrett's esophagus that contains high-grade dysplasia: a U.S. Multicenter Registry.

BACKGROUND: The management strategies for Barrett's esophagus (BE) that contains high-grade dysplasia (HGD) include intensive endoscopic surveillance, photodynamic therapy, thermal ablation, EMR, and esophagectomy. OBJECTIVE: To assess the safety and effectiveness of endoscopic circumferential balloon-based ablation by using radiofrequency energy for treating BE HGD. DESIGN: Multicenter U.S. registry. SETTING: Sixteen academic and community centers; treatment period from September 2004 to March 2007. PATIENTS: Patients with histologic evidence of intestinal metaplasia (IM) that contained HGD confirmed by at least 2 expert pathologists. A prior EMR was permitted, provided that residual HGD remained in the BE region for ablation. INTERVENTION: Endoscopic circumferential ablation with follow-up esophageal biopsies to assess the histologic response to treatment. OUTCOMES: Histologic complete response (CR) end points: (1) all biopsy specimen fragments obtained at the last biopsy session were negative for HGD (CR-HGD), (2) all biopsy specimens were negative for any dysplasia (CR-D), and (3) all biopsy specimens were negative for IM (CR-IM). RESULTS: A total of 142 patients (median age 66 years, interquartile range [IQR] 59-75 years) who had BE HGD (median length 6 cm, IQR 3-8 cm) underwent circumferential ablation (median 1 session, IQR 1-2). No serious adverse events were reported. There was 1 asymptomatic stricture and no buried glands. Ninety-two patients had at least 1 follow-up biopsy session (median follow-up 12 months, IQR 8-15 months). A CR-HGD was achieved in 90.2% of patients, CR-D in 80.4%, and CR-IM in 54.3%. LIMITATIONS: A nonrandomized study design, without a control arm, a lack of centralized pathology review, ablation and biopsy technique not standardized, and a relatively short-term follow-up. CONCLUSIONS: Endoscopic circumferential ablation is a promising modality for the treatment of BE that contains HGD. In this multicenter registry, the intervention safely achieved a CR for HGD in 90.2% of patients at a median of 12 months of follow-up.

Endoscopic ultrasound-guided fine-needle aspiration for non-small cell lung cancer staging: A systematic review and metaanalysis.

BACKGROUND: Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is a minimally invasive alternative technique for mediastinal staging of non-small cell lung cancer. A metaanalysis was performed to estimate the diagnostic accuracy of EUS-FNA for staging mediastinal lymph nodes (N2/N3 disease) in patients with lung cancer. METHODS: Relevant studies were identified using Medline (1966 to November 2005), CINAHL, and citation indexing. Included studies used histology or adequate clinical follow-up (> 6 months) as the "gold standard," and provided sufficient data for calculating sensitivity and specificity. Summary receiver operating characteristic curves metaanalysis was performed to estimate the pooled sensitivity and specificity. RESULTS: In 18 eligible studies, EUS-FNA identified 83% of patients (95% confidence interval [CI], 78 to 87%) with positive mediastinal lymph nodes (pooled sensitivity) and 97% of patients (95% CI, 96 to 98%) with negative mediastinal lymph nodes (pooled specificity). In eight studies that were limited to patients who had abnormal mediastinal lymph nodes seen on CT scans, the sensitivity was 90% (95% CI, 84 to 94%) and the specificity was 97% (95% CI, 95 to 98%). In patients without abnormal mediastinal lymph nodes seen on CT scans (four studies), the pooled sensitivity was 58% (95% CI, 39 to 75%). Minor complications were reported in 10 cases (0.8%). There were no major complications. CONCLUSIONS: EUS-FNA is a safe modality for the invasive staging of lung cancer that is highly sensitive when used to confirm metastasis to mediastinal lymph nodes seen on CT scans. In addition, among lung cancer patients with normal mediastinal adenopathy seen on CT scans, despite lower sensitivity, it has the potential to prevent unnecessary surgery in a large proportion of cases missed by CT scanning.

Endoscopic therapy for upper-GI vascular ectasias.

BACKGROUND: Upper-GI vascular ectasias, including angiodysplasia and gastric antral vascular ectasia may present with either acute or chronic bleeding. Endoscopic thermal modalities have been used to control acute bleeding and reduce transfusion requirements. METHODS: Endoscopic experience was reviewed for a 6-year period during which 32 patients requiring blood transfusions for upper-GI angiodysplasia or gastric antral vascular ectasia were evaluated. Patients seen during the first 5 years were treated with either Nd:YAG laser photocoagulation or multipolar electrocoagulation. During the most recent 12 months, all patients were treated by argon plasma coagulation. Response to therapy was assessed by change in mean Hb and transfusion requirements. RESULTS: Overall, 16 patients were treated by laser photoablation alone; 9, argon plasma coagulation with or without laser; and 7, multipolar electrocoagulation with or without laser. Mean follow-up for all patients was 19 months. After therapy, mean Hb concentration rose from 76 to 114 g/L for patients with gastric antral vascular ectasia and from 85 to 118 g/L for those with angiodysplasia. Endoscopic therapy abolished or reduced transfusion requirements in 93% of patients with gastric antral vascular ectasia and 76% with angiodysplasia. Patients with gastric antral vascular ectasia required a mean of 6 treatment sessions, while those with angiodysplasia required one to two sessions. CONCLUSIONS: Endoscopic thermal ablation effectively controls acute bleeding and reduces transfusion requirements in most patients with upper-GI vascular ectasias. Patients with gastric antral vascular ectasia require significantly more treatment sessions to achieve this effect.