Outcome of long benign esophageal strictures undergoing endoscopictherapy: a tertiary center experience.

COMPLEX BENIGN ESOPHAGEAL STRICTURES ARE DEFINED BY LENGTH (≥2 CM), SMALL DIAMETER, AND STRICTURE ANGULATION OR TORTUOSITY. THE LONG-TERM COURSE OF COMPLEX ESOPHAGEAL STRICTURES BASED ON LENGTH IS CURRENTLY UNCLEAR. WE SUSPECT THAT THE ESOPHAGEAL STRICTURE LENGTH MIGHT IMPACT THE EFFECTIVENESS OF ENDOSCOPIC DILATION THERAPY. WE PERFORMED A RETROSPECTIVE STUDY OF ALL BENIGN ESOPHAGEAL STRICTURES OF 2 CM OR LONGER TREATED AT A SINGLE CENTER BETWEEN JULY 1, 2010, AND MAY 31, 2014. PRIMARY OUTCOMES WERE CHANGED IN DYSPHAGIA SCORE AT THE END OF FOLLOW-UP COMPARED TO FIRST DILATION AT OUR FACILITY AND THE NEED FOR GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY DURING FOLLOW-UP. DATA WERE STRATIFIED INTO FOUR SUBGROUPS ACCORDING TO STRICTURE LENGTH 20­29, 30­49, 50­99, AND 100 MM OR LONGER. EIGHTY-SEVEN PATIENTS (MEAN AGE 66 YEARS, 54% WOMEN) WERE FOLLOWED OVER A MEDIAN OF 40 MONTHS. PATIENTS UNDERWENT A MEDIAN OF 6 DILATIONS, AVERAGING 0.3 DILATIONS PER MONTH. MEDIAN DYSPHAGIA SCORE REMAINED UNCHANGED AT 2; 37 (43%) PATIENTS REPORTED RESOLUTION OR IMPROVED DYSPHAGIA AND 50 (57%) PATIENTS REPORTED NO IMPROVEMENT OR WORSENED DYSPHAGIA. GASTROSTOMY PLACEMENT OR ESOPHAGECTOMY WAS NEEDED FOR 23 (26%) AND 3 (3%) PATIENTS, RESPECTIVELY. MEDIAN DEGREE OF DYSPHAGIA AT THE END OF FOLLOW-UP DID NOT DIFFER BETWEEN THE FOUR STRICTURE LENGTH SUBGROUPS, YET NO PATIENT HAD IMPROVEMENT IN THE 100 MM OR LONGER SUBGROUP. MORE THAN HALF OF PATIENTS WITH LONG BENIGN ESOPHAGEAL STRICTURES HAD UNCHANGED DYSPHAGIA OR DEVELOPED WORSE DYSPHAGIA DURING FOLLOW-UP. LONG-TERM OUTCOMES DID NOT DIFFER BETWEEN DIFFERENT STRICTURE LENGTHS: .

ZIP4 is a novel diagnostic and prognostic marker in human pancreatic cancer: a systemic comparison between EUS-FNA and surgical specimens.

Aberrant expression of a zinc transporter ZIP4 in pancreatic ductal adenocarcinoma (PDAC) has been shown to contribute to tumor progression and is a potential target for individualized therapy. The overall objective of this study was to determine whether ZIP4 could serve as a novel diagnostic and prognostic marker in human PDAC, and if it can be assessed by minimally invasive sampling using endoscopic ultrasound guided fine needle aspiration (EUS-FNA). Immunohistochemistry was performed to compare ZIP4 expression in the PDAC samples obtained from EUS-FNA and matched surgical tumors (parallel control). Samples were reported by sensitivity, specificity, and predictive values, all with 95% confidence intervals (CI). A total of 23 cases with both FNA and surgical specimens were evaluated. We found that ZIP4 was significantly overexpressed in tumor cells from both sets of samples. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ZIP4 for the diagnosis of PDAC were 72.9%, 72.5%, 76.1%, and 69.0% in EUS-FNA samples, and were 97.9%, 65.4%, 83.9%, and 94.4% in surgical specimens, respectively. The association between the positive rate of ZIP4 expression in FNA and surgical samples is statistically significant (P=0.0216). Both the intensity and percentage of ZIP4 positive cells from the surgical samples correlated significantly with tumor stage (P=0.0025 and P=0.0002). ZIP4 intensity level in FNA samples was significantly associated with tumor differentiation and patient survival. These results indicate that EUS-FNA is capable of non-operative detection of ZIP4, thus offering the potential to direct pre-operative detection and targeted therapy of PDAC.

Risk of gastric or peritoneal recurrence, and long-term outcomes, following pancreatic cancer resection with preoperative endosonographically guided fine needle aspiration.

BACKGROUND AND STUDY AIMS: There have been concerns regarding tumor cell seeding along the needle track or within the peritoneum caused by preoperative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to evaluate whether preoperative EUS-FNA is associated with increased risk of stomach/peritoneal recurrence and whether the procedure affects long term survival. METHODS: The records of patients diagnosed with malignant solid and cystic pancreatic neoplasms who underwent surgery with curative intent between 1996 and 2012 were reviewed. RESULTS: A total of 256 patients with similar baseline characteristics were included: 48 patients in the non-EUS-FNA group and 208 in the EUS-FNA group. Recurrence data were available for 207 patients. Median length of follow-up was 23 months (range 0 - 111 months). A total of 19 patients had gastric or peritoneal recurrence; 6 (15.4 %) in the non-EUS-FNA group vs. 13 (7.7 %) in the EUS-FNA group (P = 0.21). Three patients had recurrence in the stomach wall: one (2.6 %) patient in the non-EUS-FNA group vs. two patients (1.2 %) in EUS-FNA group (P = 0.46). A total of 16 patients had peritoneal recurrence: 5 patients (12.8 %) in the non-EUS-FNA group and 11 patients (6.5 %) in the EUS-FNA group (P = 0.19). In a multivariate analysis, undergoing EUS-FNA was not associated with increased cancer recurrence or decreased overall survival. CONCLUSION: Pre-operative EUS-FNA was not associated with an increased rate of gastric or peritoneal cancer recurrence in patients with resected pancreatic cancer. Two patients had gastric wall recurrence following the procedure, but this may be explained by direct tumor extension. This suggests that EUS-FNA is not associated with an increased risk of needle track seeding.

Accuracy of real-time vs. blinded offline diagnosis of neoplastic colorectal polyps using probe-based confocal laser endomicroscopy: a pilot study.

BACKGROUND AND STUDY AIMS: Probe-based confocal laser endomicroscopy (pCLE) is a new imaging modality that enables histological examination of gastrointestinal mucosa during endoscopic procedures. Most studies have evaluated offline interpretation of pCLE images. In clinical practice, real-time interpretation is necessary to assist decision-making during the procedure. The aim of this pilot study was to compare the accuracy of real-time pCLE diagnosis made during the procedure with that of blinded offline interpretation to provide accuracy estimates that will aid the planning of future studies. PATIENTS AND METHODS: pCLE was performed in patients undergoing screening and surveillance colonoscopy. Once a polyp had been identified, one endoscopist analyzed pCLE images during the procedure and made a provisional "real-time" diagnosis. Saved video recordings were de-identified, randomized, and reviewed "offline" 1 month later by the same endoscopist, who was blinded to the original diagnoses. RESULTS: Images from a total of 154 polyps were recorded (80 neoplastic, 74 non-neoplastic). The overall accuracy of real-time pCLE diagnosis (accuracy 79%, sensitivity 81%, specificity 76%) and offline pCLE diagnosis (83%, 88%, and 77%, respectively) for all 154 polyps were similar. Among polyps < 10 mm in size, the accuracy of real-time interpretation was significantly lower (accuracy 78%, sensitivity 71%, specificity 83%) than that of offline pCLE interpretation (81%, 86%, 78%, respectively). For polyps ≥ 10 mm, the accuracy of pCLE diagnosis in real-time was better (accuracy 85%, sensitivity 90%, specificity 75%) than offline pCLE diagnosis (81%, 97%, and 50%, respectively). CONCLUSIONS: These results suggest that real-time and offline interpretations of pCLE images are moderately accurate. Real-time interpretation is slightly less accurate than offline diagnosis, but overall both are comparable. Additionally, there was contrasting accuracy between the two methods for small and large polyps.

A comparison of high definition-image enhanced colonoscopy and standard white-light colonoscopy for colorectal polyp detection.

BACKGROUND AND STUDY AIMS: Colonoscopy is widely used to detect and remove precancerous polyps, but fails to detect some polyps. Recent studies evaluating different image-enhanced methods have revealed conflicting results. The efficacy of colonoscopy imaging with simultaneous use of commercially available improvements, including high definition narrow band imaging (HD-NBI), and monochromatic charge-coupled device (CCD) video, was compared with a widely used standard definition white light (SDWL) colonoscopy system for detecting colorectal polyps. The primary aim was to determine whether the combination of image-enhanced colonoscopy systems resulted in fewer missed polyps compared with conventional colonoscopy. PATIENTS AND METHODS: In a randomized controlled trial (Clinicaltrials.gov. study number NCT00825292) patients having routine screening and surveillance underwent tandem colonoscopies with SDWL and image-enhanced (HD-NBI) colonoscopy. The main outcome measurement was the per-polyp false-negative ("miss") rate. Secondary outcomes were adenoma miss rate, and per-patient polyp and adenoma miss rates. RESULTS: 100 patients were randomized and 96 were included in the analysis. In total, 177 polyps were detected; of these, 72 (41 %) were adenomatous. Polyp and adenoma miss rates for SDWL colonoscopy were 57 % (60/105) and 49 % (19/39); those for image-enhanced colonoscopy were 31 % (22/72) and 27 % (9/33) (P = 0.005 and P = 0.036 for polyps and adenomas, respectively). Image-enhanced and SDWL approaches had similar per-patient miss rates for polyps (6/35 vs. 9/32, P = 0.27) and adenomas (4/22 vs. 8/20, P = 0.11). CONCLUSIONS: Utilization of multiple recent improvements in image-enhanced colonoscopy was associated with a reduced miss rate for all polyps and for adenomatous polyps. It is not known which individual feature or combination of image-enhancement features led to the improvement.

Safety and efficacy of cytology brushings versus standard fine-needle aspiration in evaluating cystic pancreatic lesions: a controlled study.

BACKGROUND AND STUDY AIMS: Cystic pancreatic lesions (CPLs) are increasingly detected by various imaging studies. Mucinous CPLs carry a risk of malignant transformation but this is often difficult to diagnose preoperatively. In a previous report of 10 suspected mucinous CPLs, the cellular yield of endoscopic ultrasonography (EUS)-guided cytology brushings was found to be superior to the yield from standard fine-needle aspiration (FNA). The aim of this prospective and blinded study was to compare the cytology yield of mucinous epithelium from brushing with FNA in suspected mucinous CPLs. PATIENTS AND METHODS: In total, 37 patients with 39 CPLs measuring at least 20 mm were enrolled between June 2006 and July 2008 for EUS-cytobrushing and EUS-FNA of CPLs. Demographic, clinical, EUS, cytopathologic, and surgical data were recorded whenever available. Yield of cytology brushings was compared with that of FNA. Procedure morbidity was evaluated after 30 days. The main outcome assessed was yield of intracellular mucin (ICM) on cytobrushing specimens compared with EUS-FNA for the diagnosis of suspected mucinous CPL. RESULTS: Cytobrushings were more likely to detect ICM than the EUS-FNA method ( P = 0.001). In three patients with hypocellular FNA, dysplasia was found on cytology brushing and later confirmed by surgical pathology. Significant complications occurred in three patients (8 %): one postbrushing bleeding and two acute pancreatitis. CONCLUSIONS: Cytology brushings are more likely to provide an adequate mucinous epithelium specimen than standard FNA and could aid the diagnosis of CPLs in a selective group of patients.

The role of surveillance endoscopy and endosonography after endoscopic ablation of high-grade dysplasia and carcinoma of the esophagus.

Barrett's esophagus (BE) with high-grade dysplasia (HGD) or early carcinoma treated with surgery or photodynamic therapy (PDT) is at risk of recurrence. The efficacy of endoscopic ultrasound (EUS) for surveillance after PDT is unknown. Our objective was to determine if EUS is superior to esophagogastroduodenoscopy (EGD) and/or CT scan for surveillance of BE neoplasia after PDT. The study was designed as a retrospective review with the setting as a tertiary referral center. Consecutive patients with BE with HGD or carcinoma in situ treated with PDT were followed with EUS, CT scan and EGD with jumbo biopsies every 1 cm at 3, 4, or 6-month intervals. Exclusion criteria was < 6 months of follow up and/or < 2 EUS procedures. Main outcome measurements were residual or recurrent disease discovered by any method. Results showed that 67/97 patients met the inclusion criteria (56 men and 11 women). Median follow-up was 16 months. Recurrent or residual adenocarcinoma (ACA) was detected in four patients during follow-up. EGD with random biopsies or targeted nodule biopsies detected three patients. EUS with endoscopic mucosal resection of the nodule confirmed T1 recurrence in one of these three. In the fourth patient, CT scan revealed perigastric lymphadenopathy and EUS-FNA (fine needle aspiration) confirmed adenocarcinoma. There were two deaths, one related to disease progression and one unrelated. The rate of recurrent/persistent ACA after PDT was 4/67 = 6%. EUS did not detect disease when EGD and CT were normal. Limitations of this study include non-blinding of results and preferential status of non-invasive imaging (CT) over EUS. Our experience suggests that EUS has little role in the surveillance of these patients, unless discrete abnormalities are found on EGD or cross-sectional imaging.

The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study.

BACKGROUND AND STUDY AIMS: Fine-needle aspiration (FNA) is commonly performed in conjunction with endoscopic ultrasound (EUS) procedures. The complication rate associated with FNA is considered to be low but requires further evaluation with prospective studies. PATIENTS AND METHODS: A total of 483 consecutive patients who underwent EUS-guided FNA over a 12-month period were prospectively enrolled in the study. The patients were screened for postprocedural complications, including abdominal pain, nausea, vomiting, and gastrointestinal bleeding. Complications were assessed immediately after EUS-FNA and 30 days later with a telephone call, when inquiries were made about emergency room and physician's office visits or hospitalizations during this 30-day period. RESULTS: Complete information was obtained from 414 patients (86 %). Complications occurred in seven patients during the first day. Five of these patients had unplanned admissions to hospital: two patients were observed because they had abdominal pain after FNA of pancreatic cysts; one patient was observed because they developed chest pain after mediastinal lymph node FNA; and two patients were monitored after celiac node FNA, one with a transient fever and one with self-limited melena. All five of these patients were discharged within 24 hours of admission, none required blood transfusion, and none showed any evidence of pancreatitis or infection. Two other patients visited the emergency department but were discharged on oral analgesics after appropriate evaluation. By day 30 six patients had died as a result of their primary disease process. There was no unexpected morbidity or mortality attributable to the EUS-FNA. CONCLUSIONS: FNA is a safe intervention in patients undergoing EUS in a high-volume academic center, with a low postprocedural complication rate.

Photodynamic therapy and endoscopic metal stent placement for esophageal papillomatosis associated with squamous cell carcinoma.

Esophageal squamous papillomatosis is a rare condition associated with human papilloma virus infection and has been complicated by the development of squamous cell carcinoma. Photodynamic therapy using porfimer sodium has been used for the treatment of esophageal cancer but has not been utilized in the treatment of esophageal squamous papillomatosis. We report here the first case of papillomatosis and obstructing squamous cell carcinoma of the esophagus palliated with porfimer sodium photodynamic therapy indicating successful photosensitizer uptake in papilloma-laden tissue. Extensive debulking of papilloma and tumor allowed esophageal recanalization and placement of a self-expanding metal stent for long-term dysphagia palliation. This unique case highlights the combined use of endoscopic techniques for optimal treatment results.

Prostate cancer metastasizing to the small bowel.

Although prostate cancer is one of the most commonly encountered malignancies in clinical practice, it is very unusual for prostate cancer to metastasize to the small bowel. Our search of the literature found no such cases published from 1966 to the present. We report the case of a 69-year-old man who presented for evaluation of anasarca and anorexia. He had a history of prostate cancer diagnosed 9 years before and had undergone a radical prostatectomy with subsequent radiotherapy for positive tumor margins. He developed anasarca 2 years before presentation to us. His serum albumin ranged between 1.5 and 2.5 g/dL. Upper endoscopy was performed for possible protein-losing enteropathy and the appearance of gastric and duodenal mucosa was found to be normal. Random small bowel biopsies revealed submucosal infiltrating adenocarcinoma with positive prostate-specific antigen stains consistent with the diagnosis of prostate cancer metastatic to the small bowel. This is a rare presentation of metastatic prostate cancer. Even though prostate cancer is the most commonly diagnosed cancer in American men, antemortem diagnosis of small bowel metastasis has not been reported. In patients with unexplained anasarca, especially with a history of malignancy, an upper endoscopy with small bowel biopsy may be useful in establishing the diagnosis.

Solitary pelvic nodule: diagnosis of metastatic prostate cancer by endoscopic ultrasound-guided, fine-needle aspiration.

Prostate cancer manifesting as an isolated perirectal mass is a rare occurrence. The following is a report of a single pelvic nodule that was determined to be metastatic prostate cancer by endoscopic ultrasound-guided, fine-needle aspiration.

Barrett's esophagus, apoptosis and cell cycle regulation: correlation of p53 with Bax, Bcl-2 and p21 protein expression.

Dysregulation of apoptosis plays an important role in tumor development. Mutations of the p53 gene have been reported in adenocarcinomas arising from Barrett's metaplasia. The p53 gene is important in the regulation of cell growth and apoptosis, with the loss of wild-type activity associated with uncontrolled cell-cycle progression and tumor formation. P21 is a cyclin-dependent kinase inhibitor that is activated by p53. Bax is a member of the bcl-2 family whose function is that of cell-death promoter. We investigated the hypothesis that there are significant alterations in the levels of apoptotic protein as well as p21 protein expression in the neoplastic progression associated with Barrett's metaplasia.

Endo-organ and laparoscopic management of gastric leiomyomas.

Various techniques have been reported for the laparoscopic treatment of benign gastric lesions, depending on the site of the lesion. Recently, a new technique of endo-organ gastric surgery has been developed that is particular useful for the treatment of lesions on the posterior gastric wall. We report on two patients with submucosal gastric tumors. A 79-year-old man was found to have a submucosal tumor near the esophagogastric junction in the posterior wall of the stomach. Endosonography suggested that the tumor was a gastric leiomyoma. Under endoscopic guidance, three ports were inserted into the stomach and the tumor could be successfully enucleated. A 78-year-old woman was found to have a 2 x 1-cm submucosal tumor at the anterior wall of the antrum. The tumor was successfully removed by laparoscopic gastrotomy and resection. The various laparoscopic techniques for the treatment of gastric lesions are discussed.

Cancers of the stomach and the duodenum.

Gastric cancer remains the seventh most common cause of cancer death in the United States, and it is the most prevalent in populous areas, such as south China, Japan, and Korea. Duodenal cancers are rare; adenocarcinomas are the most common variety. We examine recent findings concerning pathogenesis, diagnosis, and management of gastric and duodenal malignancies.

Further studies on growth factor production by the TC-1 stromal cell line: pre-B stimulating activity.

Adherent murine stromal cells support long-term in vitro lymphopoiesis or myelopoiesis dependent on the culture conditions used. A cell line, TC-1, isolated from long-term liquid murine marrow cultures under conditions approaching those permissive for lymphoid growth, has been found to produce an activity that acts synergistically with interleukin-3 (IL-3) or colony-stimulating factor-1 (CSF-1) to stimulate in vitro myeloid colonies, but which has no intrinsic colony-stimulating activity. We report here the presence of multiple growth factors in conditioned medium (CM) from the TC-1 line, including granulocyte-macrophage colony-stimulating factor (GM-CSF) (bioassay with antibody blocking and messenger RNA [mRNA] analysis), granulocyte CSF (G-CSF) and IL-4 (factor-dependent cell line bioassay), and CSF-1 (radioimmunoassay, mRNA) along with a pre-B cell inducing activity, which appears separate from these CSFs and segregates with the myeloid synergizing activity through anion exchange, sizing, and Conconavalin A chromatography. Because these activities are not yet purified to homogeneity, their identity or lack of identity remains an open question. Assays of TC-1 CM or cellular mRNA analysis have given negative results for IL-1, IL-2, IL-3, IL-6, and IL-7, and IL-6 does not stimulate pre-B cells in this assay. However, IL-4 and G-CSF do stimulate in vitro induction of pre-B cells from pre-B and B-cell-depleted Balb/C marrow and are present in CM by selective cell line assay. A monoclonal antibody to IL-4 that inhibited its pre-B inducing activity did not inhibit pre-B inducing activity of TC-1 CM. These data suggest the existence of a unique synergizing and pre-B inducing factor(s) in TC-1 CM. Given the known capacity of subliminal levels of growth factors to act synergistically, an alternate possibility is that these biologic phenomena represent the actions of low concentrations of growth factors acting synergistically and possibly associated with some core protein.

Stromal cell regulation of lymphoid and myeloid differentiation.

In vitro microenvironmental influences seem to be critical for both B lymphocyte and myeloid differentiation. Studies on murine Dexter cultures and Whitlock-Witte lymphocyte cultures suggest the presence of two critical stromal regulatory cells: an alkaline-phosphatase-positive epithelioid cell and a macrophage. Further data suggest that these cells are capable of producing colony stimulating factor-1, granulocyte-macrophage CSF, a myeloid synergizing activity, and probably separate B cell growth factors. Isolation of a cell line from Dexter stroma was accomplished and this line produced CSF-1, GM-CSF, a pre-B cell and myeloid synergizing activity, and an activity acting on differentiated B cells. We speculate that the Dexter and Whitlock-Witte in vitro culture systems are regulated by factors produced by the two adherent cell types. A lineage nonspecific factor capable of inducing cells into the B lineage or synergizing with interleukin-3, GM-CSF, and CSF-1 is produced, which presumably acts on early stem cells. In addition, the cell line produces GM-CSF, CSF-1, and a factor acting on differentiated B cells. We speculate that in these culture systems, these "terminal differentiating hormones" regulate the final pathway of differentiation, whereas the pre-B-synergizing activity supports early stem cells that can then respond to the other differentiating hormones.