Risk of malignancy in resected cystic tumors of the pancreas < or =3 cm in size: is it safe to observe asymptomatic patients? A multi-institutional report.

Recent international consensus guidelines propose that cystic pancreatic tumors less than 3 cm in size in asymptomatic patients with no radiographic features concerning for malignancy are safe to observe; however, there is little published data to support this recommendation. The purpose of this study was to determine the prevalence of malignancy in this group of patients using pancreatic resection databases from five high-volume pancreatic centers to assess the appropriateness of these guidelines. All pancreatic resections performed for cystic neoplasms < or =3 cm in size were evaluated over the time period of 1998-2006. One hundred sixty-six cases were identified, and the clinical, radiographic, and pathological data were reviewed. The correlation with age, gender, and symptoms (abdominal pain, nausea and vomiting, jaundice, presence of pancreatitis, unexplained weight loss, and anorexia), radiographic features suggestive of malignancy by either computed tomography, magnetic resonance imaging, or endoscopic ultrasound (presence of solid component, lymphadenopathy, or dilated main pancreatic duct or common bile duct), and the presence of malignancy was assessed using univariate and multivariate analysis. Among the 166 pancreatic resections for cystic pancreatic tumors < or =3 cm, 135 cases were benign [38 serous cystadenomas, 35 mucinous cystic neoplasms, 60 intraductal papillary mucinous neoplasms (IPMN), 1 cystic papillary tumor, and 1 cystic islet cell tumor], whereas 31 cases were malignant (14 mucinous cystic adenocarcinomas and 13 invasive carcinomas and 4 in situ carcinomas arising in the setting of IPMN). A greater incidence of cystic neoplasms was seen in female patients (99/166, 60%). Gender was a predictor of malignant pathology, with male patients having a higher incidence of malignancy (19/67, 28%) compared to female patients (12/99, 12%; p < 0.02). Older age was associated with malignancy (mean age 67 years in patients with malignant disease vs 62 years in patients with benign lesions (p < 0.05). A majority of the patients with malignancy were symptomatic (28/31, 90%). Symptoms that correlated with malignancy included jaundice (p < 0.001), weight loss (p < 0.003), and anorexia (p < 0.05). Radiographic features that correlated with malignancy were presence of a solid component (p < 0.0001), main pancreatic duct dilation (p = 0.002), common bile duct dilation (p < 0.001), and lymphadenopathy (p < 0.002). Twenty-seven of 31(87%) patients with malignant lesions had at least one radiographic feature concerning for malignancy. Forty-five patients (27%) were identified as having asymptomatic cystic neoplasms. All but three (6.6%) of the patients in this group had benign disease. Of the patients that had no symptoms and no radiographic features, 1 out of 30 (3.3%) had malignancy (carcinoma in situ arising in a side branch IPMN). Malignancy in cystic neoplasms < or =3 cm in size was associated with older age, male gender, presence of symptoms (jaundice, weight loss, and anorexia), and presence of concerning radiographic features (solid component, main pancreatic duct dilation, common bile duct dilation, and lymphadenopathy). Among asymptomatic patients that displayed no discernable radiographic features suggestive of malignancy who underwent resection, the incidence of occult malignancy was 3.3%. This study suggests that a group of patients with small cystic pancreatic neoplasms who have low risk of malignancy can be identified, and selective resection of these lesions may be appropriate.

The distribution of enterotoxin and enterotoxin-like genes in Staphylococcus aureus strains isolated from nasal carriers and food samples.

Staphylococcus aureus strains were examined for the presence of 18 enterotoxin (se) and enterotoxin-like (sel) genes by PCR and four classic enterotoxins SEA to SED by reverse passive latex agglutination. We screened three groups of isolates: 53 recovered from food samples collected in years 2004-2005, 18--from food samples collected in the 1960s and 1970s and 30--from nasal carrier samples collected in the years 2000-2002. Eighty percent of all tested strains were se and sel positive, but the frequency of these genes was higher among nasal carrier strains (93%) than among food samples isolates (circa 76%). The enterotoxin genes cluster (egc) was the most prevalent among carrier strains (18/30-60%) and the least--among food strains isolated in the 1960s and 1970s (6/18 strains--33%). sea coding enterotoxin A, which was recognised as the major cause of staphylococcal food poisoning so far, was more often found among carrier strains than among the years 2004-2005 food strains (27% versus 11%), but it was the most frequent se/sel gene among food strains isolated in the 1960s and 1970s (10/18 strains). Moreover in our results certain se and sel genes coexisted, which was in accordance with current knowledge about movable genetic elements carrying those genes. The exception was for only one strain, which harboured the sole selr gene on a possibly new genetic element not yet described. As we found both types of egc, as well as seh (especially food samples strains) occurred alone in a majority of positive strains for each of those genes. The analysis of the results obtained by SET-RPLA method for the productivities of classical enterotoxins A-D and the results obtained by PCR for the presence of sea-sed genes revealed the correlation between each other. Only three of all sea-sed positive strains had silent genes--sed.

Multicenter comparative trial of the V-scope system for therapeutic ERCP.

BACKGROUND AND STUDY AIMS: A new duodenoscope (the V-scope), with a modified elevator used in combination with a dedicated short guide wire, constitutes the V-system. This system is intended to allow fixation of the guide wire at the elevator lever, thereby enhancing the speed and reliability of accessory exchange over a guide wire during ERCP. The aim of this study was to evaluate the extent to which the V-system provides improved efficiency in comparison with conventional duodenoscope and guide wire combinations. PATIENTS AND METHODS: This was an industry-sponsored multicenter randomized trial. Patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) procedures in which treatment was anticipated were randomly assigned to the V-system or to a conventional duodenoscope and accessories used routinely in each center. The parameters recorded included the total case time, fluoroscopy time, catheter/guide wire exchange time, guide wire repositioning, loss of guide wire access, and success or failure of guide wire fixation when using the V-system. RESULTS: Fifty patients were included, 22 in the conventional group and 28 in the V-system group. A total of 135 exchanges were carried out. The patients had up to six exchanges. The median exchange time was 19.4 s with the V-system and 31.7 s with the conventional systems ( P < 0.001). Guide wire repositioning was required less often in the V-system group ( P = 0.0005). The V-system effectively locked the guide wire in 63 of 71 exchanges (89 %). Loss of guide wire access occurred in two patients in the conventional group and four in the V-system group, attributable to failure to lock the guide wire early during the experience (no significant differences). CONCLUSIONS: The V-system can effectively secure the guide wire during accessory exchange in ERCP and reduces the time required to exchange accessories. This may enhance overall efficiency during ERCP.

Human esophageal cancer is distinguished from adjacent esophageal tissue by tissue cysteine concentrations.

Recent studies have suggested that cysteine, in addition to glutathione, may play a role in the genesis, pathobiology, and treatment response of rodent and human cancers. We examined the relative concentrations of cysteine and glutathione in human esophageal cancer and adjacent, minimally involved esophageal tissue. Small biopsies from tumors and adjacent esophageal tissues were placed into cold acid to allow extraction of low-molecular-mass compounds and simultaneous precipitation of macromolecules. Supernatants were analyzed by high-performance liquid chromatography with electrochemical detection for thiol content. While there was no statistically significant difference between the glutathione content of tumor versus adjacent tissue (2.2 mM vs 2.1 mM, respectively), tumor tissue had significantly higher levels of cysteine than adjacent tissue (0.21 mM vs 0.13 mM, respectively). In conclusion, cysteine content distinguishes tumor from adjacent more normal tissue.

Accuracy of EUS in the evaluation of Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma.

BACKGROUND: Nonoperative therapy with intent to cure may be considered for patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma. However, a more advanced stage of disease must be precluded before such treatment. The potential of EUS for this purpose was evaluated. METHODS: EUS was performed in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma based on endoscopy, endoscopic biopsies, and CT before esophagectomy. EUS findings were compared with surgical/pathologic evaluation. RESULTS: EUS suggested submucosal invasion in 6 patients and lymph node involvement in 5 patients. By surgical/pathologic evaluation, 5 of 22 patients (23%) had unsuspected submucosal invasion and 1 had lymph node involvement. EUS detected all 5 instances of submucosal invasion and the single instance of lymph node involvement. EUS was falsely positive for submucosal invasion in 1 patient and for lymph node involvement in 4 patients. Sensitivity, specificity, and negative predictive values of preoperative EUS for submucosal invasion were 100%, 94%, and 100%, and for lymph node involvement were 100%, 81%, and 100%, respectively. A nodule or stricture noted by endoscopy was associated with an increased likelihood of submucosal invasion. CONCLUSIONS: In patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma, EUS detected otherwise unsuspected submucosal invasion and lymph node involvement. Patients should be evaluated with EUS when nonoperative therapy is contemplated.

Juvenile hormone binding protein and transferrin from Galleria mellonella share a similar structural motif.

It has been previously suggested that juvenile hormone binding protein(s) (JHBP) belongs to a new class of proteins. In the search for other protein(s) that may contain structural motifs similar to those found in JHBP, hemolymph from Galleria mellonella (Lepidoptera) was chromatographed over a Sephadex G-200 column and resulting fractions were subjected to SDS-PAGE, transferred onto nitrocellulose membrane and scanned with a monoclonal antibody, mAb 104, against hemolymph JHBP. Two proteins yielded a positive reaction with mAb 104, one corresponding to JHBP and the second corresponding to a transferrin, as judged from N-terminal amino acid sequencing staining. Transferrin was purified to about 80% homogeneity using a two-step procedure including Sephadex G-200 gel filtration and HPLC MonoQ column chromatography. Panning of a random peptide display library and analysis with immobilized synthetic peptides were applied for finding a common epitope present in JHBP and the transferrin molecule. The postulated epitope motif recognized by mAb 104 in the JHBP sequence is RDTKAVN, and is localized at position 82-88.

Long term survival after pancreatic resection for pancreatic adenocarcinoma.

OBJECTIVE: The aim of this study was to determine the long term survival of patients with pancreatic adenocarcinoma who underwent surgical resection and to assess the association of clinical, pathological, and treatment features with survival. METHODS: Between January, 1990, and December, 1998, 125 patients underwent a pancreaticoduodenal or partial pancreatic resection for pancreatic ductal adenocarcinoma at our institution. The records of these patients were reviewed for demographics, tumor characteristics including size, histological grade, margin status, lymph node status, surgical TNM staging, and postoperative adjuvant therapy. The primary outcome variable analyzed was survival. RESULTS: A total of 116 patients had complete follow-up and were included in the final analysis. The median survival after surgery was 16 months. The 1-, 3-, 5-, and 7-yr survival rates for all 116 patients were 60%, 23%, 19%, and 11%, respectively. The 1-, 3-, 5-, and 7-yr survival rates for patients who received adjuvant therapy were 69%, 28%, 23%, and 18% compared with 20% and 0% in patients who did not receive adjuvant therapy (p < 0.0001). The 1-, 3-, 5-, and 7-yr survival rates for patients with negative lymph nodes were 73%, 38%, 26%, and 22% compared with survival rates of 52%, 14%, 14%, and 9% in patients with positive lymph nodes (p = 0.01). In multivariate analyses, adjuvant therapy was the only feature found to be strongly associated with survival (hazards ratio = 0.26, 95% CI = 0.15-0.44). CONCLUSIONS: The overall 5- and 7-yr survival rates of 19% and 11% in our study further validate that surgical resection in patients with pancreatic adenocarcinoma can result in long term survival, particularly when performed in association with adjuvant chemoradiation.

Analysis of Usp DNA binding domain targeting reveals critical determinants of the ecdysone receptor complex interaction with the response element.

The steroid hormone, 20-hydroxyecdysone (20E), directs Drosophila metamorphosis via a heterodimeric receptor formed by two members of the nuclear hormone receptors superfamily, the product of the EcR (EcR) and of the ultraspiracle (Usp) genes. Our previous study [Niedziela-Majka, A., Kochman, M., Ozyhar, A. (2000) Eur. J. Biochem. 267, 507-519] on EcR and Usp DNA-binding domains (EcRDBD and UspDBD, respectively) suggested that UspDBD may act as a specific anchor that preferentially binds the 5' half-site of the pseudo-palindromic response element from the hsp27 gene promoter and thus locates the heterocomplex in the defined orientation. Here, we analyzed in detail the determinants of the UspDBD interaction with the hsp27 element. The roles of individual amino acids in the putative DNA recognition alpha helix and the roles of the base pairs of the UspDBD target sequence have been probed by site-directed mutagenesis. The results show how the hsp27 element specifies UspDBD binding and thus the polar assembly of the UspDBD/EcRDBD heterocomplex. It is suggested how possible nucleotide deviations within the 5' half-site of the element may be used for the fine-tuning of the 20E-response element specificity and consequently the physiological response.

Toxicity of photodynamic therapy after combined external beam radiotherapy and intraluminal brachytherapy for carcinoma of the upper aerodigestive tract.

BACKGROUND AND OBJECTIVE: To describe the toxicity of photodynamic therapy (PDT) in patients with carcinoma of the upper aerodigestive tract who received prior treatment with external beam irradiation and intraluminal brachytherapy (IB). STUDY DESIGN/MATERIALS AND METHODS: Hospital records of PDT patients were reviewed. Three patients who received prior treatment with external beam irradiation and IB were identified. Two patients had esophageal carcinoma treated with combined chemotherapy and external beam irradiation (55.8 and 50.4 Gy) followed by IB (12 Gy and 35 Gy at 1 cm). These patients then received PDT for treatment of recurrence (2 mg/kg Photofrin injection and 2 light applications: 630 nm, 150--200 J/cm, 200--400 mW/cm). One patient had non-small cell lung cancer treated with external beam irradiation (60 Gy) followed by IB (36.1 Gy at 1 cm) and then received PDT for recurrence (1 mg/kg Photofrin injection and one light application: 630 nm, 150 J/cm, 200 mW/cm). RESULTS: One patient with esophagus cancer had formation of a tracheoesophageal fistula, which required stent placement. The other esophageal cancer patient developed quadriplegia due to an epidural abscess arising from a fistula with the diseased portion of the esophagus. The lung cancer patient had massive hemoptysis after the procedure and died 2 days later. Autopsy showed necrotizing arteritis of the right pulmonary artery. CONCLUSION: Patients with upper aerodigestive tract carcinoma who have received treatment with both external beam irradiation and IB seem to be at higher risk for complications when treated with PDT.

The reliability of EUS for the diagnosis of chronic pancreatitis: interobserver agreement among experienced endosonographers.

BACKGROUND: Endoscopic ultrasound (EUS) is a minimally invasive, low risk method of diagnosis for chronic pancreatitis (CP). The degree to which endosonographers agree on the features and diagnosis of CP is unknown. For EUS to be considered an accurate test for CP, there must be good interobserver agreement. METHODS: Forty-five pancreatic EUS examinations were videotaped by 3 experienced endosonographers. Examinations from 33 patients with suspected CP based on typical symptoms, as well as 12 control patients without suspected CP, were included. Eleven experienced endosonographers ("experts") who were blinded to clinical information independently evaluated all videotaped examinations for the presence of CP and the following 9 validated features of CP: echogenic foci, strands, lobularity, cysts, stones, duct dilatation, duct irregularity, hyperechoic duct margins, and visible side branches. The experts also ranked (most to least) which features they believed to be the most indicative of CP. Interobserver agreement was expressed as the kappa (kappa) statistic. RESULTS: There was moderately good overall agreement for the final diagnosis of CP (kappa = 0.45). Agreement was good for individual features of duct dilatation (kappa = 0.6) and lobularity (kappa = 0.51) but poor for the other 7 features (kappa < 0.4). The expert panel had consensus or near consensus agreement (greater than 90%) on 206 of 450 (46%) individual EUS features including 22 of 45 diagnoses of CP. Agreement on the final diagnosis of CP was moderately good for those trained in third tier fellowships (kappa = 0.42 +/- 0.03) and those with more than 1100 lifetime pancreatic EUS examinations (kappa = 0.46 +/- 0.05). The presence of stones was regarded as the most predictive feature of CP by all endosonographers, followed by visible side branches, cysts, lobularity, irregular main pancreatic duct, hyperechoic foci, hyperechoic strands, main pancreatic duct dilatation, and main duct hyperechoic margins. The most common diagnostic criterion for the diagnosis of CP was the total number of features (median 4 or greater, range 3 or greater to 5 or greater). CONCLUSIONS: EUS is a reliable method for the diagnosis of chronic pancreatitis with good interobserver agreement among experienced endosonographers. Agreement on the EUS diagnosis of chronic pancreatitis is comparable to other commonly used endoscopic procedures such as bleeding ulcer stigmata and computed tomography of the brain for stroke localization and better than the physical diagnosis of heart sounds.

Cytomegalovirus colitis complicating ulcerative colitis in the steroid-naive patient.

We report a case of cytomegalovirus (CMV) presenting as acute refractory colitis in a patient with a pre-existing 14-month history of ulcerative colitis (UC) who had never previously been treated with corticosteroids or immunosuppressants. A review of existing literature and previous cases of patients with coincident CMV and UC are examined, stratifying these cases based upon absence or presence of corticosteroid use. To date, only five previous case reports of CMV colitis in patients naive to corticosteroids have been described, and only one previous case has had UC diagnosed over 4 wk before the development of CMV colitis. We further discuss the relationship between these two diseases as well as the diagnosis, treatment, patient characteristics, and outcome of CMV infection of the colon in patients with underlying UC. We discuss the need to consider the diagnosis of CMV colitis in patients with refractory UC who are not receiving corticosteroid treatment as well as those who are refractory and are being treated with immunosuppressants and/or corticosteroids.

Dieulafoy's lesion of the small bowel causing massive gastrointestinal bleeding: two case reports and literature review.

Dieulafoy's lesions are an often unrecognized cause of obscure, massive GI hemorrhage. Their diagnosis may elude conventional investigations, including upper and lower endoscopy, arteriography, and even laparotomy. In this paper, we report two cases of small-bowel Dieulafoy lesions. The first, a jejunal lesion, occurred in a young patient and was discovered at laparotomy. The second was an ileal Dieulafoy's malformation in an older patient. An intraoperative endoscopy with surgical guidance may be needed for definitive localization of this lesion.

EUS predictors of long-term survival in esophageal carcinoma.

BACKGROUND: EUS is the most accurate nonsurgical modality for the staging of esophageal cancer, but the ability of EUS to predict outcomes or prognosis is unclear. Patients were examined who had EUS performed for esophageal cancer staging to determine which endosonographic features predict survival. METHOD: Data on 203 patients undergoing EUS for esophageal cancer staging were studied retrospectively. Median survival was calculated for each T-stage and N-stage and according to the presence or absence of celiac axis (CAx) lymphadenopathy as determined by EUS. Kaplan-Meier survival curves were generated for each stage and the log-rank test was used to test for significant differences in survival. Multivariate analysis was performed to test for the relative importance in predicting survival of the EUS stages, also considering age, gender, histology, and type of treatment. RESULTS: Significant differences were found in the ability of EUS-determined T-stage (p = 0.0005), N-stage (p < 0.0001), and presence of CAx nodes (p = 0.0049) to predict survival. Multivariate analysis showed N-stage to predict survival. CONCLUSIONS: Pretreatment EUS can predict survival in esophageal cancer based on initial T-stage, N-stage, and the presence of CAx nodes. The presence of lymphadenopathy at EUS is an important predictor of survival. EUS should be performed in all patients with esophageal cancer, not only for staging patients before therapy, but also as a valuable method of determining prognosis.

Endosonography is superior to angiography in the preoperative assessment of vascular involvement among patients with pancreatic carcinoma.

Surgical exploration in patients with pancreatic carcinoma without adequate preoperative attempts to determine resectability results in resection in only a minority of patients. Besides distant metastases, involvement of the major vessels is the most important parameter for determining resectability in patients with pancreatic adenocarcinoma. Angiography has been an integral part of pancreatic cancer staging. Lately, endoscopic ultrasound (EUS) has emerged as a more accurate tool in the diagnosis and staging of pancreatic cancer. We hypothesize that EUS is more accurate than selective venous angiography (SVA) for assessing resectability of pancreatic adenocarcinoma based on preoperative evaluation of vascular involvement. Twenty-one patients who met the inclusion criteria were prospectively evaluated with both EUS and SVA before undergoing surgical exploration for attempted curative resection. Vascular involvement was determined by EUS and SVA using previously described criteria. The sensitivity, specificity, and overall accuracy of EUS and SVA in assessing vascular involvement were compared, using surgical exploration as the gold standard. Endoscopic ultrasound had a higher sensitivity than SVA for detecting vascular involvement (86% vs. 21%, respectively; p = 0.0018). The specificity and accuracy of EUS for detecting vascular involvement was 71% and 81%, respectively. In contrast, the specificity and accuracy of SVA for detecting vascular involvement was 71% and 38%, respectively. Endoscopic ultrasound is significantly more sensitive than angiography for detecting vascu lar involvement in patients with pancreatic adenocarcinoma and, thus, may improve patient selection for attempted curative resection.

Endoscopic management of biliary tract disease.

New investigations, evaluation of controversial issues, and advances in technology continue to shape the endoscopic management of biliary disorders. This article discusses recent literature related to the diagnosis and therapy of biliary tract disease. Specifically, the diagnosis and management of choledocholithiasis, complications of biliary endoscopy and potential preventive measures, roles for endosonography in the evaluation of biliary disease, and endoscopic therapy of postoperative liver transplantation complications are reviewed. Recent advances in biliary stents and the use of cholangioscopy in biliary disorders are also assessed.

Two disulphide bridges are present in juvenile hormone binding protein from Galleria mellonella.

The hemolymph juvenile hormone binding protein (JHBP) from Galleria mellonella contains two disulphide bridges/molecule and no free Cys residues. An alignment of primary structures of other Lepidopteran JHBPs indicates that Cys residues, equivalent to Cys10,17,151,195 in G. mellonella JHBP, maybe involved in -S-S- bridge formation.