Full dose neoadjuvant FOLFIRINOX is associated with prolonged survival in patients with locally advanced pancreatic adenocarcinoma.

BACKGROUND: The efficacy of FOLFIRINOX for metastatic pancreatic cancer has led to its use in patients with earlier stages of disease. This study retrospectively analyzed a cohort of patients with locally-advanced pancreatic cancer (LAPC) treated with FOLFIRINOX. METHODS: Between 2008 and 2013, 51 treatment-naïve patients with LAPC at a single institution received first-line FOLFIRINOX with neoadjuvant intent, at the full dose as described in the PRODIGE 4/ACCORD 11 study. Combined chemoradiation was administered for those who remained unresectable after maximum response to chemotherapy. The primary outcome measure was overall survival (OS), and secondary outcomes were progression-free survival (PFS) and margin-negative (R0) resection rate, and toxicity profile. RESULTS: A total of 429 cycles of FOLFIRINOX were given with a median of 8 cycles (range 2-29) per patient; 66% of cycles were full dose. After chemotherapy, 27 (53%) received chemoradiation. The median OS was 35.4 months (95% CI 25.8-45). Ten (4 borderline resectable and 6 unresectable) patients had successful R0 resections; those who had R0 resections had a significantly longer survival than those who did not (3-year OS rate 67% versus 21%, log rank p = 0.042). Increasing number of full-dose cycles was significantly associated with increased survival. The toxicity profile was similar to previous reports of this regimen. CONCLUSIONS: FOLFIRINOX is feasible as neoadjuvant therapy for LAPC. Although the R0 resection rate was only 20%, the median OS of almost 3 years appears promising. Dose intensity and duration were associated with increased survival in this study, arguing against dose attenuated versions of this regimen.

Endoscopic ultrasound guided fine needle aspiration with fluorescence in situ hybridization analysis in 104 patients with pancreatic mass.

BACKGROUND AND AIM: Diagnosis of pancreatic malignancy is often based on cytological specimens collected by endoscopic ultrasound guided fine needle aspiration (EUS FNA). Several factors can decrease sensitivity of EUS FNA for pancreatic cancer: well-differentiated tumors, pancreatitis, blood, necrosis and slides with low cellularity. The objective of this study is to report on the use of fluorescence in situ hybridization (FISH) analysis combined with cytology in pancreatic masses. METHODS: EUS database and medical records of patients referred for EUS between January 2009 through august 2013 were reviewed. Data on cytology, FISH and surgical pathology were reviewed. Surgical pathology, death or extended clinical follow-up were used to verify correct diagnosis of malignancy. FISH performed using a four-set DNA probe for chromosomes 3, 7, 17, and band 9p21 in patients with inconclusive immediate cytology reading. Sensitivity of cytology and FISH were compared. RESULTS: Study cohort comprised of 104 patients with FISH analysis on EUS FNA specimens of pancreatic masses (74 adenocarcinoma, 7 neuroendocrine tumor and 23 benign. Sensitivity of cytology and FISH for carcinoma was respectively: 62% and 81%. Sensitivity of FISH + cytology was 89%. The specificity of FISH and cytology was 100%. The most common abnormality on FISH was a 9p21 deletion seen in 43 patients (58%) followed by polysomy of 7 (46%). FISH detected malignancy in 23 patients with negative cytology. CONCLUSIONS: In patients with inconclusive immediate cytology reading, FISH is superior to cytology and improves overall sensitivity. The 9p21 deletion is the most common abnormality seen in this cohort of patients with pancreatic cancer.

Depth of injury caused by liquid nitrogen cryospray: study of human patients undergoing planned esophagectomy.

BACKGROUND: Cryotherapy using liquid nitrogen delivered endoscopically has been used for mucosal ablation of esophageal neoplasia. There are no data for the human esophagus on the depth of injury and effects of this technique. AIM: Prospective study to examine the effect of treatment and depth of injury to the human esophagus of liquid nitrogen spray cryotherapy for subjects with esophageal neoplasia before planned esophagectomy. METHODS: Liquid nitrogen spray cryoablation was performed seven days before scheduled esophagectomy for seven males with esophageal carcinoma. Subjects were assigned to either treatment of four cycles of 10 s each (group 1) or two cycles of 20 s each (group 2) applied to a 2-cm segment of healthy esophagus above the tumor area. Main outcomes measured were: mean depth of injury (mm); surface displaying mucosal ablation, and adverse events. RESULTS: Mucosal destruction was similar for both groups (group 1, 95%; group 2, 93%; p = NS). Deeper injury was observed for group 2; mean depth was 5.4 mm compared with 4.0 mm for group 1. Cryonecrosis reached the submucosa for 60% (12/20) of subjects in group 1 versus 93% (14/15) of subjects in group 2 (p = 0.04, two-tailed Fisher's exact test). No serious adverse events occurred. No perforation was seen in the resected esophagus. CONCLUSION: Mucosal ablation with liquid nitrogen spray cryotherapy was highly effective in inducing mucosal necrosis; the doses assessed had similar effects. Ablation reached the submucosa more often with longer spray time despite fewer treatment cycles.

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma.

BACKGROUND: 5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC). METHODS: In this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate. RESULTS: Eighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22-69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %). CONCLUSIONS: FOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted.

EUS visualization and direct celiac ganglia neurolysis predicts better pain relief in patients with pancreatic malignancy (with video).

BACKGROUND: EUS-guided celiac plexus neurolysis (EUS-CPN) improves pain control in patients with pancreatic cancer. EUS allows visualization of the celiac ganglion. OBJECTIVE: To determine predictors of response to EUS-CPN in a cohort of 64 patients with pancreatic malignancy. DESIGN: Retrospective analysis of prospective database. SETTING: Academic medical center. PATIENTS: Sixty-four patients with pancreatic cancer referred for EUS between March 2008 and January 2010. INTERVENTIONS: EUS-CPN injected directly into celiac ganglia when visible by linear EUS or bilateral injection at the celiac vascular trunk. MAIN OUTCOME MEASUREMENTS: Predictors of pain improvement at week 1 by univariate and multivariate analysis. RESULTS: At week 1, 32 patients (50%) had a symptomatic response. In a multivariate model with 8 potential predictors, visualization of the ganglia was the best predictor of response; patients with visible ganglia were >15 times more likely to respond (odds ratio 15.7; P<.001). Tumors located outside the head of the pancreas and patients with a higher baseline pain level were weakly associated with a good response. LIMITATIONS: Retrospective design and lack of blinding. CONCLUSIONS: Visualization of celiac ganglia with direct injection is the best predictor of response to EUS-CPN in patients with pancreatic malignancy.

EUS-FNA with rescue fluorescence in situ hybridization for the diagnosis of pancreatic carcinoma in patients with inconclusive on-site cytopathology results.

BACKGROUND: Detection of chromosomal abnormalities by fluorescence in situ hybridization (FISH) analysis has not been well-studied in FNA samples of pancreatic masses. Selective use of FISH in patients with inconclusive on-site cytopathology results may improve the sensitivity of EUS for malignancy. OBJECTIVE: To determine the sensitivity and specificity of FISH analysis in patients with inconclusive on-site cytopathology results. DESIGN: Consecutive patients with suspected pancreatic malignancy, nonrandomized cohort study. Final diagnosis was based on either surgical biopsy or disease progression on extended follow-up or death. SETTING: Academic center, tertiary-care referral cancer center. PATIENTS: A total of 212 EUS examinations were performed in 206 patients for solid pancreatic lesions over a 24-month period (January 2009-December 2010). FISH analysis was done for 69 patients with inconclusive or nonavailable on-site cytology results. INTERVENTION: EUS-guided FNA (EUS-FNA) of solid pancreatic masses with cytology and FISH analysis for polysomy of chromosomes 3, 7, and 17 and deletion of 9p21. MAIN OUTCOME MEASUREMENTS: Sensitivity/specificity of cytology, FISH, and a composite of cytology and FISH. RESULTS: Patients with positive on-site cytology (110), neuroendocrine tumors (22), insufficient follow-up (1), FISH not obtained (3), and renal cancer with pancreatic metastasis (1) were excluded. Sixty-nine patients comprised the study cohort, 54 with malignancy and 15 with benign disease. Sensitivity for malignancy of cytology, FISH analysis, and the combination were 61%, 74%, and 85%, respectively (P = .009). FISH detected an additional 13 cases of pancreatic adenocarcinoma missed by cytology. There was no false-positive FISH analysis in 15 patients with benign disease. No major complications occurred from EUS-FNA. LIMITATIONS: Single center, selected patients underwent FISH analysis, limited number of patients with benign disease. CONCLUSION: In patients with suspected pancreatic cancer, FISH analysis can detect additional cases missed by cytology without compromising specificity. FISH analysis to detect polysomy of chromosomes 3, 7, and 17 and deletion of 9p21 should be considered when cytology is negative for malignancy in patients with a known pancreatic mass.

EUS-guided biopsy for the diagnosis and classification of lymphoma.

BACKGROUND: EUS-guided FNA and Tru-cut biopsy (TCB) is highly accurate in the diagnosis of lymphoma. Subclassification, however, may be difficult in low-grade non-Hodgkin lymphoma and Hodgkin lymphoma. OBJECTIVE: To determine the yield of EUS-guided biopsy to classify lymphoma based on the World Health Organization classification of tumors of hematopoietic lymphoid tissues. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A total of 24 patients referred for EUS-guided biopsy who had a final diagnosis of lymphoma or "highly suspicious for lymphoma." INTERVENTIONS: EUS-guided FNA and TCB combined with flow cytometry (FC) analysis. MAIN OUTCOMES MEASUREMENT: Lymphoma subclassification accuracy of EUS guided biopsy. RESULTS: Twenty-four patients were included in this study. Twenty-three patients underwent EUS-FNA, and 1 patient had only TCB. Twenty-two underwent EUS-TCB combined with FNA. EUS correctly diagnosed lymphoma in 19 out of 24 patients (79%), and subclassification was determined in 16 patients (66.6%). Flow cytometry correctly identified B-cell monoclonality in 95% (18 out of 19). In 1 patient diagnosed as having marginal-zone lymphoma by EUS-FNA/FC only, the diagnosis was changed to hairy cell leukemia after a bone marrow biopsy was obtained. EUS had a lower yield in nonlarge B-cell lymphoma (only 9 out of 15 cases [60%]) compared with large B-cell lymphoma (78%; P = .3 [Fisher exact test]). LIMITATIONS: Retrospective, small number of patients. CONCLUSION: EUS-guided biopsy has a lower yield to correctly classify Hodgkin lymphoma and low-grade lymphoma compared with high-grade diffuse large B-cell lymphoma.

Single-session endoscopic ultrasonography and endoscopic retrograde cholangiopancreatography for evaluation of pancreaticobiliary disorders.

BACKGROUND: Endoscopic ultrasonography (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) often are required in the evaluation and treatment of patients with pancreaticobiliary disorders. Few reports of single-session EUS-ERCP have raised questions regarding its safety and accuracy or about which procedure should be performed first. METHODS: Data from 2005 to 2009 were reviewed from a prospectively maintained EUS-ERCP database at a single tertiary care cancer center. Sensitivity and specificity of EUS and fine-needle aspiration (FNA), bile duct cannulation rate, duration of procedure, and complications were evaluated. RESULTS: Of the 35 patients (15 men and 20 women) studied, 28 had a final diagnosis of malignancy, and 7 had benign disorders. All the patients underwent ERCP and EUS, with FNA performed for 28 patients (80%). For 22 of the 35 patients (62.8%), EUS was the first procedure performed. The sensitivity of EUS-FNA for malignancy was 96.4%. The bile duct cannulation rate during ERCP was 97.1%. Five patients required a precut sphincterotomy for bile duct access, and one patient with chronic pancreatitis had a failed cannulation despite a EUS-guided rendezvous. A stent was successfully placed in 29 patients (96%). No major complications occurred, and no contrast leak was seen when FNA was performed before the cholangiogram. One patient had periduodenal bleeding after FNA, which was managed conservatively. The mean duration of the procedure was 83.7 min. CONCLUSION: Single-session EUS-ERCP can be performed safely and with efficacy similar to that of the procedures performed separately.

Expression of annexin-A1 in blood and tissue leukocytes of leprosy patients.

INTRODUCTION: In leprosy, immune system mediators that regulate the infectious process act in a complex manner and can lead to several clinical outcomes. To understand the behavior of these mediators we quantified the expression of annexin-A1 (ANXA1) in the peripheral blood and plasma as well as tissue leukocytes in all clinical forms of leprosy and compared with healthy controls. METHODS: Seventy healthy controls and 70 patients with leprosy, tuberculoid (TT) (n = 13), borderline tuberculoid (BT) (n = 15), borderline borderline (BB) (n = 13), borderline lepromatous (BL) (n = 15), and lepromatous leprosy (LL) (n = 14), were selected. Phenotyping of the lymphocyte cells and the intracellular expression of ANXA1 in leukocytes was performed by immunofluorescence. Plasma protein levels were determined by enzyme-linked immunosorbent assay. RESULTS: Histiocytes and CD4+ and CD8+ T cells in the skin of BL and LL patients had higher ANXA1 expression. ANXA1 expression was also high in circulating polymorphonuclear, monocytes, and CD4+ and CD8+ T cells in the blood of LL patients compared to those of TT, BT, BB, and BL patients, and these levels were similar to those in healthy controls. Plasma ANXA1 levels indicate an increase in paracrine release in patients with LL. CONCLUSIONS: The data indicate that ANXA1 expression is enhanced in the leukocytes and plasma of patients with LL, and may contribute to the inhibition of leukocyte action, leading to inadequate functioning of the immune system and thus contributing to the spread of M. leprae infection.

EUS-guided fiducial placement before targeted radiation therapy for prostate cancer.

BACKGROUND: Image-guided radiation therapy allows the delivery of precisely aimed radiation beams to tumors while minimizing radiation to adjacent normal tissue. This is particularly important in the prostate, a moving target whose positioning depends on the dynamics of its neighboring bladder and rectum. Targeted radiation therapy can be achieved by using implantable radiographic markers, or fiducials, which serve as reference points to accurately delineate tumors. OBJECTIVE: To determine the feasibility and safety of placing fiducials in the prostate under linear array EUS guidance to facilitate targeted radiation therapy. DESIGN: Retrospective analysis of a prospective database. SETTING: University of Miami Hospital and Clinics, a tertiary cancer referral center. PATIENTS: Localized prostate cancer patients scheduled to undergo intensity-modulated radiation therapy. INTERVENTIONS: A total of 16 patients underwent EUS-guided fiducial placement to delineate the prostate before planned radiation therapy. RESULTS: Fiducial placement was successful in all patients (100%). A total of 71 gold markers were deployed in a 4-quadrant manner outlining the prostate. Seven of 16 patients had an additional fiducial placed to ensure adequate prostate delineation. Patients tolerated the procedure well with minimal discomfort. No complications developed from the procedure. LIMITATIONS: Single-center experience, small sample size. CONCLUSIONS: EUS-guided placement of fiducials to facilitate image-guided radiation therapy for prostate cancer is a feasible alternative to transperineal or transrectal US approaches, thereby adding to the expanding list of indications for linear EUS. This procedure can be safely performed by endosonographers familiar with perirectal anatomy and transrectal FNA technique.

EUS-guided fine needle aspiration with and without trucut biopsy of pancreatic masses.

CONTEXT: Endoscopic ultrasound-guided trucut biopsy (EUS TCB) has a lower yield than fine needle aspiration (FNA) in pancreatic masses but the additional use of TCB to FNA may improve the diagnostic accuracy over FNA alone. OBJECTIVE: To compare the yield of EUS FNA alone or combined with EUS TCB for diagnosis of pancreatic masses. DESIGN: Single center retrospective case control study conducted at academic tertiary center. Study conducted between March 2004 and April 2007. PARTICIPANTS: A total of 126 consecutive patients referred for EUS guided biopsy of pancreatic mass; three patients excluded from analysis, final cohort comprised 123 patients (108 malignant and 15 benign). EUS FNA was performed in 72 patients and EUS FNA+TCB was performed in 51 patients. MAIN OUTCOME MEASURES: The diagnostic performance of EUS FNA versus EUS FNA+TCB was compared. RESULTS: The sensitivity, specificity and frequency of cases correctly identified for malignancy of FNA alone were 87.1% (54/62), 100% (10/10) and 88.8% (64/72), while for the combination of FNA+TCB they were: 95.7% (44/46), 100% (5/5) and 96.0% (49/51), respectively (P=0.184, 1.000, and 0.193 FNA versus FNA+TCB). No major complication occurred in either group. CONCLUSION: FNA+TCB can be safely performed in selected lesions but sensitivity is not statistically improved over FNA alone (95.7% versus 87.1%).

The Risk Factors for Acute Pancreatitis after Endoscopic Ultrasound Guided Biopsy.

BACKGROUND/AIMS: The risk of developing pancreatitis induced by endoscopic ultrasound-guided fine needle aspiration (EUS FNA) is relatively small. However, patients undergoing sampling through the normal pancreatic parenchyma or the pancreatic duct may have a higher rate of pancreatitis. Here, we determine the factors associated with increased risk of acute pancreatitis in patients undergoing FNA through normal pancreatic parenchyma/pancreatic duct. METHODS: In this prospective study at a tertiary cancer center, patients undergoing sampling through the pancreatic duct or ≥5 mm of the normal parenchyma between December 2013 and September 2017 were included. Post-EUS induced pancreatitis was diagnosed by the presence of abdominal pain with an amylase or lipase level higher than three times normal value. RESULTS: A total of 712 patients underwent pancreatic EUS FNA. A total of 163 patients were included in the high-risk group. Mean age was 63 years, 82 females, mean number of needle-passes was 3.3 (range, 1-7). Fifteen patients (15/163, 9.2%) developed pancreatitis after EUS FNA through the pancreatic parenchyma compared with only one case among the control group (＜5 mm of normal parenchyma) (0.18%, 1/549, p＜0.0001). Several factors appeared to be associated with pancreatitis, including young age, solid lesion, and a recent history of acute pancreatitis. By logistic regression, a prior history of recent pancreatitis was the only statistically significant factor associated with post-EUS-guided biopsy pancreatitis (p=0.008). CONCLUSIONS: Patients with a recent history of acute pancreatitis undergoing EUS FNA through 5 mm or more of the normal pancreatic parenchyma are at a much greater risk of acute pancreatitis.

Oxaliplatin and fixed-rate infusional gemcitabine in the second-line treatment of patients with metastatic colon cancer: final results of a Phase II trial prematurely closed as a result of poor accrual.

BACKGROUND: Second-line therapy of advanced colorectal cancer (CRC) after failure of a combination of irinotecan, a fluoropyrimidine, and bevacizumab includes the use of oxaliplatin and a fluoropyrimidine. In animal models, synergistic effects of gemcitabine and platinum agents have been established. Additionally, superior antitumor activity of prolonged administration of gemcitabine compared with bolus administration has been demonstrated in vivo against murine colon tumors. PATIENTS AND METHODS: A 2-stage phase II trial was developed to assess the efficacy (primary endpoint: response rate) and safety of gemcitabine 1000 mg/m(2) over 100 minutes on days 1 and 15 in combination with oxaliplatin 100 mg/m(2) over 2 hours on days 2 and 16, every 4 weeks. Patients with metastatic CRC in whom irinotecan and a fluoropyrimidine treatment had failed were enrolled. Calcium and magnesium infusion was routinely given before and after oxaliplatin administration. RESULTS: Because of slow accrual as a result of oxaliplatin becoming more commonly used in first-line treatment, the trial was stopped with only 10 patients enrolled. Eight were men and 2 were women. Median age was 58.5 years (range, 47-72 years). Nine patients had an Eastern Cooperative Oncology Group performance status of 0/1. A median of 3.5 cycles was administered (range, 1-9; total, 42). Six patients had stable disease and 1 had progressive disease. Two patients had confirmed partial responses, and 1 patient had a partial response but developed necrotizing fasciitis, declined surgical treatment, and died before a confirmatory scan could be performed. The regimen was otherwise well tolerated: 1 patient developed grade 3 neutropenia. With a median follow-up of 5.5 months, 4 patients have died. The time to treatment failure was 3.7 months. CONCLUSION: Despite premature study closure because of poor accrual, oxaliplatin in combination with fixed-rate infusional gemcitabine seems to be a safe and potentially effective regimen in the treatment of CRC. Further studies should be considered with the addition of targeted therapy.

Evaluation of fine needle aspiration vs. fine needle capillary sampling on specimen quality and diagnostic accuracy in endoscopic ultrasound-guided biopsy.

OBJECTIVE: To compare percutaneous and endoscopic ultrasound (EUS)-guided biopsy techniques. STUDY DESIGN: From July 2005 to February 2006, all patients referred for EUS-guided fine needle aspiration (FNA) were considered. If inclusion criteria were met, the first 2 biopsy passes were performed without suction (fine needle capillary [FNC] sampling). Two additional passes were performed using the same needle with 10 mL of applied suction (FNA). A single blinded pathologist later retrospectively evaluated each set of slides. Fifty-three patients met inclusion criteria. The study group comprised pancreatic masses (23), lymph nodes (26), subepithelial masses (3) and liver lesion (1). There were 38 malignant and 15 benign lesions. RESULTS: No statistically significant differences were found with the scoring systems considered in the study. In the subgroups of patients with pancreatic masses, lymph nodes, benign disease and malignant disease, no statistically significant outcomes were noted. CONCLUSIONS: No difference exists between quality and diagnostic accuracy of specimens obtained from EUS-guided tissue acquisition via FNC and FNA. The decision to use FNC or FNA should be left to the discretion of the individual endosonographer.

Analysis of clinical data and T helper 1/T helper 2 responses in patients with different clinical forms of leprosy.

INTRODUCTION:: Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS:: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS:: The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS:: The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.

Bare fiber photodynamic therapy using porfimer sodium for esophageal disease.

During Digestive Disease Week 2005 in Chicago, Illinois, our group of 10 gastrointestinal photodynamic therapists met to discuss variations in procedural technique and treatment protocols. An extensive review of the use of photodynamic therapy (PDT) for esophageal disease has recently been published elsewhere [Wolfsen HC. Present status of photodynamic therapy for high-grade dysplasia in Barrett's esophagus. J Clin Gastroenterol 2005;39(3):189-202]. This report, based mostly on clinical experience and common sense rather than evidence-based medicine, is a detailed discussion of pragmatic issues. In summary, our centers treat patients with Barrett's dysplasia, Barrett's or squamous cell carcinoma using the photosensitizer porfimer sodium (2mg/kg total body weight) and bare fiber PDT (no fiber centering devices). Aggressive suppression of gastric acid is uniformly emphasized. The most common technique variables were the light energy source, light dosimetry and the amount of Barrett's mucosa treated during a course of PDT. Standardization of porfimer sodium PDT procedures and light dosimetry may enhance treatment outcomes.

Expression of annexin-A1 in blood and tissue leukocytes of leprosy patients

Abstract INTRODUCTION In leprosy, immune system mediators that regulate the infectious process act in a complex manner and can lead to several clinical outcomes. To understand the behavior of these mediators we quantified the expression of annexin-A1 (ANXA1) in the peripheral blood and plasma as well as tissue leukocytes in all clinical forms of leprosy and compared with healthy controls. METHODS Seventy healthy controls and 70 patients with leprosy, tuberculoid (TT) (n = 13), borderline tuberculoid (BT) (n = 15), borderline borderline (BB) (n = 13), borderline lepromatous (BL) (n = 15), and lepromatous leprosy (LL) (n = 14), were selected. Phenotyping of the lymphocyte cells and the intracellular expression of ANXA1 in leukocytes was performed by immunofluorescence. Plasma protein levels were determined by enzyme-linked immunosorbent assay. RESULTS Histiocytes and CD4+ and CD8+ T cells in the skin of BL and LL patients had higher ANXA1 expression. ANXA1 expression was also high in circulating polymorphonuclear, monocytes, and CD4+ and CD8+ T cells in the blood of LL patients compared to those of TT, BT, BB, and BL patients, and these levels were similar to those in healthy controls. Plasma ANXA1 levels indicate an increase in paracrine release in patients with LL. CONCLUSIONS The data indicate that ANXA1 expression is enhanced in the leukocytes and plasma of patients with LL, and may contribute to the inhibition of leukocyte action, leading to inadequate functioning of the immune system and thus contributing to the spread of M. leprae infection.

Notch signaling drives stemness and tumorigenicity of esophageal adenocarcinoma.

Esophageal adenocarcinoma ranks sixth in cancer mortality in the world and its incidence has risen dramatically in the Western population over the last decades. Data presented herein strongly suggest that Notch signaling is critical for esophageal adenocarcinoma and underlies resistance to chemotherapy. We present evidence that Notch signaling drives a cancer stem cell phenotype by regulating genes that establish stemness. Using patient-derived xenograft models, we demonstrate that inhibition of Notch by gamma-secretase inhibitors (GSI) is efficacious in downsizing tumor growth. Moreover, we demonstrate that Notch activity in a patient's ultrasound-assisted endoscopic-derived biopsy might predict outcome to chemotherapy. Therefore, this study provides a proof of concept that inhibition of Notch activity will have efficacy in treating esophageal adenocarcinoma, offering a rationale to lay the foundation for a clinical trial to evaluate the efficacy of GSI in esophageal adenocarcinoma treatment.

Analysis of clinical data and T helper 1/T helper 2 responses in patients with different clinical forms of leprosy

Abstract INTRODUCTION: Currently, there are no laboratory tests or sensitive and specific molecular markers for the early diagnosis of leprosy. The aim of this study was to analyze the clinical characteristics of patients with leprosy and investigate their immunological profile, comparing this with the type of lesion and the presence or absence of a Bacillus Calmette-Guérin (BCG) vaccination scar. METHODS: Statistical analyzes were performed by employing comparative tests (Pearson´s chi-square) to evaluate the variables in different clinical forms, considering significance at the 5% level. RESULTS: The study identified a predominance of lepromatous leprosy (26.9%) in patients aged between 34-53 years. Caucasians predominantly had borderline tuberculoid (BT) clinical forms (42%); a predominance of males with borderline lepromatous (19%) and lepromatous leprosy (26.9%) forms was observed; and the presence of BCG vaccination scars (27.5%) and lower limb nerves were more affected (38%) predominantly in the BT clinical form. Significant differences were identified, which included hypochromic lesions predominantly in the BT clinical form (24%); diffuse-type lesions predominantly in the tuberculoid (TT) clinical form (28%); ill-defined lesion border dominance in lepromatous leprosy (LL) clinical forms (30%); an irregular lesion limit predominantly in LL clinical forms (32%); and a predominant Th1 immune response in the BT clinical form (41.7%). CONCLUSIONS: The evaluation of the immunological profile in leprosy patients may contribute to the more detailed diagnosis and possibly better characterization of the prognosis for these individuals.