Juan S. Barajas-Gamboa

Gene Immunotherapy of Chronic Lymphocytic Leukemia: A Phase I Study of Intranodally Injected Adenovirus Expressing a Chimeric CD154 Molecule

New therapies for chronic lymphocytic leukemia (CLL) are needed, particularly those that can eradicate residual disease and elicit anti-CLL immune responses. CD40 ligation on CLL cells, which can be achieved using adenovirus encoding chimeric CD154 (Ad-ISF35), enhances their ability to function as antigen-presenting cells and increases their sensitivity to clearance by immune-effector mechanisms. In this study, we report the results of a first-in-man phase I trial of intranodal direct injection (IDI) of Ad-ISF35 in patients with CLL to evaluate toxicity, safety, and tolerability. Fifteen patients received a single IDI of 1 × 10(10) to 33 × 10(10) Ad-ISF35 viral particles (vp), with a defined maximum tolerated dose as 1 × 10(11) vp. Although the most common adverse events were transient grade 1 to 2 pain at the injection site and flu-like symptoms following IDI, some patients receiving the highest dose had transient, asymptomatic grade 3 to 4 hypophosphatemia, neutropenia, or transaminitis. Increased expression of death receptor, immune costimulatory molecules, and Ad-ISF35 vector DNA was detected in circulating CLL cells. Notably, we also observed preliminary clinical responses, including reductions in leukemia cell counts, lymphadenopathy, and splenomegaly. Six patients did not require additional therapy for more than 6 months, and three achieved a partial remission. In conclusion, Ad-ISF35 IDI was safely delivered in patients with CLLs and induced systemic biologic and clinical responses. These results provide the rationale for phase II studies in CLLs, lymphomas, and CD40-expressing solid tumors.

Outcomes of Robotic-Assisted Transhiatal Esophagectomy for Esophageal Cancer After Neoadjuvant Chemoradiation

BACKGROUND We previously reported our experience performing robotic-assisted transhiatal esophagectomy (RATE) in patients with early-stage esophageal cancer who had had no preoperative treatment. The purpose of this report was to determine if RATE could be performed safely with good outcomes for esophageal cancer in a more recent series of patients, the majority of whom were treated with neoadjuvant chemoradiation. SUBJECTS AND METHODS This was a retrospective review of patients with adenocarcinoma of the distal esophagus or gastroesophageal junction who underwent RATE between November 2006 and November 2012 at a single tertiary-care hospital. Main outcome measures included operative and oncologic parameters, morbidity, and mortality. RESULTS In total, 23 patients underwent RATE, consisting of 20 men and 3 women with a median age of 64 years (range, 40-81 years). The majority of patients (19/23 [83%]) underwent neoadjuvant chemoradiation, although 1 patient had preoperative chemotherapy only, and 3 patients went straight to surgery. Median operative time was 231 minutes (range, 179-319 minutes), and median estimated blood loss was 100 mL (range, 25-400 mL). There were no conversions to open surgery. Complications included seven strictures, two anastomotic leaks, and two pericardial/pleural effusions requiring drainage. One patient required pyloroplasty 3 months after esophagectomy. One patient died from pulmonary failure 21 days after surgery (30-day mortality rate of 4%). The median length of stay was 9 days (range, 7-37 days). Seven of the 19 patients who underwent preoperative chemoradiation had a complete response on final pathology. The mean lymph node yield was 15 (range, 5-29), and surgical margins were negative for cancer in 21 cases. CONCLUSIONS RATE can be performed safely with good oncologic outcomes following neoadjuvant chemoradiation in patients with esophageal cancer. This technique has become our choice of operation for most patients with esophageal cancer.

Chronic lymphocytic leukemia associated with immunotactoid glomerulopathy: a case report of successful treatment with high-dose methylprednisolone in combination with rituximab followed by alemtuzumab.

Glomerular diseases (GDs) associated with chronic lymphocytic leukemia (CLL) are unusual [1]. Th e many causes of renal failure in patients with CLL include immune-complex deposition, hyperkalemia, amyloid deposition, sepsis, hemoglobinuria in the setting of hemolysis, uric acid nephropathy caused by tumor lysis syndrome (TLS) and therapy related complications. Th e most common clinical manifestations of these nephropathies include proteinuria, hematuria, electrolyte abnormalities (hyperkalemia) and progressive renal failure [2,3]. Th e most frequent GD associated with CLL is membranoproliferative glomerulonephritis (MPGN) (45%), followed by membranous glomerulonephritis (MGN) (20%), with occasional reports of proliferative, minimal change disease, immunotactoid glomerulopathy (ITG), and amyloid or

Complex choristoma of the lacrimal caruncle: a case report of an unusual congenital tumor with clinical and histopathological classification

Rare congenital tumors can be localized in the peribulbar area. Here we report an unusual case presented in a 3-year-old child with a history of a congenital tumor in the lacrimal caruncle of the right eye, associated with epiphora and constant discomfort. A surgical resection was performed, and the final histopathological diagnosis was lacrimal caruncle complex choristoma. Choristomas are growths of apparently normal tissue in an abnormal location, which can be situated anywhere in the body, including ocular and peribulbar structures. These almost unknown congenital tumors constitute the most common conjunctival tumors in children and can be interpreted clinically as different lesions, which are only differentiated through precise histopathological analysis.

Transvaginal Hybrid NOTES Cholecystectomy: Current Techniques and Advantages

Laparoscopic cholecystectomy has proven to be a safe and effective procedure, with low rates of complications and mortality since its introduction in the late 1980s. However, surgeons have been working to develop alternatives to this technique to improve clinical outcomes and the level of patient satisfaction. Natural orifice transluminal endoscopic surgery (NOTES) is one such alternative. NOTES has potential benefits compared to conventional laparoscopic and open surgery, including reduced abdominal wall trauma and trocar site complications, lower infection rates, less postoperative pain, decreased hospital stays, and excellent cosmetic results. Transvaginal hybrid NOTES cholecystectomy is the most common NOTES procedure performed. The objective of this article is to review this surgical technique and its clinical outcomes based on the current scientific evidence available in the literature.

Bariatric surgery and prevention of type 2 diabetes.

The authors reply: We disagree with Haines that there is a wide disparity in treatment distributions between the screened and control groups of the ERSPC trial. Of course the purpose of screening is to reach a significant shift in the stage distribution, which is followed by more effective curative treatment. The proportions cited by Haines are uncorrected values at the group level, but since men in the screened group are younger at the time of diagnosis and have more favorable tumor characteristics, these proportions have to be corrected. After correction was made for age, PSA level, and tumor characteristics, the trial group had only a small effect on treatment choice, including the use of hormones.1 An increase in watchful waiting can potentially alter the loss in QALYs resulting from radical surgery and radiation therapy, but the maximal effect will be an increase of 10 QALYs. Differences in hormone use would also have had only small effects, and those potential effects would be in favor of screening. We agree with Nagata and colleagues that age is an important issue to be considered in cancer screening in general. In our analysis, screening of men older than 70 years of age resulted in less favorable outcomes, but the choice of an upper age limit depends on life expectancy. Therefore, in countries with a different life expectancy or for people with coexisting conditions, this upper age limit needs to be adjusted. Our analysis clearly shows that a free PSA checkup without upper and lower age limits is undesirable when one is looking at the harms versus benefits of screening.

Systolic heart murmur as first manifestation of high output heart failure due to the vein of galen malformation

The vein of Galen aneurysmal malformation (VGAM) is an extremely rare arterio-venous malformation. The VGAM clinical manifestations vary depending on the magnitude of vascular compromise and the age at initial presentation. Neonates typically present with severe congestive heart failure. Here we present a case in which a systolic heart murmur was the first manifestation of high output heart failure due to a VGAM.

Features of Patients with Eagle Syndrome

Objective: Eagle syndrome is a rare syndrome in which pain occurs cervico-facially, due to the mineralization of the styloid process. We evaluated the features of Eagle syndrome in a Colombian (Latin American) population. Method: We described the clinical and pathological features of 5 patients with Eagle syndrome, and conducted a discussion of this disorder during an observational study from 2005 to 2008, with targeted sampling of patients with Eagle syndrome in the Centers of Head and Neck Surgery in Bucaramanga, Colombia. Results: The patients collectively consulted for sore throat and referred otodinia. Two patients had pain at the opening of the oral cavity, and no patient had foreign body sensation or syncope. On physical examination the patients had great tenderness from bimanual palpations on the postero-inferior face of the palatine tonsil. All patients underwent computed tomography and elongation of the styloid process was found. The patients underwent resection of the styloid process externally and endorally in 2 cases and in 3 cases respectively; none of them presented with disease recurrence after a mean follow-up period of 11.4 months. Conclusion: In conclusion, this rare disease must be considered in the differential diagnosis of cervical-facial pain, through imaging, plain radiography, or computed tomography. Treatment can be surgical or nonsurgical, although surgery is recommended.

Is the Angioimmunoblastic T-Cell Lymphoma Beneficial to Avoid CD4+ Lymphopenia and Other AIDS Manifestations in Patients Infected With Human Immunodeficiency Virus?

Introduction Angioimmunoblastic T-cell lymphoma (AITL) is one of the more rare T-cell lymphomas in Western countries. AITL involves multiple organs and is characterized by generalized lymphadenopathy, hepatomegaly, splenomegaly, fever, and skin rash. This neoplasm requently presents with autoimmune features and polyclonal hyperammaglobulinemia, which previously led AITL to be considered a ype of non-neoplastic hyperplasia. AITL is now widely recognized as a type of lymphoma, but a limited understanding of its athogenesis and behavior persists. It is known that AITL derives rom centrofollicular CD4 helper T-cells, which are believed to ndergo a series of mutations influenced by the Epstein-Barr virus EBV) and other viral infections. AIDS is characterized by human immunodeficiency virus (HIV) induced depletion of CD4 T cells, which creates an immunocomromised environment and renders the host increasingly susceptible o opportunistic infections and development of B-cell lymphomas.