Factors affecting outcome after Frey procedure for chronic pancreatitis

Background. Debilitating abdominal pain remains the most common presentation of chronic pancreatitis and the treatment remains challenging. Objective. This prospective study analyzed the outcome of Frey''s procedure in patients with inflammatory head mass. Methods. For the period between 2002 and 2007, 77 patients with chronic pancreatitis underwent Frey procedure for intractable abdominal pain. The mean follow-up was 14 months. For the purpose of analysis of the outcome, patients were grouped as poor pain control (19%) and good pain control groups (81%) based on the pain scores during follow-up. Results. There was no 30-day mortality. The logistic regression analysis showed that decreased volume percentage (48%) of head mass resected (p=0.003) and small diameter of the pancreatic duct (p=0.05) were associated with poor pain outcome. Subgroup analysis revealed that patients with small duct disease were associated with increased operative time (p=0.001), poor pain scores (p=0.001), and increased weight loss (p=0.003) during follow-up. Conclusions. Frey procedure can be performed with zero mortality and low morbidity in a high-volume center. It provides good pain relief in majority of the patients. Volume of the head mass cored affects pain outcome. Correlation between poor results in terms of pain relief and weight loss following Frey''s procedure, and small duct disease supports the view that duct diameter is an important predictor of pain relief.     

Immunoglobulin VH usage analysis by fluorescent in situ hybridization and flow cytometry.

We have devised a flow cytometry-based fluorescent in situ hybridization assay that permits analysis of gene expression in a large number of single cells. In this technique, fixed and permeabilized cells are incubated with biotinylated single-stranded RNA probes and by means of a fluorescently labelled second-step reagent, the cells are analyzed by flow cytometry. This is a rapid and simple method that allows all of the steps in the procedure to be performed on cells in suspension. Using this approach, we demonstrate here that immunoglobulin heavy chain variable region (VH) gene expression can be analyzed among individual cells using particular VH family-specific probes. This technique has a high degree of accuracy (greater than 97%) in detecting the fraction of cells expressing a specific message in a population and is sensitive enough to detect immunoglobulin message in LPS activated B cells. The technique has been applied successfully to monitor gene expression in homogeneous and heterogeneous populations. It also allows concurrent analysis of cell surface proteins and gene expression through two-color flow cytometry. This method of monitoring gene expression in individual cells may have a number of applications in immunology and cell biology.     

Ewings Sarcoma of the Hand—A Case Report

Ewings sarcoma of the hand is relatively rare. Ewings sarcoma can present with minimal pain and swelling of the affected digit. The Erythrocyte sedimentation rate and C-reactive protein may be high. Radiologically, Ewings sarcoma can present with a plethora of features from permeative bone destruction to expansile lesions with or without periosteal reaction. Because of these features, this can be confused with Tuberculosis especially in a country like ours where Tuberculosis is endemic. This leads to starting of inappropriate treatment and delay in diagnosis. We report a case of an 18 year old boy who was initially diagnosed as Tuberculous dactylytis of the proximal phalanx of the little finger. He was started on anti-tuberculous treatment and did not respond to it. Subsequent investigation in our centre which also included an open biopsy, confirmed the diagnosis of Ewings sarcoma. He was treated with ray excision, and chemotherapy. This case is being presented for its rarity and also to emphasize the fact that an open biopsy in suspected cases would be appropriate to confirm the diagnosis. This would prevent delay in diagnosis of rare conditions like Ewings sarcoma.     

Functional outcome after total knee arthroplasty revision: a meta-analysis

The objective of this study was to perform a systematic literature review to describe patient outcome after total knee arthroplasty revision procedures using various global knee score ratings. English language articles published from 1966 through 2000 were identified through a computerized literature search and bibliography review. A multistage assessment was used to determine the articles containing data that could meet our objective. Meta-analyses of global knee scores were undertaken using a fixed effects model with the assumption that the variances of each individual measurement were identical across studies. The initial inclusion criteria were met by 58 articles with a total of 1965 patients. There were 42 articles comprising 45 unique patient cohorts and a total of 1515 patients that had sufficient global knee score data for analysis and were used in the meta-analyses. Revision total knee arthroplasty is an effective procedure for failed knee arthroplasties based on global knee rating scales.     

Population pharmacokinetics of trastuzumab emtansine (T-DM1), a HER2-targeted antibody–drug conjugate,in patients with HER2-positive metastatic breast cancer: clinical implications of the effect of covariates

Purpose

Trastuzumab emtansine (T-DM1) is an antibody–drug conjugate comprising the humanized monoclonal antibody trastuzumab linked to DM1, a highly potent cytotoxic agent. A population pharmacokinetic (PK) analysis was performed to estimate typical values and interindividual variability of T-DM1 PK parameters and the effects of clinically relevant covariates.

Methods

Serum samples were collected from 671 patients with human epidermal growth factor receptor 2-positive locally advanced or metastatic breast cancer (MBC) who received single-agent T-DM1 in five phase I to phase III studies. Nonlinear mixed-effects modeling with the first-order conditional estimation method was used.

Results

A linear two-compartment model with first-order elimination from the central compartment described T-DM1 PKs in the clinical dose range. T-DM1 elimination clearance was 0.676 L/day, volume of distribution in the central compartment (V _c) was 3.127 L, and terminal elimination half-life was 3.94 days. Age, race, region, and renal function did not influence T-DM1 PK. Given the low-to-moderate effect of all statistically significant covariates on T-DM1 exposure, none of these covariates is expected to result in a clinically meaningful change in T-DM1 exposure.

Conclusions

T-DM1 PK properties are consistent and predictable in patients. A further refinement of dose based on baseline covariates other than body weight for the current 3.6 mg/kg regimen would not yield clinically meaningful reductions in interindividual PK variability in patients with MBC.     

Simultaneous Determination of Celecoxib, Erlotinib, and its Metabolite Desmethyl-Erlotinib (OSI-420) in Rat Plasma by Liquid chromatography/Tandem Mass Spectrometry with Positive/Negative Ion-Switching Electrospray Ionisation

A new method for the simultaneous determination of celecoxib, erlotinib, and its active metabolite desmethyl-erlotinib (OSI-420) in rat plasma, by liquid chromatography/tandem mass spectrometry with positive/negative ion-switching electrospray ionization mode, was developed and validated. Protein precipitation with methanol was selected as the method for preparing the samples. The analytes were separated on a reverse-phase C₁₈ column (50mm×4.6mm i.d., 3μ) using methanol: 2 mM ammonium acetate buffer, and pH 4.0 as the mobile phase at a flow rate 0.8 mL/min. Sitagliptin and Efervirenz were used as the internal standards for quantification. The determination was carried out on a Theremo Finnigan Quantam ultra triple-quadrupole mass spectrometer, operated in selected reaction monitoring (SRM) mode using the following transitions monitored simultaneously: positive m/z 394.5→278.1 for erlotinib, m/z 380.3→278.1 for desmethyl erlotinib (OSI-420), and negative m/z −380.1→ −316.3 for celecoxib. The limits of quantification (LOQs) were 1.5 ng/mL for Celecoxib, erlotinib, and OSI-420. Within- and between-day accuracy and precision of the validated method were within the acceptable limits of < 15% at all concentrations. The quantitation method was successfully applied for the simultaneous estimation of celecoxib, erlotinib, and desmethyl erlotinib in a pharmacokinetic study in Wistar rats.     

Clinical implications of pathophysiological and demographic covariates on the population pharmacokinetics of trastuzumab emtansine, a HER2-targeted antibody-drug conjugate, in patients with HER2-positive metastatic breast cancer

Trastuzumab emtansine (T-DM1) is a HER2-targeted antibody-drug conjugate in development for treatment of HER2-positive cancers. T-DM1 has been tested as a single agent in a phase I and 2 phase II studies of patients with heavily pretreated metastatic breast cancer (MBC), with the maximum tolerated dose established at 3.6 mg/kg intravenously for every-3-week dosing. The authors present results from the population pharmacokinetics analysis for T-DM1. Population pharmacokinetics for T-DM1 were characterized using a clinical database of 273 patients from the 3 studies. Pharmacokinetics was best described by a linear 2-compartment model. Population estimates (interindividual variability [IIV]) for pharmacokinetic parameters were clearance, 0.7 L/d (21.0%); central compartment volume (V(c)), 3.33 L (13.2%); peripheral compartment volume (V(p)), 0.89 L (50.4%); and intercompartmental clearance, 0.78 L/d. Body weight, albumin, tumor burden, and aspartate aminotransferase levels were identified as statistically significant covariates accounting for interindividual variability in T-DM1 pharmacokinetics, with body weight having a greater effect on IIV of clearance and V(c) than other covariates. T-DM1 exposure was relatively consistent across the weight range following body weight-based dosing. This analysis suggests no further T-DM1 dose adjustments are necessary in heavily pretreated patients with MBC.     

Elongated styloid process: an unusual cause of neck pain and difficulty in swallowing

An elongated styloid process is an unusual source of craniofacial and cervical pain. This condition is characterized by a dull, nagging pharyngeal pain and a palpatory finding in the tonsillar fossa. Eagle described it for the first time in 1937 as Eagle's Syndrome and divided it into two subtypes: the "classic syndrome" and the "stylo-carotid syndrome." The syndrome generally follows tonsillectomy or trauma. Diagnosis is confirmed by radiological findings. Palpation of the styloid process in the tonsillar fossa and infiltration with anesthetic are also used for making a diagnosis. This article presents a case report of a patient with a history of throat pain that was relieved after surgical treatment.