Extensive Cytoreductive Surgery for Appendiceal Carcinomatosis: Morbidity, Mortality, and Survival

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemoperfusion (HIPEC) are frequently used to treat appendiceal carcinomatosis. Some patients require multivisceral resection because of the volume of disease. It is unclear whether extent of CRS impacts survival in appendiceal carcinomatosis.

Methods

We analyzed 282 patients undergoing attempted CRS/HIPEC for appendiceal carcinomatosis. Patients were defined as having undergone Extensive CRS (n = 60) if they had >3 organ resections or >2 anastomoses; a subgroup of Extreme CRS patients (n = 10) had ≥5 organ resections and ≥3 anastomoses. Kaplan–Meier survival curves and multivariate Cox-regression models were used to identify prognostic factors affecting outcomes.

Results

Relative to the comparison group, patients undergoing Extensive CRS had a higher median peritoneal carcinomatosis index, operative duration, blood loss, and length of stay. No difference in completeness of cytoreduction, severe morbidity, or 60-day mortality was evident. Subgroup analysis of 10 patients undergoing extreme CRS likewise revealed no increase in severe morbidity or mortality. Median progression-free (PFS) and overall survival (OS) were 23.5 and 74 months in the comparison group; 18.5 (p = 0.086) and 51 (p = 0.85) months in the Extensive CRS group; and 40 months and not reached in the Extreme CRS subgroup. In a multivariable analysis, extent of CRS was not independently associated with PFS or OS.

Conclusions

Extensive CRS is associated with greater OR time, blood loss, and length of stay, but is not associated with higher morbidity, mortality, or inferior oncologic outcomes in patients with appendiceal carcinomatosis.     

Effect of Intrathecal Baclofen Concentration on Spasticity Control: Case Series

Background/Objective: Intrathecal baclofen (ITB) has been shown to be an effective treatment for severe spasticity of spinal or cerebral origin. Although most patients respond well to an ITB trial, there are often difficulties in achieving and/or maintaining such effectiveness with ITB pump treatment. There are few published guidelines for dosing efficacy and no studies looking at the effect of concentration of ITB on spasticity management.

Methods: Case series of 3 adults with severe spasticity treated with ITB pump: a 44-year-old man with C7 tetraplegia using a 40-mL Medtronic SynchroMed II pump with 500-μg/mL concentration; a 35-year-old woman with traumatic brain injury with right spastic hemiplegia using a 18-mL Medtronic SynchroMed EL pump with 2,000-μg/mL concentration; and a 43-year-old woman with spastic diplegic cerebral palsy using a 40-mL Medtronic SynchroMed II pump with 2,000-μg/mL concentration.

Results: After reducing ITB concentrations in the pump, either as part of a standard protocol for dye study to assess the integrity of pump and catheter system or secondary to plateau in therapeutic efficacy, patients experienced temporary, significant reduction in spasticity based on range of motion, Modified Ashworth scores, and verbal feedback.

Conclusions: Decreasing the concentration of ITB seems to affect spasticity control. Further research in this area is needed for those patients with refractory spasticity to optimize efficacy of ITB therapy.     

Surgical delivery of drug releasing poly(lactic-co-glycolic acid)/poly(ethylene glycol) paste with in vivo effects against glioblastoma

Introduction

The median survival of patients with glioblastoma multiforme (astrocytoma grade 4) remains less than 18 months despite radical surgery, radiotherapy and systemic chemotherapy. Surgical implantation of chemotherapy eluting wafers into the resection cavity has been shown to improve length of survival but the current licensed therapy has several drawbacks. This paper investigates in vivo efficacy of a novel drug eluting paste in glioblastoma.

Methods

Poly(lactic-co-glycolic acid)/poly(ethylene glycol) (PLGA/PEG) self-sintering paste was loaded with the chemotherapeutic agent etoposide and delivered surgically into partially resected tumours in a flank murine glioblastoma xenograft model.

Results

Surgical delivery of the paste was successful and practical, with no toxicity or surgical morbidity to the animals. The paste was retained in the tumour cavity, and preliminary results suggest a useful antitumour and antiangiogenic effect, particularly at higher doses. Bioluminescent imaging was not affected significantly by the presence of the paste in the tumour.

Conclusions

Chemotherapy loaded PLGA/PEG paste seems to be a promising technology capable of delivering active drugs into partially resected tumours. The preliminary results of this study suggest efficacy with no toxicity and will lead to larger scale efficacy studies in orthotopic glioblastoma models.     

Neuropeptide Y Attenuates Stress‐Induced Bone Loss Through Suppression of Noradrenaline Circuits

Chronic stress and depression have adverse consequences on many organ systems, including the skeleton, but the mechanisms underlying stress‐induced bone loss remain unclear. Here we demonstrate that neuropeptide Y (NPY), centrally and peripherally, plays a critical role in protecting against stress‐induced bone loss. Mice lacking the anxiolytic factor NPY exhibit more anxious behavior and elevated corticosterone levels. Additionally, following a 6‐week restraint, or cold‐stress protocol, Npy‐null mice exhibit three‐fold greater bone loss compared to wild‐type mice, owing to suppression of osteoblast activity. This stress‐protective NPY pathway acts specifically through Y2 receptors. Centrally, Y2 receptors suppress corticotropin‐releasing factor expression and inhibit activation of noradrenergic neurons in the paraventricular nucleus. In the periphery, they act to control noradrenaline release from sympathetic neurons. Specific deletion of arcuate Y2 receptors recapitulates the Npy‐null stress response, coincident with elevated serum noradrenaline. Importantly, specific reintroduction of NPY solely in noradrenergic neurons of otherwise Npy‐null mice blocks the increase in circulating noradrenaline and the stress‐induced bone loss. Thus, NPY protects against excessive stress‐induced bone loss, through Y2 receptor‐mediated modulation of central and peripheral noradrenergic neurons. © 2014 American Society for Bone and Mineral Research.     

Markers for faecal fat estimation in monitoring steatorrhoea in cystic fibrosis.

Polyethylene glycol (PEG) 4000 is one of numerous substances used as non-absorbable markers to correct for variable faecal output when assessing daily faecal losses of nutrients. The introduction of enteric coated micro-encapsulated pancreatic enzyme (EMPE) preparations has greatly improved the control of fat malabsorption in cystic fibrosis and chronic pancreatitis patients. Unfortunately, these enzyme preparations contain significant quantities of PEG 4000 or polyvinyl pyrrolidine (PVP) as components of the enteric coating and thus PEG 4000 cannot be used either as a faecal marker, or in intubation studies, if these enzyme preparations are being used.