Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Asian Patients: 100 Consecutive Patients in a Single Institution

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients.

Methods

Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS.

Results

Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n = 39), colorectal cancer (n = 28), primary peritoneal (n = 6), appendiceal cancer (n = 20), and mesothelioma (n = 7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3 % and OS was 50.9 %. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56 %, and there were no 30-day mortalities.

Conclusions

CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.     

Novel nondopaminergic targets for motor features of Parkinson's disease: Review of recent trials

Neurotransmitters other than dopamine are recognized as having modulatory roles within the basal ganglia and can influence the basal ganglia dopaminergic system to alter activity of the direct and indirect pathways. Many nondopaminergic neurotransmitter systems have been implicated in the mechanisms contributing to the motor features of Parkinson's disease (PD). Thus, it is now well established that neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic, opioidergic, histaminergic, and adenosinergic systems, are affected in the pathogenesis of PD. Nondopaminergic neurotransmitter systems are thus targets for the development of novel therapies for motor symptoms and motor complications in PD. Over the last 5 years, more than 20 randomized, control trials (RCTs) in PD investigating drugs that target several of these nondopaminergic neurotransmitter systems for the treatment of motor features have been completed. There are at least 15 additional RCTs that are ongoing or planned. Here, we review these RCTs to highlight the potential nondopaminergic pharmacological therapies for treatment of motor features of PD. Nondopaminergic drugs are not expected to replace dopaminergic strategies, but further development of these drugs will likely yield novel approaches with positive clinical implications. © 2012 Movement Disorder Society     

Failure of explicit movement control in patients with functional motor symptoms

Functional neurological symptoms are one of the most common conditions observed in neurological practice, but understanding of their underlying neurobiology is poor. Historic psychological models, based on the concept of conversion of emotional trauma into physical symptoms, have not been implemented neurobiologically, and are not generally supported by epidemiological studies. In contrast, there are robust clinical procedures that positively distinguish between organic and functional motor signs that rely primarily on distracting attention away from movement or accessing it covertly. We aimed to investigate the neurobiological principles underpinning these techniques and implications for understanding functional symptoms. We assessed 11 patients with functional motor symptoms and 11 healthy controls in three experimental set‐ups, where voluntary movements were made either with full explicit control or could additionally be influenced automatically by factors of which participants were much less aware (one‐back reaching, visuomotor transformation, and precued reaction time with variable predictive value of the precue). Patients specifically failed in those tasks where preplanning of movement could occur and under conditions of increasing certainty regarding the movement to be performed. However, they implicitly learned to adapt to a visuomotor transformation as well as healthy controls. We propose that when the movement to be performed can be preplanned or is highly predicted, patients with functional motor symptoms shift to an explicit attentive mode of processing that impairs kinematics of movement control, but movement becomes normal when such processes cannot be employed (e.g., during unexpected movement or implicit motor adaptation). © 2013 Movement Disorder Society     

Longitudinal study of levodopa in Parkinson's disease: Effects of the advanced disease phase

Thirty‐four patients have been studied from the time of initiation of pharmacological treatment in a long‐term prospective study of levodopa effects and disease progression in Parkinson's disease. Objective motor scoring of the response to levodopa in defined off states was performed every 3 years. The mean time from the initiation of levodopa treatment to the most recent measurements was 18.2 years. Of 8 patients who are still alive, only 3 had none of the features of the advanced disease phase (dementia, hallucinations, frequent falling). Off‐phase motor function worsened at a yearly rate of 1.9% of the maximum disability score, although the plots of the serial scores showed that the magnitude of the levodopa response is well preserved. There was little difference in the rate of progression between patients with tremor‐dominant and non‐tremor‐dominant motor subtypes. Those who developed dementia had more rapid deterioration of motor scores, with significantly worse off‐phase (P = .008) and on‐phase (P = .03) motor function. A graph of serial scores of patients who have died, aligned for time of death, showed an upward curving trend of motor disability in the last 5 years of the disease course. Its advanced phase may reveal that Parkinson's disease has an exponential pattern of progression. © 2013 Movement Disorder Society