The Landmark Series: Surgical Treatment of Colorectal Cancer Peritoneal Metastases

Background

Peritoneal metastases (PM) are a form of metastatic spread affecting approximately 5-15% of colon cancer patients. The attitude towards management of peritoneal metastases has evolved from therapeutic nihilism towards a more comprehensive and multidisciplinary approach, in large part due to the development of cytoreductive surgery (CRS), usually coupled with heated intraperitoneal chemotherapy (HIPEC), along with the constant improvement of systemic chemotherapy of colorectal cancer. Several landmark studies, including 5 randomized controlled trials have marked the development and refinement of surgical approaches to treating colorectal cancer peritoneal metastases.

Methods

This review article focuses on these landmark studies and their influence in 4 key areas: the evidence supporting surgical resection of peritoneal metastases, the identification and standardization of important prognostic variables influencing patient selection, the role of surgery and intraperitoneal chemotherapy in prevention of colorectal PM and the role of intraperitoneal chemotherapy as an adjuvant to surgical resection.

Results

These landmark studies indicate that surgical resection of colorectal PM should be considered as a therapeutic option in appropriately selected patients and when adequate surgical expertise is available. Standardized prognostic variables including the Peritoneal Cancer Index and the Completeness of Cytoreduction Score should be used for evaluating both indications and outcomes.

Conclusions

Current evidence does not support the use of second look surgery with oxaliplatin HIPEC or prophylactic oxaliplatin HIPEC in patients with high risk colon cancer nor the use of oxaliplatin HIPEC with CRS of colorectal PM.

     

Presynaptic dopamine receptors: Insensitivity to kainic acid and the development of supersensitivity following chronic haloperidol

Summary The effects of kainic acid lesions and chronic haloperidol treatment on rat striatal dopaminergic presynaptic receptors were studied. Following the -butyrolactone-induced inhibition of dopaminergic impulse flow, and after dopa decarboxylase inhibition, dopa accumulation and its reversal by dopamine agonists was measured in vivo.³H-apomorphine (a dopamine receptor ligand with purported presynaptic specificity) was used for in vitro binding experiments. Presynaptic dopamine receptors, as assessed by both methods, were unaffected by intrastriatal kainic acid injection 5–6 days before sacrifice. Seven days after termination of chronic haloperidol treatment (28 days, 0.5 mg/kg/day s.c.) both an increased apomorphine response using the dopa accumulation method and an increase in³H-apomorphine binding were observed, indicating the development of presynaptic dopamine receptor supersensitivity.     

A multivariate neuromonitoring approach to neuroplasticity-based computerized cognitive training in recent onset psychosis

Two decades of studies suggest that computerized cognitive training (CCT) has an effect on cognitive improvement and the restoration of brain activity. Nevertheless, individual response to CCT remains heterogenous, and the predictive potential of neuroimaging in gauging response to CCT remains unknown. We employed multivariate pattern analysis (MVPA) on whole-brain resting-state functional connectivity (rsFC) to (neuro)monitor clinical outcome defined as psychosis-likeness change after 10-hours of CCT in recent onset psychosis (ROP) patients. Additionally, we investigated if sensory processing (SP) change during CCT is associated with individual psychosis-likeness change and cognitive gains after CCT. 26 ROP patients were divided into maintainers and improvers based on their SP change during CCT. A support vector machine (SVM) classifier separating 56 healthy controls (HC) from 35 ROP patients using rsFC (balanced accuracy of 65.5%, P < 0.01) was built in an independent sample to create a naturalistic model representing the HC-ROP hyperplane. This model was out-of-sample cross-validated in the ROP patients from the CCT trial to assess associations between rsFC pattern change, cognitive gains and SP during CCT. Patients with intact SP threshold at baseline showed improved attention despite psychosis status on the SVM hyperplane at follow-up (p < 0.05). Contrarily, the attentional gains occurred in the ROP patients who showed impaired SP at baseline only if rsfMRI diagnosis status shifted to the healthy-like side of the SVM continuum. Our results reveal the utility of MVPA for elucidating treatment response neuromarkers based on rsFC-SP change and pave the road to more personalized interventions.Subject terms: Predictive markers, Psychosis