Evidence that increased cholecystokinin (CCK) in the periaqueductal gray (PAG) facilitates changes in Resident-Intruder social interactions triggered by peripheral nerve injury.

Individual differences in the effects of a chronic neuropathic injury on social behaviours characterize both the human experience and pre-clinical animal models. The impacts of these changes to the well-being of the individual are often underappreciated. Earlier work from our laboratory using GeneChip® microarrays identified increased cholecystokinin (CCK) gene expression in the periaqueductal gray (PAG) of rats that showed persistent changes in social interactions during a Resident-Intruder encounter following sciatic nerve chronic constriction injury (CCI). In this study, we confirmed these gene regulation patterns using RT-PCR and identified the anatomical location of the CCK-mRNA as well as the translated CCK peptides in the midbrains of rats with a CCI. We found that rats with persistent CCI-induced changes in social behaviours had increased CCK-mRNA in neurons of the ventrolateral PAG and dorsal raphe nuclei, as well as increased CCK-8 peptide expression in terminal boutons located in the lateral and ventrolateral PAG. The functional significance of these changes was explored by microinjecting small volumes of CCK-8 into the PAG of uninjured rats and observing their Resident-Intruder social interactions. Disturbances to social interactions identical to those observed in CCI rats were evoked when injection sites were located in the rostral lateral and ventrolateral PAG. We suggest that CCI-induced changes in CCK expression in these PAG regions contributes to the disruptions to social behaviours experienced by a subset of individuals with neuropathic injury.

Frozen section of the pancreatic neck margin in pancreatoduodenectomy for pancreatic adenocarcinoma is of limited utility.

The use of frozen section to assess resection margins intraoperatively during pancreaticoduodenectomy facilitates further resection. However, it is unclear whether this actually improves patient survival.We reviewed the overall survival and resection margin status in consecutive pancreaticoduodenectomies performed for carcinoma. An R1 resection was defined as an incomplete excision (≤1 mm margin); R0(p) resection as complete excision without re-resection and R0(s) resection as an initially positive neck margin which was converted to R0 resection after re-resection. Between 2007 and 2012, 116 pancreatoduodenectomies were performed for adenocarcinoma; 101 (87%) underwent frozen section of the neck margin which was positive in 19 (19%). Sixteen of these patients had negative neck margins after re-excision but only seven patients had no other involved margins [true R0(s) resections]. Median survival for the R0(p), R0(s) and R1 groups were 29, 16, 23 months, respectively (p = 0.049; R0(p) versus R0(s) p = 0.040). Intra-operative frozen section increased the overall R0 rate by 7% but this did not improve survival. Our findings question the clinical benefit of intraoperative margin assessment, particularly if re-excision cannot be performed easily and safely.