Octogenarians undergoing pancreaticoduodenectomy: Assessing outcomes, disposition, and timing of chemotherapy.

BACKGROUND: Inclusion of pancreaticoduodenectomy has demonstrated higher rates of curative treatment in pancreatic cancer, yet prior research has suggested increased postoperative complications in octogenarians (patients older than 80 years). This study aimed to understand the impact of age on patients undergoing a pancreaticoduodenectomy, focusing on postoperative outcomes and return to intended oncologic treatment. MATERIALS AND METHODS: We conducted a single-institution retrospective cohort study for patients undergoing pancreaticoduodenectomy from 2007 to 2018. Collected data included demographics, preoperative comorbidities, and postoperative data (length of stay, 30-day mortality, 1-year mortality, infection, discharge location). Data were separated into 2 cohorts: octogenarians (≥ 80 years) and nonoctogenarians (< 80). χ2 and independent-sample t tests were used for analysis. RESULTS: A total of 649 patients underwent pancreaticoduodenectomy from 2007 to 2018; 63 (9.7%) were octogenarians. No differences were found in infectious complications (P = .607), 30-day mortality (P = .363), or 1-year mortality (P = .895). Octogenarians had a longer length of stay (P = .003) and were more likely to be discharged to skilled nursing facilities (P < .001). There was no significant difference in neoadjuvant chemotherapy administration, although octogenarians were less likely to receive adjuvant chemotherapy (P = .048) and declined adjuvant therapy at a higher rate (P = .003). CONCLUSION: Performing a pancreaticoduodenectomy in octogenarians can be safe and effective in a properly selected cohort. Although postoperative morbidity and mortality are similar to younger patients, elderly patients are more likely to be discharged to nursing facilities and less likely to receive adjuvant chemotherapy. This study suggests that age alone should not be a discriminating factor when discussing surgical therapy for pancreatic cancer treatment in octogenarians.

Stigma and cervical cancer prevention: A scoping review of the U.S. literature.

Cervical cancer is preventable through HPV vaccination and screening however, uptake falls below national targets. A scoping review was conducted to describe stigmas related to HPV infection and vaccination and cervical cancer and screening in the US. Results were organized into the domains proposed by Stangl and colleagues' Health Stigma and Discrimination Framework. Common drivers of stigma were fear of social judgement and rejection, self-blame, and shame. Positive facilitators included social norms that provided motivation to receive HPV vaccination and screening. Gender and social norms were notable negative facilitators of stigma. HPV infection and cervical cancer resulted in stigma marking through the belief that both result from incautious behavior-either multiple sexual partners or failing to get screening. Stereotyping and prejudice were stigma practices attributed to HPV infection and cervical cancer through these same behaviors. Stigma experiences related to HPV infection, cervical cancer, and abnormal screening results included altered self-image based on perceived/anticipated stigma, as well as discrimination. This review advances understanding of the multiple dimensions of stigma associated with these outcomes in the US population. Three areas warrant additional consideration. Future studies should 1) assess how stigma dimensions affect uptake of cervical cancer preventions efforts; 2) focus on US women most affected by cervical cancer incidence and mortality to identify potential differences in these dimensions and tailor interventions accordingly; 3) include women from geographic areas of the US with high rates of cervical cancer to adapt interventions that address potential regional variations in resources and need.

Abnormal epiphyseal development in a feline model of Sandhoff disease.

Sandhoff disease (SD) is caused by decreased function of the enzyme ß-N-acetylhexosaminidase, resulting in accumulation of GM2 ganglioside in tissues. Neural tissue is primarily affected and individuals with the infantile form of the disease generally do not survive beyond 4 years of age. Current treatments address neurometabolic deficits to improve lifespan, however, this extended lifespan allows clinical disease to become manifest in other tissues, including the musculoskeletal system. The impact of SD on bone and joint tissues has yet to be fully determined. In a feline model of infantile SD, animals were treated by intracranial injection of adeno-associated virus vectors to supply the central nervous system with corrective levels of hexosaminidase, resulting in a twofold to threefold increase in lifespan. As treated animals aged, signs of musculoskeletal disease were identified. The present study characterized bone and joint lesions from affected cats using micro-computed tomography and histology. All affected cats had similar lesions, whether or not they were treated. SD cats displayed a significant reduction in metaphyseal trabecular bone and markedly abnormal size and shape of epiphyses. Abnormalities increased in severity with age and appear to be due to alteration in the function of chondrocytes within epiphyseal cartilage, particularly the articular-epiphyseal complex. Older cats developed secondary osteoarthritic changes. The changes identified are similar to those seen in humans with mucopolysaccharidoses. Statement of clinical significance: the lesions identified will have significant implications on the quality of life of individuals whose lifespans are extended due to treatments for the primary neurological effects of SD.

Involvement of ventral pallidal vasopressin in the sex-specific regulation of sociosexual motivation in rats.

The ventral pallidum (VP) is a critical node of the mesocorticolimbic reward circuit and is known to modulate social behaviors in rodents. Arginine vasopressin (AVP) signaling via the V1A receptor (V1AR) within the VP is necessary for the expression of socially motivated affiliative behaviors in monogamous voles. However, whether the VP-AVP system regulates socially motivated behaviors in non-monogamous species remains unknown. Here, we determined the extent of AVP fiber innervation in the VP as well as the involvement of the VP-AVP system in sociosexual motivation in adult male and female rats. We found that males have nearly twice the density of AVP-immunoreactive (AVP-ir) fibers in the VP compared to females, suggesting the possibility that males experience enhanced AVP signaling in the VP. We further found that this sex difference in VP-AVP-ir fiber density likely arises from an observed sex difference (males > females) in the percentage of VP-projecting AVP-ir cell bodies located in the bed nucleus of the stria terminalis and medial amygdala. To determine the behavioral implications of this sex difference, we next blocked AVP signaling in the VP by antagonizing VP-V1ARs in male and female rats and tested their preference to investigate an unfamiliar male rat or unfamiliar estrus female rat confined to corrals located on opposite ends of a three-chamber apparatus. Under vehicle conditions, males showed a significantly greater innate preference to investigate an opposite sex over same sex conspecific than estrus females. Interestingly, VP-V1AR antagonism significantly reduced males' opposite sex preference, while enhancing estrus females' opposite sex preference. Importantly, all subjects reliably discriminated between male and female stimulus rats regardless of drug treatment, demonstrating a change in motivational state rather than a perceptual impairment induced by VP-V1AR blockade. These results provide a novel functional link between a sex difference in ventral pallidal AVP fiber density and the sex-specific regulation of a sexually motivated behavior necessary for reproductive success.

Quantitative mapping reveals age and sex differences in vasopressin, but not oxytocin, immunoreactivity in the rat social behavior neural network.

The neuropeptides vasopressin (AVP) and oxytocin (OT) have been implicated in the regulation of numerous social behaviors in adult and juvenile animals. AVP and OT signaling predominantly occur within a circuit of interconnected brain regions known collectively as the "social behavior neural network" (SBNN). Importantly, AVP and OT signaling within the SBNN has been shown to differentially regulate diverse social behaviors, depending on the age and/or sex of the animal. We hypothesized that variation in the display of these behaviors is due in part to age and sex differences in AVP and OT synthesis within the SBNN. However, a thorough characterization of AVP and OT-immunoreactive (ir) fibers and cell bodies across age and sex within the SBNN has been lacking in rats. We therefore quantified AVP- and OT-ir fibers and cell bodies in 22 subregions of the forebrain SBNN in juvenile and adult, male and female rats. We found numerous age (16 subregions) and sex (10 subregions) differences in AVP-ir fiber fractional areas, and AVP-ir cell body numbers, which were mainly observed in the medial amygdala/bed nucleus of the stria terminalis to lateral septum circuit. In contrast to AVP, we observed no age or sex differences in OT-ir fiber fractional areas or cell bodies in any of the 22 subregions of the forebrain SBNN. Thus, unlike the static pattern observed for OT, AVP innervation of the forebrain SBNN appears to undergo developmental changes, and is highly sexually dimorphic, which likely has significant functional consequences for the regulation of social behavior.