The aborted Whipple: Why, and what happens next?

BACKGROUND: For patients with periampullary adenocarcinoma (PAC), pancreatoduodenectomy (PD) provides the best survival. Surgery on a subset of patients is aborted during PD. We analyzed these patients. METHODS: Patients who underwent laparotomy for planned PD for PAC were identified (2006-2019). From operative notes, we identified the subset with intraoperative decision to abort. Patient, treatment, and outcome data were analyzed. The subset with pancreatic ductal adenocarcinoma (PDAC) was analyzed for survival. RESULTS: Only 6.7% (n = 55/819) of cases were aborted. Majority 78% (n = 43) had pathologically-confirmed diagnoses at time of surgery, and 18.2% (n = 10) received preoperative chemotherapy. Reasons for aborted PD included: distant metastases (65.5%, n = 36) and local invasion (34.5%, n = 19). Of patients with metastatic disease, 75% (n = 27) had liver metastases. Eighty-nine percent (n = 49) of patients underwent at least one palliative bypass procedure and 81.8% (n = 45) had both gastric and biliary bypass. Patients with computed tomography (CT) scans before surgery more commonly had missed metastatic disease (79.2% CT compared to 54.8% magnetic resonance imaging [MRI], χ2 = 3.54, p = 0.059). In PDAC, 61.4% (n = 27/44) were aborted for metastatic disease and 38.7% (n = 17/44) for local invasion. Median overall survival for all PDAC patients after aborted PD was 334 days. CONCLUSION: Majority of pancreatoduodenectomies for periampullary adenocarcinoma are done to completion. Liver metastases is the most common reason for aborting. Preoperative MRI may help identify hepatic metastases.

Does Major Pancreatic Surgery Have Utility in Nonagenarians with Pancreas Cancer?

OBJECTIVE: This study aims to define the role of surgery and assess different therapies for nonagenarians with localized, nonmetastatic pancreatic adenocarcinoma (PDAC). METHODS: The National Cancer Database (NCDB) was queried for patients ≥ 90 years of age with nonmetastatic, localized PDAC from 2004-2016. Postoperative mortality was assessed at 30 and 90 days in patients receiving pancreatoduodenectomy or total pancreatectomy. Overall survival (OS) was compared between three treatment groups: surgery alone, chemotherapy alone, and chemoradiation (chemoRT) alone. RESULTS: Of 380,524 patients with PDAC, 98 patients ≥ 90 years of age underwent curative-intent resection; 55% were female and 75% had a Charlson-Deyo comorbidity score of 0. A total of 17% received postoperative chemotherapy, 51.1% had poorly differentiated tumors with a median tumor size of 3 cm, 55.1% had positive lymph nodes, and 19.4% had positive resection margins. Postoperative median length of stay was 11 days. Postoperative 30- and 90-day mortality was 10.0% and 18.9%, respectively. Median OS for the surgery alone group was 11.6 months compared with 20.4 months in those receiving adjuvant therapy (p = 0.01). Among nonoperative PDAC patients, median OS in patients receiving chemotherapy only (n = 207) was 7.2 months, while chemoRT only (n = 100) was similar to surgery only (11 versus 11.6 months, p = 0.97). CONCLUSIONS: Even in well-selected nonagenarians, pancreatoduodenectomy or total pancreatectomy carries a high mortality rate. While adjuvant therapy after resection provides the best survival, it is seldom achieved, and chemoRT alone affords identical survival statistics as surgery alone. These data suggest it is reasonable to consider chemoRT as initial therapy, then reassess candidacy for resection if performance status allows.

Standardization of operative technique in minimally invasive right hepatectomy: improving cost-value relationship through value stream mapping in hepatobiliary surgery.

BACKGROUND: With current emphasis on improving cost-quality relationship in medicine, it is imperative to evaluate cost-value relationships for surgical procedures. Previously the authors demonstrated comparable clinical outcomes for minimally invasive right hepatectomy (MIRH) and open right hepatectomy (ORH). MIRH had significantly higher intraoperative cost, though overall costs were similar. METHODS: MIRH was decoded into its component critical steps using value stream mapping, analyzing each associated cost. MIRH technique was prospectively modified, targeting high cost steps and outcomes were re-examined. Records were reviewed for elective MIRH before (pre-MIRH n = 50), after (post MIRH n = 25) intervention and ORH (n = 98), between January 1, 2008 and November 30, 2016. RESULTS: Average overall cost was significantly lower for post-standardization MIRH (post-MIRH $21 768, pre-MIRH $28 066, ORH $33 020; p < 0.001). Average intraoperative blood loss was reduced with MIRH (167, 292 and 509 mL p < 0.001). Operative times were shorter (147, 190 and 229 min p < 0.001) and LOS was reduced for MIRH (3, 4, 7 days p < 0.002). CONCLUSIONS: Using a common quality improvement tool, the authors established a model for cost effective clinical care. These tools allow surgeons to overcome personal or traditional biases such as stapler choices, but most importantly eliminate non-value added interventions for patients.

Adipose stem cells-conditioned medium blocks 6-hydroxydopamine-induced neurotoxicity via the IGF-1/PI3K/AKT pathway.

Previous studies suggest that the delivery of neurotrophic factors secreted from adipose stromal cells (ASC) protect the brain from 6-hydroxydopamine (6-OHDA)-induced neurotoxicity. However, it remains unclear which secreted neurotrophic factor has an important role in protecting 6-OHDA-treated neurons. Through the use of antibodies in this study, we demonstrated that specific neutralization of IGF-1 activity in ASC conditioned media (ASC-CM) significantly blocks ASC-CM-induced neuroprotection against 6-OHDA neurotoxicity. Consistently, this neuroprotection was mostly attributed to the activation of the AKT-mediated signaling pathway. In contrast, brain derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) in ASC-CM did not play a role in ASC-CM-induced neuroprotection against 6-OHDA.

Olfactory coding: a plastic approach to timing precision.

Spike-timing dependent plasticity has been associated with neural development, learning, and memory. Recently, this mechanism was found to stabilize spike timing relationships across populations of neurons in the locust olfactory system.

Spatiotemporal specificity of neuronal activity directs the modification of receptive fields in the developing retinotectal system.

The precise temporal relation between pre- and postsynaptic activity modulates the strength of synaptic connections. Despite its extensive characterization in vivo and in vitro, the degree to which spike timing-dependent plasticity can shape receptive field properties is unclear. We use in vivo patch-clamp recordings of tectal neurons in developing Xenopus tadpoles to control the precise timing of action potentials with respect to the arrival of a subset of visual inputs evoked by local light stimulation on the retina. The pattern of visual inputs onto a tectal neuron was tracked over time by rapid reverse correlation mapping of receptive fields. Spike timing-dependent potentiation or depression of a subset of synapses reliably shifts the spatial receptive fields toward or away from the trained subregion of visual space, respectively. These results demonstrate that natural patterns of activity evoked by sensory stimuli play an instructive role in the developing nervous system.