A Therapeutic Strategy for Resectable Pancreatic Cancer Based on Risk Factors of Early Recurrence.

OBJECTIVES: The aim of this study was to identify risk factors for early recurrence and assess the prognostic benefit of neoadjuvant therapy (NAT) for resectable pancreatic cancer. METHODS: Patients with radiographically resectable pancreatic cancer according to the National Comprehensive Cancer Network guidelines were enrolled. We regarded recurrence within 6 months after surgery as early recurrence. RESULTS: This study involved 115 patients (80 who underwent upfront surgery and 35 who received NAT). Serum carbohydrate antigen 19-9 greater than 85 U/mL and p53 expression in 0 or more than 80% of tumor cells were independent risk factors for early recurrence after upfront surgery. We classified patients into a high-risk group (1 or 2 risk factors) and a low-risk group (no risk factors). In the high-risk group, the median overall survival time of patients with NAT was significantly longer than that of patients without NAT (P = 0.028). By contrast, the median overall survival time was not different according to NAT in the low-risk group. CONCLUSIONS: Serum carbohydrate antigen 19-9 and p53 expression of the primary tumor could be predictors of early recurrence in patients with resectable pancreatic cancer. The prognosis of patients with a high risk of early recurrence may be improved using NAT.

Convergence of Lemniscal and Local Excitatory Inputs on Large GABAergic Tectothalamic Neurons.

Large GABAergic (LG) neurons form a distinct cell type in the inferior colliculus (IC), identified by the presence of dense VGLUT2-containing axosomatic terminals. Although some of the axosomatic terminals originate from local and commissural IC neurons, it has been unclear whether LG neurons also receive axosomatic inputs from the lower auditory brainstem nuclei, i.e., cochlear nuclei (CN), superior olivary complex (SOC), and nuclei of the lateral lemniscus (NLL). In this study we injected recombinant viral tracers that force infected cells to express GFP in a Golgi-like manner into the lower auditory brainstem nuclei to determine whether these nuclei directly innervate LG cell somata. Labeled axons from CN, SOC, and NLL terminated as excitatory axosomatic endings, identified by colabeling of GFP and VGLUT2, on single LG neurons in the IC. Each excitatory axon made only a few axosomatic contacts on each LG neuron. Inputs to a single LG cell are unlikely to be from a single brainstem nucleus, since lesions of individual nuclei failed to eliminate most VGLUT2-positive terminals on the LG neurons. The estimated number of inputs on a single LG cell body was almost proportional to the surface area of the cell body. Double injections of different viruses into IC and a brainstem nucleus showed that LG neurons received inputs from both. These results demonstrated that both ascending and intrinsic sources converge on the LG somata to control inhibitory tectothalamic projections.

Safety and efficacy of early postoperative hyperbaric oxygen therapy with restriction of transfusions in patients with HCC who have undergone partial hepatectomy.

BACKGROUND: Recent studies have shown that intraoperative blood loss and blood transfusions promote postoperative recurrence of hepatocellular carcinoma (HCC). Hyperbaric oxygen therapy (HBOT) is a specific method of oxygen administration, which is independent of fluid therapy or blood transfusion. The aim of the present study was to assess the usefulness of acute HBOT after liver resection for patients with HCC in order to minimize the requirement for perioperative blood transfusions. PATIENTS AND METHODS: Forty-one consecutive patients who showed Hb level < 9.0 mg/dl at the end of hepatic resection were randomly assigned to a control group (n = 21) or an HBOT group (n = 20). HBOT at 2.0 atm. with inhalation of 100% oxygen for a duration of 60 min was performed at 3, 24, and/or 48 h after the end of the hepatectomy. Regarding postoperative hepatic hemodynamics, liver function tests, and outcome data, prospective comparisons were completed in both groups. The two groups of patients were similar with respect to results from preoperative assessments. RESULTS: In six patients from the HBOT group, who experienced intraoperative major bleeding or showed fatal hepatic hypoxia (ShvO(2) < 50%), the levels of ShvO(2) and serum lactate were significantly improved after HBOT. When compared to the control group, the HBOT group showed better changes of ShvO(2), serum lactate, and bilirubin levels for the first 3 postoperative days following surgery. Additionally, the HBOT group did not experience any fatal complications and had a lower incidence of postoperative hyperbilirubinemia than the control group. We also observed that postoperative NK cell activity and cancer-free survival in the HBOT group tended to be better than in the control group, although the differences did not reach significance. CONCLUSION: These results suggest that acute HBOT after hepatectomy, aimed at reducing perioperative erythrocyte transfusions, may be employed for overcoming deficiencies in systemic and hepatic oxygen supply and thus diminishing postoperative complications. As an added benefit, such therapy may affect postoperative immunological responses and long-term survival after liver resection in HCC patients. Further analyses of the use of HBOT is warranted to confirm surgical outcome data and to assess the economic impact on healthcare costs.

Acupuncture modulates mechanical responses of smooth muscle produced by transmural nerve stimulation in gastric antrum of genetically hyperglycemic rats.

Effects of acupuncture treatment on mechanical responses produced by transmural nerve stimulation (TNS) and acetylcholine (ACh) were investigated in circular smooth muscle preparations isolated from the antrum of the stomach of genetically hyperglycemic rats. While control rats had blood glucose levels of about 140 mg/dl, this was approximately tripled in the genetically hyperglycemic rats, but only doubled in the acupuncture treated genetically hyperglycemic rats. Antrum smooth muscle produced phasic contractions spontaneously, with a similar frequency and amplitude in the three groups of rats. Effects of atropine and Nomega-nitro-L-arginine (L-NA) on TNS-induced responses revealed that in the antrum smooth muscle of the control rats, cholinergic excitatory, non-adrenergic non-cholinergic excitatory (NANCE), nitrergic inhibitory and off-responses produced projections: the last projection was considered to be non-adrenergic non-cholinergic non-nitrergic (NANCNN) in nature. In genetically hyperglycemic rats, nitrergic and NANCNN projections were enhanced and NANCE projections were absent. Acupuncture treated genetically hyperglycemic rats showed a reduction of NANCNN projection and enhancement of cholinergic projection, with no alteration to nitrergic projection, but a recovery of NANCE projection. ACh elicited inhibitory responses at low concentrations (1-30 nM) and excitatory responses at high concentrations (100-300 nM), in the three groups of rats. L-NA converted the ACh-induced inhibitory responses to excitatory responses. Immunohistochemical examination indicated no significant difference in the distribution of c-Kit expressing cells in the antrum smooth muscle from the three groups of rats. The results indicated that in antral smooth muscle, hyperglycemia was associated with enhanced activity in nitrergic and NANCNN projections and attenuation of NANCE projections, and that acupuncture treatment caused both a reduced blood glucose level and attenuated NANCNN projections. In genetically hyperglycemic rats, cholinergic responses were enhanced by acupuncture, possibly due to the enhanced cholinergic projections, with no change in the sensitivity of postjunctional muscarinic receptors to ACh.