Colorectal Cancer with Synchronous Resectable Liver Metastases: Monocentric Management in a Hepatobiliary Referral Center Improves Survival Outcomes

Background

Management of patients with synchronous colorectal liver metastases (SCRLM) should be individually tailored. This study compares patients managed by hepatobiliary centers from diagnosis with those referred for liver resection (LR).

Methods

Between 1998 and 2010, a total of 284 patients with SCRLM underwent resection; 106 resectable patients (1–3 unilobar metastases, diameter <100 mm, liver-only disease) were divided into two groups: 66 managed from diagnosis (group A) and 40 referred for LR (group B).

Results

Group A contained a greater proportion of multiple metastases (55.0 vs. 34.8 %, P = 0.042). Group B always received colorectal surgery as up-front treatment (vs. 18.2 %, P < 0.0001). In group B, chemotherapy before LR was more common (72.5 vs. 33.3 %, P = 0.0001) and lasted longer (P = 0.010). More patients in group B exhibited disease progression before LR (17.5 vs. 3.0 %, P = 0.025). Group A underwent fewer surgical procedures (80.3 % simultaneous resection vs. 0 %, P < 0.00001), with similar short-term outcomes. After a median follow-up of 42.0 months, group A exhibited higher 5 year disease-free survival (DFS, 64.8 vs. 30.8 %, P = 0.005) and fewer extrahepatic recurrences (21.5 vs. 47.5 %, P = 0.005). The late-referral group (>6 months, n = 24) had shorter median overall survival (OS) and DFS than group A (49.1 and 25.3 months vs. not achieved and not achieved, P < 0.05). The early-referral group exhibited OS and DFS similar to group A. Multivariate analysis confirmed late referral as a negative predictive factor of OS and DFS.

Conclusions

Monocentric management of SCRLM in hepatobiliary centers is associated with shorter preoperative chemotherapy, better disease control, fewer surgical procedures (simultaneous resection), and, compared with late-referred patients, better survival.     

Distribution and intrinsic membrane properties of basal forebrain GABAergic and parvalbumin neurons in the mouse

The basal forebrain (BF) strongly regulates cortical activation, sleep homeostasis, and attention. Many BF neurons involved in these processes are GABAergic, including a subpopulation of projection neurons containing the calcium‐binding protein, parvalbumin (PV). However, technical difficulties in identification have prevented a precise mapping of the distribution of GABAergic and GABA/PV+ neurons in the mouse or a determination of their intrinsic membrane properties. Here we used mice expressing fluorescent proteins in GABAergic (GAD67‐GFP knock‐in mice) or PV+ neurons (PV‐Tomato mice) to study these neurons. Immunohistochemical staining for GABA in GAD67‐GFP mice confirmed that GFP selectively labeled BF GABAergic neurons. GFP+ neurons and fibers were distributed throughout the BF, with the highest density in the magnocellular preoptic area (MCPO). Immunohistochemistry for PV indicated that the majority of PV+ neurons in the BF were large (>20 μm) or medium‐sized (15–20 μm) GFP+ neurons. Most medium and large‐sized BF GFP+ neurons, including those retrogradely labeled from the neocortex, were fast‐firing and spontaneously active in vitro. They exhibited prominent hyperpolarization‐activated inward currents and subthreshold “spikelets,” suggestive of electrical coupling. PV+ neurons recorded in PV‐Tomato mice had similar properties but had significantly narrower action potentials and a higher maximal firing frequency. Another population of smaller GFP+ neurons had properties similar to striatal projection neurons. The fast firing and electrical coupling of BF GABA/PV+ neurons, together with their projections to cortical interneurons and the thalamic reticular nucleus, suggest a strong and synchronous control of the neocortical fast rhythms typical of wakefulness and REM sleep. J. Comp. Neurol., 521:1225–1250, 2013. © 2012 Wiley Periodicals, Inc.     

Association among Oral Health,Apical Periodontitis,CD14 Polymorphisms,and Coronary Heart Disease in Middle-aged Adults

Introduction

There is evidence to suggest that an association exists between oral infections and coronary heart disease (CHD). Subjects presenting lesions of endodontic origin (LEOs) or pulpal inflammation had an increased risk of developing CHD. However, findings concerning systemic manifestations of apical periodontitis (AP) remain controversial. An association between CD14 gene polymorphisms and atherosclerosis-associated diseases has been shown, but there are no data regarding an association between CD14 polymorphism and AP. This study evaluated associations between clinical oral health status, CD14 polymorphisms, and CHD.

Methods

A case-controlled clinical trial was designed to compare middle-aged adults with acute myocardial infarction or unstable angina (n = 51) within 12 months of the acute event defined as first manifestation with healthy controls (n = 49). Participants were matched for age, sex, and socioeconomic status. Indicators of oral disease and compliance were evaluated. CD14 polymorphisms were analyzed by restriction fragment length polymorphism–polymerase chain reaction.

Results

CHD subjects had a higher prevalence of oral diseases and lower compliance to oral preventive strategies than healthy controls. Multivariate analysis showed a positive association between missing teeth (odds ratio [OR] = 1.37; 95% confidence interval [CI], 1.02–1.85), the number of LEOs (OR = 4.37; 95% CI, 1.69–11.28), chronic periodontitis (OR = 5.87; 95% CI, 1.17–29.4), and CHD. No statistically significant association emerged between the CD14 C(−260)T and the CD14 C(−159)T polymorphism, endodontic or periodontal disease, and CHD.

Conclusions

Chronic oral diseases may increase the risk of CHD and may be an unconventional risk factor for CHD.     

Episodic ataxia and severe infantile phenotype in spinocerebellar ataxia type 14: expansion of the phenotype and novel mutations

Journal of Neurology - Spinocerebellar ataxia type 14 (SCA14) is a dominantly inherited neurological disorder characterized by slowly progressive cerebellar ataxia. SCA14 is caused by mutations in...     

Continuous Metabolic Monitoring in Infant Cardiac Surgery: Toward an Individualized Cardiopulmonary Bypass Strategy

Cardiopulmonary bypass (CPB) in infants is associated with morbidity due to systemic inflammatory response syndrome (SIRS). Strategies to mitigate SIRS include management of perfusion temperature, hemodilution, circuit miniaturization, and biocompatibility. Traditionally, perfusion parameters have been based on body weight. However, intraoperative monitoring of systemic and cerebral metabolic parameters suggest that often, nominal CPB flows may be overestimated. The aim of the study was to assess the safety and efficacy of continuous metabolic monitoring to manage CPB in infants during open‐heart repair. Between December 2013 and October 2014, 31 consecutive neonates, infants, and young children undergoing surgery using normothermic CPB were enrolled. There were 18 male and 13 female infants, aged 1.4 ± 1.7 years, with a mean body weight of 7.8 ± 3.8 kg and body surface area of 0.39 m². The study was divided into two phases: (i) safety assessment; the first 20 patients were managed according to conventional CPB flows (150 mL/min/kg), except for a 20‐min test during which CPB was adjusted to the minimum flow to maintain MVO₂ >70% and rSO₂ >45% (group A); (ii) efficacy assessment; the following 11 patients were exclusively managed adjusting flows to maintain MVO2 >70% and rSO2 >45% for the entire duration of CPB (group B). Hemodynamic, metabolic, and clinical variables were compared within and between patient groups. Demographic variables were comparable in the two groups. In group A, the 20‐min test allowed reduction of CPB flows greater than 10%, with no impact on pH, blood gas exchange, and lactate. In group B, metabolic monitoring resulted in no significant variation of endpoint parameters, when compared with group A patients (standard CPB), except for a 10% reduction of nominal flows. There was no mortality and no neurologic morbidity in either group. Morbidity was comparable in the two groups, including: inotropic and/or mechanical circulatory support (8 vs. 1, group A vs. B, P = 0.07), reexploration for bleeding (1 vs. none, P = not significant [NS]), renal failure requiring dialysis (none vs. 1, P = NS), prolonged ventilation (9 vs. 4, P = NS), and sepsis (2 vs. 1, P = NS). The present study shows that normothermic CPB in neonates, infants, and young children can be safely managed exclusively by systemic and cerebral metabolic monitoring. This strategy allows reduction of at least 10% of predicted CPB flows under normothermia and may lay the ground for further tailoring of CPB parameters to individual patient needs.     

Same strategy for pitfalls of radiotherapy in different anatomical districts

Oral mucositis (OM) and radiodermatitis (RD) are serious side effects of radiotherapy (RT), often leading to its suspension, need for analgesics, and enteral/parenteral nutrition. Laser therapy is becoming a recommended treatment option. This prospective study aimed at demonstrating the beneficial effect of class IV laser therapy (HPLT) on RT-induced OM, an off-label use of HPLT to treat RD in breast cancer patients. Fifty-three cancer patients, during/after RT and/or chemotherapy (CT), affected by OM, were treated with HPLT during four consecutive days (970?±?15 nm, 5 W (50 %), 35–6000 Hz, 240 s). Assessment of OM (Grading Objective Scale, WHO-SCALE), pain (visual analogue scale, VAS), functional ability, subjective parameters, and site/severity of OM were recorded over time. Similarly, 27 breast cancer patients affected by RD were treated by HPLT and monitored over time for grade, discomfort, itching, and bleeding. Progressive improvement of WHO-SCALE from day 7 on, and of VAS from day 2 on (p?<?0.000) was registered. All patients’ functional capacity improved on day 4 (p?<?0.05). All subjective parameters improved on day 14 (p?<?0.001) except for voice, which improved on day 21 (p?<?0.000). Ulcerations’ dimension and erythema’s severity significantly decreased in all sites examined (p?<?0.05). Similarly, HPLT proved to be beneficial in managing RD for all the parameters considered (p?<?0.002). Regardless of OM grade/site and of kind/site of tumor, HPLT proved to be effective in healing OM as well as RD. In both cases, effective treatment can improve life quality through a safe, easy, innovative approach. Therefore, HPLT may become an integral part of everyday practice in the management of RT adverse effects.