Anastomotic leak after surgery for colon cancer and effect on long-term survival.

AIM: An anastomotic leak after surgery for colon cancer is a recognized complication but how it may adversely affect long-term survival is less clear because data are scarce. The aim of the study was to investigate the long-term impact of Grade C anastomotic leak in a large, population-based cohort. METHOD: Data on patients undergoing resection for Stage I-III colon cancer between 2008 and 2012 were collected from the Swedish, Norwegian and Danish Colorectal Cancer Registries. Overall relative survival and conditional 5-year relative survival, under the condition of surviving 1 year, were calculated for all patients and stratified by stage of disease. RESULTS: A total of 22 985 patients were analysed. Anastomotic leak occurred in 849 patients (3.7%). Five-year relative survival in patients with anastomotic leak was 64.7% compared with 87.0% for patients with no leak (P < 0.001). Five-year relative survival among the patients who survived the first year was 88.6% vs 81.3% (P = 0.003). Stratification by cancer stage showed that anastomotic leak was significantly associated with decreased relative survival in patients with Stage III disease (P = 0.001), but not in patients with Stage I or II (P = 0.950 and 0.247, respectively). CONCLUSION: Anastomotic leak after surgery for Stage III colon cancer was associated with significantly decreased long-term relative survival.

Long-Term Follow-Up and Survivorship After Completing Systematic Surveillance in Stage I-III Colorectal Cancer: Who Is Still at Risk?

PURPOSE: In patients with a high life expectancy at the time of surgery for colorectal cancer (CRC), the long-term outcome may be influenced by factors other than their cancer. We aimed to investigate the long-term outcome and cause of death beyond a 5-year surveillance programme. METHODS: We evaluated the overall survival (OS) and cancer-specific survival (CSS) of a population-based cohort of stage I-III CRC patients <75 years old who completed a systematic surveillance programme. RESULTS: In total, 161 patients <75 years old, 111 (69 %) of whom were node negative (pN0), were included. The median follow-up time was 12.1 years. The OS was 54 % at 15 years and differed significantly between the pN0 and pN+ patients (65 vs. 30 %; P < 0.001); CSS (72 %) also differed between the pN0 and pN+ patients (85 vs. 44 %; P < 0.001). For the 5-year survivors (n = 119), 14 (12 %) died of CRC during additional long-term follow-up (7 each for pN0 and pN+), and 6 patients (5 %; all pN0) died of other cancers. Patients aged <65 years exhibited better long-term survival (81 %), but most of the deaths were due to CRC (10/12 deaths). Only two of the 14 cancer-related deaths involved microsatellite instable (MSI) CRC. Females exhibited better OS and CSS beyond 5 years of surveillance. CONCLUSIONS: The long-term survival beyond 5-year survivorship for stage I-III CRC is very good. Nonetheless, cancer-related deaths are encountered in one-third of patients and occur most frequently in patients who are <65 years old at disease onset-pointing to a still persistent risk several years after surgery.

Significant increase in systemic exposure of atorvastatin after biliopancreatic diversion with duodenal switch.

Biliopancreatic diversion with duodenal switch is a combined restrictive and malabsorptive surgical weight loss procedure. Given that this procedure introduces a bypass of the proximal small intestine, it is a suitable model for investigating the influence of the proximal intestine on drug bioavailability. Eight-hour pharmacokinetic profiles were obtained the day before surgery and again after surgery at (median) 6 weeks (range, 4-8 weeks) in 10 morbidly obese patients who were receiving treatment with 20-80 mg atorvastatin each morning. The bioavailability of atorvastatin acid was significantly increased, with a mean twofold higher AUC(0-8) after surgery (range 1.0-4.2, P = 0.001). Time to maximum plasma concentration (C(max)) increased from 1.2 h before surgery to 2.3 h after surgery (P = 0.03). The results emphasize the protective nature of the proximal small intestine against ingested exogenous compounds. Consequently, retitration to the lowest effective dose should be considered after biliopancreatic diversion with duodenal switch in the case of drugs with a high degree of intestinal first pass metabolism and a narrow therapeutic window.

Significantly altered systemic exposure to atorvastatin acid following gastric bypass surgery in morbidly obese patients.

The impact of gastric bypass on atorvastatin pharmacokinetics was investigated in 12 morbidly obese patients being treated with 20-80 mg atorvastatin each morning. Eight-hour pharmacokinetic investigations were performed the day before the surgery and at a median of 5 weeks (range 3-6 weeks) after the surgery. Gastric bypass surgery produced a variable effect on individual systemic exposure to atorvastatin acid (area under the plasma concentration vs. time curve from 0 to 8 h postdose (AUC(0-8))), ranging from a threefold decrease to a twofold increase (median ratio = 1.1, P = 0.99). Patients with the highest systemic exposure to atorvastatin before surgery showed reduced exposure after surgery (n = 3, median ratio = 0.4, range = 0.3-0.5, P < 0.01), whereas those with lower systemic exposure before surgery showed a median 1.2-fold increase in atorvastatin AUC(0-8) (n = 9, range = 0.8-2.3, P = 0.03) after surgery. This study indicates that the presurgical first-pass metabolic capacity influences the effect of gastric bypass on atorvastatin bioavailability. Because individual first-pass metabolic capacity is not readily assessable clinically, retitration up to the lowest effective dose should be performed after the surgery.

Alcoholics' selective attention to alcohol stimuli: automated processing?

OBJECTIVE: This study investigated alcoholics' selective attention to alcohol words in a version of the Stroop color-naming task. METHOD: Alcoholic subjects (n = 23) and nonalcoholic control subjects (n = 23) identified the color of Stroop versions of alcohol, emotional, neutral and color words. Manual reaction times (RTs), skin conductance responses (SCRs) and heart rate (HR) were recorded. RESULTS: Alcoholics showed overall longer RTs than controls while both groups were slower in responding to the incongruent color words than to the other words. Alcoholics showed longer RTs to both alcohol (1522.7 milliseconds [ms]) and emotional words (1523.7 ms) than to neutral words (1450.8 ms) which suggests that the content of these words interfered with the ability to attend to the color of the words. There was also a negative correlation (r = -.41) between RT and response accuracy to alcohol words for the alcoholics, reflecting that the longer time the alcoholics used to respond to the color of the alcohol words, the more incorrect their responses were. The alcoholics also showed significantly greater SCRs to alcohol words (0.16 microSiemens) than to any of the other words (ranging from 0.04-0.08 microSiemens), probably reflecting the emotional significance of the alcohol words. Finally, the alcoholics evidenced smaller HR acceleration to alcohol (1.9 delta bpm) compared to neutral (2.8 delta bpm), which could be related to difficulties alcoholics experience in terminating their attention to the alcohol words. CONCLUSIONS: These findings indicate that it is difficult for alcoholics to regulate their attention to alcohol stimuli, suggesting that alcoholics' processing of alcohol information is automated.

Heart rate responses indicate locked-in attention in alcoholics immediately prior to drinking.

Twenty alcohol-dependent subjects and 10 social drinkers were tested in two experimental conditions: (a) when they were informed that their drinks contained alcohol and (b) when they were informed that their drinks were soft drinks. When told "alcohol," alcoholics evidenced a heart rate (HR) acceleration, whereas control subjects were unaffected by the instruction. Moreover, severely dependent (SD) alcoholics' HR remained elevated within the evaluation period whereas moderately dependent (MD) alcoholics' HR returned to baseline levels. The sustained HR acceleration in SD alcoholics suggests that their attention became "locked in" on the alcohol information immediately prior to drinking in the "told-alcohol" condition. Such an inward focus of attention will seriously reduce the alcoholic's ability to shift attention away from alcohol information, which may explain the difficulties alcoholics experience in coping with high-risk situations for drinking. In the SD alcoholics, HR acceleration correlated with the time it took to start drinking subsequent beverages containing alcohol in the told-alcohol instruction. In the MD alcoholics, HR responses were related to the reported urge to drink, whereas it was only in the nondependent subjects that self-reported urge to drink was related to the actual alcohol-use behavior.

Left hemisphere advantage for classical conditioning to auditory verbal CSs: effects of nonattended extinction.

The effects of brain laterality, or hemispheric asymmetry, on electrodermal classical conditioning during both attended and nonattended stimulus conditions were studied. Participants were conditioned to consonant-vowel (CV) syllables during an acquisition, or learning, phase of the experiment. During a subsequent extinction phase, the conditioned stimuli (CS) were presented in a dichotic mode of presentation. Half of the participants attended to the left ear (right hemisphere) during the extinction phase and the other half of the participants attended to the right ear (left hemisphere). The results showed effects of conditioning for all participants during the acquisition phase. During dichotic extinction, the left hemisphere group showed remaining learning effects in both the attended and nonattended conditions, whereas the right hemisphere group demonstrated conditioning only in the attended condition.

Selective processing of visual alcohol cues in abstinent alcoholics: an approach-avoidance conflict?

When symptomatic individuals selectively attend to emotionally relevant stimuli, the ability to shift attention away from such material is impaired. Subjects may, however, seek to avoid further processing of these stimuli, which would facilitate attentional shifts. This was examined in a group of abstinent alcoholics' responses to stimuli related to alcohol. Eight alcohol and eight neutral words served as cues in a covert attention task. The cues were either valid (2/3 of trials) or invalid (1/3 of trials) indicators of where a response target would appear after 100 or 500 milliseconds. The short interval was expected to interact with an initial approach toward the alcohol word, while the long interval would interact with a subsequent avoidance of the stimulus. As predicted, the alcoholics showed slower reaction times (RTs) to targets invalidly cued by alcohol words in the short interval, reflecting increased difficulties to shift attention. However, the alcoholics demonstrated faster RTs to targets invalidly cued by the alcohol words in the long interval. This indicates that the alcohol cue elicited emotional associations that, subsequent to initial stimulus identification, trigger an interrupting function of the attentional system.

Conditioned emotional cueing of spatial attentional shifts in a go/no-go RT task.

The influence of conditioned emotional arousal on selective attention was evaluated in a go/no-go version of Posner's covert attention spatial orienting task (Posner et al., 1982). Ten males and 10 females participated in the study, which consisted of two phases; an initial conditioning phase and a subsequent attention phase. In the conditioning phase, the Conditioning group received a 90-dB white noise unconditioned stimulus (UCS) contingent with presentations of a frame-lit rectangle, which thus became a conditioned stimulus (CS+), while a completely-lit rectangle was never paired with the noise and became a CS-. The Control group received non-contingent presentations of the noise and the two rectangles. In the attention phase, both groups participated in a go/no-go version of the attention orienting task, where targets were cued by both the CS+ and the CS-. Half of the subjects in both the Conditioning and the Control group were instructed to respond only to targets cued by the CS+ (go cue) and ignore targets cued by the CS- (no-go cue). The other half of the subjects responded to targets cued by the CS- and ignored targets cued by CS+. The Conditioning group identified targets at the opposite location of the CS+ significantly faster than targets at the same location. The emotional salience of the cue thus reversed the typical cost of shifting attention to targets outside the cued location.

Peripheral cuing of covert spatial attention before and after emotional conditioning of the cue.

Spatial cuing of attentional shifts were investigated before and after the visual cue had acquired emotional significance through a classical conditioning procedure. The study consisted of three phases; an attention preconditioning phase, the conditioning phase and an attention postconditioning (extinction) phase. In the attention phases, subjects participated in a trial-by-trial cuing task, in which the location of the target was validly or invalidly cued by either a frame-lit or a completely lit rectangle. During conditioning half the subjects (Conditioning group) had a 90 dB white noise unconditioned stimulus (UCS) presented together with one of the two attentional cues. This cue was, thus, turned into a conditioned stimulus (CS+), while the other cue became a CS-. The Control group received the noise uncontingent upon presentations of these stimuli. The Conditioning group showed greater skin conductance responses (SCRs) to the CS+ compared to the CS-, reflecting that a conditioned response was established. When the CS+ served as attentional cue, there was no difference in RTs between validly and invalidly cued targets, while responses to invalidly cued targets were delayed on all other trials. This suggests that the CS+ reduced the cognitive cost of shifting attention from the cued to the uncued location.

Autonomic cued reactivity in alcoholics: the effect of olfactory stimuli.

The present study was designed to investigate autonomic cued reactivity to olfactory alcohol stimuli in alcoholics. Twenty outpatient alcoholics and 20 social drinkers were exposed to high- and low-potency alcohol and neutral odors. The alcoholics showed greater skin conductance responses and increased heart rate acceleration responses to the high-potency alcohol odor than social drinkers, while there was no difference between the groups' responses to the low-potency alcohol odor. Alcoholics also reported greater difficulties in resisting a potential offer for a drink after relative to before the experiment, while there was no change in the desire to drink. The results indicate that alcohol cues are perceived as emotionally aversive and elicit a defensive response to avoid further processing of these stimuli. The increased autonomic reactivity may thus reflect a shift of focus from the environmental alcohol cues to internal thoughts and feelings. A rigid internal focus may constrain the ability to resist alcohol consumption and thus be a critical determinant in promoting craving and relapse in alcoholics.

Habituation of electrodermal reactivity to visual alcohol stimuli in alcoholics.

This study address the question of cued reactivity in alcoholics. Twenty alcoholic in-patients and 20 control subjects were presented with repeated exposures to a alcohol-related (A) and a neutral (B) slide, in either an ABA or BAB sequence. Skin Conductance Level (SCL) and Skin Conductance Responses (SCR) were recorded. Alcohol-dependent subjects showed increased SCR compared to the control subjects. This was, however, independent of whether the presented stimuli were alcohol-related or neutral. Thus, the results did not support the hypothesis of cued reactivity, but point to a nonspecific hyper-reactivity in alcohol-dependent subjects. The results are discussed in relation to risk-factors for alcoholism and relapse.