Timing of colonoscopy after resection for colorectal cancer: are we looking too soon?

BACKGROUND: Based on current National Comprehensive Cancer Network guidelines, colonoscopic surveillance after colorectal cancer resection should begin at 1 year. OBJECTIVE: The aim of this study was to determine whether the incidence of cancer or advanced polyp detection rate was high enough to justify colonoscopy at 1 year. DESIGN: The Ochsner Clinic Tumor Registry Database was queried for patients who underwent a segmental colectomy or proctectomy between 2002 and 2010. Patients who had a preoperative colonoscopy and at least 1 documented postoperative colonoscopy were included. We considered new cancer or polyps of ≥1 cm as missed on the preoperative colonoscopy. Patients with an identified genetic trait causing a predisposition to colorectal cancer were excluded. RESULTS: Five hundred twelve patients underwent resection, and 155 met our inclusion criteria. The average age was 64 years, and 53% patients were male. There were 32.9% with stage I disease, 35% with stage II disease, 27.1% with stage III disease, and 5.2% with stage IV disease. Of these patients, 52.2% had a right colectomy, 7.1% had a left colectomy, 16.8% had a sigmoid colectomy, 22% had a low anterior resection, and 1.3% had a transanal resection. The average time to first postoperative colonoscopy was 478 days (SD ±283 days). Twenty-four patients had adenomatous polyps detected on their first surveillance colonoscopy, but only 5 (3.2%) polyps were ≥1 cm, and there was no correlation between stage of cancer and finding a polyp. No new cancers were detected, but 3 (1.9%) had an anastomotic recurrence. CONCLUSIONS: The performance of surveillance colonoscopy at 1 year resulted in the detection of only 5 missed polyps ≥1 cm and no metachronous cancers. Anastomotic recurrences were rare, and the majority were in patients who had rectal cancer that could be evaluated by in-office flexible sigmoidoscopy. Extending the time to first colonoscopy appears to be safe and would help conserve valuable resources, including physician and facility time, which is imperative in the current health care climate.

The envelope glycoprotein ectodomains determine the efficiency of CD4+ T lymphocyte depletion in simian-human immunodeficiency virus-infected macaques.

CD4+ T lymphocyte depletion in human immunodeficiency virus type 1 (HIV-1)-infected humans underlies the development of acquired immune deficiency syndrome. Using a model in which rhesus macaques were infected with chimeric simian-human immunodeficiency viruses (SHIVs), we show that both the level of viremia and the structure of the HIV-1 envelope glycoprotein ectodomains individually contributed to the efficiency with which CD4(+) T lymphocytes were depleted. The envelope glycoproteins of recombinant SHIVs that efficiently caused loss of CD4(+) T lymphocytes exhibited increased chemokine receptor binding and membrane-fusing capacity compared with those of less pathogenic viruses. These studies identify the HIV-1 envelope glycoprotein ectodomains as determinants of CD4(+) T lymphocyte loss in vivo and provide a foundation for studying pathogenic mechanisms.

Amphetamine-induced dopaminergic hypersensitivity in guinea pigs. Implications in psychosis and human movement disorders.

Following chronic amphetamine pretreatment, guinea pigs demonstrate an increased sensitivity to both d-amphetamine sulfate- and apomorphine hydrochloride-induced stereotyped behavior. This observation suggests that chronic exposure to high doses of a dopamine agonist (d-amphetamine) alters the response of the brain to the subsequent administration of both indirect (d-amphetamine) and direct (apomorphine) dopamine agonists. This altered response may be due to the development of dopamine receptor site hypersensitivity. Clinical evidence suggests that a similar agonist-induced hypersensitivity may play a role in the development of dyskinetic movement disorders and psychoses in humans following the chronic use of such dopamine agonists as amphetamine and levodopa.

Cognitive neuropsychology. Resolving enigmas about Wernicke's aphasia and other higher cortical disorders.

Cognitive neuropsychology is a young branch of neuroscience whose ancestral influences include a rich pool of experimental (eg, cognitive, psychology), theoretical (eg, epistemology), and clinical (eg, neurology, neuropsychology) disciplines. An essential principle of cognitive neuropsychology is that disorders of higher cortical functions can be understood in terms of breakdowns of one or more information-processing modules. Each module is the most basic element of intelligence that can be defined based on current knowledge. This approach is a refinement of-not a fundamental departure from-the 19th-century "localizationist" view of language disorders. Wernicke's aphasia, for example, classical attributed to a single cognitive deficit (loss of word sounds), is shown in this review to require damage to multiple distinct information-processing modules. Cognitive neuropsychology provides the tools for the type of fine-grained analyses of behavior that are needed to capitalize on recent advances in neuroimaging techniques, including the development of more sophisticated models of brain-behavior relationships.

Cognitive slowing in Parkinson's and Alzheimer's patients: distinguishing bradyphrenia from dementia.

The contribution of cognitive slowing to the slowed performance of patients with Parkinson's disease (PD) is a matter of long-standing debate. In this study, we contrasted the performance of PD patients on two reaction-time tasks with the performance of Alzheimer's disease (AD) patients, young normal subjects, and elderly normal subjects. Both nondemented and demented PD patients showed cognitive as well as motor slowing, and the extent of cognitive slowing varied with overall cognitive status. Moreover, by comparison with the cognitive slowing in AD patients, cognitive slowing in PD patients was disproportionate to their general level of cognitive performance. We suggest that this disproportionality be used to differentiate the concepts of bradyphrenia and nonspecific cognitive slowing.

Intracranial calcification in hyperparathyroidism associated with gait apraxia and parkinsonism.

Two patients with hyperparathyroidism had symmetric calcification of the brain, including the basal ganglia. In both patients, the neurologic disorder included parkinsonism and gait apraxia. Computerized tomography may help define the prevalence and clinical manifestations of this rare syndrome.

Criteria for the diagnosis of ischemic vascular dementia proposed by the State of California Alzheimer's Disease Diagnostic and Treatment Centers.

Accurate diagnosis of vascular dementia is important for the recognition of underlying pathophysiology and the institution of appropriate therapy. It is also important for the determination of the incidence and prevalence of not only vascular dementia but also Alzheimer's disease (AD), since differentiating between these two entities is often problematic. The State of California Alzheimer's Disease Diagnostic and Treatment Centers (ADDTC) herein propose criteria for the diagnosis of ischemic vascular dementia (IVD). These criteria broaden the conceptualization of vascular dementia, include the results of neuroimaging studies, emphasize the importance of neuropathologic confirmation, refine nosology, and identify areas that require further research. Parallel use of the proposed definitions of "possible" and "mixed" categories in the diagnosis of both AD and IVD would ensure compatibility between the National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) criteria for AD and the ADDTC criteria for IVD. Uniform classification of subtypes of IVD will improve the generalizability of individual studies and aid in multicenter collaborations.

HIV-1 gp120: a novel viral B cell superantigen.

The envelope glycoprotein of the human immunodeficiency virus (HIV-1), gp120, has recently been characterized as a novel immunoglobulin superantigen (Ig-SAg) [1,2]. Analogous to the interaction of SAgs with T cells, gp120 binds to an unusually large proportion of immunoglobulins (lgs) from HIV-uninfected individuals; most, if not all of these Igs are members of the VH3 family [3]. Functionally, gp120 preferentially stimulates VH3 B cells in vitro. This stimulation correlates with an in vivo VH3 activation during HIV infection. Curiously, this initial activation is followed by a subsequent depletion of VH3-expressing B cells as individuals progress to AIDS. In this article we will review our current understanding of the superantigenic properties of HIV gp120. Specifically we will focus on structural aspects of the binding interaction. on the ontological development of these superantigen-binding antibodies, and on potential roles that this unconventional Ig-pathogen interaction might play in the pathogenesis of HIV-induced disease.

The hyperkinetic child syndrome and brain monoamines: pharmacology and therapeutic implications.

Decreased catecholaminergic activity within the central nervous system has been associated with altered arousal, attention, learning, and kinetic function in animals and humans. The hyperkinetic child syndrome (HCS) involves dysfunction in all these spheres and may thus reflect diminished catecholamine activity, particularly as related to brain dopamine. Accordingly, the efficacy of catecholaminergic agents in treating the HCS is a predictable rather than a paradoxical effect of these agents. Sufficient evidence is now available to strongly implicate catecholamine hypoactivity in the pathopharmacology of the HCS.

Endogenous opiate reward induced by an enkephalinase inhibitor, thiorphan, injected into the ventral midbrain.

Opiates are known to be reinforcing when injected into the ventral tegmental area (VTA). The present study produced conditioned reinforcement with local injections of exogenous d-ala2-met5-enkephalinamide (DALA), a potent analogue of met-enkephalin, and with thiorphan , an enkephalinase inhibitor which protects endogenous opiates from enzymic degradation. In a conditioned place preference paradigm, rats received injections of DALA (1.0, 3.0, or 8.0 micrograms), thiorphan (60 micrograms), and/or naloxone (10 micrograms), or saline vehicle. Conditioned reinforcement was obtained with 8.0 micrograms of DALA and also with thiorphan but not with thiorphan plus naloxone. This suggests that reward can be generated by endogenous opiates in the VTA. Tests during the light phase and dark phase suggested that diurnal periodicity may play a role in opiate reward. It is concluded that the VTA can generate conditioned reward through transmitter-receptor interaction involving an endogenous opiate substrate which is probably enkephalinergic.

Motor disorder and the timing of repetitive movements.

This paper is concerned with the timing of regular repetitive movements. The two-process model of Wing and Kristofferson attributes variability in self-paced interresponse intervals to imprecision in a timekeeper and to temporal noise in the execution of motor responses triggered by the timekeeper. Assuming independence of timekeeper intervals and motor delays, the variance of each may be estimated from interresponse-interval statistics. Comparison of changes in timing performance associated with alterations in motor-system functioning offer the possibility of a new approach to investigation of this model. Illustrative data are presented from a case study of a patient with Parkinson's disease whose lesions affecting the dopaminergic pathways of the basal ganglia have given rise to asymmetric symptoms, including differences in timing performance of the two hands. Analysis of interresponse-interval variability according to the two-process model indicates that the elevated variability of the side more greatly affected by parkinsonism is attributable to the timekeeper intervals rather than the motor delays.

Primary cardiac lymphoma.

A case of primary cardiac non-Hodgkin's B cell lymphoma is described in a patient presenting with obstructive right heart failure. Unlike the majority of cases, in this case the tumor was diagnosed ante mortem. THe patient's history combined with the aggressive use of noninvasive echocardiography are helpful in diagnosing this rare lesion.

Efficacy and safety of a loading-dose regimen versus a no-loading-dose regimen of metrifonate in the symptomatic treatment of Alzheimer's disease: a randomized, double-masked, placebo-controlled trial. Metrifonate Study Group.

This prospective, randomized, double-masked, placebo-controlled, parallel-group study assessed the safety and efficacy of 2 dosage regimens of once-daily metrifonate in patients with probable Alzheimer's disease (AD) of mild-to-moderate severity. A total of 395 patients were randomized to receive placebo (n = 134) or metrifonate in 1 of 2 regimens. The loading-dose group (n = 133) received a daily loading dose of metrifonate 100 mg or 150 mg (by weight) for 2 weeks, followed by a daily maintenance dose of metrifonate 50 mg for 4 weeks; the no-loading-dose group (n = 128) received the daily maintenance dose of metrifonate 50 mg for 6 weeks. The primary measure of efficacy was the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog); secondary measures of efficacy included the Mini-Mental State Examination (MMSE), the Clinician's Interview Based Impression of Change with Caregiver Input (CIBIC-Plus), the Clinician's Interview Based Impression of Severity with Caregiver Input (CIBIS-Plus), and the ADAS-Noncognitive Subscale (ADAS-Noncog). Safety was assessed by the prevalence of premature study termination and treatment-emergent adverse events, as well as by changes in vital signs, findings on electrocardiographic and neurologic examinations, and abnormalities on laboratory tests. At 4 weeks of treatment, defined by the protocol as the target efficacy determination, the mean ADAS-Cog scores of the intent-to-treat population (last observation carried forward) favored the loading-dose group versus the placebo group, but the difference was not statistically significant. However, at week 6, the difference in mean ADAS-Cog scores was statistically significant compared with placebo. At neither week 4 nor week 6 was there a statistically significant difference in the mean ADAS-Cog scores of the no-loading-dose and placebo groups. For the CIBIC-Plus, the treatment difference between the placebo and loading-dose groups significantly favored metrifonate at week 6 but not at week 4, whereas the treatment difference between the placebo and no-loading-dose groups was statistically significant at both time points. For the MMSE, CIBIS-Plus, and ADAS-Noncog, treatment differences for both groups versus placebo did not reach statistical significance at either week 4 or 6. Assessment of the frequency of adverse events in metrifonate-treated patients revealed that the no-loading-dose regimen was better tolerated than the loading-dose regimen. Given the overall similar efficacy and more favorable safety profile associated with the no-loading-dose regimen versus the loading-dose regimen observed in this study, the no-loading-dose regimen appears to be the better strategy for initiating metrifonate treatment in patients with probable AD of mild-to-moderate severity.

Neurotensin: a new 'reward peptide'.

oeurotensin (NT) is a tridecapeptide which is thought to bind to receptors located on dopamine cells in the ventral tegmental area (VTA). Rats with cannulas implanted in the VTA showed a significant increase in time spent in an environment in which they had received bilateral injections of neurotensin on previous days. This is indicative of conditioned reinforcement in which the neuropeptide was the primary reinforcer. In order to determine the specificity of neurotensin receptor interactions, 3 fragments of the peptide were examined at 2 doses. NT1-8 and NT8-13 were found to be inactive while NT1-11 demonstrated significant activity. The results suggest that NT in the VTA is capable of inducing reinforcing effects. This is the first evidence for a non-opiate 'reward peptide'.

Naloxone blockade of apomorphine-induced stereotyped behavior: interaction of endogenous opiates with dopamine.

The specific opiate antagonist, naloxone, inhibits the in vivo and in vitro activity of the endogenous opiate compounds which have heretofore been identified. In this study systemic naloxone administration successfully blocked the production of stereotyped behavior induced by the direct dopamine agonist apomorphine. This implies that the endogenous opiates contribute to the production of stereotyped behavior initiated by dopaminergic stimulation and that endogenous opiates may function as central neurotransmitters with dopaminergic activity.

Supersensitivity to d-amphetamine- and apomorphine-induced stereotyped behavior induced by chronic d-amphetamine administration.

Guinea pigs exhibit an increased sensitivity to both d-amphetamine- and apomorphine-induced stereotyped behavior following chronic pretreatment with d-amphetamine. This chronic agonist or "innervation" supersensitivity is believed to be a reflection of an increased sensitivity of dopamine receptor sites within the corpus striatum to dopaminergic agonists. The appearance of dyskinetic movement disorders in humans following the chronic use of levodopa or amphetamine may be a manifestation of similarly increased dopamine receptor site sensitivity within the striatum. It is suggested that the animal model of "innervation" supersensitivity may be useful in the investigation of these human movement disorders.

Use of the surgical towel in colorectal hand-assisted laparoscopic surgery (HALS).

The use of laparotomy pads or towels to displace the small intestine away from the operative site is a well-established technique in open surgery; however, its application is unfeasible or extremely challenging in standard laparoscopic surgery. We describe the use of standard surgical towels in hand-assisted laparoscopic surgery (HALS). A Pfannenstiel incision is made and a Gelport hand-access device is assembled. A sterilized surgical towel, 65 x 44 cm in size, is inserted via the Gelport, unfolded, and placed over the bowel loops laparoscopically with the assistance of the hand. The bowel loops are then housed gently in the towel and displaced away from of the operative site. HALS enables the easy insertion and handling of a large surgical towel inside the peritoneal cavity. The towel successfully retracts the small intestine, enabling the surgeon to concentrate the use of his or her hand on the targeted structures. This practical and inexpensive tip adds another advantageous component to the practice of colorectal HALS.

Ulcerative colitis and colonic lymphoma: a theoretical link.

Ulcerative colitis (UC) is an inflammatory disease of the colon and rectum. Although colonic adenocarcinoma is a recognized complication of UC there have been few reported cases of gastrointestinal lymphoma arising in this setting. We describe our experience with such a case and review the literature that attempts to explain possible genetic etiologies for the malignant transformation of gastrointestinal lymphoid tissue to lymphoma as well as a link between UC and lymphoma.

The management of common bile duct stones in patients undergoing laparoscopic cholecystectomy.

The management of suspected and/or unsuspected common bile duct (CBD) stones in patients undergoing laparoscopic cholecystectomy (LC) is controversial. Decisions on whether to perform an open CBD exploration versus employing therapeutic options such as preoperative/post-operative endoscopic retrograde cholangiography (ERCP) or endoscopic duct exploration are polemic. To determine indications, timing, benefits, and potential morbidity of these approaches, we gathered data on 401 patients undergoing LC within the last 18 months. Indications for preoperative ERCP included jaundice (40%), dilated ducts (28%), elevated amylase (19%) or alkaline phosphatase (21%), suspicion of CBD stones by ultrasound (17%) and "other" (17%). Indications for postoperative ERCP were retained stones (33%) and CBD evaluation (67%). Indications for CBD exploration included abnormal cholangiogram (64%), palpable stones (18%), and other (18%). A significant correlation was observed between suspected stones by ultrasound and stones found by ERCP (P < 0.01). For patients in the "other" category, preoperative ERCP was universally negative (P = 0.04). Overall ERCP morbidity was 4/59 (6.8%), and the overall failure rate for clearing CBD stones was 2/28 (7.1%). The timing of the ERCP did not affect morbidity/mortality. Multivariate analysis revealed that age (P << 0.001), the presence of pre-existing medical risk factors (P << 0.001), and duration of LC (P = 0.0034), but not ERCP (P = 0.08), were the important factors determining LC morbidity. In summary, common bile duct stones can be successfully cleared endoscopically in the majority of patients undergoing LC. Patients with suspected CBD stones should undergo pre-operative ERCP, and strict criteria should be applied in the selection of these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute colonic perforation associated with colorectal cancer.

Our purpose was to evaluate long-term outcome in patients presenting with acute colonic perforation in the setting of colorectal cancer. We conducted a retrospective review of 48 consecutive patients presenting with acute colonic perforation associated with colorectal cancer at a single institution. Patients presented either with free air or acute peritonitis. No patients with colonic obstruction were included. Forty-eight patients presented with colon perforation. Thirty-six had perforation at the tumor, 11 proximal to the tumor, and one distal to the primary tumor. Patients who perforated proximal to the tumor were older (74.5 +/- 2 vs 64.7 +/- 3; P < 0.04) and had a longer length of stay (46.8 +/- 17 vs 11.6 +/- 1 P < 0.001). Fourteen patients had stage II disease, 19 stage III, and 15 stage IV. Thirty-day mortality was 14 per cent (n = 7) with nine in-hospital deaths. Of 30-day survivors 29 (60%) had curative resection (21 with local perforation and nine with proximal perforation). Of these 14 received adjuvant chemotherapy. Eleven patients (33%) had either unresectable or metastatic disease on exploration. Mean follow-up was 21.5 months. Ten patients developed metastatic disease after potentially curative resections. Of these nine patients had perforations of the primary tumor. Three patients developed local recurrence and all had local tumor perforations. One-year survival was 55 per cent (n = 16). Five-year disease-free survival was 14 per cent (n = 4). There were no long-term survivors after perforation proximal to the tumor, although disease stage was comparable in both groups. We conclude that perforation proximal to a cancer is associated with a higher perioperative mortality and worse long-term outcome when compared with acute perforations at the site of the tumor. Long-term survival requires both aggressive management of the concomitant sepsis and definitive oncologic surgery.