Pannexin 1 dysregulation in Duchenne muscular dystrophy and its exacerbation of dystrophic features in mdx mice.

BACKGROUND: Duchenne muscular dystrophy (DMD) is associated with impaired muscle regeneration, progressive muscle weakness, damage, and wasting. While the cause of DMD is an X-linked loss of function mutation in the gene encoding dystrophin, the exact mechanisms that perpetuate the disease progression are unknown. Our laboratory has demonstrated that pannexin 1 (Panx1 in rodents; PANX1 in humans) is critical for the development, strength, and regeneration of male skeletal muscle. In normal skeletal muscle, Panx1 is part of a multiprotein complex with dystrophin. We and others have previously shown that Panx1 levels and channel activity are dysregulated in various mouse models of DMD. METHODS: We utilized myoblast cell lines derived from DMD patients to assess PANX1 expression and function. To investigate how Panx1 dysregulation contributes to DMD, we generated a dystrophic (mdx) mouse model that lacks Panx1 (Panx1-/-/mdx). In depth characterization of this model included histological analysis, as well as locomotor, and physiological tests such as muscle force and grip strength assessments. RESULTS: Here, we demonstrate that PANX1 levels and channel function are reduced in patient-derived DMD myoblast cell lines. Panx1-/-/mdx mice have a significantly reduced lifespan, and decreased body weight due to lean mass loss. Their tibialis anterior were more affected than their soleus muscles and displayed reduced mass, myofiber loss, increased centrally nucleated myofibers, and a lower number of muscle stem cells compared to that of Panx1+/+/mdx mice. These detrimental effects were associated with muscle and locomotor functional impairments. In vitro, PANX1 overexpression in patient-derived DMD myoblasts improved their differentiation and fusion. CONCLUSIONS: Collectively, our findings suggest that PANX1/Panx1 dysregulation in DMD exacerbates several aspects of the disease. Moreover, our results suggest a potential therapeutic benefit to increasing PANX1 levels in dystrophic muscles.

Angiotensin 1-7 increases fiber cross-sectional area and force in juvenile mouse skeletal muscle.

Recent studies reported that in skeletal muscle angiotensin 1-7 (Ang 1-7), via its receptor Mas (MasR), prevents the atrophy induced by angiotensin II and by cast immobilization; it also improves muscle integrity and function in the mdx mouse, a muscular dystrophy model. The objectives of this study were to document 1) the extent of the Ang 1-7's hypertrophic effect in terms of muscle mass and muscle fiber cross-sectional area (CSA), 2) how Ang 1-7 affects muscle contractile function in terms of twitch and tetanic force, force-frequency relationship, and 3) whether the effect involves MasR. Wild-type and MasR-deficient [Mas receptor knockout mouse model (MasR-/-)] mice were treated with Ang 1-7 (100 ng/kg body wt·min using an osmotic pump) for 4 or 16 wk. Ang 1-7 significantly increased skeletal muscle/body weight ratio of soleus, tibialis, and gastrocnemius, but not of extensor digitorum longus (EDL). It significantly increased fiber cross-sectional area in the order of type I > IIA > IIB. In EDL and soleus muscles, it significantly increased twitch and tetanic force while causing a shift in the force-frequency relationship toward lower stimulation frequencies. It had no effect on fiber type composition. None of the Ang 1-7 effects observed in wild-type mice were observed in MasR-/- muscles. It caused a transient increase in phosphorylated protein kinase B (Akt) and 4EBP proteins while having no effect on S6 phosphorylation, MuRF-1, and atrogin-1 and a decrease in PAX7 expression in satellite cells. This is the first study demonstrating the hypertrophic effects of Ang 1-7 in normal muscle acting via its MasR.

In Vivo Sentinel Lymph Node Detection with Indocyanine Green in Colorectal Cancer.

Introduction: The indocyanine green fluorescence imaging system allows the identification of lymphatic vessels, lymph nodes and blood flow during surgery. Colorectal cancer is the second commonest cancer in women, the third in men, being the fourth commonest cause of cancer death. One of the most important factors for staging and prognosis in colorectal cancer is the involvement of the regional lymph nodes. In the literature, there are several methods for identifying sentinel lymph nodes, including methylene blue, technetium (99m Tc) and indocyanine green. The current article presents the use of indocyanate in the identification of sentinel node/nodes in malignant tumors of the colon, by a technique performed in vivo, before the primary ligation of the vascular pedicles. Material and methods:The study was prospectively conducted on a group of 23 patients who had undergone a standard surgical resection - 21 of them for a malignant tumor of the colon and two patients for a malignant rectal tumor - in the 1st General Surgery Department, Emergency University Hospital, Bucharest, Romania, between January 2020-March 2022. During surgery, sentinel lymph node detection was performed using indocyanine green and the Karl Storz® Vitom ICG probe. Sentinel lymph nodes were separately excised and sent to the Department of Pathological Anatomy for analysis. Results:Sentinel nodes were successfully identified in 13 patients and the overall identification rate was 56.52% (13/23 cases). In seven cases, the number of invaded nodes was the same as that of identified and invaded sentinel nodes. Complete lymphadenectomy was performed in all cases regardless of the staining status of the sentinel lymph nodes. Conclusions:The use of fluorescence imaging with indocyanine green in colorectal cancer remains controversial. Since no specific receptor target is used, the fluorescent signal is not specific for lymph node metastases. The learning curve is particularly important for increasing the accuracy of the technique and is responsible for the negative results in some cases. Cases in which lymph nodes have not been invaded require further evaluation through immunohistochemistry and chain polymerization reaction (RT-PCR).

Role of methylene blue in detecting the sentinel lymph node in colorectal cancer: In vivo vs. ex vivo technique.

The identification of sentinel lymph nodes is a valuable oncological method, which aims at mapping lymphatic drainage and has the advantage of correctly staging the disease and assessing prognosis. Lymph node invasion is an important prognostic feature. In colorectal cancer, lymphadenectomy is not influenced by the positive or negative status of the sentinel lymph node. The identification of lymph nodes with possible invasion by staining the primary tumor with methylene blue can lead to improved staging and management. In other words, the consequent administration of neoadjuvant therapy (chemotherapy) to the appropriate patients may result in lower recurrence rates. Thus, the aim of the present study was to use methylene blue to identify the sentinel node/nodes in colorectal cancer and to determine whether the dye-capturing nodes were invaded by the tumor. This is a non-randomized prospective study, in which 26 patients with colon cancer with surgical indication were enrolled. Two types of methods were utilized: in vivo (16 patients) and ex vivo (10 patients). The identification rate was 75% for the in vivo technique and 60% for the ex vivo technique, resulting in a 69.26% overall identification rate. Of 18 patients with sentinel lymph nodes identified using dye, routine histological examination detected metastases in 6 (33.33%) of these patients. In conclusion, further research should be conducted into how the clinical application of sentinel node detection can be employed in colorectal cancer.

Lower Ca2+ enhances the K+-induced force depression in normal and HyperKPP mouse muscles.

Hyperkalemic periodic paralysis (HyperKPP) manifests as stiffness or subclinical myotonic discharges before or during periods of episodic muscle weakness or paralysis. Ingestion of Ca2+ alleviates HyperKPP symptoms, but the mechanism is unknown because lowering extracellular [Ca2+] ([Ca2+]e) has no effect on force development in normal muscles under normal conditions. Lowering [Ca2+]e, however, is known to increase the inactivation of voltage-gated cation channels, especially when the membrane is depolarized. Two hypotheses were tested: (1) lowering [Ca2+]e depresses force in normal muscles under conditions that depolarize the cell membrane; and (2) HyperKPP muscles have a greater sensitivity to low Ca2+-induced force depression because many fibers are depolarized, even at a normal [K+]e. In wild type muscles, lowering [Ca2+]e from 2.4 to 0.3 mM had little effect on tetanic force and membrane excitability at a normal K+ concentration of 4.7 mM, whereas it significantly enhanced K+-induced depression of force and membrane excitability. In HyperKPP muscles, lowering [Ca2+]e enhanced the K+-induced loss of force and membrane excitability not only at elevated [K+]e but also at 4.7 mM K+. Lowering [Ca2+]e increased the incidence of generating fast and transient contractures and gave rise to a slower increase in unstimulated force, especially in HyperKPP muscles. Lowering [Ca2+]e reduced the efficacy of salbutamol, a ß2 adrenergic receptor agonist and a treatment for HyperKPP, to increase force at elevated [K+]e. Replacing Ca2+ by an equivalent concentration of Mg2+ neither fully nor consistently reverses the effects of lowering [Ca2+]e. These results suggest that the greater Ca2+ sensitivity of HyperKPP muscles primarily relates to (1) a greater effect of Ca2+ in depolarized fibers and (2) an increased proportion of depolarized HyperKPP muscle fibers compared with control muscle fibers, even at normal [K+]e.

One drug-sensitive subunit is sufficient for a near-maximal retigabine effect in KCNQ channels.

Retigabine is an antiepileptic drug and the first voltage-gated potassium (Kv) channel opener to be approved for human therapeutic use. Retigabine is thought to interact with a conserved Trp side chain in the pore of KCNQ2-5 (Kv7.2-7.5) channels, causing a pronounced hyperpolarizing shift in the voltage dependence of activation. In this study, we investigate the functional stoichiometry of retigabine actions by manipulating the number of retigabine-sensitive subunits in concatenated KCNQ3 channel tetramers. We demonstrate that intermediate retigabine concentrations cause channels to exhibit biphasic conductance-voltage relationships rather than progressive concentration-dependent shifts. This suggests that retigabine can exert its effects in a nearly "all-or-none" manner, such that channels exhibit either fully shifted or unshifted behavior. Supporting this notion, concatenated channels containing only a single retigabine-sensitive subunit exhibit a nearly maximal retigabine effect. Also, rapid solution exchange experiments reveal delayed kinetics during channel closure, as retigabine dissociates from channels with multiple drug-sensitive subunits. Collectively, these data suggest that a single retigabine-sensitive subunit can generate a large shift of the KCNQ3 conductance-voltage relationship. In a companion study (Wang et al. 2018. J. Gen. Physiol. https://doi.org/10.1085/jgp.201812014), we contrast these findings with the stoichiometry of a voltage sensor-targeted KCNQ channel opener (ICA-069673), which requires four drug-sensitive subunits for maximal effect.

Understanding the physiology of the asymptomatic diaphragm of the M1592V hyperkalemic periodic paralysis mouse.

The diaphragm muscle of hyperkalemic periodic paralysis (HyperKPP) patients and of the M1592V HyperKPP mouse model rarely suffers from the myotonic and paralytic symptoms that occur in limb muscles. Enigmatically, HyperKPP diaphragm expresses the mutant NaV1.4 channel and, more importantly, has an abnormally high Na(+) influx similar to that in extensor digitorum longus (EDL) and soleus, two hindlimb muscles suffering from the robust HyperKPP abnormalities. The objective was to uncover the physiological mechanisms that render HyperKPP diaphragm asymptomatic. A first mechanism involves efficient maintenance of resting membrane polarization in HyperKPP diaphragm at various extracellular K(+) concentrations compared with larger membrane depolarizations in HyperKPP EDL and soleus. The improved resting membrane potential (EM) results from significantly increased Na(+) K(+) pump electrogenic activity, and not from an increased protein content. Action potential amplitude was greater in HyperKPP diaphragm than in HyperKPP soleus and EDL, providing a second mechanism for the asymptomatic behavior of the HyperKPP diaphragm. One suggested mechanism for the greater action potential amplitude is lower intracellular Na(+) concentration because of greater Na(+) K(+) pump activity, allowing better Na(+) current during the action potential depolarization phase. Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm. Action potential amplitude was not different between wild-type and HyperKPP diaphragm. There was also no evidence for an increased activity of the Na(+)-Ca(2+) exchanger working in the reverse mode in the HyperKPP diaphragm compared with the wild-type diaphragm. So, a third mechanism remains to be elucidated to fully understand how HyperKPP diaphragm generates more force compared with wild type. Although the mechanism for the greater force at depolarized resting EM remains to be determined, this study provides support for the modulation of the Na(+) K(+) pump as a component of therapy to alleviate weakness in HyperKPP.

Monochromatic Infrared Photo Energy Versus Low Level Laser Therapy in Chronic Low Back Pain.

INTRODUCTION: Low back pain (LBP) is the most common musculoskeletal disease. Monochromatic infrared photo energy (MIPE) and low level laser therapy (LLLT) are light modalities used to reduce pain and increase blood flow. The aim of this study was to compare the effects of the MIPE and LLLT in reducing functional disability and pain as well as improving lumbar range of motion (ROM) in patients with chronic LBP. METHODS: Seventy participants with LBP completed the program and were randomly assigned into 2 groups. Group 1 (n = 35) received MIPE and therapeutic exercises. Group 2 (n = 35) received LLLT and therapeutic exercises. Both groups received 2 visits per week for 6 weeks. Outcome measures were functional rating index (FRI), visual analogue scale (VAS) and modified-modified Schober test at baseline and after 6 weeks. RESULTS: There were statistically significant improvements in functional disability, pain and lumbar ROM (P < .05) in each group. However, no significant differences were recorded between the groups (P > .05). CONCLUSION: Therefore, MIPE and LLLT may play a role in treating chronic LBP and there are no differences between the two modalities in improving functional disability, pain and lumbar ROM in patients with chronic LBP.

Physiological basis for muscle stiffness and weakness in a knock-in M1592V mouse model of hyperkalemic periodic paralysis.

The mechanisms responsible for the onset and progressive worsening of episodic muscle stiffness and weakness in hyperkalemic periodic paralysis (HyperKPP) are not fully understood. Using a knock-in HyperKPP mouse model harboring the M1592V NaV1.4 channel mutant, we interrogated changes in physiological defects during the first year, including tetrodotoxin-sensitive Na(+) influx, hindlimb electromyographic (EMG) activity and immobility, muscle weakness induced by elevated [K(+)]e, myofiber-type composition, and myofiber damage. In situ EMG activity was greater in HyperKPP than wild-type gastrocnemius, whereas spontaneous muscle contractions were observed in vitro. We suggest that both the greater EMG activity and spontaneous contractions are related to periods of hyperexcitability during which fibers generate action potentials by themselves in the absence of any stimulation and that these periods are the cause of the muscle stiffness reported by patients. HyperKPP muscles had a greater sensitivity to the K(+)-induced force depression than wild-type muscles. So, an increased interstitial K(+) concentration locally near subsets of myofibers as a result of the hyperexcitability likely produced partial loss of force rather than complete paralysis. NaV1.4 channel protein content reached adult level by 3 weeks postnatal in both wild type and HyperKPP and apparent symptoms did not worsen after the first month of age suggesting (i) that the phenotypic behavior of M1592V HyperKPP muscles results from defective function of mutant NaV1.4 channels rather than other changes in protein expression after the first month and (ii) that the lag in onset during the first decade and the progression of human HyperKPP symptoms during adolescence are a function of NaV1.4 channel content.

Effects of aerobic exercise on blood pressure and lipids in overweight hypertensive postmenopausal women.

Menopause may increase risk of hypertension and abnormal lipid profile. The aim of the study was to examine the effects of morning and afternoon aerobic exercises on hypertension and lipids in overweight hypertensive postmenopausal women. Forty five women aged from 49 to 60 years were randomly assigned into three groups. Group (A) 15 patients received medicine, (B) 15 patients performed morning aerobic exercises and received medicine, and group (C) 15 patients performed afternoon aerobic exercises and received medicine. Blood pressure measurement and lipid profile tests were performed before and after the study. The results showed that there was a statistical significant difference among all groups in systolic and diastolic blood pressure, favoring group C. Also there was a statistical significant difference among all groups in lipid levels, favoring group C. Therefore, it can be concluded that morning aerobic exercises were more effective in reducing the blood pressure and lipids than afternoon exercises in overweight hypertensive postmenopausal women.

Contractile abnormalities of mouse muscles expressing hyperkalemic periodic paralysis mutant NaV1.4 channels do not correlate with Na+ influx or channel content.

Hyperkalemic periodic paralysis (HyperKPP) is characterized by myotonic discharges that occur between episodic attacks of paralysis. Individuals with HyperKPP rarely suffer respiratory distress even though diaphragm muscle expresses the same defective Na(+) channel isoform (NaV1.4) that causes symptoms in limb muscles. We tested the hypothesis that the extent of the HyperKPP phenotype (low force generation and shift toward oxidative type I and IIA fibers) in muscle is a function of 1) the NaV1.4 channel content and 2) the Na(+) influx through the defective channels [i.e., the tetrodotoxin (TTX)-sensitive Na(+) influx]. We measured NaV1.4 channel protein content, TTX-sensitive Na(+) influx, force generation, and myosin isoform expression in four muscles from knock-in mice expressing a NaV1.4 isoform corresponding to the human M1592V mutant. The HyperKPP flexor digitorum brevis muscle showed no contractile abnormalities, which correlated well with its low NaV1.4 protein content and by far the lowest TTX-sensitive Na(+) influx. In contrast, diaphragm muscle expressing the HyperKPP mutant contained high levels of NaV1.4 protein and exhibited a TTX-sensitive Na(+) influx that was 22% higher compared with affected extensor digitorum longus (EDL) and soleus muscles. Surprisingly, despite this high burden of Na(+) influx, the contractility phenotype was very mild in mutant diaphragm compared with the robust abnormalities observed in EDL and soleus. This study provides evidence that HyperKPP phenotype does not depend solely on the NaV1.4 content or Na(+) influx and that the diaphragm does not depend solely on Na(+)-K(+) pumps to ameliorate the phenotype.

Monochromatic Infrared Photo Energy versus Low Level Laser Therapy in Patients with Knee Osteoarthritis.

INTRODUCTION: Knee osteoarthritis (KO) is the most common joint disease for which there is no optimal treatment. Monochromatic infrared photo energy (MIPE) is a relatively new light modality used to reduce pain and increase circulation. Low Level Laser Therapy (LLLT) is another light modality used to reduce pain in KO. METHODS: The aim of this study was to compare the effects of the MIPE and LLLT in improving pain and function in KO. Sixty participants with KO completed the program and were randomly assigned into two groups. Group 1 (experimental, n=30) received MIPE and exercises. Group 2 (control, n=30) received LLLT and exercises. Both groups received two visits per week for six weeks. Outcome included pain intensity measured on a visual analogue scale and physical function measured with the lower extremity functional scale, before and after the 12 therapy sessions (6 weeks after the start of the intervention). RESULTS: There were statistically significant improvements in pain intensity and lower extremity functional scale scores (p<0.05) in each group. However, no significant differences were recorded between the groups (p>0.05). CONCLUSION: Therefore, MIPE and LLLT reduce pain and improve function in KO; however, there are no differences between the two modalities in reducing pain and increasing physical function in KO.

Use of a pancreatic duct stent or guidewire facilitates bile duct access with low rates of precut sphincterotomy: a randomized clinical trial.

BACKGROUND AND STUDY AIMS: Among cases of difficult biliary cannulation, alternatives include use of a pancreatic duct stent (PDS) or guidewire (PDW) to facilitate access. We compared the effectiveness of a PDS versus a PDW to facilitate common bile duct (CBD) cannulation. PATIENTS AND METHODS: We conducted a randomized, crossover trial at two endoscopy referral centers, limited to patients undergoing ERCP without a history of biliary sphincterotomy. After meeting predefined criteria for difficult cannulation, patients were randomized to using a PDS or PDW to facilitate CBD cannulation. Outcomes included cannulation rate within 6 min, overall cannulation rate, frequency of precut, and complication rates. RESULTS: Among 442 eligible patients, 87 (19.7 %) met criteria for difficult cannulation. Forty two were randomized to PDW, 54 to PDS (including 9 PDW patients crossed over to PDS). The rate of CBD cannulation within 6 min was similar in the PDW (38.1 %) and PDS (51.9 %) groups (p = 0.18). In a secondary analysis limited to patients who successfully underwent PDW or PDS deployment, the rate was also comparable (PDW 59.3 %, PDS 65.1 %; p = 0.62). The overall frequency of CBD cannulation was 66.7 % in PDW and 90.7 % in PDS patients. Precut was required in 9.5 % of PDW and 25.9 % of PDS patients. Complication rates were similar, with 4 (4.6 %) patients having post-ERCP pancreatitis and 1 (1.1 %) having post-ERCP pain without confirmation of pancreatitis. CONCLUSIONS: Use of a PDS or PDW facilitates CBD cannulation while maintaining a low complication rate and reducing the need for precut sphincterotomy in the majority of cases.

Training in EUS-Guided Fine Needle Aspiration: Safety and Diagnostic Yield of Attending Supervised, Trainee-Directed FNA from the Onset of Training.

Background. The optimal time to initiate hands-on training in endoscopic ultrasound fine needle aspiration (EUS-FNA) is unclear. We studied the feasibility of initiating EUS-FNA training concurrent with EUS training. Methods. Three supervised trainees were instructed on EUS-FNA technique and allowed hands-on exposure from the onset of training. The trainee and attending each performed passes in no particular order. During trainee FNA, the attending provided verbal instruction as needed but no hands-on assistance. A blinded cytopathologist assessed the adequacy (cellularity) and diagnostic yield of individual passes. Primary outcomes compared cellularity and diagnostic yield of attending versus fellow FNA passes. Results. We analyzed 305 FNA sites, including pancreas (51.2%), mediastinal/upper abdominal lymph node (LN) (28.5%) and others (20.3%). The average proportion of fellow passes with AC was similar to attending FNA-pancreas: 70.3 versus 68.8%; LN: 79.0 versus 81.7%; others 65.5 versus 68.7%; P > 0.05); these did not change significantly during the training period. Among cases with confirmed malignancy (n = 179), the sensitivity of EUS-FNA was 78.8% (68.4% fellow-only versus 69.6% attending only). There were no EUS-FNA complications. Conclusions. When initiated at the onset of EUS training, attending-supervised, trainee-directed FNA is safe and has comparable performance characteristics to attending FNA.

Physician-controlled wire-guided cannulation of the minor papilla.

Background. Minor papilla (MiP) cannulation is frequently performed using specialized small-caliber accessories. Outcomes data for MiP cannulation with standard-sized accessories are lacking. Methods. This is a case series describing MiP cannulation outcomes in consecutive patients treated by two endoscopists between July 2005 and November 2008 at two tertiary referral centers. MiP cannulation was attempted using a 4.4 Fr tip sphincterotome loaded with a 0.035(″), 260 cm hydrophilic-tip guidewire, using a wire-guided technique under physician control. Results. 25 patients were identified (14 women, mean age 45). Procedure indications included recurrent acute pancreatitis in 16 patients (64%) and chronic pancreatitis in 2 (8%), among other indications. MiP cannulation was successful in 24 patients (96%). Sphincterotomy followed by pancreatic stent placement was performed in 21 patients (84%). Mild post-ERCP pancreatitis occurred in 3 patients (12%). Conclusion. Physician-controlled wire-guided MiP cannulation using a 4.4 Fr sphincterotome and 0.035(″) guidewire is an effective and safe technique.

Fiducial placement for stereotactic radiation by using EUS: feasibility when using a marker compatible with a standard 22-gauge needle.

BACKGROUND: Stereotactic radiation by using fiducial markers permits higher doses of radiation while reducing the exposure of uninvolved, adjacent structures. EUS has been used to deploy fiducials, although a 19-gauge needle has traditionally been required. OBJECTIVE: To report a new technique and the feasibility of deploying a fiducial compatible with a 22-gauge needle under EUS guidance. DESIGN: Single-center, case series. SETTING: Tertiary care referral center. PATIENTS: Thirteen patients with primary or metastatic cancer referred for stereotactic radiation. INTERVENTIONS: EUS-guided placement of a single fiducial marker that is compatible with a 22-gauge EUS-FNA needle. MAIN OUTCOME MEASUREMENTS: Technical success and complications. RESULTS: Thirteen patients referred for EUS-guided placement of a fiducial marker were identified in the endoscopic database. Targeted lesions measured 27 +/- 13 mm (range 8-50) x 21 +/- 10 mm (range 6-42). All fiducials were successfully deployed, 9 using a transgastric and 4 using a transduodenal approach. There were no EUS-associated complications. Two patients did not proceed to radiation therapy as a result of interval peritoneal metastasis. However, all fiducials were visible on the roentogram. Eleven of 13 patients (85%) required placement of 1 fiducial, whereas 2 patients (15%) required 2 fiducials. LIMITATIONS: Uncontrolled feasibility study with limited sample size and follow-up. CONCLUSION: EUS-guided placement of a fiducial using a 22-gauge needle is technically feasible and may permit greater access compared with the 19-gauge needle technique.

Stenting for malignant colonic obstruction: a comparison of efficacy and complications in colonic versus extracolonic malignancy.

BACKGROUND: Self-expandable metal stent placement for palliation of malignant colonic obstruction for colorectal cancer (CRC) is safe and efficacious. In contrast, outcomes of stent placement for extracolonic malignancy (ECM) are unclear. OBJECTIVE: To compare the success and complication rates of colorectal stenting in patients with CRC versus those with ECM. DESIGN: Retrospective chart review. SETTING: Tertiary-care academic medical center. PATIENTS AND INTERVENTIONS: Between September 2000 and December 2007, all patients with malignant colon obstruction in whom endoscopy was performed with the intention of placing a colonic metal stent. MAIN OUTCOME MEASUREMENTS: Technical and clinical success rates, surgical interventions, and procedure-related complications. RESULTS: Colonic stenting was performed for CRC in 34 patients and for ECM in 15 patients. Patients with CRC were more likely to have clinical success after all endoscopic therapy (94.1%) than those with ECM (20.0%) (P < .0001). Surgical diversion to relieve persistent obstructive symptoms was required in significantly more patients with ECM. Five patients with ECM (33.3%) had at least one complication, including 2 deaths, compared with 3 patients with CRC (8.8%) (P = .046). Only underlying ECM was predictive of failed colon stent placement by multivariate analysis (hazard ratio 21.0, P = .0013). A history of radiation therapy was the sole predictor of complications (hazard ratio 7.8, P = .048). LIMITATIONS: Single institution, retrospective analysis, relatively small sample size. CONCLUSIONS: Colon stenting for large-bowel obstruction from ECM is infrequently successful and is associated with a significantly higher risk of complications in comparison with patients with CRC.