The management of the hospitalized ulcerative colitis patient: the medical-surgical conundrum.

PURPOSE OF REVIEW: In this review article, we address emerging evidence for the medical and surgical treatment of the hospitalized patient with ulcerative colitis. RECENT FINDINGS: Ulcerative colitis is a chronic inflammatory disease involving the colon and rectum. About one-fifth of patients will be hospitalized from ulcerative colitis, and about 20-30%, experiencing an acute flare will undergo colectomy. Because of the significant clinical consequences, patients hospitalized need prompt evaluation for potential complications, stratification of disease severity, and a multidisciplinary team approach to therapy, which involves both the gastroenterologist and surgeon. Although corticosteroids remain first-line therapy, second-line medical rescue options, primarily infliximab or cyclosporine, are considered within 3-5 days of presentation. In conjunction, an early surgical consultation to present the possibility of a staged proctocolectomy as one of the therapeutic options is equally important. SUMMARY: A coordinated multidisciplinary, individualized approach to treatment, involving the patient preferences throughout the process, is optimal in providing patient-centered effective care.

Phosphaaluminirenes: Synthons for Main Group Heterocycles.

The phosphaaluminirenes HC[(CMe)(NDipp)]2Al[C(R)═P] (Dipp = 2,6-i-Pr2C6H3, R = tBu or adamantyl) 2 and 3, featuring an unsaturated three-membered AlCP ring, have been synthesized as crystalline solids via a [1 + 2] cycloaddition reaction of the aluminum(I) complex HC[(CMe)(NDipp)]2Al (1) with phosphaalkynes. Computational investigations infer three-centered 2π-electron aromaticity of the AlCP rings. Compound 3 is readily protonated by tBuOH to induce a ring-opening σ-bond metathesis, giving an alumina-substituted P-hydrogeno phosphaalkene 4. Remarkably, the high strain of the AlCP ring of 3 allows for facile ring enlargement in reactions with CyNC, bis(diisopropylamino) cyclopropenylidene (BAC), elemental Se, Ph2CO, PhCH═CHCOPh, and PhCN at room temperature. These furnish a series of unprecedented main group heterocycles 5-10 with the C═P unsaturated bonds remaining intact. The mechanisms are considered in light of thorough density functional theory (DFT) calculations.

Reversible Intramolecular Cycloaddition of Phosphaalkene to an Arene Ring.

The phosphepinium cation 1 is deprotonated by base generating a phosphaalkene that undergoes cycloaddition to the N-bound aromatic ring affording the 2-phosphabicyclo[2.2.2]octa-5,7-diene 2. The analogous deprotonation reaction of the less bulky phosphepinium cation 3 affords a reversible equilibrium between the phosphaalkene 4 and the corresponding cycloaddition product 5. This latter observation represents the first reversible cycloaddition of a main group multiply bonded species with an arene ring. The bicyclic species 2 was also shown to be oxidized or alkylated in reactions with S8 and MeOTf, affording 6 and 7, respectively. This finding and its implications for related cycloadditions of other main group multiply bonded species are considered computationally.

Base-Stabilized [PO]+ /[PO2 ]+ Cations.

The salts [(BAC)2 PO][BF4 ] (5) and [(BAC)2 PO2 ][BF4 ] (4) (BAC=bis(diisopropylamino) cyclopropenylidene), consisting of the PO+ and PO2 + cations, respectively, coordinated to the singlet carbenes, have been prepared. Computational investigations reveal that the electronic structure of the PO+ cation is a hybrid between the charge-localized and charge-delocalized resonance forms, resulting in ambiphilic reactivity. Compound 5 reacts as a donor with the transition-metal complex K2 PtCl4 to furnish [[(BAC)2 PO]2 PtCl2 ][BF4 ]2 (6) and KCl. Remarkably, both 5 and 4 have shown to act as electrophiles undergoing reactions with fluoride anion, leading to [OPF2 ]- and (BAC)PO2 F, respectively.

Single Electron Transfer to Diazomethane-Borane Adducts Prompts C-H Bond Activations.

While (Ph2 CN2 )B(C6 F5 )3 is unstable, single electron transfer from Cp*2 Co affords the isolation of stable products [Cp*2 Co][Ph2 CNNHB(C6 F5 )3 ] 1 and [Cp*Co(C5 Me4 CH2 B(C6 F5 )3 )] 2. The analogous combination of Ph2 CN2 and BPh3 showed no evidence of adduct formation and yet single electron transfer from Cp*2 Cr affords the species [Cp*2 Cr][PhC(C6 H4 )NNBPh3 ] 3 and [Cp*2 Cr][Ph2 CNNHBPh3 ] 4. Computations showed both reactions proceed via transient radical anions of the diphenyldiazomethane-borane adducts to effect C-H bond activations.

Facile Cleavage of the P=P Double Bond in Vinyl-Substituted Diphosphenes.

The reactions of the cyclic alkyl amino carbene (CAAC) 1 with phosphaalkynes generate the kinetically unstable CAAC-derived phosphirenes 4 and 5, which undergo rearrangement/dimerization reactions to give the vinyl-substituted diphosphenes 2, 3, and 6. The P=P double bond scission of 2 or 3 is unprecedentedly effected by S8 , [AuCl(tht)], or MeOTf at room temperature, which affords a dithiophosphorane 7, a phosphepine Au complex 8, or phosphepinium cations 9 and 10, respectively. The cationic species feature little homoaromaticity while representing the first examples of the phosphorus-containing analogue of the tropylium ion.

The Arene-Stabilized η5 -Pentamethylcyclopentadienyl Arsenic Dication [(η5 -Cp*)As(toluene)]2.

Double chloride abstraction of Cp*AsCl2 gives the dicationic arsenic species [(η5 -Cp*)As(tol)][B(C6 F5 )4 ]2 (2) (tol=toluene). This species is shown to exhibit Lewis super acidity by the Gutmann-Beckett test and by fluoride abstraction from [NBu4 ][SbF6 ]. Species 2 participates in the FLP activation of THF affording [(η2 -Cp*)AsO(CH2 )4 (THF)][B(C6 F5 )4 ]2 (5). The reaction of 2 with PMe3 or dppe generates [(Me3 P)2 As][B(C6 F5 )4 ] (6) and [(σ-Cp*)PMe3 ][B(C6 F5 )4 ] (7), or [(dppe)As][B(C6 F5 )4 ] (8) and [(dppe)(σ-Cp*)2 ][B(C6 F5 )4 ]2 (9), respectively, through a facile cleavage of C-As bonds, thus showcasing unusual reactivity of this unique As-containing compound.

A Transient Vinylphosphinidene via a Phosphirene-Phosphinidene Rearrangement.

A room-temperature-stable crystalline 2H-phosphirene (1) was prepared by treatment of an electrophilic diamidocarbene with tert-butylphosphaalkyne. Compound 1 is shown to react as a vinylphosphinidene generated via phosphirene-phosphinidene rearrangement. Thermolysis is shown to affect C-N bond scission while reactions with C6Cl4O2 or (tht)AuCl afford formal oxidation of the phosphindene center and the phosphinidene-insertion into an aromatic C-C bond of a mesityl group, respectively. The latter reaction is the first example of a phosphorus analog of the Büchner ring expansion reaction.

Reductive Coupling and Loss of N2 from Magnesium Diazomethane Derivatives.

The reductive coupling of two diazomethanes is affected by reaction with [(NacNacMes )Mg]2 affording the species [(NacNacMes )Mg(N2 CPh2 )]2 2 and [(NacNacMes )Mg(N2 C(C6 H4 )2 )]2 3. These species containing N4 linkages readily evolve the central N2 at 50 and 75 °C to give the Mg-imide products [(NacNacMes )Mg(NCPh2 )]2 (4) and [(NacNacMes )Mg(NC(C6 H4 )2 )]2 (5), respectively. The mechanism for the loss of N2 was considered computationally. Compounds 2 and 3 reacted with O2 to liberate the tetrazene (Ph2 N2 )2 6 and the hydrazine ((C6 H4 )2 CN)2 7, whereas reactions with Me3 SiOSO2 CF3 or Me3 SiCl with 2 and 3 provide the related silyl imines 8 and 9, respectively.

Zinc-Containing Radical Anions via Single Electron Transfer to Donor-Acceptor Adducts.

Reactions of [Cp*2 Fe] with the Lewis acid [Zn(C6 F5 )2 ] in the presence of [(PhC(S)S)2 ], 9,10-phenanthrenedione or 4,5-pyrenedione yield the salt [Cp*2 Fe][(PhC(S)S)Zn(C6 F5 )2 ] 1, [Cp*2 Fe][((C14 H8 O2 )Zn(C6 F5 )2 )⋅] 4, and [Cp*2 Fe][((C16 H8 O2 )Zn(C6 F5 )2 )⋅] 5, respectively. The latter two species represent the first examples of isolable zinc-containing radical anions. While [(PhC(S)S)2 ] binds weakly to [Zn(C6 F5 )2 ], the diones afford the isolable adducts [(C14 H8 O2 )Zn(C6 F5 )2 ] 2 and [(C16 H8 O2 )Zn(C6 F5 )2 ] 3. Cyclic voltammetry and computational studies support the view that 4 and 5 are formed via single electron transfer (SET) to the donor-acceptor adducts, 2 and 3, respectively. Subsequent treatment of 4 and 5 with [NC5 H4 NMe2 ] affords [Zn(C6 F5 )2 (NC5 H4 NMe2 )2 ] with liberation of the dione, and regeneration of [Cp*2 Fe].

Nitrogen-Based Lewis Acids: Synthesis and Reactivity of a Cyclic (Alkyl)(Amino)Nitrenium Cation.

A room-temperature-stable crystalline cyclic (alkyl)(amino)nitrenium cation 2 features cationic nitrogen atom with a smaller HOMO-LUMO gap compared to that of a 1,2,3-triazolium 5 (an N-heterocyclic nitrenium cation). The low-lying LUMO of 2 results in an enhanced electrophilicity, which allowed for the formation of Lewis adducts with neutral Lewis bases, such as Me3 P, nBu3 P, and IiPr. The N-based Lewis acid 2 also forms an FLP with tBu3 P but subsequently reacts with (PrS)2 to cleave the S-S bond. Both experimental and theoretical results suggest that the Lewis acidity of 2 is stronger than its N3 analogues.

Single Electron Delivery to Lewis Pairs: An Avenue to Anions by Small Molecule Activation.

Single electron transfer (SET) reactions are effected by the combination of a Lewis acid (e.g., E(C6F5)3 E = B or Al) with a small molecule substrate and decamethylferrocene (Cp*2Fe). Initially, the corresponding reactions of (PhS)2 and (PhTe)2 were shown to give the species [Cp*2Fe][PhSB(C6F5)3] 1 and [Cp*2Fe][(µ-PhS)(Al(C6F5)3)2] 2 and [Cp*2Fe][(µ-PhTe)(Al(C6F5)3)2] 3, respectively. Analogous reactions with di-tert-butyl peroxide yielded [Cp*2Fe][(µ-HO)(B(C6F5)3)2] 4 with isobutene while with benzoyl peroxide afforded [Cp*2Fe][PhC(O)OE(C6F5)3] (E = B 5, Al 6). Evidence for a radical pathway was provided by the reaction of Ph3SnH and p-quinone afforded [Cp*2Fe][HB(C6F5)3] 7 and [Cp*2Fe]2[(µ-O2C6H4)(E(C6F5)3)2] (E = B 8, Al 9). In addition, the reaction of TEMPO with Lewis acid and Cp*2Fe afforded [Cp*2Fe][(C5H6Me4NOE(C6F5)3] (E = B 10, Al 11). Finally, reactions with O2, Se, Te and S8 gave [Cp*2Fe]2[((C6F5)2Al(µ-O)Al(C6F5)3)2]2 12, [Cp*2Fe]2[((C6F5)2Al(µ-Se)Al(C6F5)3)2]2 13, [Cp*2Fe][(µ-Te)2(Al(C6F5)2)3] 14 and [Cp*2Fe]2[(µ-S7)B(C6F5)3)2] 15, respectively. The mechanisms of these SET reactions are discussed, and the ramifications are considered.

Rectal Indomethacin Does Not Prevent Post-ERCP Pancreatitis in Consecutive Patients.

BACKGROUND & AIMS: Rectal indomethacin, a nonsteroidal anti-inflammatory drug, is given to prevent pancreatitis in high-risk patients undergoing endoscopic retrograde cholangiopancreatography (ERCP), based on findings from clinical trials. The European Society for Gastrointestinal Endoscopy guidelines recently recommended prophylactic rectal indomethacin for all patients undergoing ERCP, including those at average risk for pancreatitis. We performed a randomized controlled trail to investigate the efficacy of this approach. METHODS: We performed a prospective, double-blind, placebo-controlled trial of 449 consecutive patients undergoing ERCP at Dartmouth Hitchcock Medical Center, from March 2013 through December 2014. Approximately 70% of the cohort were at average risk for PEP. Subjects were assigned randomly to groups given either a single 100-mg dose of rectal indomethacin (n = 223) or a placebo suppository (n = 226) during the procedure. The primary outcome was the development of post-ERCP pancreatitis (PEP), defined by new upper-abdominal pain, a lipase level more than 3-fold the upper limit of normal, and hospitalization after ERCP for 2 consecutive nights. RESULTS: There were no differences between the groups in baseline clinical or procedural characteristics. Sixteen patients in the indomethacin group (7.2%) and 11 in the placebo group (4.9%) developed PEP (P = .33). Complications and the severity of PEP were similar between groups. Per a priori protocol guidelines, the study was stopped owing to futility. CONCLUSIONS: In a randomized controlled study of consecutive patients undergoing ERCP, rectal indomethacin did not prevent post-ERCP pancreatitis. ClincialTrials.gov no: NCT01774604.

Quality of optical diagnosis of diminutive polyps and associated factors.

BACKGROUND AND AIMS: The aim of the study was to identify endoscopist-related and procedural factors that may be associated with the quality of optical diagnosis of diminutive polyps using narrow-band imaging (NBI). METHODS: All subjects who participated in a randomized trial on cap-assisted colonoscopy were eligible for the current study. Optical polyp diagnosis was an a priori outcome of the initial trial. Ten participating endoscopists used NBI to assess all of the diagnosed polyps as adenomatous or non-adenomatous in real-time and provided a degree of diagnostic certainty. The main outcome measures were quality benchmarks of optical diagnosis (negative predictive value [NPV] for diminutive rectosigmoid adenomas, agreement with pathology-based surveillance interval) and assessment of endoscopist-related and procedural factors potentially associated with the quality of optical diagnosis. RESULTS: A total of 1650 polyps were found in 607 patients, with 1311 polyps (79 %) being diminutive, of which 672 (53 %) were adenomatous. The NPV of optical diagnosis for rectosigmoid adenomas was 95 %. The optical diagnosis-based surveillance interval agreed with the pathology-based recommendation in 93 % of patients. Prior experience with image-enhanced endoscopy had no effect on optical diagnosis. Low and high adenoma detectors were not different in achieving the quality benchmarks. Cap-assisted colonoscopy was not associated with quality of optical diagnosis. Quality metrics of optical diagnosis remained similar during the first and second half of the study period. CONCLUSION: High quality optical diagnosis of diminutive polyps can be achieved and sustained by endoscopists previously inexperienced in this practice with minimal training. None of the examined factors appear to affect the quality of optical diagnosis; particularly, endoscopists' adenoma detection was not associated with optical diagnosis.

Cap-assisted colonoscopy and detection of Adenomatous Polyps (CAP) study: a randomized trial.

BACKGROUND AND STUDY AIM: Cap-assisted colonoscopy has improved adenoma detection in some but not other studies. Most previous studies have been limited by small sample sizes and few participating endoscopists. The aim of the current study was to evaluate whether cap-assisted colonoscopy improves adenoma detection in a two-center, multi-endoscopist, randomized trial. PATIENTS AND METHODS: Consecutive patients who presented for an elective colonoscopy were randomized to cap-assisted colonoscopy (4-mm cap) or standard colonoscopy performed by one of 10 experienced endoscopists. Primary outcome measures were mean number of adenomas per patient and adenoma detection rate (ADR). Secondary outcomes included procedural measures and endoscopist variation; a logistic regression model was employed to examine predictors of increased detection with cap use. RESULTS: A total of 1113 patients (64 % male, mean age 62 years) were randomized to cap-assisted (n = 561) or standard (n = 552) colonoscopy. The mean number of adenomas detected per patient in the cap-assisted and standard groups was similar (0.89 vs. 0.82; P = 0.432), as was the ADR (42 % vs. 40 %; P = 0.452). Cap-assisted colonoscopy achieved a faster cecal intubation time (4.9 vs. 5.8 minutes; P < 0.001), a similar cecal intubation rate (99 % vs. 98 %; P = 0.326), and a higher terminal ileum intubation rate (93 % vs. 89 %; P < 0.028). Cap-assisted colonoscopy resulted in a 20 % increase in ADR for some endoscopists and in a 15 % decrease for others. Individual preference for the cap was an independent predictor of increased adenoma detection in adjusted analysis (P < 0.001), whereas baseline low adenoma detection was not. CONCLUSION: Although the efficiency of cecal and terminal ileum intubation was slightly improved by cap-assisted colonoscopy, adenoma detection was not. Cap-assisted colonoscopy may be beneficial for selected endoscopists. TRIAL REGISTRATION: clinicalTrials.gov (NCT01935180).

The Scientific Basis of Uncertainty Factors Used in Setting Occupational Exposure Limits.

The uncertainty factor concept is integrated into health risk assessments for all aspects of public health practice, including by most organizations that derive occupational exposure limits. The use of uncertainty factors is predicated on the assumption that a sufficient reduction in exposure from those at the boundary for the onset of adverse effects will yield a safe exposure level for at least the great majority of the exposed population, including vulnerable subgroups. There are differences in the application of the uncertainty factor approach among groups that conduct occupational assessments; however, there are common areas of uncertainty which are considered by all or nearly all occupational exposure limit-setting organizations. Five key uncertainties that are often examined include interspecies variability in response when extrapolating from animal studies to humans, response variability in humans, uncertainty in estimating a no-effect level from a dose where effects were observed, extrapolation from shorter duration studies to a full life-time exposure, and other insufficiencies in the overall health effects database indicating that the most sensitive adverse effect may not have been evaluated. In addition, a modifying factor is used by some organizations to account for other remaining uncertainties-typically related to exposure scenarios or accounting for the interplay among the five areas noted above. Consideration of uncertainties in occupational exposure limit derivation is a systematic process whereby the factors applied are not arbitrary, although they are mathematically imprecise. As the scientific basis for uncertainty factor application has improved, default uncertainty factors are now used only in the absence of chemical-specific data, and the trend is to replace them with chemical-specific adjustment factors whenever possible. The increased application of scientific data in the development of uncertainty factors for individual chemicals also has the benefit of increasing the transparency of occupational exposure limit derivation. Improved characterization of the scientific basis for uncertainty factors has led to increasing rigor and transparency in their application as part of the overall occupational exposure limit derivation process.

Incomplete polyp resection during colonoscopy-results of the complete adenoma resection (CARE) study.

BACKGROUND & AIMS: Although the adenoma detection rate is used as a measure of colonoscopy quality, there are limited data on the quality of endoscopic resection of detected adenomas. We determined the rate of incompletely resected neoplastic polyps in clinical practice. METHODS: We performed a prospective study on 1427 patients who underwent colonoscopy at 2 medical centers and had at least 1 nonpedunculated polyp (5-20 mm). After polyp removal was considered complete macroscopically, biopsies were obtained from the resection margin. The main outcome was the percentage of incompletely resected neoplastic polyps (incomplete resection rate [IRR]) determined by the presence of neoplastic tissue in post-polypectomy biopsies. Associations between IRR and polyp size, morphology, histology, and endoscopist were assessed by regression analysis. RESULTS: Of 346 neoplastic polyps (269 patients; 84.0% men; mean age, 63.4 years) removed by 11 gastroenterologists, 10.1% were incompletely resected. IRR increased with polyp size and was significantly higher for large (10-20 mm) than small (5-9 mm) neoplastic polyps (17.3% vs 6.8%; relative risk = 2.1), and for sessile serrated adenomas/polyps than for conventional adenomas (31.0% vs 7.2%; relative risk = 3.7). The IRR for endoscopists with at least 20 polypectomies ranged from 6.5% to 22.7%; there was a 3.4-fold difference between the highest and lowest IRR after adjusting for size and sessile serrated histology. CONCLUSIONS: Neoplastic polyps are often incompletely resected, and the rate of incomplete resection varies broadly among endoscopists. Incomplete resection might contribute to the development of colon cancers after colonoscopy (interval cancers). Efforts are needed to ensure complete resection, especially of larger lesions. ClinicalTrials.gov Number: NCT01224444.

Clinical Decision Making in Inflammatory Bowel Disease Mimics: Practice Management from Inflammatory Bowel Disease LIVE.

Background: Since 2009, inflammatory bowel disease (IBD) specialists have utilized "IBD LIVE," a weekly live video conference with a global audience, to discuss the multidisciplinary management of their most challenging cases. While most cases presented were confirmed IBD, a substantial number were diseases that mimic IBD. We have categorized all IBD LIVE cases and identified "IBD-mimics" with consequent clinical management implications. Methods: Cases have been recorded/archived since May 2018; we reviewed all 371 cases from May 2018-February 2023. IBD-mimics were analyzed/categorized according to their diagnostic and therapeutic workup. Results: Confirmed IBD cases made up 82.5% (306/371; 193 Crohn's disease, 107 ulcerative colitis, and 6 IBD-unclassified). Sixty-five (17.5%) cases were found to be mimics, most commonly medication-induced (n = 8) or vasculitis (n = 7). The evaluations that ultimately resulted in correct diagnosis included additional endoscopic biopsies (n = 13, 21%), surgical exploration/pathology (n = 10, 16.5%), biopsies from outside the GI tract (n = 10, 16.5%), genetic/laboratory testing (n = 8, 13%), extensive review of patient history (n = 8, 13%), imaging (n = 5, 8%), balloon enteroscopy (n = 5, 8%), and capsule endoscopy (n = 2, 3%). Twenty-five patients (25/65, 38%) were treated with biologics for presumed IBD, 5 of whom subsequently experienced adverse events requiring discontinuation of the biologic. Many patients were prescribed steroids, azathioprine, mercaptopurine, or methotrexate, and 3 were trialed on tofacitinib. Conclusions: The diverse presentation of IBD and IBD-mimics necessitates periodic consideration of the differential diagnosis, and reassessment of treatment in presumed IBD patients without appropriate clinical response. The substantial differences and often conflicting treatment approaches to IBD versus IBD-mimics directly impact the quality and cost of patient care.

Using macrophage activation to augment immunotherapy of established tumours.

BACKGROUND: Successful immunotherapy will require alteration of the tumour microenvironment and/or decreased immune suppression. Tumour-associated macrophages (TAMs) are one major factor affecting tumour microenvironment. We hypothesised that altering TAM phenotype would augment the efficacy of immunotherapy. METHODS: We and others have reported that 5,6-Dimethylxanthenone-4-acetic-acid (DMXAA, Vadimezan) has the ability to change TAM phenotypes, inducing a tumour microenvironment conducive to antitumour immune responses. We therefore combined DMXAA with active immunotherapies, and evaluated anti-tumour efficacy, immune cell phenotypes (flow cytometry), and tumour microenvironment (RT-PCR). RESULTS: In several different murine models of immunotherapy for lung cancer, DMXAA-induced macrophage activation significantly augmented the therapeutic effects of immunotherapy. By increasing influx of neutrophils and anti-tumour (M1) macrophages to the tumour, DMXAA altered myeloid cell phenotypes, thus changing the intratumoural M2/non-M2 TAM immunoinhibitory ratio. It also altered the tumour microenvironment to be more pro-inflammatory. Modulating macrophages during immunotherapy resulted in increased numbers, activity, and antigen-specificity of intratumoural CD8(+) T cells. Macrophage depletion reduced the effect of combining immunotherapy with macrophage activation, supporting the importance of TAMs in the combined effect. CONCLUSION: Modulating intratumoural macrophages dramatically augmented the effect of immunotherapy. Our observations suggest that addition of agents that activate TAMs to immunotherapy should be considered in future trials.

Risk factors for local and regional recurrence in patients with resected N0-N1 non-small-cell lung cancer, with implications for patient selection for adjuvant radiation therapy.

BACKGROUND: The purpose of this study was to evaluate the actuarial risk of local and regional failure in patients with completely resected non-small-cell lung cancer (NSCLC), and to assess surgical and pathological factors affecting this risk. PATIENTS AND METHODS: Between January 1998 and December 2009, 1402 consecutive stage I-III (N0-N1) NSCLC patients underwent complete resection without adjuvant radiation therapy. The median follow-up was 42 months. RESULTS: Local-regional recurrence was identified in 9% of patients, with local failure alone in 3% of patients, regional failure alone in 4% of patients, and both local and regional failure simultaneously in 2% of patients. Patients who had local failure were found to be at increased risk of mortality. By multivariate analyses, three variables were shown to be independently significant risk factors for local [surgical procedure (single/multiple wedges+segmentectomy versus lobectomy+bilobectomy+pneumonectomy), tumor size>2.7 cm, and visceral pleural invasion] and regional (pathologic N1 stage, visceral pleural invasion, and lymphovascular space invasion, LVI) recurrence, respectively. CONCLUSION: Patients with N0-N1 disease have low rates of locoregional recurrence after surgical resection. However, several prognostic factors can be identified that increase this risk and identify patients who may benefit from adjuvant treatment.