Tissue-targeted and localized AAV5-DCN and AAV5-PEDF combination gene therapy abrogates corneal fibrosis and concurrent neovascularization in rabbit eyes in vivo.

PURPOSE: Corneal fibrosis and neovascularization (CNV) after ocular trauma impairs vision. This study tested therapeutic potential of tissue-targeted adeno-associated virus5 (AAV5) mediated decorin (DCN) and pigment epithelium-derived factor (PEDF) combination genes in vivo. METHODS: Corneal fibrosis and CNV were induced in New Zealand White rabbits via chemical trauma. Gene therapy in stroma was delivered 30-min after chemical-trauma via topical AAV5-DCN and AAV5-PEDF application using a cloning cylinder. Clinical eye examinations and multimodal imaging in live rabbits were performed periodically and corneal tissues were collected 9-day and 15-day post euthanasia. Histological, cellular, and molecular and apoptosis assays were used for efficacy, tolerability, and mechanistic studies. RESULTS: The AAV5-DCN and AAV5-PEDF combination gene therapy significantly reduced corneal fibrosis (p < 0.01 or p < 0.001) and CNV (p < 0.001) in therapy-given (chemical-trauma and AAV5-DCN + AAV5-PEDF) rabbit eyes compared to the no-therapy given eyes (chemical-trauma and AAV5-naked vector). Histopathological analyses demonstrated significantly reduced fibrotic α-smooth muscle actin and endothelial lectin expression in therapy-given corneas compared to no-therapy corneas on day-9 (p < 0.001) and day-15 (p < 0.001). Further, therapy-given corneas showed significantly increased Fas-ligand mRNA levels (p < 0.001) and apoptotic cell death in neovessels (p < 0.001) compared to no-therapy corneas. AAV5 delivered 2.69 × 107 copies of DCN and 2.31 × 107 copies of PEDF genes per µg of DNA. AAV5 vector and delivered DCN and PEDF genes found tolerable to the rabbit eyes and caused no significant toxicity to the cornea. CONCLUSION: The combination AAV5-DCN and AAV5-PEDF topical gene therapy effectively reduces corneal fibrosis and CNV with high tolerability in vivo in rabbits. Additional studies are warranted.

Toxicological effects of ocular acrolein exposure to eyelids in rabbits in vivo.

Acrolein is a highly reactive volatile toxic chemical that injures the eyes and many organs. It has been used in wars and terrorism for wounding masses on multiple occasions and is readily accessible commercially. Our earlier studies revealed acrolein's toxicity to the cornea and witnessed damage to other ocular tissues. Eyelids play a vital role in keeping eyes mobile, moist, lubricated, and functional utilizing a range of diverse lipids produced by the Meibomian glands located in the upper and lower eyelids. This study sought to investigate acrolein's toxicity to eyelid tissues by studying the expression of inflammatory and lipid markers in rabbit eyes in vivo utilizing our reported vapor-cap model. The study was approved by the institutional animal care and use committees and followed ARVO guidelines. Twelve New Zealand White Rabbits were divided into 3 groups: Naïve (group 1), 1-min acrolein exposure (group 2), or 3-min acrolein exposure (group 3). The toxicological effects of acrolein on ocular health in live animals were monitored with regular clinical eye exams and intraocular pressure measurements and eyelid tissues post-euthanasia were subjected to H&E and Masson's trichrome histology and qRT-PCR analysis. Clinical eye examinations witnessed severely swollen eyelids, abnormal ocular discharge, chemosis, and elevated intraocular pressure (p < 0.001) in acrolein-exposed eyes. Histological studies supported clinical findings and exhibited noticeable changes in eyelid tissue morphology. Gene expression studies exhibited significantly increased expression of inflammatory and lipid mediators (LOX, PAF, Cox-2, and LTB4; p < 0.001) in acrolein-exposed eyelid tissues compared to naïve eyelid tissues. The results suggest that acrolein exposure to the eyes causes acute damage to eyelids by altering inflammatory and lipid mediators in vivo.

Risk Factors for Hyphema Following Kahook Dual Blade Goniotomy Combined With Phacoemulsification.

PRCIS: Hyphema development after Kahook Dual Blade (KDB) excisional goniotomy was significantly associated with postoperative day 1 intraocular pressure (IOP) ≤12 mm Hg, male sex, and narrow iridocorneal angles, but not with continuation of anticoagulation or antiplatelet therapy. PURPOSE: To identify risk factors of hyphema development after KDB goniotomy combined with phacoemulsification. METHODS: In all, 202 eyes in 145 patients who received a KDB goniotomy combined with phacoemulsification between February 21, 2017 and February 18, 2020 were evaluated for preoperative factors that were predictive of postoperative hyphema. Hyphema was defined as the development of ≥1 mm layered blood in the anterior chamber. The primary outcome was the association between various preoperative factors and the development of postoperative hyphema. Binomial logistic regression was used to analyze risk factors of hyphema development while controlling for other variables. RESULTS: Hyphema occurred in 8.4% (17/202) of patients on day 1 after KDB goniotomy combined with phacoemulsification. Male sex ( P =0.008), angle closure glaucoma ( P =0.036), and postoperative day 1 IOP ≤12 mm Hg ( P =0.049) were significantly correlated with hyphema development while controlling for other variables. Preoperative anticoagulation and antiplatelet therapy had no association with hyphema development ( P =0.538). CONCLUSIONS: Postoperative hyphema was associated with male sex, narrow iridocorneal angles, and a postoperative day 1 IOP lower than typical episcleral venous pressure when controlling for other variables. Preoperative anticoagulation or antiplatelet therapy was not associated with developing postoperative hyphema in this study; however, further investigation is needed before recommendations can be made.

MicroPulse Transscleral Laser Therapy Dosimetry Utilizing the Revised P3 Delivery Device: A Randomized Controlled Trial.

PURPOSE: To compare the long-term effectiveness and safety outcomes of 2 treatment dosages of the MicroPulse Transscleral Laser Therapy (MPTLT) procedure on intraocular pressure (IOP) control in patients with primary open-angle glaucoma. DESIGN: Single-blinded randomized controlled trial. SUBJECTS: A total of 19 patients with POAG without prior history of incisional glaucoma surgery. METHODS: Subjects randomized into 2 treatment groups, 100-second (total energy 78.25 joules [J], fluence 109.2 J/cm2) or 120-second (total energy 93.9 J, fluence 131.0 J/cm2) total treatment duration, underwent the MPTLT procedure with the revised P3 delivery probe delivering 2.5 W energy, 31.3% duty cycle, applied in 3 sweeps per hemisphere, avoiding 3 and 9 o'clock. All subjects were followed at 1, 3, 6, 9, and 12 months to compare reduction in IOP and medication. MAIN OUTCOME MEASURES: Absolute and percentage IOP reduction at 6 months. RESULTS: The treatment groups were similar in age, sex, and stage of glaucoma at baseline (all P > 0.05). The 120-second group had significantly better baseline best-corrected visual acuity (BCVA) and a higher percentage of patients with prior MPTLT therapy (ranging from 4-19 months before study). Significantly greater IOP reduction was noted in the 120-second group compared with the 100-second group at 3 months, with mean IOP reduction of 7.3 ± 4.2 mmHg (vs. 0.9 ± 2.5 mmHg, P = 0.006) and percentage IOP reduction of 32.2% ± 18.3% (vs. 4.1% ± 13.7%, P = 0.007). The 120-second group continued to outperform at 6-month follow-up: mean IOP reduction of 9.0 ± 4.8 mmHg (vs. 0.8 ± 2.5 mmHg, P = 0.016) and percentage IOP reduction of 37.8% ± 19.8% (vs. 3.6% ± 13.3%, P = 0.021). At 12 months, 37.5% and 18.2% of the 100- and 120-second groups, respectively, required an additional IOP-lowering procedure (P = 0.35); however, Kaplan-Meier analysis of time to intervention was not significantly different (P = 0.38). There were no vision-threatening complications or changes in BCVA during the study period. CONCLUSIONS: This study demonstrates a dose-response relationship with improved IOP control and excellent safety profile in patients treated with higher treatment total energy and fluence using the revised MPTLT probe. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.

Predictive Factors of Outcomes in Kahook Dual Blade Excisional Goniotomy Combined with Phacoemulsification.

Aim: To identify factors that were significant predictors of Kahook Dual Blade (KDB) excisional goniotomy outcomes. Materials and methods: One hundred and thirty-two eyes from 99 adult glaucoma patients who underwent combined KDB and phacoemulsification (KDB-phaco) with a minimum 6-month follow-up were assessed for baseline patient characteristics to determine correlation to the success of KDB-phaco at 6 and 12 months postoperatively. Success was defined as ≥20% intraocular pressure (IOP) reduction or ≥1 medication reduction as well as IOP ≤18 mm Hg without any additional IOP-lowering procedures after KDB-phaco. Results: 63.6% (84/132) and 46.1% (41/89) of cases were successful at the 6- and 12-month follow-ups, respectively. KDB-phaco reduced patient's preoperative IOP (in mm Hg) from 17.6 ± 4.6 to 14.9 ± 3.2 at 6 months (15.3%, p < 0.001) and 15.4 ± 4.7 at 12 months (12.5%, p = 0.001). KDB-phaco reduced patient's preoperative IOP-lowering medications from 2 ± 1.2 to 1.1 ± 1.2 at 6 months (45%, p < 0.001) and 1.32 ± 1.3 at 12 months (34%, p < 0.001). At 6 months, patients on >1 IOP lowering medication had a greater chance of meeting our success criteria (p = 0.037). Visually significant postoperative hyphema was not associated with the use of anticoagulation (p = 0.943) but was significantly associated with postoperative day 1 IOP ≤ 10 mm Hg (p = 0.011). Conclusion: Patients who underwent KDB-phaco significantly reduced their IOP and medication burden at both 6 and 12 months compared with their baseline preoperative values. KDB-phaco outcome was associated with higher baseline IOP-lowering medications and increased rate of hyphema was associated with lower postoperative day 1 IOP, regardless of anticoagulation status. Age, ethnicity, prior laser trabeculoplasty, type and severity of glaucoma, and baseline preoperative IOP were not associated with surgical success. Clinical significance: Patients with a higher number of baseline medications may experience a greater probability of success following KDB-phaco. How to cite this article: Pratte EL, Cho J, Landreneau JR, et al. Predictive Factors of Outcomes in Kahook Dual Blade Excisional Goniotomy Combined with Phacoemulsification. J Curr Glaucoma Pract 2022;16(1):47-52.

Anterior segment reconstruction due to cosmetic iris implants placed in the anterior chamber.

A 27-year-old woman had BrightOcular iris implants placed for cosmetic purposes that changed eye color from brown to blue bilaterally. Of note, BrightOcular implants are not approved by the U.S. Food and Drug Administration (FDA) for use in the United States and have been associated with severe ocular complications. In keeping with their design, they were placed in the anterior chamber (AC) in both eyes of this patient; surgery was performed outside the United States. As has been described previously and tragically in other cases, she developed chronic inflammation, intolerable glare, angle-closure glaucoma, corneal edema, and cataracts in both eyes. For medically unmanageable elevated intraocular pressure (IOP), she underwent diode laser cyclophotocoagulation (CPC) in both eyes, and eventually, an Ahmed tube shunt (New World Medical, Inc.) was placed in the right eye. Although she was advised and urged to have the iris implants removed, despite her ocular issues, she refused removal until intolerable glare and reduced vision ensued. Ultimately, both iris implants were extracted 5 years after implantation by a U.S. surgeon; the procedures resulted in corneal decompensation and progressive cataract development. Subsequent penetrating keratoplasty (PKP) was performed for the right eye, but it failed because of contact with the glaucoma tube shunt. She sought additional consultation and presented with the following findings: corrected distance visual acuity was 20/400 in the right eye and 20/40 in the left eye, IOP of 18 mm Hg in the right eye and 16 mm Hg in the left eye, pupils were nonreactive and fixed, and extraocular muscles and central visual field were normal. Pachymetry was 868 µm in the right eye and 653 µm in the left eye. Anterior segment examination in the right eye revealed a failed corneal graft with 3+ edema, peripheral anterior synechiae (PAS) for 360 degrees, shallow AC, Ahmed tube shunt at the 11 o'clock position and remnant iris adherent to the graft-host junction for 270 degrees, 3+ posterior subcapsular cataract, and 2+ cortical cataract (Figure 1JOURNAL/jcrs/04.03/02158034-202208000-00024/figure1/v/2022-08-01T210317Z/r/image-tiff). The sclera revealed multiple circular and circumferential atrophic blue spots consistent with high-energy transscleral CPC (Figure 2JOURNAL/jcrs/04.03/02158034-202208000-00024/figure2/v/2022-08-01T210317Z/r/image-tiff). In the left eye, she had remnant fixed dilated iris for 270 degrees, missing iris superiorly for 3 clock hours, an adequate AC, and 2+ cortical cataract (Figure 3JOURNAL/jcrs/04.03/02158034-202208000-00024/figure3/v/2022-08-01T210317Z/r/image-tiff). Posterior segment examination revealed a 0.5 cup-to-disc ratio in both eyes with normal vessels, macula, vitreous, and retinal periphery, bilaterally. Given this constellation of findings, how would you proceed?

Evaluation of CRISPR/Cas9 mediated TGIF gene editing to inhibit corneal fibrosis in vitro.

Corneal wound healing is influenced by many factors including transcriptional co-repressors and co-activators. Interactions of co-activators and co-repressors with Smads influence mechanistic loop facilitating transcription of alpha-smooth muscle actin (α-SMA), a key profibrotic gene, in corneal repair. The role of a transcriptional repressor, 5'TG3'-interacting factor (TGIF), in the regulation of α-SMA and myofibroblast formation in the cornea was shown previously by our group. This study tested a hypothesis if TGIF1 gene editing via CRISPR/Cas9 can ease myofibroblast formation in the cornea using an in vitro model. Primary human corneal stromal fibroblasts (hCSFs) generated from donor corneas received gene-editing plasmid facilitating loss (CRISPR/Cas9 knockout) or gain (CRISPR activation) of TGIF function by UltraCruz transfection reagent. Phase-contrast microscopy, immunoblotting, immunocytochemistry and quantitative polymerase chain reaction (qPCR) were used to measure levels of myofibroblast profibrotic genes (α-SMA, fibronectin, Collagen-I, and Collagen-IV) in hCSFs lacking or overexpressing TGIF1 after growing them in± transforming growth factor beta1 (TGF-ß1) under serum-free conditions. The CRISPR-assisted TGIF1 activation (gain of function) in hCSFs demonstrated significantly decreased myofibroblast formation and messenger ribonucleic acid (mRNA) and protein levels of profibrotic genes. Conversely, CRISPR/Cas9-assisted TGIF knockdown (loss of function) in hCSFs demonstrated no significant change in the levels of myofibroblast formation or profibrotic genes under similar conditions. These results suggest that TGIF gene-editing approach can be employed to modulate the transcriptional activity of α-SMA in controlling pathological and promoting physiological wound healing in an injured cornea.

Long-Term Safety and Tolerability of BMP7 and HGF Gene Overexpression in Rabbit Cornea.

Purpose: Tissue-targeted localized BMP7+HGF genes delivered into the stroma via nanoparticle effectively treats corneal fibrosis and rehabilitates transparency in vivo without acute toxicity. This study evaluated the long-term safety and tolerability of BMP7+HGF nanomedicine for the eye in vivo. Methods: One eye each of 36 rabbits received balanced salt solution (group 1, naïve; n = 12), naked vector with polyethylenimine-conjugated gold nanoparticles (PEI2-GNP; group 2, naked-vector; n = 12), or BMP7+HGF genes with PEI2-GNP (group 3, BMP7+HGF; n = 12) via a topical delivery technique. Safety and tolerability measurements were performed by clinical biomicroscopy in live rabbits at predetermined time intervals up to 7 months. Corneal tissues were collected at 2 months and 7 months after treatment and subjected to histology, immunofluorescence, and quantitative real-time PCR analyses. Results: Clinical ophthalmic examinations and modified MacDonald-Shadduck scores showed no significant changes in corneal thickness (P = 0.3389), tear flow (P = 0.2121), intraocular pressure (P = 0.9958), epithelial abrasion, or ocular abnormality. Slit-lamp, stereo, confocal, and specular biomicroscopy showed no signs of blepharospasm chemosis, erythema, epiphora, abnormal ocular discharge, or changes in epithelium, stroma, and endothelium after BMP7+HGF therapy for up to 7 months, as compared with control groups. Throughout the 7-month period, no significant changes were recorded in endothelial density (P = 0.9581). Histological and molecular data were well corroborated with the subjective clinical analyses and showed no differences in the naïve, naked-vector, and BMP7+HGF groups. Conclusions: Localized BMP7+HGF therapy is a safe, tolerable, and innovative modality for the treatment of corneal fibrosis. Translational Relevance: Nanoparticle-mediated BMP7+HGF combination gene therapy has the potential to treat corneal fibrosis in vivo without short- or long-term toxicity.

Review on the Myopia Pandemic: Epidemiology, Risk Factors, and Prevention.

Nearsightedness, or myopia, is becoming more prevalent worldwide. The eye experiences dynamic growth throughout adolescence, but the etiopathogenesis of myopia progression is not fully understood. Myopia is associated with several pathologic eye conditions, leading to irreversible vision loss. Treatment for preventing myopia progression is reliant on effective screening and initiating treatment early in life. This article will review risk factors for myopia progression and discuss treatment strategies that are most effective in halting its spread.

A Novel Topical Ophthalmic Formulation to Mitigate Acute Mustard Gas Keratopathy In Vivo: A Pilot Study.

Purpose: This pilot study investigated the in vivo therapeutic potential and tolerability of a multimodal ophthalmic formulation, topical eye drops (TED), for acute mustard gas keratopathy (MGK) using a rabbit model. Methods: Twenty New Zealand White rabbits were used. Only right eyes of 18 rabbits (oculus dexter [OD]) received single sulfur mustard gas (SM) vapor injury, whereas contralateral eyes were left untreated or received TED for tolerabilty evaluation. Two rabbit eyes received no treatment and served as age-matched naive control. The four groups were: Naive (oculus sinister [OS] untreated eyes; n = 9); TED (OS treated only with TED BID for 3 days; n = 9); SM (OD exposed to SM vapor; n = 9); and SM+TED (OD exposed to SM+TED BID for 3 days; n = 9). Ocular examination in live rabbits were performed utilizing slit-lamp biomicroscopy, Fantes grading system, fluorescein staining, Schirmer's tests, pachymetry, and applanation tonometry. Cellular and molecular changes in rabbit corneas were assessed after humane euthanasia on day-3 and day-7 with histopathological and real-time polymerase chain reaction PCR techniques. Results: TED to rabbit eyes was found tolerable in vivo. SM-exposed eyes showed significant increase in Fantes scores, central corneal thickness (CCT), Schirmer's test, epithelium-stroma separation, and corneal edema. TED mitigated clinical symptoms by reducing corneal edema, Fantes scores, CCT, and Schirmer's test. Further, TED decreased SM-induced corneal haze, inflammatory and profibrotic markers, transforming growth factor-TGF-ß1 and cyclooxygenase-2COX-2, and damage to corneal structure, including epithelial-stromal integrity. Conclusions: The developed multimodal eyedrop formulation, TED, has potential to mitigate acute MGK effectively in vivo. Translational Relevance: TED is effective against MGK.

Preoperative (3-dimensional) computed tomography lung reconstruction before anatomic segmentectomy or lobectomy for stage I non-small cell lung cancer.

OBJECTIVES: Accurate cancer localization and negative resection margins are necessary for successful segmentectomy. In this study, we evaluate a newly developed software package that permits automated segmentation of the pulmonary parenchyma, allowing 3-dimensional assessment of tumor size, location, and estimates of surgical margins. METHODS: A pilot study using a newly developed 3-dimensional computed tomography analytic software package was performed to retrospectively evaluate preoperative computed tomography images of patients who underwent segmentectomy (n = 36) or lobectomy (n = 15) for stage 1 non-small cell lung cancer. The software accomplishes an automated reconstruction of anatomic pulmonary segments of the lung based on bronchial arborization. Estimates of anticipated surgical margins and pulmonary segmental volume were made on the basis of 3-dimensional reconstruction. RESULTS: Autosegmentation was achieved in 72.7% (32/44) of preoperative computed tomography images with slice thicknesses of 3 mm or less. Reasons for segmentation failure included local severe emphysema or pneumonitis, and lower computed tomography resolution. Tumor segmental localization was achieved in all autosegmented studies. The 3-dimensional computed tomography analysis provided a positive predictive value of 87% in predicting a marginal clearance greater than 1 cm and a 75% positive predictive value in predicting a margin to tumor diameter ratio greater than 1 in relation to the surgical pathology assessment. CONCLUSIONS: This preoperative 3-dimensional computed tomography analysis of segmental anatomy can confirm the tumor location within an anatomic segment and aid in predicting surgical margins. This 3-dimensional computed tomography information may assist in the preoperative assessment regarding the suitability of segmentectomy for peripheral lung cancers.

Anterior thoracic surgical approaches in the treatment of spinal infections and neoplasms.

BACKGROUND: Thoracic surgeons are commonly consulted to provide anterior thoracic exposure for infection and malignant neoplasms involving the thoracolumbar spine. These cases can present significant technical and management challenges secondary to the underlying pathology, associated anatomic inflammation, and impaired functional status. In this study, we review the perioperative outcomes in patients undergoing anterior spinal exposure for infection and neoplasm. METHODS: 130 consecutive patients (61 women, 69 men) undergoing corpectomy, debridement, or debulking for osteomyelitis (n=50) or neoplasms (n=80) with decompression/stabilization at a single institution were analyzed. Primary endpoints included morbidity, mortality, and perioperative neurologic outcomes. RESULTS: The mean age was 61.1 years. A cervical/sternotomy (n=8) approach was used for levels C7 to T2, thoracotomy (n=79) for levels T3 to T10, and thoracoabdominal (n=43) for T11 to L2 involvement. Primary spinal neoplasms (n=22, 16.9 %) and metastases (n=58, 44.6%) were treated with corpectomy and prosthetic stabilization and were associated with increased operative time (310 vs 243 minutes, p=0.02) and blood loss (825 vs 500 mL, p=0.002). Osteomyelitis was associated with longer hospital stays (12 vs 7 days, p<0.001). The 30-day and 90-day mortality was 9.2% and 20.8%, respectively. The major complication rate was 27.7%. The median length of stay was 9 days. Surgical intervention resulted in significant improvement in pain, numbness, weakness, and bowel and bladder dysfunction. CONCLUSIONS: Anterior spinal exposure represents an important modality in facilitating the treatment of patients with osteomyelitis, pathologic fractures, and spinal cord compression syndromes. These procedures are associated with a significant risk of morbidity and mortality, but they are effective in achieving spinal stabilization and alleviating neurologic symptoms.

Extended Chamberlain minithoracotomy: a safe and versatile approach for difficult lung resections.

BACKGROUND: We present the perioperative outcomes of patients undergoing an anterior "extended Chamberlain" minithoracotomy as an alternative approach to a hemi-clamshell sternotomy or extended lateral thoracotomy for safe and reliable access to the pulmonary hilum and subsequent anatomic pulmonary resection. METHODS: This study is a retrospective review of 162 patients undergoing anatomic lung resection through a mini anterior thoracotomy from 2002 to 2010. An 8-cm anterior thoracotomy was performed with the patient in a supine position, entering the chest through the second intercostal space. The pectoralis muscle fibers were split with preservation of the mammary artery medially and the thoracoacromial neurovascular bundle laterally. Primary outcome variables included hospital course, complications, and mortality rate. RESULTS: The mean age was 63.9 (range, 20 to 85 years); female to male ratio was 71:91. Neoadjuvant therapy was used in 49 (30.2%) patients. Proposed resections were successful in 161 of 162 (99%) patients. Conversion to hemi-clamshell was required in 1 patient for vascular control. Complications occurred in 48 (29.6%) patients. Three (1.9%) perioperative deaths (2 pneumonectomies [6.3%], 1 lobectomy [1.0%]) occurred. Median length of stay was 8 days. CONCLUSIONS: The "extended Chamberlain" mini anterior thoracotomy provides direct and expeditious, less-invasive access to the pulmonary hilum. This approach preserves muscle function and avoids partial sternotomy or extended lateral thoracotomy, and their associated incisional-related morbidity.

Impact of angiolymphatic and pleural invasion on surgical outcomes for stage I non-small cell lung cancer.

BACKGROUND: In the current study, we analyze the impact of pathologic variables (angiolymphatic invasion, visceral pleural invasion, and tumor inflammation) upon survival outcomes after segmentectomy or lobectomy for stage I non-small cell lung cancer. METHODS: A retrospective review was made of 524 patients undergoing resection of stage I non-small cell lung cancer through either lobectomy (n = 285) or anatomic segmentectomy (n = 239). Primary outcome variables include recurrence-free and overall survival. Statistical comparisons were performed with the t test and Fisher's exact test. Recurrence-free and overall survival was estimated utilizing the Kaplan-Maier method, with statistical significance being assessed by the log rank test. RESULTS: The incidence of angiolymphatic invasion, visceral pleural invasion, and degree of tumor inflammation, as well as morbidity, mortality, and length of stay were similar between segmentectomy and lobectomy. The presence of angiolymphatic invasion or visceral pleural invasion was associated with a significant decrease in recurrence-free survival (p < 0.01) and overall survival (p < 0.01). There was a trend for decreased recurrence with increasing tumor inflammation (mild versus severe, p = 0.066). There was no difference in rates of local recurrence (5.6% versus 7.9%, p = 0.59) or survival (p = 0.455) between segmentectomy and lobectomy, respectively. CONCLUSIONS: Angiolymphatic and visceral pleural invasion appear to be strong adverse prognostic factors after anatomic resection by segmentectomy or lobectomy for stage I non-small cell lung cancer. Overall survival is not affected by the extent of anatomical surgical resection. These data may have implications regarding the role of adjuvant systemic therapy after surgical resection for tumors with these pathologic characteristics.

The use of esophageal transit and gastric emptying studies in the evaluation of patients undergoing laparoscopic fundoplication.

BACKGROUND: Preservation of esophageal and gastric function is a hallmark principle in ensuring optimal surgical outcomes after gastric fundoplication. In this study, we evaluated the impact of fundoplication on esophageal transit and gastric emptying using scintigraphy studies and related these functional findings to symptomatic outcomes. METHODS: A total of 106 consecutive patients (37 women, 69 men) with both preoperative and 6-month postoperative nuclear scintigraphy studies undergoing partial (Toupet) fundoplication at a single institution were analyzed. Primary variables included alterations in esophageal transit and gastric emptying times after fundoplication (1 = rapid; 2 = normal; 3 = mild delay; 4 = severe delay). Symptomatic variables included heartburn, regurgitation, dysphagia, pulmonary symptoms, and bloating. RESULTS: Mean age was 57.2 years. Symptomatic improvement was achieved in 91.5% of patients. Significant reduction of all symptoms (heartburn, regurgitation, pulmonary symptoms, and dysphagia) was noted after fundoplication, except gas bloating (4.7 vs. 20.8%). There were no significant differences in preoperative and postoperative esophageal transit (2.53 vs. 2.52) and gastric emptying (2.13 vs. 2.06) scores after fundoplication. Interestingly, 17% of esophageal transit times and 18% of gastric emptying times improved after fundoplication. However, worsening scores were seen in 16 and 12%, respectively. There was no significant postoperative dysphagia, even in patients with impaired transit times. CONCLUSIONS: Nuclear scintigraphic assessment of esophageal transit and gastric emptying are valuable, user-friendly tools to identify and avoid functional motility problems in the setting of fundoplication. These studies seem to be a reasonable alternative to manometry in assessing esophageal function before surgery in this setting. Postoperative symptoms may be related to objective changes in esophageal transit or gastric emptying. The causes may be iatrogenic in nature or related to vagal denervation with associated changes in esophagogastric compliance. Awareness of these physiologic changes may prompt further technical precautions at the time of surgery to avoid vagal injury and also may facilitate postoperative medical management.

Anterior minithoracotomy: a direct approach to the difficult hilum for upper lobectomy, pneumonectomy, and sleeve lobectomy.

BACKGROUND: Central lung cancers with pulmonary hilar involvement can pose a technical challenge when a lateral thoracotomy is used. Proximal vascular control and pulmonary vascular dissection from this approach can be challenging and potentially dangerous. We describe the use of a Chamberlain anterior minithoracotomy as an alternative approach for safe and reliable access to the pulmonary hilum. METHODS: One hundred two consecutive patients undergoing the Chamberlain approach were identified through retrospective chart review from 2002 to 2009. The supine position was used, thus reducing the likelihood of down-lung syndrome. An 8-cm anterior thoracotomy was performed over the second interspace along the line of the pectoral fibers, with preservation of the mammary artery medially and the thoracoacromial neurovascular bundle laterally. Primary outcome variables included hospital course, complications, and mortality rate. RESULTS: The mean age was 64.8 years (range, 20-89 years). Sex ratio (female:male) was 44:58. Neoadjuvant therapy was used in 43 patients (42.2%). Proposed resections were successful in 101 (99%) of 102 patients. Conversion to hemiclamshell was required in 1 patient for vascular control. Three perioperative deaths (2.9%; two pneumonectomies, one lobectomy) occurred. CONCLUSIONS: The Chamberlain mini anterior thoracotomy provides direct access to the pulmonary hilum, facilitating dissection and vascular control for large and central tumors. Reduced perioperative pain and down-lung syndrome compared to lateral approaches can be achieved. Muscle function is preserved, and intrapericardial/hilar access is expeditious. This approach enhances hilar access and avoids the vascular control and hilar exposure challenges inherent with lateral thoracotomy.

Anatomic segmentectomy for stage I non-small-cell lung cancer: comparison of video-assisted thoracic surgery versus open approach.

OBJECTIVES: Anatomic segmentectomy is increasingly being considered as a means of achieving an R0 resection for peripheral, small, stage I non-small-cell lung cancer. In the current study, we compare the results of video-assisted thoracic surgery (n = 104) versus open (n = 121) segmentectomy in the treatment of stage I non-small-cell lung cancer. METHODS: A total of 225 consecutive anatomic segmentectomies were performed for stage IA (n = 138) or IB (n = 87) non-small-cell lung cancer from 2002 to 2007. Primary outcome variables included hospital course, complications, mortality, recurrence, and survival. Statistical comparisons were performed utilizing the t test and Fisher exact test. The probability of overall and recurrence-free survival was estimated with the Kaplan-Meier method, with significance being estimated by the log-rank test. RESULTS: Mean age (69.9 years) and gender distribution were similar between the video-assisted thoracic surgery and open groups. Average tumor size was 2.3 cm (2.1 cm video-assisted thoracic surgery; 2.4 cm open). Mean follow-up was 16.2 (video-assisted thoracic surgery) and 28.2 (open) months. There were 2 perioperative deaths (2/225; 0.9%), both in the open group. Video-assisted thoracic surgery segmentectomy was associated with decreased length of stay (5 vs 7 days, P < .001) and pulmonary complications (15.4% vs 29.8%, P = .012) compared with open segmentectomy. Overall mortality, complications, local and systemic recurrence, and survival were similar between video-assisted thoracic surgery and open segmentectomy groups. CONCLUSIONS: Video-assisted thoracic surgery segmentectomy can be performed with acceptable morbidity, mortality, recurrence, and survival. The video-assisted thoracic surgery approach affords a shorter length of stay and fewer postoperative pulmonary complications compared with open techniques. The potential benefits and limitations of segmentectomy will need to be further evaluated by prospective, randomized trials.

Contemporaneous management of esophageal perforation.

BACKGROUND: Esophageal perforation is an important therapeutic challenge. We hypothesized that patients with minimal mediastinal contamination at the time of diagnosis could be managed successfully with nonoperative treatment modalities. METHODS: We performed a retrospective review of 119 consecutive patients with esophageal perforation from 1998 to 2008. Demographics, cause of perforation, clinical presentation, diagnostic methods, and management results were evaluated. The decision to operate was based on the extent of mediastinal contamination and systemic sepsis rather than cause of perforation. RESULTS: Median time to diagnosis among all patients was 12 hours (range, 1-120). Spontaneous (Boerhaave's) perforation occurred in 44 (37%) patients. Iatrogenic perforations constituted the remaining patients (n = 75). After instrumental perforation, 9 patients (13%) required esophagectomy, 48 patients were managed with repair and drainage, and the remaining 18 were managed nonoperatively. All 34 patients undergoing operative therapy for spontaneous perforations were treated with esophageal repair. Overall mortality was 14%, with intrathoracic perforations having 18% mortality, cervical 8%, and gastroesophageal junction 3%. Patients undergoing nonoperative therapy had a shorter hospitalizations (13 vs 24 days), fewer complications (36% vs 62%), and less mortality (4% vs 15%) compared with those undergoing operative intervention. CONCLUSION: An approach to esophageal perforation based on injury severity and the degree of mediastinal and pleural contamination is of paramount importance. Although operative management remains the standard in the majority of patients with esophageal perforation, nonoperative management may be successfully implemented in selected patients with a low morbidity and mortality if favorable radiographic and clinical characteristics are present.

Anatomic segmentectomy for stage I non-small cell lung cancer in the elderly.

BACKGROUND: Anatomic segmentectomy for stage I non-small cell lung cancer (NSCLC) offers the potential of surgical cure with preservation of lung function. This may be of particular importance in elderly NSCLC patients with declining cardiopulmonary status and a limited life expectancy. METHODS: The study compared outcomes of 78 elderly patients (aged > 75 years) with stage I NSCLC undergoing segmentectomy and 106 undergoing lobectomy for stage I NSCLC from 2002 to 2007. Primary outcome variables included perioperative morbidity and mortality, hospital course, recurrence patterns, and survival. RESULTS: Age, gender, tumor histology, and surgical approach were similar between groups. Comorbidities were similar except for a higher incidence of chronic obstructive pulmonary disease and diabetes in segmentectomy patients. The tumors in the lobectomy group were significantly larger (3.5 vs 2.5 cm, p = 0.0001). Operative mortality was 1.3% for segmentectomy and 4.7% for lobectomy. Segmentectomy patients had fewer major complications (11.5% vs 25.5%, p = 0.02). There were no differences in median hospitalization (7 vs 6 days). The estimated overall survival at 2, 3, and 5 years was 76%, 69%, and 46% for segmentectomy patients and 68%, 59%, and 47% for lobectomy patients (p = 0.28). The 5-year disease-free survival was equivalent (segmentectomy, 49.8%; lobectomy, 45.5%; p = 0.80). CONCLUSIONS: Anatomic segmentectomy can be performed safely in elderly patients with early-stage NSCLC. This approach is associated with reduced perioperative complications and comparable oncologic efficacy compared with lobectomy in older patients with a limited life expectancy.