Oncologic Outcomes of Surgery Versus SBRT for Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-analysis.

BACKGROUND: The optimal treatment of stage I non-small-cell lung carcinoma is subject to debate. The aim of this study was to compare overall survival and oncologic outcomes of lobar resection (LR), sublobar resection (SR), and stereotactic body radiotherapy (SBRT). METHODS: A systematic review and meta-analysis of oncologic outcomes of propensity matched comparative and noncomparative cohort studies was performed. Outcomes of interest were overall survival and disease-free survival. The inverse variance method and the random-effects method for meta-analysis were utilized to assess the pooled estimates. RESULTS: A total of 100 studies with patients treated for clinical stage I non-small-cell lung carcinoma were included. Long-term overall and disease-free survival after LR was superior over SBRT in all comparisons, and for most comparisons, SR was superior to SBRT. Noncomparative studies showed superior long-term overall and disease-free survival for both LR and SR over SBRT. Although the papers were heterogeneous and of low quality, results remained essentially the same throughout a large number of stratifications and sensitivity analyses. CONCLUSION: Results of this systematic review and meta-analysis showed that LR has superior outcomes compared to SBRT for cI non-small-cell lung carcinoma. New trials are underway evaluating long-term results of SBRT in potentially operable patients.

Oncological Outcomes of Lobar Resection, Segmentectomy, and Wedge Resection for T1a Non-Small-Cell Lung Carcinoma: A Systematic Review and Meta-Analysis.

The optimal treatment of early-stage non-small-cell lung cancer (NSCLC) remains subject to debate. Lobar resection is considered the standard of care, but sublobar resections are a lung parenchymal-sparing treatment offering promising results. We conducted a systematic review and meta-analysis to compare oncological outcomes of lobar resections and parenchymal-sparing resections for T1a NSCLC. PubMed, EMBASE, Web of Knowledge Search, and the Cochrane Central Register of Controlled Trials were searched for studies reporting oncological outcomes following lobar or parenchymal-sparing resections. Two researchers independently identified studies and extracted data. Oncological outcomes were compared for each surgical modality using the Mantel-Haenszel method, and outcomes were pooled for each modality using the inverse variance method. A total of 11,195 studies were identified and 28 articles were included. For pT1a tumors, there was no difference in 5-year overall survival when lobar resection (n = 15,003) was compared to parenchymal-sparing resection (n = 1224), with a relative risk of 0.92 (95% confidence interval: 0.84-1.01). Five-year overall survival and disease-free survival after segmentectomy yielded equal survival compared to lobar resection in directly comparing studies and point estimates of noncomparative studies. In most comparisons, wedge resection showed comparable results to lobar resections and segmentectomy. Subanalysis of intentional parenchymal-sparing surgery showed favorable results. This study shows that parenchymal-sparing surgery yields equivocal survival compared to lobar surgery for stage T1a NSCLC. However, a drawback in implementing parenchymal-sparing resection for lobectomy-tolerable patients is the risk of nodal upstaging.

Survival After Stereotactic Body Radiation Therapy for Clinically Diagnosed or Biopsy-Proven Early-Stage NSCLC: A Systematic Review and Meta-Analysis.

INTRODUCTION: Stereotactic body radiation therapy (SBRT) is a promising curative treatment for early-stage NSCLC. It is unclear if survival outcomes for SBRT are influenced by a lack of pathological confirmation of malignancy and staging of disease in these patients. In this systematic review and meta-analysis, we assess survival outcomes after SBRT in studies with patients with clinically diagnosed versus biopsy-proven early-stage NSCLC. METHODS: The main databases were searched for trials and cohort studies without restrictions to publication status or language. Two independent researchers performed the screening and selection of eligible studies. Outcomes were overall survival, cancer-specific survival, and disease-free survival. The inverse variance method and the random effects method for meta-analysis were used to assess pooled survival estimates. RESULTS: A total of 11,195 nonduplicate records were identified by the original search strategy. After screening by title and abstract, 1051 potentially eligible records were identified. A total of 43 articles were included. The comparative studies showed lower 3-year overall survival and lower 2-year and 5-year cancer-specific survival for biopsy-proven disease compared to clinical disease. However, 5-year overall survival was the same for both groups. For the pooled estimates, 3-year disease-free survival and 2-year cancer-specific survival were lower for biopsied disease. CONCLUSIONS: Results of this systematic review and meta-analysis show a discrepancy in oncological outcomes for patients undergoing SBRT for suspected early-stage NSCLC in whom there is pathologic conformation of malignancy and those who there is only a clinical diagnose of NSCLC. These results emphasize the importance of obtaining pathologic proof of malignancy.

Induction Therapy for Locally Advanced, Resectable Esophagogastric Cancer: A Phase I Trial of Vandetanib (ZD6474), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiotherapy Followed by Resection.

OBJECTIVES: Preoperative chemotherapy and radiation for localized esophageal cancer produces cure rates near 30% when combined with surgical resection. Vandetanib, a small molecule receptor tyrosine kinase inhibitor of VEGFR-2, VEGFR-3, RET, and EGFR, demonstrated synergy with radiation and chemotherapy in preclinical models. We conducted a phase I study to assess the safety and tolerability of vandetanib when combined with preoperative chemoradiation in patients with localized esophageal carcinoma who were surgical candidates. METHODS: Patients with stage II-III esophageal and gastroesophageal junction carcinoma without prior therapy were enrolled in a 3+3 phase I design. Patients received once-daily vandetanib (planned dosing levels of 100, 200, and 300 mg) with concomitant daily radiotherapy (1.8 Gy/d, 45 Gy total) and chemotherapy, consisting of infusional 5-FU (225 mg/m/d over 96 h, weekly), paclitaxel (50 mg/m, days 1, 8, 15, 22, 29) and carboplatin (AUC of 5, days 1, 29). RESULTS: A total 9 patients were enrolled with 8 having either distal esophageal or gastroesophageal junction carcinomas. All patients completed the planned preoperative chemoradiation and underwent esophagectomy. Nausea (44%) and anorexia (44%) were the most common acute toxicities of any grade. One grade 4 nonhematologic toxicity was observed (gastrobronchial fistula). One additional patient suffered a late complication, a fatal aortoenteric hemorrhage, not definitively related to the investigational regimen. Five (56%) patients achieved a pathologic complete response. Three (33%) additional patients had only microscopic residual disease. Five (56%) patients remain alive and disease free with a median follow-up of 3.7 years and median overall survival of 3.2 years. The maximum tolerated dose was vandetanib 100 mg/d. CONCLUSIONS: Vandetanib at 100 mg daily is tolerable in combination with preoperative chemotherapy (5-FU, paclitaxel, carboplatin) and radiation therapy with encouraging efficacy worthy of future study.

Open access phone triage for veterans with suspected malignant pleural mesothelioma.

BACKGROUND: Phone triaging patients with suspected malignant pleural mesothelioma (MPM) within the Veterans Healthcare Administration (VHA) system offers a model for rapid, expert guided evaluation for patients with rare and treatable diseases within a national integrated healthcare system. To assess feasibility of national open access telephone triage using evidence-based treatment recommendations for patients with MPM, measure timelines of the triage and referral process and record the impact on "intent to treat" for patients using our service. METHODS: A retrospective study. The main outcome measures were: (1) ability to perform long distance phone triage, (2) to assess the speed of access to a mesothelioma surgical specialist for patients throughout the entire VHA, and (3) to determine if access to a specialist would alter the plan of care. RESULTS: Sixty veterans were screened by our phone triage program, 38 traveled an average of 997 miles to VA Boston Healthcare system. On average, 14 d elapsed from initial phone contact until the patient was physically evaluated in our general thoracic clinic in Boston. The treatment plan was altered for 71% of patients evaluated at VA Boston Healthcare system based on 2012 International Mesothelioma Interest Group guidelines. CONCLUSIONS: Our initial experience demonstrates that in-network centralized care for Veterans with MPM is feasible within the VHA. National open access phone triage improves access to expert surgical advice and can be delivered in a timely manner for Veterans using our service. Guideline-based treatment recommendations ("intent to treat") changed the therapeutic course for the majority of patients who used our service.

Results of a Tailored Approach to Zenker's Diverticulum: A Single VA Experience.

The transoral division of the esophageal-diverticula septum with a linear stapler, with CO2 laser, or with harmonic scalpel under rigid endoscopy has revolutionized the surgical management of Zenker's diverticula. Nevertheless, the open approach still plays a role in select cases. Our goals are to illustrate the techniques and the results of our tailored approach to the surgical management of Zenker's diverticula in U.S. veterans.

Benign Metastasizing Leiomyomas to the Lungs: An Institutional Case Series and a Review of the Recent Literature.

BACKGROUND: Benign metastasizing leiomyomas (BMLs) represent the extrauterine spread of a benign uterine process. Pulmonary BMLs are the most common example of distant spread of uterine leiomyomas and are usually found incidentally in premenopausal women. The rarity of BMLs accounts for the limited literature that currently exists regarding their underlying pathophysiology, disease course, and management. METHODS: A retrospective analysis was performed of all BML cases diagnosed and managed at Brigham and Women's Hospital during a 22-year period. The demographic and clinical characteristics of these patients were compared with a PubMed-derived cohort of BML cases reported since 2006. RESULTS: Benign metastasizing leiomyoma tumors were identified in 10 Brigham and Women's Hospital patients, whereas 57 cases were reported in the literature. The average age at diagnosis was 54.1 and 46.7 years, respectively. Mean interval time from a pertinent gynecologic procedure to BML diagnosis was 23 years at Brigham and Women's Hospital. All patients demonstrated positivity for actin, desmin, and estrogen/progesterone receptors, confirming the diagnosis of uterine leiomyomas. Management primarily consisted of diagnostic resection with subsequent observation with or without hormonal suppression for residual pulmonary nodules. Progression of residual BMLs was noticed in 30% and 8.3% of Brigham and Women's Hospital and literature patients, respectively, when follow-up was reported. One patient in our series required further surgical management. CONCLUSIONS: Benign metastasizing leiomyomas are a rare cause of pulmonary nodules. They likely represent a clonal spread of uterine leiomyomas to the lungs. Management includes pathologic diagnosis with long-term surveillance with or without hormonal manipulation.

Early Surgical Outcomes of En Bloc Resection Requiring Vertebrectomy for Malignancy Invading the Thoracic Spine.

BACKGROUND: En bloc vertebral resection of locally invasive T4 lung cancers led to the development of a surgical sequence for resection; posterior stabilization, reposition, thoracotomy, lobectomy, vertebrectomy, and anterior spine stabilization in 1 procedure. This technique expanded indications for vertebrectomy to selected patients with sarcoma and metastatic disease. We review our experience to identify areas for clinical improvement. METHODS: Operative case logs were cross-checked with billing data from 2003 to 2014 with Current Procedural Terminology (CPT, American Medical Association) codes for vertebrectomy. Thirty-two cases involving en bloc resection of malignancy invading at least 1 thoracic vertebra were selected. Outcomes data were analyzed using summary statistics. RESULTS: Series includes 14 men and 18 women, median age 50 years. Twenty-five patients (78%) received preoperative chemoradiation. Nineteen total and 13 partial vertebrectomy were performed. Average number of vertebrae resected was 1.6 (range, 1 to 4). Median operative length was 8.5 hours (range, 2.8 to 14.5), mean blood loss 923 mL (SD ± 477 mL), and median length of stay 8 days (range, 3 to 56). Major morbidity followed 56% of cases. Thirty-day mortality was 3%. Overall median survival was 43.6 months, 1-year survival was 73.6%, and 5-year survival was 40.3%. CONCLUSIONS: En bloc vertebrectomy for malignant disease is feasible. Our 1 stage and 2 team approach allows completion of the operation within a standard day, but is associated with long operative time. Complication rates may improve with decreased operative times. Review of available data warrants future prospective studies.

The 3-Hole Minimally Invasive Esophagectomy: A Safe Procedure Following Neoadjuvant Chemotherapy and Radiation.

Induction therapy followed by esophagectomy has become standard for treatment of intermediate-stage esophageal cancer in many centers. Herein we evaluate the feasibility and safety of the 3-hole minimally invasive esophagectomy (3HMIE) approach in patients who received induction radiation and chemotherapy. Between 2003 and 2012, the records of 119 consecutive patients with esophageal cancer who underwent 3HMIE were reviewed for perioperative complications and long-term outcomes. Comparison was made between procedures performed for patients receiving neoadjuvant chemoradiation and patients who were treated with only surgery. Of them, 78 patients received neoadjuvant chemoradiation and 41 patients were treated with only surgery. Tumor locations were upper (2), middle (16), distal (64), and gastroesophageal junction (37). In all, 76 patients were at clinical stage IIA or above at presentation. Increased requirement for blood replacement in the induction therapy group was significant compared with the surgery-only group. Operative time, estimated blood loss, proximal and distal margin lengths, and length of stay were not significantly different between the cohorts. There was a 30-day perioperative death (0.8%), and this patient was from the surgery-only group. No conduit necrosis or need for diversion was recorded. Overall, 5-year survival was 62% among the 107 patients with early-stage esophageal cancer. 3HMIE is feasible with low mortality and acceptable morbidity even in patients with locally advanced esophageal cancer who received neoadjuvant radiochemotherapy. Overall perioperative and survival outcomes are similar to or better than those reported in the published literature on esophagectomy after induction therapy.

Trauma education in a state of emergency: a curriculum-based analysis.

BACKGROUND: Trauma is the leading cause of death from ages 1-44-y in the United States and the fifth leading cause of death overall, but there are few studies quantifying trauma education in medical school. This study reviews curriculum hours devoted to trauma education at a northeastern medical school. MATERIALS AND METHODS: We reviewed the preclinical curriculum at a northeastern medical school affiliated with three adult and two pediatric level I trauma centers verified by the American College of Surgeons. We reviewed curricular hours and we categorized them according to the leading ten causes of death in the United States. We also compared the number of educational hours devoted to trauma to other leading causes of death. RESULTS: The total amount of time devoted to trauma education in the first 2 y of medical school was 6.5 h. No lectures were given on the fundamentals of trauma management, traumatic brain injury, or chest or abdominal trauma. The most covered topic was heart disease (128 h), followed by chronic lower respiratory disease (80 h). Curricular time for heart disease, chronic lower respiratory disease, cancer, diabetes, renal disease, and influenza and pneumonia far exceeded that devoted to trauma, after adjusting for the mortality burden of these diseases (P < 0.05 for all). CONCLUSIONS: Our study demonstrates that trauma education at a northeastern medical school is nearly absent. With the large burden of trauma and rise in mass casualty incidence, the preclinical curriculum might not be sufficient to expose students to the fundamentals of trauma management. A broader multi-institutional study may shed more insight on these curricular deficiencies in trauma education and detect if these deficiencies are widespread nationally.

Treatment and controversies in paraesophageal hernia repair.

BACKGROUND: Historically all paraesophageal hernias were repaired surgically, today intervention is reserved for symptomatic paraesophageal hernias. In this review, we describe the indications for repair and explore the controversies in paraesophageal hernia repair, which include a comparison of open to laparoscopic paraesophageal hernia repair, the necessity of complete sac excision, the routine performance of fundoplication, and the use of mesh for hernia repair. METHODS: We searched Pubmed for papers published between 1980 and 2015 using the following keywords: hiatal hernias, paraesophageal hernias, regurgitation, dysphagia, gastroesophageal reflux disease, aspiration, GERD, endoscopy, manometry, pH monitoring, proton pump inhibitors, anemia, iron-deficiency anemia, Nissen fundoplication, sac excision, mesh, and mesh repair. RESULTS: Indications for paraesophageal hernia repair have changed, and currently symptomatic paraesophageal hernias are recommended for repair. In addition, it is important not to overlook iron-deficiency anemia and pulmonary complaints, which tend to improve with repair. Current practice favors a laparoscopic approach, complete sac excision, primary crural repair with or without use of mesh, and a routine fundoplication.

Diagnostic evaluation of achalasia: from the whalebone to the Chicago classification.

From the earliest description of dysphagia relieved by dilatation with a whalebone in 1674 we have witnessed the evolution of esophageal function testing from the conventional manometry to the high-resolution manometry (HRM) and esophageal topography pressure plotting that have led to the revised Chicago classification for esophageal motility disorders in 2014. The goals of this paper are, therefore, (1) to highlight the historical milestones that have led to the diagnostic definition of achalasia, as we know it today; (2) to describe the evaluation process of patients with suspected achalasia; (3) to describe the diagnostic value of the HRM and the usefulness of the Chicago classification in predicting treatment outcomes. The value of Chicago classification is linked to the ability of the clinician to perform a thorough clinical evaluation to identify and correlate specific clinical phenotypes to specific manometric subtypes and predict treatment outcomes. Chicago classification, however, cannot predict which treatment, pneumatic dilatation, or Heller myotomy, should be selected for those with a specific subtype of achalasia.

Transdiaphragmatic minimally invasive lobectomy is feasible in a pig.

Video-assisted thoracoscopic surgery lobectomy has gained acceptance as a safe and oncologically sound alternative to the open procedure. Intercostal incisions alter chest wall mechanics and lead to postoperative pain. We postulated that performing the procedure without disruption of the intercostal spaces may lead to better outcomes because of the decreased effect on chest wall mechanics and postoperative pain. This initial experiment attempts to test the feasibility and possible changes in technique during transdiaphragmatic lobectomy and lymphadenectomy based on currently available instrumentation. Three access ports were placed beneath the costal margin of an anesthetized adult pig, and the thoracic cavity was accessed through the diaphragm. A transdiaphragmatic minimally invasive right lower lobectomy with complete lymph node dissection was performed. We report the first transdiaphragmatic minimally invasive right lower lobectomy and lymphadenectomy in a pig. The procedure is feasible using current commercially available standard instrumentation in a pig. Further, study is warranted to further refine the surgical technique.

Primary high-grade neuroendocrine carcinoma of the esophagus: a clinicopathologic and immunohistochemical study of 42 resection cases.

Primary high-grade neuroendocrine carcinoma of the esophagus (HNCE) is rare and poorly understood. In this study, we aimed at delineating the clinicopathologic and immunohistochemical characteristics of HNCE diagnosed on the basis of the World Health Organization criteria for pulmonary neuroendocrine carcinomas. We identified 42 (3.8%) consecutive resection cases of HNCE among 1105 esophageal cancers over a 7-year period. Patients' mean age was 62 years (range, 47 to 79 y) with a male to female ratio of 3.7. Dysphagia was present in 79% of patients and tobacco abuse in 50%. Most tumors were centered in the middle (52%) or lower (36%) esophagus; 48% were ulcerated and 31% exophytic. All tumors were sharply demarcated with a pushing border in either solid sheet (83%) or nodular (17%) growth patterns. Pure HNCE was found in 57%, and the remainder also exhibited small components of squamous cell carcinoma (SqCC) or glandular, signet ring cell differentiations. SqCC in situ was present in 50%. Most tumors (88%) were the small cell type with pure oat-like cells in 52%, and the larger spindled, anaplastic, and giant cells were common. Tumor crush artifact (98%) and the Azzopardi effect (88%) were widespread. Extensive lymphovascular (50%) and perineural (33%) invasion and metastasis to regional (48%) and abdominal celiac lymph nodes (29%) were observed. Neoplastic cells were immunoreactive to synaptophysin (100%), CD56 (93%), chromogranin A (67%), p63 (55%), TTF-1 (71%), CK8/18 (90%), CD117 (86%), HER2 (16%), and p16 (84%) antibodies. The 5-year survival rate was 25%, similar to that of SqCC. Lymphovascular and perineural invasion was associated with a worse prognosis.

Multiple nerve blocks after video-assisted thoracic surgery (VATS).

INTRODUCTION: Epidural analgesia and/or systemic narcotics are used for pain control after video-assisted thoracic surgery (VATS) lobectomy despite side effects. We report a video of a technique to safely place subpleural catheters in order to provide multiple nerve blocks and the results from our series comparing this technique to a standard post-operative analgesia protocol after VATS. METHODS: At the end of the VATS wedge resection, two small incisions were made below and parallel to the position of the trocars, at the level of the anterior and posterior axillary line and an introducer was used to place a catheter subcutaneously. At this point, the introducer was curved, in a way to follow the anatomic shape of the costal margin of the patient, inserted into posterior incision and advanced in between the thoracic pleura and the ribs. Under direct vision from the thoracoscope and paying careful attention not to perforate the pleura, the guide was pushed toward the first rib by using a combination of blunt and hydro dissection. Once the guide reached the first rib, the introducer was removed and the catheter was left in place. RESULTS: We evaluated 64 patients (29 patient-controlled analgesia (PCA), 35 SC). Propensity weighting produced two matched groups for further analysis. Mean total morphine dose and mean total morphine dose/body mass index (BMI) were both significantly decreased in the SC group for the 0-24 h period only (mean total morphine 38.1 vs. 27.8; P = 0.024 and mean total morphine/BMI 1.15 vs 0.79; P = 0.024). Complication rates did not differ between groups. CONCLUSIONS: PCA narcotic analgesia with subpleural local anesthetic infusion provided similar pain control with less narcotic use in patients during the first 24 h after VATS lobectomy compared with PCA narcotic analgesia alone.

Modified T-tube repair of delayed esophageal perforation results in a low mortality rate similar to that seen with acute perforations.

BACKGROUND: Esophageal perforation carries a high mortality and morbidity rate, especially if treatment is delayed more than 24 hours. We present a large series of patients requiring operative treatment of esophageal perforations with attention to an infrequently used method of dealing with delayed intrathoracic perforations. METHODS: All patients undergoing operative treatment for intrathoracic esophageal perforation at the Brigham and Women's hospital between 1989 and 2003 were reviewed. Mortality, morbidity, length of stay, nature of esophageal injury, type of repair, and outcome were reviewed. RESULTS: Forty-three operations for perforation of the thoracic esophagus were performed. Overall 30-day or in-hospital mortality was 7.0%, and overall morbidity was 47%. Most acute thoracic esophageal perforations were treated with primary repair and had a mortality rate of 5%, whereas most delayed perforations were treated with T-tube repair and had a mortality rate of 8.7%. The complication rate in the group repaired within 24 hours was 20%, whereas it was 61% in the group repaired after 24 hours. The complication rate in the group repaired within 72 hours was 42%, and it was 82% in the group repaired after 72 hours. CONCLUSIONS: Treatment of delayed (more than 24 hours) thoracic esophageal perforations with a controlled fistula through T-tube results in a very low mortality similar to that seen with acute perforations (less than 24 hours). Morbidity and length of stay remain high. Delay in treatment of intrathoracic esophageal perforations beyond 24 and 72 hours results in a doubling of morbidity at each interval.

Duplication cyst of the duodenum as an unusual cause of massive gastrointestinal bleeding in an infant.

Duplication cysts of the gastrointestinal tract are rare and very rarely present as massive intestinal bleeding. The authors present a case in which massive bleeding was caused by a bleeding duodenal duplication cyst and was treated successfully by surgical excision. A review of the literature also is presented.