Resident training in a new robotic thoracic surgery program.

BACKGROUND: The volume of robot-assisted operations has drastically increased over the past decade. New programs have focused on training surgeons, whereas resident training has lagged behind. The objective of this study was to evaluate our institutional experience with resident participation in thoracic robotic surgery cases since the initiation of our program. METHODS: The first 100 robotic thoracic surgery cases at our institution were retrospectively reviewed and categorized into three sequential cohorts. Procedure type, patient and operative characteristics, level of resident participation (primary surgeon [PS] or assistant), and postoperative variables were evaluated. RESULTS: Of the first 100 cases, 38% were lung resections, 23% were esophageal operations, and 20% were sympathectomies. The distribution of cases changed over time with the proportion of pulmonary resections significantly increasing. Patient age (P < 0.05), body mass index (P = not significant [NS]), and comorbidities (P = NS) increased over time. Resident participation as PS increased from 33%-59% between the early and late cohorts (P < 0.05). A subset analysis of the 20 lobectomies (7 attending PS, 13 residents) showed similar patient characteristics (P = NS): age (67 versus 69), body mass index (29.5 versus 26.1), and American Society of Anesthesiologists category (2.8 versus 2.8). Operative and postoperative characteristics were also similar (P = NS) regardless of PS: operative time (260 versus 249 min), estimated blood loss (187 versus 203 mL), and length of stay (4.8 versus 4.7 d). CONCLUSIONS: Residents can participate as the PS in a variety of thoracic operations during the implementation of a robotics program. Operative time, estimated blood loss, and length of stay were similar regardless of level of resident participation.

Checkpoint kinase 1 protein expression indicates sensitization to therapy by checkpoint kinase 1 inhibition in non-small cell lung cancer.

BACKGROUND: When presenting with advanced stage disease, lung cancer patients have <5% 5-y survival. The overexpression of checkpoint kinase 1 (CHK1) is associated with poorer outcomes and may contribute to therapy resistance. Targeting CHK1 with small-molecule inhibitors in p53 mutant tumors might improve the effectiveness of chemotherapy and radiotherapy in non-small cell lung cancer (NSCLC). METHODS: We evaluated CHK1 messenger RNA and protein levels in multiple NSCLC cell lines. We assessed cell line sensitization to gemcitabine, pemetrexed, and radiotherapy by CHK1 inhibition with the small molecule AZD7762 using proliferation and clonogenic cell survival assays. We analyzed CHK1 signaling by Western blotting to confirm that AZD7762 inhibits CHK1. RESULTS: We selected two p53 mutant NSCLC cell lines with either high (H1299) or low (H1993) CHK1 levels for further analysis. We found that AZD7762 sensitized both cell lines to gemcitabine, pemetrexed, and radiotherapy. Chemosensitization levels were greater, however, for the higher CHK1 protein expressing cell line, H1299, when compared with H1993. Furthermore, analysis of the CHK1 signaling pathway showed that H1299 cells have an increased dependence on the CHK1 pathway in response to chemotherapy. There was no increased sensitization to radiation in H1299 versus H1993. CONCLUSIONS: CHK1 inhibition by AZD7762 preferentially sensitizes high CHK1 expressing cells, H1299, to anti-metabolite chemotherapy as compared with low CHK1 expressing H1993 cells. Thus, CHK1 inhibitors may improve the efficacy of standard lung cancer therapies, especially for those subgroups of tumors harboring higher expression levels of CHK1 protein.

Chronic Infections of the Chest Wall.

Chronic chest wall infections may occur in soft tissue, cartilage, and bone. They may present as localized chest wall pain, a discrete mass initially mistaken for neoplasm, a superficial infection, or a draining sinus. Chronic chest wall infections are typically non-necrotizing and associated with lower morbidity than their more acute and necrotizing counterparts. Effective management of chest wall infections ranges from antimicrobial administration to wide surgical resection and subsequent reconstruction.

Neuroprotection Strategies in Aortic Surgery.

Neurologic injury is a potentially devastating complication of aortic surgery. The methods used in aortic surgery, including systemic cooling, initiation of circulatory arrest, and rewarming during the replacement of the aortic arch, are the most complex circulatory management and surgical procedures performed in modern-day surgery. Despite the plethora of published literature, neuroprotection in aortic surgery is largely based on observational studies and institutional-based practices. This article summarizes the current evidence and emerging strategies for neuroprotection in aortic arch operations.

Endoscopic ultrasound is inadequate to determine which T1/T2 esophageal tumors are candidates for endoluminal therapies.

OBJECTIVES: Esophageal endoscopic ultrasound is now regarded as essential in the staging of esophageal carcinoma. There is an increasing trend toward endoluminal therapies (ie, endoscopic mucosal resection and radiofrequency ablation) for pre-cancer or early-stage cancers because of concerns of high morbidity associated with esophagectomy. This study reviews our institutional experience with preoperative endoscopic ultrasound staging of early esophageal cancers in patients who underwent an esophagectomy to evaluate the accuracy of staging by endoscopic ultrasound and how this affects treatment recommendations. METHODS: A prospective esophagectomy database of all patients undergoing an esophagectomy for esophageal cancer at a single high-volume institution was retrospectively reviewed for patients with early-stage esophageal cancer. This study analyzed patients with clinical Tis to T1 disease, as predicted by preoperative endoscopic ultrasound, and correlated this with the pathologic stages after esophagectomy. The surgical outcomes were evaluated to assess the safety of esophagectomy as a treatment modality. RESULTS: From 2005 to 2011, 107 patients (93 male, 14 female) with a mean age of 66 years (range, 39-91 years) were staged by preoperative endoscopic ultrasound to have esophageal high-grade dysplasia, carcinoma in situ, or T1 cancer and underwent an esophagectomy. Tumor depth was correctly staged by endoscopic ultrasound in only 39% (23/59) of pT1a tumors (invading into the lamina propria or muscularis mucosa) and 51% (18/35) of pT1b tumors (submucosal). Of the endoscopic ultrasound-staged cT1a-lpN0 lesions, there were positive lymph nodes in 15% of pathologic specimens (2/13). Patients with pT1a-mm lesions had a 9% rate of pathologic lymph node involvement (1/11), and those with pT1b tumors had a 17% rate of lymph node spread (6/35). Esophagectomy was performed in all 107 patients with a 30-day mortality rate of less than 1% (1/107). CONCLUSIONS: The sensitivity and specificity of endoscopic ultrasound for determining true pathologic staging are poor for early-stage esophageal cancers. Lesions thought to be cT1a-lpN0 by endoscopic ultrasound have at least pN1 disease in 15% of cases. Endoluminal therapy of these lesions based on endoscopic ultrasound undertreats a significant number of patients. Esophagectomy is still the standard therapy for early-stage esophageal cancers in the majority of patients.

CHK1 levels correlate with sensitization to pemetrexed by CHK1 inhibitors in non-small cell lung cancer cells.

OBJECTIVE: Overexpression of checkpoint kinase 1 (CHK1) is associated with poorer patient outcome and therapeutic resistance in multiple tumor models. Inhibition of CHK1 has been proposed as a strategy to increase the effectiveness of chemotherapeutic agents, especially in p53-deficient tumors. In this study, we evaluated the effects of a novel CHK1 inhibitor, MK-8776, in combination with pemetrexed (PMX) on cell proliferation and survival in a panel of p53 mutant non-small cell lung cancer (NSCLC) cell lines. METHODS: We examined CHK1 expression in 442 resected lung adenocarcinoma specimens using Affymetrix U133A gene expression arrays. We correlated CHK1 mRNA expression with patient survival, tumor differentiation and genomic complexity. We evaluated CHK1 levels in NSCLC cell lines and identified four p53 mutant cell lines with variable CHK1 expression (H1993, H23, H1437 and H1299) based on publicly available gene expression data. We confirmed differential CHK1 mRNA and CHK1 protein levels by qRT-PCR, ELISA, Western Blot analysis (WB) and immunohistochemistry. We examined cell line sensitization to PMX in response to CHK1 inhibition with MK-8776 using WST-1 and clonogenic survival assays. RESULTS: We found that elevated CHK1 expression in primary lung adenocarcinomas correlates with poor tumor differentiation and significantly worse patient survival. Tumors with elevated CHK1 mRNA levels have a higher number of gene mutations and DNA copy number gain or amplifications. CHK1 inhibition by MK-8776 enhances sensitivity of NSCLC cell lines to PMX. CHK1 mRNA and protein expression are variable among NSCLC cell lines, and cells expressing higher levels of CHK1 protein are more sensitive to the CHK1 inhibition by MK-8776 as compared to low CHK1 expressing cells. CONCLUSIONS: These findings suggest that CHK1 levels may not only serve as a biomarker of poor prognosis in surgically-resected lung adenocarcinomas, but could also be a predictive marker for CHK1 inhibitor sensitivity, pending in vivo and clinical confirmation.

Feeding jejunostomy tubes placed during esophagectomy: are they necessary?

BACKGROUND: Jejunostomy tubes (JT) are routinely placed at the time of esophagectomy and can be associated with low--but not insignificant--morbidity. Increased emphasis on evidence-based medicine prompted this critical review of JT use during esophagectomy and factors that predict the absolute need for JT. METHODS: All esophagectomies performed at one tertiary care institution from 1995 through 2009 were retrospectively reviewed. Statistical analyses were performed to determine preoperative variables that would assist in selecting patients who should receive a JT. RESULTS: A total of 143 JTs were placed in 151 patients undergoing esophagectomy for carcinoma (83.4%), high-grade dysplasia (13.2%), and perforation (2.6%). Of these, 110 patients (76.9%) had returned to oral intake before discharge (median, 7 days), whereas 33 patients (23.1%) still required tube feedings. Of 8 patients who did not undergo intraoperative JT placement, 6 had resumed oral intake at discharge. Two patients were discharged on total parenteral nutrition. Logistic regression analysis of preoperative variables showed a body mass index of less than 18.5 kg/m2 conferred a likelihood of requiring a JT at discharge (odds ratio, 7.56; p<0.05). Age, sex, albumin level, type of esophagectomy, histology, stage, preoperative neoadjuvant therapy, and type of cancer were not significant predictors of JT need at discharge. CONCLUSIONS: The only absolute indication for JT placement after esophagectomy was a body mass index of less than 18.5 kg/m2. Other patients may have selective JT placement based on the surgeon's judgment.