Esophageal Cancer: Associations With (pN+) Lymph Node Metastases.

OBJECTIVES: To identify the associations of lymph node metastases (pN+), number of positive nodes, and pN subclassification with cancer, treatment, patient, geographic, and institutional variables, and to recommend extent of lymphadenectomy needed to accurately detect pN+ for esophageal cancer. SUMMARY BACKGROUND DATA: Limited data and traditional analytic techniques have precluded identifying intricate associations of pN+ with other cancer, treatment, and patient characteristics. METHODS: Data on 5806 esophagectomy patients from the Worldwide Esophageal Cancer Collaboration were analyzed by Random Forest machine learning techniques. RESULTS: pN+, number of positive nodes, and pN subclassification were associated with increasing depth of cancer invasion (pT), increasing cancer length, decreasing cancer differentiation (G), and more regional lymph nodes resected. Lymphadenectomy necessary to accurately detect pN+ is 60 for shorter, well-differentiated cancers (<2.5 cm) and 20 for longer, poorly differentiated ones. CONCLUSIONS: In esophageal cancer, pN+, increasing number of positive nodes, and increasing pN classification are associated with deeper invading, longer, and poorly differentiated cancers. Consequently, if the goal of lymphadenectomy is to accurately define pN+ status of such cancers, few nodes need to be removed. Conversely, superficial, shorter, and well-differentiated cancers require a more extensive lymphadenectomy to accurately define pN+ status.

Gastric Cancer, Version 3.2016, NCCN Clinical Practice Guidelines in Oncology.

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of death from cancer in the world. Several advances have been made in the staging procedures, imaging techniques, and treatment approaches. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Gastric Cancer provide an evidence- and consensus-based treatment approach for the management of patients with gastric cancer. This manuscript discusses the recommendations outlined in the NCCN Guidelines for staging, assessment of HER2 overexpression, systemic therapy for locally advanced or metastatic disease, and best supportive care for the prevention and management of symptoms due to advanced disease.

Esophageal and esophagogastric junction cancers, version 1.2015.

Esophageal cancer is the sixth most common cause of cancer deaths worldwide. Adenocarcinoma is more common in North America and Western European countries, originating mostly in the lower third of the esophagus, which often involves the esophagogastric junction (EGJ). Recent randomized trials have shown that the addition of preoperative chemoradiation or perioperative chemotherapy to surgery significantly improves survival in patients with resectable cancer. Targeted therapies with trastuzumab and ramucirumab have produced encouraging results in the treatment of advanced or metastatic EGJ adenocarcinomas. Multidisciplinary team management is essential for patients with esophageal and EGJ cancers. This portion of the NCCN Guidelines for Esophageal and EGJ Cancers discusses management of locally advanced adenocarcinoma of the esophagus and EGJ.

Gastric cancer, version 2.2013: featured updates to the NCCN Guidelines.

The NCCN Clinical Practice Guidelines in Oncology for Gastric Cancer provide evidence- and consensus-based recommendations for a multidisciplinary approach for the management of patients with gastric cancer. For patients with resectable locoregional cancer, the guidelines recommend gastrectomy with a D1+ or a modified D2 lymph node dissection (performed by experienced surgeons in high-volume centers). Postoperative chemoradiation is the preferred option after complete gastric resection for patients with T3-T4 tumors and node-positive T1-T2 tumors. Postoperative chemotherapy is included as an option after a modified D2 lymph node dissection for this group of patients. Trastuzumab with chemotherapy is recommended as first-line therapy for patients with HER2-positive advanced or metastatic cancer, confirmed by immunohistochemistry and, if needed, by fluorescence in situ hybridization for IHC 2+.

Optimum lymphadenectomy for esophageal cancer.

OBJECTIVE: Using Worldwide Esophageal Cancer Collaboration data, we sought to (1) characterize the relationship between survival and extent of lymphadenectomy, and (2) from this, define optimum lymphadenectomy. SUMMARY BACKGROUND DATA: What constitutes optimum lymphadenectomy to maximize survival is controversial because of variable goals, analytic methodology, and generalizability of the underpinning data. METHODS: A total of 4627 patients who had esophagectomy alone for esophageal cancer were identified from the Worldwide Esophageal Cancer Collaboration database. Patient-specific risk-adjusted survival was estimated using random survival forests. Risk-adjusted 5-year survival was averaged for each number of lymph nodes resected and its relation to cancer characteristics explored. Optimum number of nodes that should be resected to maximize 5-year survival was determined by random forest multivariable regression. RESULTS: For pN0M0 moderately and poorly differentiated cancers, and all node-positive (pN+) cancers, 5-year survival improved with increasing extent of lymphadenectomy. In pN0M0 cancers, no optimum lymphadenectomy was defined for pTis; optimum lymphadenectomy was 10 to 12 nodes for pT1, 15 to 22 for pT2, and 31 to 42 for pT3/T4, depending on histopathologic cell type. In pN+M0 cancers and 1 to 6 nodes positive, optimum lymphadenectomy was 10 for pT1, 15 for pT2, and 29 to 50 for pT3/T4. CONCLUSIONS: Greater extent of lymphadenectomy was associated with increased survival for all patients with esophageal cancer except at the extremes (TisN0M0 and >or=7 regional lymph nodes positive for cancer) and well-differentiated pN0M0 cancer. Maximum 5-year survival is modulated by T classification: resecting 10 nodes for pT1, 20 for pT2, and >or=30 for pT3/T4 is recommended.

Surgical treatment of metastatic disease to the lung.

The presence of distant metastases usually implies disease not amenable to cure through surgical resection. In such cases, chemotherapy is the mainstay of treatment, with surgery or radiation reserved for palliative measures. However, metastases limited to the lung may be resected with resultant prolonged patient survival compared to unresectable, widely disseminated metastases. Isolated pulmonary metastases should therefore not be considered untreatable. In this review, we discuss the pathophysiology of pulmonary metastases. We outline prognostic factors associated with metastases, and propose criteria to help select patients for metastasectomy. Surgical approaches, including various open techniques and video-assisted thoracoscopy, are covered. Surgical issues, including the need for unilateral versus bilateral exploration, the extent of resection to achieve cure, the need for lymph node dissection, and the benefit of repeat operations, are discussed. Finally, we review some of the more common tumors that metastasize to the lungs, and the role of metastasectomy in their treatment. Resection of pulmonary metastases confers a survival benefit to a select group of patients so long as the primary tumor is controlled, metastases are limited to the lungs, the patient can tolerate the operation from a cardiopulmonary standpoint, and the metastases are completely resected.

Lung Resection in the Postpneumonectomy Patient.

Pulmonary resection after pneumonectomy is a reasonable option in selected patients. Wedge resection for single peripheral metachronous disease has the best outcome with 5-year survival as high as 63%. Current and predicted postoperative cardiopulmonary reserve should be evaluated carefully. Stereotactic body radiotherapy is a promising alternative for inoperable patients.

Treatment of non-small cell lung cancer stage I and stage II: ACCP evidence-based clinical practice guidelines (2nd edition).

BACKGROUND: The surgical treatment of stage I and II non-small cell lung cancer (NSCLC) continues to evolve in the areas of intraoperative lymph node staging (specifically the issue of lymph node dissection vs sampling), the role of sublobar resections instead of lobectomy for treatment of smaller tumors, and the use of video-assisted techniques to perform anatomic lobectomy. Adjuvant therapy (both chemotherapy and radiation therapy) and the use of larger fractions of radiotherapy delivered to a smaller area for nonoperative treatment of early stage NSCLC have shown promising results. METHODS: The panel selected the following areas for review based on clinical relevance and the amount and quality of data available for analysis: surgical approaches to resecting early stage NSCLC, methods of lymph node staging at the time of surgical resection, adjuvant chemotherapy in the treatment of early stage NSCLC, and the use of radiation therapy for primary treatment of early stage NSCLC as well as in the adjuvant setting. Recommendations by the multidisciplinary writing committee were based on literature review using established methods. RESULTS AND CONCLUSIONS: Surgical resection remains the treatment of choice for stage I and II NSCLC, although surgical methods continue to evolve. Adjuvant chemotherapy for patients with stage II, but not stage I, NSCLC is well established. Radiotherapy remains an important treatment for either cases of early stage NSCLC that are medically inoperable or patients who refuse surgery.

Benefits of Supplemental Jejunostomy Tube Feeding During Neoadjuvant Therapy in Patients with Locally Advanced, Potentially Resectable Esophageal Cancer.

BACKGROUND: Standard treatment for locally advanced esophageal cancer includes neoadjuvant therapy followed by surgical resection. However, many patients experience a period of decreased oral intake during neoadjuvant treatment and are at risk for malnutrition. We hypothesize that use of jejunostomy tube (j-tube) feedings during neoadjuvant therapy in selected patients may be associated with better perioperative outcomes. METHODS: A prospectively collected database at a single institution was retrospectively analyzed. The study period was from 2005 to 2015. Patients who underwent j-tube placement before neoadjuvant therapy before definitive resection for esophageal cancer were included in the analysis. Perioperative outcomes were compared between patients who adhered to recommended tube feeds during neoadjuvant therapy (users) and patients who did not adhere (nonusers). RESULTS: During the study period, 94/301 patients received a j-tube before or during neoadjuvant therapy for esophageal cancer. Seventy-three patients utilized tube feeds regularly during the neoadjuvant phase, while 21 patients did not. The groups did not differ significantly with respect to clinical factors such as dysphagia on presentation, postneoadjuvant therapy performance status, or Charlson Comorbidity Index. Perioperative pneumonia rates were lower in j-tube users compared to nonusers (6.8% [5 of 73] versus 23.8% [5 of 21]), respectively, P = .036); this difference remained significant with adjustment for type of surgery (odds ratio = 0.16, P = .018). CONCLUSIONS: j-Tube users had a significantly lower incidence of pneumonia within 30 days of curative resection when compared to nonusers. j-Tube feedings during neoadjuvant therapy for selected patients with locally advanced esophageal cancer should be encouraged.

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.

Complete response to neoadjuvant chemoradiotherapy in esophageal carcinoma is associated with significantly improved survival.

PURPOSE: Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. A large single-center experience was reviewed to determine which treatment-related variables could predict survival and recurrence. PATIENTS AND METHODS: All patients undergoing esophagectomy between January 1994 and December 2002 were reviewed. Univariate and multivariate analyses were performed using log-rank and Cox proportional hazards models, and survival curves were estimated using the Kaplan-Meier method. RESULTS: Of 171 patients with invasive cancer, 131 (77%) underwent preoperative CRT. The average age was 60 years, and most patients were male (85%). Operations performed included Ivor-Lewis (60%), transhiatal (8%), three-hole (23%), or left thoracoabdominal (8%) esophagectomy. Perioperative mortality rate was 5%. Median overall survival (OS) of the entire group was 33 months, and the 5-year OS rate was 26%. Induction CRT was associated with a 33% 5-year survival rate compared with 11% for surgery alone (P = .43). Patients downstaged to pathologic stage 0 or I had an improved OS and disease-free survival (DFS) compared with those patients who were not downstaged (P = .022). Additionally, the ability to perform an R0 resection was a significant factor for OS and DFS (n = 130; P < .0001 and P <.0002, respectively). CONCLUSION: Response to CRT and the ability to perform an R0 resection are associated with significantly improved survival in patients with esophageal carcinoma.

Minimally Invasive versus Open Thymectomy for Thymic Malignancies: Systematic Review and Meta-Analysis.

Complete resection is the standard of care for treatment of thymic malignancies. The use of minimally invasive surgery remains controversial. We searched online databases and identified studies from 1995 to 2014 that compared minimally invasive to open thymectomy for thymic malignancies. Study end points included operative blood loss, operative time, respiratory complications, cardiac complications, length of hospital stay, R0 resection, and recurrence. We summarized outcomes across studies using random-effects meta-analysis to account for study heterogeneity. We calculated ORs for binary outcomes and standardized mean differences for continuous outcomes. We calculated incidence rate ratios for the number of recurrences, accounting for total person-time observed in each study. Of 516 potential reference studies, 30 with a total of 2038 patients met the inclusion criteria. Patients with Masaoka stage I or II thymic malignancy constituted 94.89% of those in the minimally invasive surgery (MIS) group and 78.62% of those in open thymectomy (open) group. Mean tumor size was 4.09 cm (MIS) versus 4.80 (open). Of the 1355 MIS cases, 32 were converted to open cases. Patients in the MIS group had significantly less blood loss; however, no significant differences in operating time, respiratory complications, cardiac complications, or overall complications were identified. Length of stay was shorter for patients in the MIS group. When patients with Masaoka stage I and II thymic malignancy only were analyzed, there was no difference in rate of R0 resection or overall recurrence rate. One postoperative death occurred in the open group. The results of this unadjusted meta-analysis of published reports comparing minimally invasive with open thymectomy suggest that in selected patients with thymic malignancy, minimally invasive thymectomy is safe and can achieve oncologic outcomes similar to those of open thymectomy.

Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.

PURPOSE: There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. METHODS AND MATERIALS: We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. RESULTS: A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. CONCLUSIONS: Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning.

Morbidity and mortality are not increased after induction chemoradiotherapy followed by esophagectomy in patients with esophageal cancer.

Attempts to improve survival of patients with esophageal cancer have been made using induction chemoradiotherapy (CRT) followed by surgery. This approach may be associated with higher complication rates. A large single-center experience was reviewed to determine whether induction CRT was associated with increased morbidity and mortality among 179 patients undergoing esophagectomy between January 1994 and December 2002. Morbidity was recorded as any complication requiring additional intervention. Mortality was defined as patient death within the first 30 postoperative days or death during the initial hospitalization. In total, 131 patients underwent induction CRT followed by surgery. The most common operation was an Ivor-Lewis esophagogastrectomy (60%). Median survival of the entire group was 33 months and 5-year survival was 26%. Perioperative mortality was 5% and did not differ between induction (4.6%) and non-induction (6.3%) groups. The overall complication rate was 57%, reflecting a very liberal definition of postoperative complications. There were no differences between the two groups in terms of such major complications as anastomotic leak, pneumonia, acute respiratory distress syndrome, respiratory failure, chylothorax, atrial arrhythmia, and wound infections. There were only two complications that occurred more frequently in the induction group--venous thrombosis (8.4% v 0%) and vocal cord paresis (7.6% v 2.1%). The median hospital stay was similar in patients who had complications versus those who did not (12 v 13 days) and in patients who underwent induction CRT versus those that did not (12 days v 13.5 days). Esophagectomy can be performed safely with low mortality and acceptable morbidity following neoadjuvant chemotherapy and radiation with no increase in hospital stay for patients with complications.

Radiofrequency ablation of primary lung cancer: results from an ablate and resect pilot study.

STUDY OBJECTIVES: The role of radiofrequency ablation (RFA) for primary lung cancer remains poorly defined. The purpose of this "ablate and resect" pilot study was to evaluate the safety of performing RFA in patients with primary non-small cell lung cancer (NSCLC) and to characterize the histologic changes in tumor tissue following such ablation. DESIGN: This prospective study was undertaken at a single institution, and 10 patients were accrued from June 2002 to June 2003. Eligible patients included those with clinical stage I or II disease. RFA of the tumor was performed through a standard thoracotomy followed by conventional lobectomy and lymph node dissection. Extent of cell death was determined histologically. MEASUREMENTS AND RESULTS: Following the exclusion of two patients, the treated portions of eight tumors were examined for tumor cell viability. Gross inspection and routine histologic staining could not reliably identify the "immediately ablated" tissue. However, using a supravital staining technique, the treated areas from seven of the eight tumors (87.5%) demonstrated > 80% nonviability (100% nonviability was noted in the treated areas from three of the eight tumors). No bleeding or thermal complications were noted at the time of RFA, and none of the patients had skin burns at the electrode dispersive pad sites. CONCLUSIONS: RFA of primary NSCLC is feasible and can be performed safely in the setting of an open thoracotomy. Complete tumor cell necrosis, as determined by supravital staining, was noted in the treated areas from three of eight tumors (37.5%). Such complete ablation was observed in the treated areas from smaller tumors (< 2 cm), whereas the treated areas from larger tumors demonstrated incomplete ablation. Additional investigation with histopathologic correlation is needed to fully assess the long-term efficacy of RFA for NSCLC.

Increased time from neoadjuvant chemoradiation to surgery is associated with higher pathologic complete response rates in esophageal cancer.

BACKGROUND: The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in nonesophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer. METHODS: Two hundred thirty-one sequentially treated patients from 2000 to 2011 were identified for this study; 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also into 3-week interval groups. Treatment factors and surgical morbidity data, including the estimated blood loss and length of operative stay, were also assessed. RESULTS: Quartiles for the neoadjuvant chemoradiation to surgery interval were less than 45 days, 46 to 50 days, 51 to 63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7%, and 40.9% (p = 0.03). Results for 3-week intervals were similar (p = 0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks. CONCLUSIONS: A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.

Bilateral granulosa cell tumors: a novel malignant manifestation of multiple endocrine neoplasia 1 syndrome found in a patient with a rare menin in-frame deletion.

INTRODUCTION: Multiple endocrine neoplasia 1 (MEN1) is a cancer syndrome resulting from mutations of the MEN1 gene. The syndrome is characterized by neoplasia of the parathyroid and pituitary glands, and malignant tumors of the endocrine pancreas. Other manifestations include benign lipomas, angiofibromas, and carcinoid tumors commonly originating in the colon, thymus, and lung. This is the first report of MEN1 syndrome manifesting as bilateral granulosa cell ovarian tumors, and which is associated with a rare intronic mutation of the MEN1 gene. CASE REPORT: A 41-year-old woman presented with abdominal pain, increasing abdominal girth, and dysmenorrhea. Ultrasound demonstrated enlarged ovaries and uterine fibroids. After an exploratory laparotomy, she subsequently underwent bilateral salpingo-oophorectomy with hysterectomy where the pathology revealed bilateral cystic granulosa cell tumors of the ovaries. Additional workup including computed tomography imaging discovered a thymic mass, which the pathology showed was malignant, along with a pancreatic mass suspicious for a neuroendocrine tumor. Hyperparathyroidism was also discovered and was found to be secondary to a parathyroid adenoma. Genetic testing revealed an exceedingly rare mutation in the MEN1 gene (c.654 + 1 G>A). DISCUSSION: Mutations of the menin gene leading to MEN1 syndrome are classically nonsense or missense mutations producing a dysfunctional protein product. Recently, researchers described a novel mutation of MEN1 (c.654 + 1 G>A) in a male proband meeting the criteria for clinical MEN1 syndrome. Functional analysis performed on the stable mutant protein showed selective disruption of the transforming growth factor beta signaling pathway, yet it maintained its wild-type ability to inhibit nuclear factor kappa B and to suppress JunD transcriptional activity. CONCLUSION: To our knowledge, this is the first report of MEN1 syndrome associated with bilateral granulosa cell malignancy. We postulate that this presentation may be due to the novel menin gene mutation recently described.

Treatment of stage II non-small cell lung cancer.

Based on clinical assessment alone, patients with stage II non-small cell lung cancer (NSCLC) comprise only 5% of all patients with NSCLC. In addition, patients with stage II NSCLC represent a heterogeneous group, since stage II consists of patients with T1-2N1 or T3N0 tumors. By definition, patients with tumor invading the chest wall apex, mediastinum, diaphragm, or even the mainstem bronchus may all have T3 tumors. The extent of the data available regarding treatment of each of these different groups is therefore limited. The quality of the data is limited as well, because information often comes from small series of patients. Studies of adjuvant therapy after complete resection of stage II NSCLC are an important exception to this generalization, since data from large, randomized studies of adjuvant radiation therapy, chemotherapy, or a combination of the two are available for analysis. Superior sulcus tumors are discussed elsewhere in these guidelines.

Treating tobacco use and dependence: an evidence-based clinical practice guideline for tobacco cessation.

The prevention of tobacco-related morbidity and mortality through smoking cessation intervention is among the most vital missions of the chest clinician. This article summarizes the major findings and clinical recommendations of the US Department of Health and Human Services/Public Health Service Guideline, Treating Tobacco Use and Dependence, which is a comprehensive, evidence-based blueprint for smoking cessation. By becoming fluent in the clinical interventions and by implementing the simple institutional changes described in this article and in the guideline, chest clinicians can more effectively intervene with their patients who smoke.